Background: Posttraumatic stress disorder (PTSD) is associated with metabolic syndrome and various addictive behaviours. Food addiction (FA) is associated with obesity, and individuals with PTSD have higher rates of FA than those without. It is unclear whether addictive-like eating patterns contribute to the metabolic dysfunction in PTSD.Objective: We examined the relative contributions of PTSD, FA, and sex - as well as their interactive effects - to the systemic inflammation (CRP) and metabolic syndrome components (MetS: waist circumference, glucose, triglycerides, HDL cholesterol, insulin) in a general population of the Upper Silesia region in Poland.Method: N = 187 participants (52.7% women) completed Yale Food Addiction Scale 2.0 (FA symptoms count), Clinician-Administered PTSD Scale for DSM-5 (CAPS-5) semi-structured interview (PTSD or other trauma and stressor-related disorder (OTSR) diagnosis presence), anthropometric assessment, and phlebotomy in a fasted state.Results: A series of hierarchical linear regressions indicated that greater number of FA symptoms had a significant effect on greater waist circumference, while PTSD/OTSR diagnosis had a significant effect on higher insulin levels. Sex did not moderate these relationships.Conclusions: It appears that dysregulated eating patterns are associated with greater abdominal obesity, but not with metabolic dysfunction. PTSD/OTSR, but not FA, contributes to greater insulin levels. The average metabolic indices were within normal limits reflecting a non-clinical nature of the sample. Future longitudinal studies should examine whether detection of and intervention for PTSD/OTSR symptoms may be a strategy for preventing progression of metabolic dysfunction.

Identifying effective predictors early in life is crucial to enable timely prevention and intervention to improve cardiometabolic health outcomes. Adiposity rebound (AR) is an important period in early life, with earlier AR increasing the risk of cardiometabolic abnormalities. However, the role and mechanism of genetic factors in this association are unclear. Therefore, this study reviews the potential genetic mechanisms influencing the age at AR, as well as the genetic mechanisms linking earlier AR with cardiometabolic abnormalities.

A comprehensive literature search was conducted in PubMed and China National Knowledge Infrastructure databases using a combination of medical subject headings terms and related keywords, including "adiposity rebound", "cardiometabolic", "obesity", "BMI trajectory", "diabetes mellitus", "dyslipidemias", "hypertension", "metabolic syndrome", "genetics", and "epigenetic". Citation tracking was performed as a supplementary search strategy. All potentially relevant articles were subsequently subjected to full-text evaluation for eligibility assessment.

Polymorphisms in the DMRT1, FTO, LEPR, and TFAP2B genes, along with obesity susceptibility, can influence the age at AR. Single-nucleotide polymorphisms associated with the age at AR are enriched in the insulin-like growth factor 1 (IGF-1) signaling pathway, which can be modulated by the LEPR and TFAP2B genes. Shared genetic mechanisms between cardiometabolic abnormalities and the age at AR are influenced by obesity-related genetic variants. These variants regulate the growth hormone (GH)/IGF-1 axis, advancing AR and leading to cardiometabolic abnormalities. Earlier AR alters adiponectin and leptin levels, further activating the GH/IGF-1 axis and creating a vicious cycle. Long-term breastfeeding can counteract the adverse effects of obesity-related genetic susceptibility on AR timing, thereby reducing the genetic risk of cardiometabolic abnormalities.

Our results support earlier AR as a marker for identifying cardiometabolic risk and screening high-risk populations at the genetic level.

Obesity is a complex, chronic, and recurrent disease marked by abnormal or excessive fat accumulation that poses significant health risks. The distribution of body fat, especially ectopic fat deposition, plays a crucial role in the development of chronic metabolic diseases. Under normal conditions, fatty acids are primarily stored in subcutaneous adipose tissue; however, excessive intake can lead to fat accumulation in visceral adipose tissue and ectopic sites, including the pancreas, heart, and muscle. This redistribution is associated with disruptions in energy metabolism, inflammation, and insulin resistance, impairing organ function and raising the risk of cardiovascular disease, diabetes, and fatty liver. This review explores the roles of visceral and ectopic fat in the development of insulin resistance and related diseases such as type 2 diabetes and metabolic dysfunction-associated steatotic liver disease. Specifically, we examine the structure and characteristics of different fat types, their associations with disease, and the underlying pathogenic mechanisms. Future strategies for managing obesity-related diseases may include lifestyle modifications, surgical interventions, and emerging medications that target lipid metabolism and energy regulation, aiming to improve patient outcomes.

The combustion of diesel in engines contributes polycyclic aromatic hydrocarbons to Diesel Particulate Matter (DPM) present in the atmosphere, therefore causing toxic mitigating consequences by eliciting oxidative modulation. Currently, type 2 diabetes mellitus is reported as a global menace, causing about 1.5 million deaths in 2019 and contributing to about 48% of related deaths among the populace aged below 70 years. (GBDCN, 2020). Silibinin (SIL) is a flavolignan from milk thistle with substantive therapeutic potential. This work elucidates the effects of SIL on glucose modulatory pathways (PI3K-AKT-GLUT 2 and AMPK-GLUT 2), inflammation and redox imbalance in the pancreas of diabetic rats subjected to DEP. Streptozocin was used to induce Type-2 diabetes mellitus in rats, which were further endangered to DEP (0.4 and 0.5 mg/kg) later, post-treated with SIL 40 mg/kg. For comparison, a parallel group of nondiabetic rats were exposed to DEP and afterwards treated with SIL, whilst the results were compared to the diabetic group. Results state that SIL leads to marked/substantial modulation in insulin-associated genes (PI3K, AKT, AMPK, GLUT 2), inflammatory markers (IL-1β, IL-10), peroxidation (MDA, CD) and antioxidative status (SOD, CAT, GPX, GSH, HO-1) in vivo as negatively induced by DEP and hyperglycaemia, thereby restoring glucose homeostasis. Taken together, SIL proffers the potential to ameliorate pancreatic-toxicity caused by DEP and high blood glucose/elevated glucose levels.

Insulin resistance plays a pivotal role in the preclinical stages of type 1 diabetes (T1D).

This study aims at exploring the genetic, metabolic, and immunological features associated with insulin resistance among individuals at risk of developing T1D.

We retrospectively selected relatives of individuals with T1D from participants in the TrialNet Pathway to Prevention study. They were categorized into two groups: high-H (n = 27) and low-H (n = 30), based on the upper and lower quartiles of insulin resistance assessed using the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Genetic predisposition was determined using the T1D Genetic Risk Score 1 (GRS1). Additionally, glucose control was evaluated through an oral glucose tolerance test and levels of metabolic hormones and inflammatory cytokines were measured in the serum. Flow cytometry analysis was employed to assess frequency and phenotype of islet-specific CD8 T cells.

While GRS1 were similar between the low-H and high-H groups, high-H individuals displayed a distinct metabolic profile, characterized by compensatory hyperinsulinemia, even while maintaining normoglycemia. Circulating cytokine levels were similar between the two groups. However, immune profiling revealed a central memory and activated profile of GAD65-specific CD8 T cells, along with an increased frequency of insulin-specific CD8 T cells in high-H individuals. The enrichment in insulin-specific CD8 T cells was independent of body mass.

These findings highlight the intricate interplay between insulin resistance, genetic factors, and immune activation in the context of T1D susceptibility, indicating potential connections between insulin resistance and immune responses specific to islet cells.

