Insulin: A connection between pancreatic β cells and the hypothalamus

Table 1 Mechanism of action of nutraceuticals

Nutraceutical	Mechanism of action	Study model	Ref.
Resveratrol	Reduces blood glucose and serum insulin levels, improves insulin and glucose tolerance, increases Sirt1, p-AMPK, p-IRS1 and p