The leading cause of death in type 2 diabetes mellitus (T2DM) patients is cardiovascular-related events, including myocardial infraction-induced ventricular arrhythmia. Previous studies have shown that T2DM-induced functional remodeling of cardiac vagal postganglionic (CVP) neurons contributes to ventricular arrhythmogenesis. As leptin resistance is common in T2DM patients, and CVP neurons are located in epicardial adipose pads, a tissue that secretes leptin, in this study we aimed to elucidate a correlation between leptin resistance and CVP neuronal dysfunction in T2DM.

A high fat-diet/low dose streptozotocin-induced T2DM rat model was used in this study to characterize T2DM-induced alterations in cardiac parasympathetic tone, determined by changes in baroreflex sensitivity and CVP neuronal excitability. The impact of leptin resistance on CVP neurons was also studied by examining the expression of leptin in epicardial adipose pads, and leptin receptors and uncoupling protein 2 (UCP2) in CVP neurons.

T2DM rats exhibited diminished baroreflex sensitivity, and decreased CVP neuronal excitability, demonstrated by a reduced frequency of action potentials, diminished nAChR currents, and an attenuated response to nicotine stimulation. Additionally, compared to sham animals, the expression of leptin receptors and UCP2 in CVP neurons was reduced as early as 4 weeks post-T2DM although the leptin levels in epicardial adipose pads was increased during the progression of T2DM, which demonstrated the occurrence of leptin resistance in T2DM CVP neurons.

Cardiac parasympathetic dysfunction in T2DM rats is due, in part, to functional remodeling of CVP neurons. As leptin resistance develops as early as 4 weeks post-T2DM induction, diminished leptin receptors-UCP2 signaling may contribute to CVP neuronal dysregulation.

The pancreas, an organ with dual functions, regulates blood glucose levels through the endocrine system by secreting hormones such as insulin and glucagon. It also aids digestion through the exocrine system by secreting digestive enzymes. Complex interactions and signaling mechanisms between the endocrine and exocrine functions of the pancreas play a crucial role in maintaining metabolic homeostasis and overall health. Compelling evidence indicates direct and indirect crosstalk between the endocrine and exocrine parts, influencing the development of diseases affecting both. From a developmental perspective, the exocrine and endocrine parts share the same origin-the "tip-trunk" domain. In certain circumstances, pancreatic exocrine cells may transdifferentiate into endocrine-like cells, such as insulin-secreting cells. Additionally, several pancreatic diseases, including pancreatic cancer, pancreatitis, and diabetes, exhibit potential relevance to both endocrine and exocrine functions. Endocrine cells may communicate with exocrine cells directly through cytokines or indirectly by regulating the immune microenvironment. This crosstalk affects the onset and progression of these diseases. This review summarizes the history and milestones of findings related to the exocrine and endocrine pancreas, their embryonic development, phenotypic transformations, signaling roles in health and disease, the endocrine-exocrine crosstalk from the perspective of diseases, and potential therapeutic targets. Elucidating the regulatory mechanisms of pancreatic endocrine and exocrine signaling and provide novel insights for the understanding and treatment of diseases.

The escalating cases of type II diabetes combined with adverse side effects of current antidiabetic drugs spurred the advancement of innovative approaches for the management of postprandial glucose levels. α-Amylase is an endoamylase responsible for the breakdown of internal α-1,4-glycosidic linkages in dietary starch, producing oligosaccharides. Subsequently, α-glucosidase degraded these oligosaccharides to monosaccharides, which are absorbed into the bloodstream and become available to the body. The inhibitors of α-amylase reduced the digestibility of carbohydrates accompanied by delayed glucose absorption, leading to decreased blood glucose levels after meals and thus, inhibition of the enzyme seems to be a crucial strategy for diabetes management and improving overall glycemic control in diabetic patients. The present review article emphasizes the therapeutic promise of recently discovered potential α-amylase inhibitors, highlighting their in vitro, in silico and in vivo profiles. Ultimately, we addressed the contemporary challenges and potential routes ahead in the search for safe and reliable α-amylase inhibitors for clinical use, summarizing the most recent research in the field.

Cancer has become the leading cause of death among individuals with type 2 diabetes (T2D) in high-income countries. T2D is suggested to directly influence cancer progression. However, the association between T2D and melanoma stage at diagnosis remains uncertain, as well as any potential sex disparities.

To investigate the association between T2D and the melanoma TNM stage (Breslow thickness, ulceration status, lymph node metastases, and distant metastases) at the time of diagnosis and to assess whether the association is affected by sex.

A nationwide cross-sectional study was conducted, including all patients diagnosed with melanoma between 2004 and 2022 identified in the Danish Cancer Register. T2D status was ascertained using a validated register based algorithm. The association between T2D and melanoma stage was estimated using univariable and multivariable logistic regression analyses adjusted for sex, age, comorbidity, and year of diagnosis.

The study included 30,315 individuals with melanoma. The multivariable analyses showed that T2D was associated with an increased adjust odds ratio (aOR) of tumour thickness > 4 mm (aOR 1.30, 95 %CI: [1.10-1.52]), the presence of ulceration (aOR: 1.25, 95 % CI: [1.09-1.43]), lymph node metastases (aOR 1.27 [1.10-1.47]), and distant metastases (aOR: 1.26 [1.01-1.56]). Furthermore, sex stratified analyses showed that T2D was associated with distant metastases in women, but not in men.

Individuals with T2D were more likely to be diagnosed with advanced stages of local, regional, and distant melanoma. This highlights the need for greater melanoma awareness and further research into treatment responses in individuals with T2D.

Type 2 diabetes mellitus (T2DM) accelerates brain aging and disrupts brain functional network connectivity, though the specific mechanisms remain unclear. This study aimed to investigate T2DM-driven alterations in brain functional network connectivity and topology.

Eighty-five T2DM patients and 67 healthy controls (HCs) were included. All participants underwent clinical, neuropsychological, and laboratory tests, followed by MRI examinations, including resting-state functional magnetic resonance imaging (rs-fMRI) and three-dimensional high-resolution T1-weighted imaging (3D-T1WI) on a 3.0 T MRI scanner. Post-image preprocessing, brain functional networks were constructed using the Dosenbach atlas and analyzed with the DPABI-NET toolkit through graph theory.

In T2DM patients, functional connectivity within and between the default mode network (DMN), frontal parietal network (FPN), subcortical network (SCN), ventral attention network (VAN), somatosensory network (SMN), and visual network (VN) was significantly reduced compared to HCs. Conversely, two functional connections within the VN and between the DMN and SMN were significantly increased. Global network topology analysis showed an increased shortest path length and decreased clustering coefficient, global efficiency, and local efficiency in the T2DM group. MoCA scores were negatively correlated with the shortest path length and positively correlated with global and local efficiency in the T2DM group. Node network topology analysis indicated reduced clustering coefficient, degree centrality, eigenvector centrality, and nodal efficiency in multiple nodes in the T2DM group. MoCA scores positively correlated with clustering coefficient and nodal efficiency in the bilateral precentral gyrus in the T2DM group.

This study demonstrated significant abnormalities in connectivity and topology of large-scale brain functional networks in T2DM patients. These findings suggest that brain functional network connectivity and topology could serve as imaging biomarkers, providing insights into the underlying neuropathological processes associated with T2DM-related cognitive impairment.

The impact of islet neuronal nitric oxide synthase (nNOS) on glucose-stimulated insulin secretion (GSIS) is less understood. We investigated this issue by performing simultaneous measurements of the activity of nNOS versus inducible NOS (iNOS) in GSIS using isolated murine islets. Additionally, the significance of extracellular NO on GSIS was studied. Islets incubated at basal glucose showed modest nNOS but no iNOS activity. Glucose-induced concentration-response studies revealed an increase in both NOS activities in relation to secreted insulin. Culturing at high glucose increased both nNOS and iNOS activities inducing a marked decrease in GSIS in a following short-term incubation at high glucose. Culturing at half-maximal glucose showed strong iNOS expression revealed by fluorescence microscopy also in human islets. Experiments with nNOS-inhibitors revealed that GSIS was inversely related to nNOS activity, the effect of iNOS activity being negligible. The increased GSIS after blockade of nNOS was reversed by the intracellular NO-donor hydroxylamine. The enhancing effect on GSIS by nNOS inhibition was independent of membrane depolarization and most likely exerted in the pentose phosphate pathway (PPP). GSIS was markedly reduced, 50%, by glucose-6-phosphate dehydrogenase (G-6-PD) inhibition both in the absence and presence of nNOS inhibition. NO gas stimulated GSIS at low and inhibited at high NO concentrations. The stimulatory action was dependent on membrane thiol groups. In comparison, carbon monoxide (CO) exclusively potentiated GSIS. CO rather than NO stimulated islet cyclic GMP during GSIS. It is suggested that increased nNOS activity restrains GSIS, and that the alternative pathway along the PPP initially might involve as much as 50% of total GSIS. In the PPP, the acute insulin response is downregulated by a negative feedback effect executed by a marked upregulation of nNOS activity elicited from secreted insulin exciting insulin receptors at exocytotic sites of an nNOS-associated population of secretory granules.

Emerging evidence suggests that the JAK/STAT/SOCS signaling pathway is crucial for maintaining homeostasis, and its dysregulation contributes to diabetes development. This study aimed to evaluate the roles of SOCS-1 and SOCS-3 in the pancreas, liver, and kidney and to explore the involvement of the JAK/STAT pathway in the molecular mechanisms underlying their effects on inflammation and apoptosis, as well as organ injury in a diabetes mellitus (DM) model. Additionally, we sought to elucidate the role of the JAK/STAT/SOCS pathway in mediating the effects of lycopene (LYC).

Forty Sprague-Dawley rats were divided into control, DM, LYC, and LYC+DM groups. Diabetes was induced in the DM groups using streptozotocin. LYC was administered to the LYC and LYC+DM groups for 30 days. After the study, pancreas, liver, and kidney tissues were analyzed using histopathological, immunohistochemical, and PCR methods.

Significant vacuolization and degenerative changes were observed in the DM group's pancreatic islet cells. Kidney and liver tissues showed hyperemia, hemorrhage, and degenerative changes. Immunohistochemical analysis revealed increased expression of Cas-3, TNF-α, IFN-α, and IL-6, while IL-10 was significantly reduced in the DM group. PCR analysis showed elevated levels of TNF-α and Cas-3, with decreased SOCS-1 and SOCS-3 expression in the DM group.

This study highlights the therapeutic potential of targeting the JAK/STAT/SOCS pathway with lycopene, demonstrating its promise in mitigating diabetes and related complications.

Diabetes mellitus is one of the leading causes of morbidity and mortality among non-communicable diseases worldwide. The etiology of diabetes can be mainly attributed to factors such as genetic susceptibility, unhealthy diets, and chronic medications. Chronic medications such as HIV-antiretrovirals (ARVs) have been previously associated with the risks of developing metabolic complications. Hence, this protocol outlines the process for conducting a systematic review to investigate the association between chronic ARV treatment and the onset of metabolic syndrome complications.

The studies included in the systematic review are selected according to the inclusion and exclusion criteria. These studies are searched using search engines or databases such as PUBMED, GOOGLE SCHOLAR, MEDLINE, ScienceDirect, and EMBASE DATABASE. The articles that remained after full article screening will be assessed for bias using the Downs and Black checklist, and the data will be extracted. Additionally, heterogeneity tests will be conducted using both Χ2 and I 2 tests, meta-analysis will be conducted using the Review Manager version 5.4 software (RevMan), and data will be presented in forest plots. Grading of Recommendations Assessment, Development, and Evaluation approach (GRADE) will be used to assess the strength of evidence in eligible reports.

The findings intend to give an insight into the ARVs as a risk factor for metabolic diseases and further elaborate on the regimen that possesses a high risk between the first and second regimens. This protocol has been registered on PROSPERO Database #CRD42024521322.

Previous studies have established a correlation between elevated levels of remnant cholesterol (RC) and the occurrence of type 2 diabetes mellitus (T2D) as well as insulin resistance (IR); however, the precise nature of these associations remains incompletely elucidated. This study aimed to evaluate the relationships between RC and IR, as well as RC and T2D, and to determine the extent to which IR mediated the relationship between RC and T2D.

This was an observational study that utilized cross-sectional methods to examine the general population in the National Health and Nutrition Examination Survey (NHANES) 1999-2020. The participants were divided into 4 groups according to the RC quartiles. The outcome was the prevalence of IR and T2D. Survey-weighted binary logistic regression analysis was used to analyze the associations, and the restricted cubic spline (RCS) curve was used to further analyze the nonlinear relationship. Receiver operating characteristic (ROC) curves were generated to evaluate the diagnostic performance, and the areas under the curves (AUC) of RC, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and triglycerides (TG) were compared using the DeLong test. The mediating effect of IR on the relationship between RC and T2D was evaluated through mediation analysis.

A total of 23,755 participants (46.02 ± 18.48 years, 48.8% male) were included in our study. Higher RC levels were significantly associated with increased prevalence of both IR and T2D. After adjusting for potential confounders, logistic regression analysis showed that higher RC quartiles were associated with the increased prevalence of IR [Quartile 4 vs. Quartile 1: odds ratio (OR) (95% confidence interval, CI): 1.65 (1.41-1.94), p < 0.001] and T2D [Quartile 4 vs. Quartile 1: OR (95% CI): 1.24 (1.03-1.50), p = 0.024]. RCS analysis revealed two distinct nonlinear relationships: one between RC levels and the prevalence of IR (nonlinear p < 0.001), and another between RC levels and the prevalence of T2D (nonlinear p < 0.001). ROC curve analysis demonstrated that RC had the highest discriminative ability, significantly outperforming LDL-C, HDL-C, and TG in predicting both IR and T2D risk (all P < 0.001 by DeLong test). Mediation analysis revealed that IR significantly mediated the relationship between RC and T2D, with approximately 54.1% of the effect of RC on T2D being indirect through IR.

Higher RC level was associated with increased prevalence of IR and T2D. IR mediated 54.1% of the association between RC and T2D, suggesting that managing IR could be crucial in reducing the risk of T2D in individuals with elevated RC levels.

SPINT1, a membrane-anchored serine protease inhibitor, regulates cascades of pericellular proteolysis while its tissue-specific functions remain incompletely characterized. In this study, we generate Spint1-lacZ knock-in mice and observe Spint1 expression in embryonic pancreatic epithelium. Pancreas-specific Spint1 disruption significantly diminishes islet size and mass, causing glucose intolerance and downregulation of MAFA and insulin. Mechanistically, the serine protease HEPSIN interacts with SPINT1 in β cells, and Hepsin silencing counteracts the downregulation of Mafa and Ins1 caused by Spint1 depletion. Furthermore, we demonstrate a potential interaction between HEPSIN and GLP1R in β cells. Spint1 silencing or Hepsin overexpression reduces GLP1R-related cyclic AMP levels and Mafa expression. Spint1-disrupted mice also exhibit a significant reduction in Exendin-4-induced insulin secretion. Moreover, SPINT1 expression increases in islets of prediabetic humans compared to non-prediabetic groups. The results unveil a role for SPINT1 in β cells, modulating glucose homeostasis and insulin production via HEPSIN/MAFA signaling.

Grifola frondosa polysaccharide (GFP) has a positive effect in regulating type 2 diabetes mellitus (T2DM), but the understanding of its regulatory mechanism is still limited. Accumulating evidence suggests that hepatic inflammation is crucial in the onset and progression of insulin resistance (IR) and T2DM. However, the question of whether GFP can modulate T2DM via regulating hepatic inflammation and the underlying mechanism has not yet been reported.

High-fat diet (HFD) fed combined with streptozocin (STZ) injections rat model and Lipopolysaccharides (LPS)-treated bone marrow-derived macrophages (BMDM) model are used. The results showed that GFP intervention reduces weight loss and hyperglycemia symptoms, besides lowers FINS, HOMA-IR, IPGTT-AUC, and IPITT-AUC in T2DM rats. Meanwhile, GFP intervention reduces the secretion level of inflammatory factors and increases the secretion level of anti-inflammatory factors in the liver tissue of T2DM rats. Furthermore, GFP reduces macrophage infiltration in liver tissue, inhibits macrophage M1-type polarization, and promotes M2-type polarization.

These results suggest that GFP intervention could attenuate the hepatic inflammatory and insulin resistance in T2DM rats by inhibiting hepatic macrophage infiltration and modulating M1/M2 polarization. The findings provide new evidence for GFP in the early prevention and treatment of T2DM.

Metabolic syndrome is a complex disorder defined by a cluster of interconnected factors including obesity, insulin resistance, hypertension, hyperlipidemia and hyperglycemia which increase the risk of cardiovascular disease, non-alcoholic fatty liver disease, type 2 diabetes mellitus and other related diseases. Histamine, as a biogenic amine, participates in various physiological processes. Increasing evidence suggests histamine plays critical roles in Metabolic syndrome as well as its associated diseases by interacting with four histamine receptors. In this review, we summarize the functions and mechanisms of histamine in Metabolic syndrome, indicating histamine as a possible target in treating Metabolic syndrome and its associated diseases.

Although numerous trials have demonstrated the benefits of purslane on patients with type 2 diabetes mellitus (T2DM), the results of some studies reject such effect. We elucidated the influence of purslane on c-reactive protein (CRP), lipid profile, and glycemic control in patients with T2DM. We conducted a systematic search on Web of Sciences, Scopus, the Cochrane Library, PubMed, and Embase, to identify studies published from their inception to February 10, 2024. The random effect model was used to calculate the combined effect, the weighted mean differences (WMDs) and its 95 % confidence interval (CI). Purslane supplementation significantly reduced fasting blood glucose (FBG) levels (WMD: -15.01; 95 % CI: -25.31, -4.71, p= 0.004), total cholesterol (TC) (WMD: -17.75; 95 % CI: -26.06, -9.45; p< 0.001), triglyceride (TG) (WMD: -21.30; 95 % CI: -32.59, -10.00; p< 0.001), low-density lipoprotein cholesterol (LDL-C) (WMD: -6.10; 95 % CI: -9.52, -2.68; p< 0.001), and CRP levels (WMD: -1.44; 95 % CI: -2.25, -0.63; p< 0.001), and increased high-density lipoprotein cholesterol (HDL-C) (WMD: 6.17; 95 % CI: 2.53, 9.80; p< 0.001). Also, purslane did not significant effect on serum levels of insulin, hemoglobin A1C (HbA1c), and homeostatic model Assessment for insulin resistance (HOMA-IR). The results of our study showed that purslane supplementation improved FBG, and lipid profile levels, but did not affect HOMA-IR, insulin, and HbA1c levels. However, high-quality trials are needed to approve our results.

This study is designed to investigate the differential microRNA (miRNA) expression profiles in individuals with and without type 2 diabetes mellitus (T2DM). The focus is on miRNAs that play a crucial role in the onset and progression of T2DM, particularly in glucose metabolism, inflammation, platelet reactivity, and endothelial dysfunction.

Twenty samples were categorized into groups of T2DM and non-T2DM, and miRNA profiling was conducted using microarray analysis. The expression levels of the candidate miR-25-3p, as well as its target genes platelet-activating factor receptor (PTAFR) and insulin-like growth factor 2 mRNA binding protein 3 (IGF2BP3), were validated using quantitative polymerase chain reaction (qPCR).

The present study revealed a significant reduction in the level of miR-25-3p in the T2DM group compared to the non-T2DM group. This suggests higher levels of PTAFR and IGF2BP3 in individuals with T2DM, indicating a potential biomarker for the condition.

The downregulation of miR-25-3p, which is associated with increased PTAFR levels, may contribute to heightened platelet reactivity and inflammation, worsening endothelial dysfunction, and potentially influencing vascular complications in diabetes. Additionally, the upregulation of IGF2BP3 is correlated with insulin resistance and β-cell dysfunction, which may contribute to elevated hyperglycemia and hyperinsulinemia, further aggravating the progression of diabetes. These findings highlight the potential of miR-25-3p and IGF2BP3 as biomarkers for T2DM and suggest their possible relevance for improving diagnosis and treatment strategies.

Diabetic eye disease is the most common microvascular complication of diabetes mellitus. This complication has some direct impact on an individual's well-being and health. Some lifestyle habits have been associated with the incidence of these co-morbidities.

To classify the diabetic population into sufferers or non-sufferers of diabetes eye disease according to lifestyle and demographic variables, and to identify which of these variables are significant for this classification.

The present cross-sectional study based on the NHANES 2011-2020 used the Classification and Regression Tree (CRT) analysis for classifying the diabetic population into sufferers and non-sufferers of diabetes eye disease. The odds ratio (OR) and relative risks (RR) of suffering this diabetes complication of the subgroups formed by the model were studied. The final sample formed 2657 individuals (1537 males and 1120 females).

A 79.4% accuracy was found for the CRT model. The independent variables of sleep hours (100.0%), physical activity (PA) group (92.8%), gender (76.2%), age (46.4%), education level (38.4%), sedentary time (38.1%), and diet (10.0%) were found to be significant for the classification of cases. The variable high alcohol consumption was not found significant. The analysis of the OR and RR of the subgroups formed by the model evidenced greater odds of suffering diabetes eye disease for diabetes sufferers from the inactive and walk/bicycle PA group compared to those from the Low, Moderate, and High PA groups (OR: 1.48 and RR: 1.36), for males compared to females (OR: 1.77 and RR: 1.61), for those sleeping less than 6 h or more than 9 compared to those who sleep between 6 and 8 h (OR: 1.61 and RR: 1.43), and for diabetes sufferers aged over 62 compared to younger ones (OR: 1.53 and RR: 1.40).

sleep hours, PA group, gender, age, education level, sedentary time, and diet are significant variables for classifying the diabetic population into sufferers and non-sufferers of diabetes eye disease. Additionally, being in the inactive or walk/bicycle PA group, being a male, sleeping less than 6 or more than 9 h, and being aged over 62 were identified as risk factors for suffering this diabetes complication.

We investigated potential antihyperglycemic effects of HM-chromanone (HMC), a homoisoflavonoid isolated from Portulaca oleracea, in mice fed a high-fat diet (HFD).

Five-week-old male C57BL/6J mice (n = 24) were divided into three groups: controls, mice fed an HFD (11 weeks), and HFD-fed mice receiving HMC supplementation (8 weeks). Various analyses assessed liver and skeletal muscle proteins, pancreatic β-cell histology, blood glucose and HbA1c levels, and homeostatic index of insulin resistance (HOMA-IR).

HMC supplementation significantly reduced fasting blood glucose and postprandial blood glucose levels in HFD-fed mice. HbA1c and serum insulin levels reduced significantly, and HOMA-IR improved. Compensatory β-cell hyperplasia was reduced, and pancreatic β-cell function improved. AMP-activated protein kinase (AMPK) was significantly activated in skeletal muscle and liver tissues. IRS-1tyr612 expression increased significantly. PI3K activation and Akt phosphorylation in skeletal muscles improved insulin signaling. Forkhead box protein O1 phosphorylation increased through hepatic AMPK activation. Phosphoenolpyruvate carboxykinase and glucose-6-phosphatase expression was inhibited. Glycogen synthase kinase 3β phosphorylation increased.

HMC supplementation alleviated hyperglycemia by activating the AMPK and PI3K/Akt pathways in skeletal muscles and the AMPK pathway in the liver of HFD-fed mice.

Clinical trials revealed that pioglitazone (PGZ) and dapagliflozin (DGZ) not only maintain normal blood glucose levels but also reduce complications of diabetes mellitus. To meet the demand for simultaneous measurement of these drugs in fixed combinations, an optimized and green UPLC method is required. The present study utilized Design of Experiments (DoE) software to optimize analytical parameters for simultaneous drug analysis. The method was validated for its linearity, accuracy, and precision. Furthermore, the drug content was estimated in different pharmaceutical dosage forms. Finally, Analytical Greenness (AGREE) software was utilized to assess the environmental sustainability of the optimized UPLC method. Drugs were successfully separated using optimized conditions on the C18 Acquity BEH column (2.1 mm × 100 mm, 1.7 μm) at a temperature of 45 °C. The mobile phase consisted of ethanol and 9 mM ammonium formate buffer (43.7:56.3), with elution carried out at a flow rate of 0.246 mL/min. The optimized method showed excellent linearity (R 2 > 0.999), accuracy (92.45-109.25%), and good precision (RSD < 6.27%) for both drugs. In addition, the optimized UPLC method was able to determine the drug content within the marketed pharmaceutical dosage form accurately. The developed UPLC method also prioritized eco-friendliness by using green solvents to minimize the negative impact on the environment. The green UPLC method provides a reliable and accurate approach to estimate PGZ and DGZ in a fixed diabetes treatment combination. It promotes sustainable lab practices and paves the way for analytical methods for new dose combinations.

The purpose of this study was to examine the association between refractive errors and common chronic diseases using blood biochemistry tests, and to investigate the associated modifiable risk factors, with the goal of informing and developing effective preventive strategies.

A total of 116,245 participants with refractometry at baseline enrolled in the UK Biobank were included in this prospective cohort study. Restricted cubic spline and Cox proportional hazards models were used to detect associations between refractive error, blood biochemistry tests, and common chronic diseases. Interaction effects on the additive scale and effect modification analysis were used to explore excess modifiable risk factors for disease prevention.

Spherical equivalent significantly associated with vitamin D, sex hormone binding globulin, apolipoprotein A, blood glucose, and aspartate aminotransferase levels. Subjects with myopia demonstrated a 13% higher risk of type 2 diabetes mellitus (T2DM) incidence compared to those without myopia (hazard ratio [HR] = 1.13, 95% confidence interval [CI] = 1.08-1.19) throughout a median follow-up of 9.12 years. Interaction analysis revealed 15% (95% CI = 9%-21%) of this risk was due to myopia-obesity interaction. However, active engagement in physical activity could potentially mitigate this risk (HR = 1.06, 95% CI = 0.93-1.20).

Refractive errors were associated with specific blood indicators, particularly noting the association between myopia and higher T2DM incidence in middle-aged and elderly populations. This effect interacts with obesity, and promoting physical activity among myopia individuals provides greater benefits in the prevention of T2DM compared to non-myopic individuals.

Diabetes is a major global health concern. This study aimed to investigate the correlation between differentially expressed lncRNAs in mice with type 2 diabetes mellitus (T2DM) and alterations in the intestinal flora and intestinal pathology. A T2DM mouse model was constructed by feeding mice a high-fat diet. Serum fat metabolism-related indices and insulin levels were biochemically detected. Serum inflammatory factors (IL-1β, IL-6, TNF-α, IL-10) and endotoxin (LPS) were measured by ELISA. Histopathological changes in the small intestines of mice were observed by HE. The short-chain fatty acid (SCFA) content was analyzed using GC-MS. Analysis of altered intestinal flora in T2DM mice was performed using a 16sRNA sequencing assay. Differences in lncRNA expression profiles in small intestinal tissues were analyzed using RNA-seq assays. Spearman's correlation analysis was used to correlate the expression of candidate lncRNAs with changes in differential gut flora. Spearman's correlation analysis was used to analyze the correlation between the expression of candidate differentially expressed lncRNAs, small intestinal permeability, and glucose absorption. We found that serum levels of LPS, BUN, Scr, TC, TG, LDL-C, IL-1β, IL-6, and TNF-α were elevated and levels of HDL-C, insulin, and IL-10 were decreased in T2DM mice. The ileal enterochromes of T2DM mice were disorganized and broken, the number of enterochromes was reduced, the local epithelial cells were necrotic, and the plasma membrane layer was locally absent. In addition, the protein expression of ZO-1 and occludin was decreased, and the protein expression of SGLT-1 and GLUT-2 was elevated in the model group compared to the control group. The levels of Acetic acid, Propionic acid and Butyric acid were decreased and the levels of Isobutyric acid and Isovaleric acid were increased, the abundance of beneficial bacteria was decreased and the abundance of harmful bacteria was increased in the feces of T2DM mice. RNA-seq identified nine differentially expressed lncRNAs (LINC00675, Gm33838, Gm11655, LOC6613926, LOC6613788, LOC6613791, LOC6613795, Arhgap27os3, and A330023F24Rik). In addition, we found significant correlations between differentially expressed lncRNAs and a variety of intestinal flora, as well as between small intestinal permeability and glucose absorption. A significant correlation was observed between differentially expressed lncRNAs in the intestinal tissues of T2DM mice and intestinal flora imbalance, small intestinal permeability, and glucose absorption.

Type 2 diabetes mellitus (T2DM), a high-incidence chronic metabolic disorder, has emerged as a global health issue, where most patients need lifelong medication. Gaining insights into molecular mechanisms involved in T2DM development is expected to provide novel strategies for clinical prevention and treatment. Growing evidence validates that non-coding RNAs (ncRNAs) including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs) function as crucial regulators in multiple biological processes of T2DM, inspiring various potential targets and drug candidates. In this review, we summarize the current understanding of ncRNA roles in T2DM and discuss the potential use of ncRNAs as targets and active molecules for drug discovery.

Type 2 diabetes (T2D) is a chronic metabolic disorder characterized by reduced responsiveness of body cells to insulin, leading to elevated blood sugar levels. CNOT6L is involved in glucose metabolism, insulin secretion regulation, pancreatic beta-cell proliferation, and apoptosis. These functions may be closely related to the pathogenesis of T2D. However, the exact molecular mechanisms linking CNOT6L to T2D remain unclear. Therefore, this study aims to elucidate the role of CNOT6L in T2D.

The T2D datasets GSE163980 and GSE26168 profiles were downloaded from the Gene Expression Omnibusdatabase generated by GPL20115 and GPL6883.The R package limma was used to screen differentially expressed genes (DEGs). A weighted gene co-expression network analysis was performed. Construction and analysis of the protein-protein interaction (PPI) network, functional enrichment analysis, gene set enrichment analysis, and comparative toxicogenomics database (CTD) analysis were performed. Target Scan was used to screen miRNAs that regulate central DEGs. The results were verified by reverse transcription quantitative real-time polymerase chain reaction (RT-qPCR), western blotting (WB), and blood glucose measurements in mice.

A total of 1951 DEGs were identified. GO and KEGG enrichment analysis revealed that differentially expressed genes were mainly enriched in the insulin signaling pathway, ECM-receptor interaction, and PPAR signaling pathway. Metascape analysis indicated enrichment primarily in the cAMP signaling pathway and enzyme-linked receptor protein signaling pathway. WGCNA analysis yielded 50 intersecting genes. PPI network construction and algorithm identification identified two core genes (CNOT6L and GRIN2B), among which CNOT6L gene was associated with multiple miRNAs. CTD analysis revealed associations of core genes with type 2 diabetes, diabetic complications, dyslipidemia, hyperglycemia, and inflammation. WB and RT-qPCR results showed that in different pathways, CNOT6L protein and mRNA levels were upregulated in type 2 diabetes.

CNOT6L is highly expressed in type 2 diabetes mellitus, and can cause diabetes complications, inflammation and other physiological processes by regulating miRNA, PPAR and other related signaling pathways, with poor prognosis. CNOT6L can be used as a potential therapeutic target for type 2 diabetes.

Among all nephropathies, diabetic kidney disease (DKD) is the most common cause of kidney impairment advancement to end-stage renal disease (ESRD). Although DKD has no cure, the disease is commonly managed by strict control of blood glucose and blood pressure, and in most of these cases, kidney function often deteriorates, resulting in dialysis, kidney replacement therapy, and high mortality. The difficulties in finding a cure for DKD are mainly due to a poor understanding of the underpinning complex cellular mechanisms that could be identified as druggable targets for the treatment of this disease. The review is thus aimed at giving insight into the interconnection between chronic hyperglycaemia and cellular mechanistic perturbations of nephropathy in diabetes. A comprehensive literature review of observational studies on DKD published within the past ten years, with 57 percent published within the past three years was carried out. The article search focused on original research studies and reviews published in English. The articles were explored using Google Scholar, Medline, Web of Science, and PubMed databases based on keywords, titles, and abstracts related to the topic. This article provides a detailed relationship between hyperglycaemia, oxidative stress, and various cellular mechanisms that underlie the onset and progression of the disease. Moreover, it also shows how these mechanisms affect organelle dysfunction, resulting in fibrosis and podocyte impairment. The advances in understanding the complexity of DKD mechanisms discussed in this review will expedite opportunities to develop new interventions for treating the disease.

Glucose sensors are essential tools for monitoring blood glucose concentration in diabetic patients. In recent years, with the increasing number of individuals suffering from diabetes, blood glucose monitoring has become extremely necessary, which expedites the iteration and upgrade of glucose sensors greatly. Currently, two main types of glucose sensors are available for blood glucose testing: enzyme-based glucose sensor (EBGS) and enzyme-free glucose sensor (EFGS). For EBGS, several progresses have been made to comprehensively improve detection performance, ranging from enhancing enzyme activity, thermostability, and electron transfer properties, to introducing new materials with superior properties. For EFGS, more and more new metallic materials and their oxides are being applied to further optimize its blood glucose monitoring. Here the latest progress of electrochemical glucose sensors, their manufacturing methods, electrode materials, electrochemical parameters, and applications were summarized, the development glucose sensors with various noninvasive sampling modes were also compared.

The concept of "type 3 diabetes" has emerged to define alterations in glucose metabolism that predispose individuals to the development of Alzheimer's disease (AD). Novel evidence suggests that changes in the insulin/insulin-like growth factor 1 (IGF-1)/growth hormone (GH) axis, which are characteristic of Diabetes Mellitus, are one of the major factors contributing to excessive amyloid-beta (Aβ) production and neurodegenerative processes in AD. Moreover, molecular findings suggest that insulin resistance and dysregulated IGF-1 signaling promote atherosclerosis via endothelial dysfunction and a pro-inflammatory state. As the pathophysiological role of Aβ1-40 in patients with cardiovascular disease has attracted attention due to its involvement in plaque formation and destabilization, it is of great interest to explore whether a paradigm similar to that in AD exists in the cardiovascular field. Therefore, this review aims to elucidate the intricate interplay between insulin resistance, IGF-1, and Aβ1-40 in the cardiovascular system and assess the applicability of the type 3 diabetes concept. Understanding these relationships may offer novel therapeutic targets and diagnostic strategies to mitigate cardiovascular risk in patients with insulin resistance and dysregulated IGF-1 signaling.

Dahlia (Dahlia variabilis), a widely cultivated ornamental plant in Indonesia, is known to contain 84.08% inulin in its tubers. Numerous studies have demonstrated the antidiabetic potential of inulin from various plant sources. However, most of the research is in the form of a mixture of inulin with other active substances, and no one has analyzed the effects of inulin derived from dahlia tubers. This study examines the effect of inulin from dahlia tuber extract on blood glucose levels, serum insulin expression, pancreatic tissue insulin expression, homeostatic model assessment of insulin resistance (HOMA-IR), and the extent of insulitis in diabetic rats.

In this experimental study, 20 male Wistar rats were randomly allocated to five groups. Group I served as the control, Group II as the STZ-induced diabetic group, Group III as the STZ-induced diabetic group treated with inulin (0.5 g/kgBW), Group IV as the STZ induced diabetic group treated with inulin (1.0 g/kgBW), and Group V as the STZ-induced diabetic group treated with inulin (1.5 g/kgBW). The inulin was administered for 21 days. The degree of insulitis was evaluated using a scoring system, serum insulin concentration via ELISA, and insulin expression in the pancreas through immunohistochemistry.

Administration of inulin from dahlia tubers significantly reduced serum glucose concentrations in diabetic rats. Notably, only inulin extracts at doses of 1 g/kgBW and 1.5 g/kgBW showed a significant reduction in insulitis and HOMA-IR index in diabetic rats, while the 0.5 g/kgBW inulin extract reduced insulitis without affecting HOMA-IR. Inulin extract administration did not affect insulin expression in serum or pancreatic tissue.

Inulin from dahlia tuber can exert antidiabetic properties by improving insulin resistance and insulitis. These studies suggest the great potential of dahlia tubers as the source of inulin for prebiotic functional foods.

Diabetic encephalopathy (DE), a significant micro-complication of diabetes, manifests as neurochemical, structural, behavioral, and cognitive alterations. This condition is especially dangerous for the elderly because aging raises the risk of neurodegenerative disorders and cognitive impairment, both of which can be made worse by diabetes. Despite its severity, diagnosis of this disease is challenging, and there is a paucity of information on its pathogenesis. The pivotal roles of various cellular pathways, activated or influenced by hyperglycemia, insulin sensitivity, amyloid accumulation, tau hyperphosphorylation, brain vasculopathy, neuroinflammation, and oxidative stress, are widely recognized for contributing to the potential causes of diabetic encephalopathy. We also reviewed current pharmacological strategies for DE encompassing a comprehensive approach targeting metabolic dysregulations and neurological manifestations. Antioxidant-based therapies hold promise in mitigating oxidative stress-induced neuronal damage, while anti-diabetic drugs offer neuroprotective effects through diverse mechanisms, including modulation of insulin signaling pathways and neuroinflammation. Additionally, tissue engineering and nanomedicine-based approaches present innovative strategies for targeted drug delivery and regenerative therapies for DE. Despite significant progress, challenges remain in translating these therapeutic interventions into clinical practice, including long-term safety, scalability, and regulatory approval. Further research is warranted to optimize these approaches and address remaining gaps in the management of DE and associated neurodegenerative disorders.

Gegen Qinlian Decoction (GGQLT) is a traditional Chinese herbal medicine that has been reported to have a significant therapeutic effect in the management of type II diabetes mellitus (T2DM). In this study, we constructed a T2DM rat model by feeding a high-fat diet and injecting streptozotocin (STZ) and tested the effects of feeding GGQLT and fecal transplantation on the physiological indices, microbiota, and metabolism of rats. The results showed that the administration of GGQLT can significantly improve the growth performance of rats and has a remarkable antihyperlipidemic effect. In addition, GGQLT altered the composition of gut microbiota by increasing beneficial bacteria such as Coprococcus, Bifidobacterium, Blautia, and Akkermansia. In addition, GGQLT elevated levels of specific bile acids by metabolomic analysis, potentially contributing to improvements in lipid metabolism. These findings suggest that GGQLT may have beneficial effects on T2DM by influencing lipid metabolism and gut microbiota. However, further studies are needed to elucidate its mechanisms and assess clinical applications.

Benign paroxysmal positional vertigo (BPPV) is a common neurological disorder with a high recurrence rate. Type 2 diabetes mellitus (T2DM) is recognized as a risk factor for BPPV recurrence. However, the genomic association between T2DM and BPPV recurrence remains understudied.

Differential gene expression analysis and weighted gene co-expression network analysis were used to identify shared genes between BPPV recurrence and T2DM. The MCC algorithm was employed to select hub genes from the protein-protein interaction network of the shared genes. The predictive efficacy of hub genes for BPPV recurrence and T2DM was assessed using ROC curve analysis. Genemania database was used to identify downstream targets of hub genes. The immune infiltration landscape of BPPV and T2DM was characterized using the CIBERSORT algorithm. Correlation analysis was performed to explore the relationship between hub genes and immune cells. The expression levels of hub genes in patient blood samples were validated using qPCR.

Thirteen shared genes were identified and a protein-protein interaction network was constructed for BPPV recurrence and T2DM. Subsequently, four hub genes were selected, and their expression levels effectively predicted the occurrence of BPPV recurrence and T2DM. These hub genes were highly correlated with immune cell infiltration, indicating a common mechanism underlying recurrent BPPV and T2DM. Finally, the upregulation of hub genes in patients with T2DM comorbid with BPPV recurrence was confirmed in blood samples. These hub genes may serve as predictive biomarkers for assessing the recurrence rate in BPPV patients with comorbid T2DM.

We proposed shared gene characteristics between BPPV recurrence and T2DM, revealing an immune-mediated inflammatory regulation as a common pathway and identifying four immune-related biomarkers and potential therapeutic targets for T2DM comorbid with recurrent BPPV.

Effective management of diabetes mellitus (DM) involves comprehensive knowledge, attitudes, and practices (KAP) by nurses, which is essential for optimal patient care and aiding patients in their self-management of the condition.

This survey evaluates nurses' self-assessed knowledge, attitudes, and practices (KAP) related to diabetes management, focusing on their perceptions of personnel expertise and care approaches. Using a stratified sampling method, the survey was disseminated across various online platforms from January 2023 to February 2024 within China, including WeChat and Sina Weibo. We employed binary logistic regression and Chi-square tests to explore the statistical correlates of KAP related to DM.

A total of 4,011 nurses participated, revealing significant perceived knowledge deficiencies in specialized DM management areas, with only 34% (n = 1,360) proficient in current pharmacological treatments. Attitudinal assessments showed that 54% (n = 2,155) recognized the importance of cultural competence in dietary counseling. Practices were strong in routine glucose monitoring (96%, n = 3,851) but weaker in psychological support (68%, n = 2,736). Regression analysis indicated significant effects of experience on KAP, where nurses with 1-5 years of experience were more likely to show better knowledge (OR = 1.09; p = 0.08), and those with advanced degrees demonstrated higher competence (OR = 1.52; p = 0.028). Marital status influenced attitudes, with single nurses more likely to exhibit positive attitudes (OR = 0.49; p < 0.001), and work environment impacted knowledge, with hospital-based nurses more knowledgeable (OR = 1.15; p = 0.14). Additionally, gender differences emerged, with male nurses showing greater knowledge (OR = 1.65; p = 0.03) and better practices in diabetes care (OR = 1.47; p = 0.04).

The study underscores the critical need for targeted educational programs and policy interventions to enhance nursing competencies in DM management. While the study provides valuable insights into nurses' perceptions of their competencies, future research should incorporate objective knowledge assessments to ensure a comprehensive understanding of their actual capabilities. Interestingly, the data also suggests a substantial opportunity to leverage technology and inter-professional collaboration to further enhance DM management efficacy among nurses, fostering an integrated care approach.

The escalating global burden of diabetes and its associated cognitive impairment underscores the urgency for effective interventions. Bergenin shows promise in regulating glucose metabolism, mitigating inflammation, and improving cognitive function. Zebrafish models offer a unique platform for assessing drug efficacy and exploring pharmacological mechanisms, complemented by subsequent investigations in cell and rat models.

The experimental subjects included zebrafish larvae (CZ98:Tg (mpeg1:EGFP) ihb20Tg/+ ), adult zebrafish (immersed in 2% glucose), BV2 cell line (50 mM glucose + 10 μm Aβ1-42), and a streptozotocin (STZ) bilateral intracerebroventricular injection rat model. Bergenin's effects on the toxicity, behavior, and cognitive function of zebrafish larvae and adults were evaluated. The Morris water maze assessed cognitive function in rats. Neuronal histopathological changes were evaluated using HE and Nissl staining. qPCR and Western blot detected the expression of glycolysis enzymes, inflammatory factors, and Bergenin's regulation of PPAR/NF-κB pathway in these three models.

1) In zebrafish larvae, Bergenin interventions significantly reduced glucose levels and increased survival rates while decreasing teratogenicity rates. Microglial cell fluorescence in the brain notably decreased, and altered swimming behavior tended to normalize. 2) In adult zebrafish, Bergenin administration reduced BMI and blood glucose levels, altered swimming behavior to slower speeds and more regular trajectories, enhanced recognition ability, decreased brain glucose and lactate levels, weakened glycolytic enzyme activities, improved pathological changes in the telencephalon and gills, reduced expression of pro-inflammatory cytokines, decreased ins expression and increased expression of irs1, irs2a, and irs2b, suggesting a reduction in insulin resistance. It also altered the expression of pparg and rela. 3) In BV2 cell line, Bergenin significantly reduced the protein expression of glycolytic enzymes (GLUT1, HK2, PKFKB3, and PKM2), lowered IL-1β, IL-6, and TNF-α mRNA expression, elevated PPAR-γ protein expression, and decreased P-NF-κB-p65 protein expression. 4) In the rat model, Bergenin improves learning and memory abilities in STZ-induced rats, mitigates neuronal damage in the hippocampal region, and reduces the expression of inflammatory factors IL-1β, IL-6, and TNF-α. Bergenin decreases brain glucose and lactate levels, as well as glycolytic enzyme activity. Furthermore, Bergenin increases PPARγ expression and decreases p-NF-κB p65/NF-κB p65 expression in the hippocampus.

Bergenin intervenes through the PPAR-γ/NF-κB pathway, redirecting glucose metabolism, alleviating inflammation, and preventing high glucose-induced neuronal damage.

Type 2 diabetes mellitus (T2DM) is a serious endocrine and metabolic disease that is highly prevalent and causes high mortality and morbidity rates worldwide. This review aims to focus on the potential of probiotics in the management of T2DM and its complications and to summarise the various mechanisms of action of probiotics with respect to T2DM. In this review, experimental studies conducted between 2016 and 2022 were explored. The possible mechanisms of action are based on their ability to modulate the gut microbiota, boost the production of short-chain fatty acids (SCFAs) and glucagon-like peptides, inhibit α-glucosidase, elevate sirtuin 1 (SIRT1) levels while reducing fetuin-A levels, and regulate the level of inflammatory cytokines. This review recommends carrying out further studies, especially human trials, to provide robust evidence-based knowledge on the use of probiotics for the treatment of T2DM.IMPACT STATEMENTT2DM is prevalent worldwide causing high rates of morbidity and mortality.Gut microbiota play a significant role in the pathogenesis of T2DM.Probiotics can be used as possible therapeutic tools for the management of T2DM.The possible mechanisms of action of probiotics include modulation of the gut microbiota, production of SCFAs and glucagon-like peptides, inhibition of α-glucosidase, raising SIRT1, reducing fetuin-A levels, and regulating the level of inflammatory cytokines.

Type 2 diabetes mellitus (T2DM) is a metabolic disease primarily characterized by insulin resistance (IR) and insufficient insulin secretion. The unfolded protein response (UPR) overactivation induced by endoplasmic reticulum stress (ERS) appears to play a key role in this process, although the exact pathogenesis of T2DM is not fully understood. Studies have demonstrated that appropriate exercise can regulate ERS in the heart, liver, pancreas, skeletal muscle, and other body tissues leading to an improvement in diabetes and its complications. However, the exact mechanism remains unclear. By analyzing the relationship between ERS, T2DM pathology, and exercise intervention, this review concludes that exercise can increase insulin sensitivity, inhibit IR, promote insulin secretion and alleviate T2DM by regulating ERS. This paper specifically reviews the signaling pathways by which ERS induces diabetes, the mechanisms of exercise regulation of ERS in diabetes, and the varying effects of different types of exercise on diabetes improvement through ERS mechanisms. Physical exercise is an effective non-pharmacological intervention for T2DM. Thus, further exploration of how exercise regulates ERS in diabetes could refine "precision exercise medicine" for diabetes and identify new drug targets.

In insulin dysregulation, hyperinsulinemia (HI) can be accompanied by peripheral insulin resistance (IR) in horses, which can be diagnosed with an insulin-tolerance test (ITT). The administration of 0.1 IU/kg body weight of recombinant regular human insulin (RHI) should elicit a 50 % reduction of the initial blood glucose concentration at 30 min after insulin administration in insulin sensitive horses. Compared to RHI, porcine zinc insulin (PZI) is veterinary-approved and therefore easier accessible for many practitioners. The aim of this study was to compare the insulin and glucose dynamics during a standard ITT with RHI to an ITT performed with PZI. Twelve Icelandic horses were subjected to an ITT with RHI (ITT-RHI) and with PZI (ITT-PZI) at same dosages in a randomised crossover design. The insulin and glucose dynamics that resulted from these tests were compared, and the consistency of classification into insulin-sensitive and IR categories was evaluated. No complications were observed with the use of either RHI or PZI in ITT. A good correlation of the test results was observed (r = 0.88; P < 0.001). The blood glucose concentrations and the percentage reduction in glucose concentration did not differ significantly between the two tests (P = 0.053), but four out of twelve horses were classified as IR in the ITT-RHI whereas with the ITT-PZI seven out of twelve horses were classified as IR with the 50 % glucose reduction from baseline. Based on the Youden index, when using the ITT-PZI, an adjusted cut-off value for blood glucose reduction of 40 % at 30 min resulted in better test performance. With consideration for the seemingly weaker effect of PZI and the adjusted cut-off value, PZI can be an appropriate substitute to RHI in an ITT.

Early detection of PDAC remains challenging due to the lack of early symptoms and the absence of reliable biomarkers. The aim of the present project was to identify miRNA and proteomics signatures discriminating PDAC patients with DM from nondiabetic PDAC patients. Proteomics analysis and miRNA array were used for protein and miRNA screening. We used Western blotting and Real-Time Quantitative Reverse Transcription polymerase chain reaction (qRT-PCR) for protein and miRNA validation. Comparisons between experimental groups with normal distributions were performed using one-way ANOVA followed by Tukey's post hoc test, and pairwise tests were performed using t-tests. p ≤ 0.05 was considered statistically significant. Protein clusters of differentiation 166 (CD166), glycoprotein CD63 (CD63), S100 calcium-binding protein A13 (S100A13), and tumor necrosis factor-β (TNF-β) were detected in the proteomics screening. The miRNA assay revealed a differential miRNA 1285 regulation. Previously described target proteins of miR-1285 cadherin-1 (CDH-1), cellular Jun (c-Jun), p53, mothers against decapentaplegic homolog 4 (Smad4), human transglutaminase 2 (TGM2) and yes-associated protein (YAP), were validated via Western blotting. miR-1285-3p was successfully validated as differentially regulated in PDAC + DM via qRT-PCR. Overall, our data suggest miRNA1285-3p, TGM2, CDH-1, CD166, and S100A13 as potential meaningful biomarker candidates to characterize patients with PDAC + DM. Data are available via ProteomeXchange with the identifier PXD053169.

In this study, the antidiabetic activities of Lepionurus sylvestris Blume extract (LSB) in rats was investigated. The in vitro antidiabetic properties of LSB was evaluated using α-amylase, α-glucosidase and DPP-IV inhibitory assays, while the antioxidant assay was analysed using DPPH, ABTS and FRAP assays. Type 2 diabetes was with high-fructose/streptozotocin, and the diabetic animals were treated with LSB for 5 weeks. At the end of the experiment, the effects of LSB were evaluated via insulin level, lipid profile and hepatorenal function biomarkers. The level of oxido-inflammatory parameters, histopathology and insulin immunohistochemical staining in the pancreas was evaluated. Diabetic rats manifested significant increases in the blood glucose level, food/water intake, lipid profiles, hepatorenal function biomarkers, as well as a marked decreases in the body weight and serum insulin levels. Histopathological and insulin immunohistochemical examination also revealed decreased pancreatic beta cells and insulin positive cells, respectively. These alterations were associated with significant increases in malondialdehyde, TNF-α and IL-1β, in addition to significant declines in GSH, SOD and CAT activities. LSB significantly reduced blood glucose level, glucose intolerance, serum lipids, restored altered hepatorenal and pancreatic functions in the treated diabetic rats. Further, LSB showed antioxidant and anti-inflammatory activities by reducing malondialdehyde, TNF-α, IL-1β, and increasing antioxidant enzymes activities in the pancreatic tissues. A total of 77 secondary metabolites were tentatively identified in the UPLC-Q-TOF-MS analysis of LSB. Overall, these findings provides insight into the potentials of LSB as an antidiabetic agent which may be associated to the plethora bioactive compounds in the plant.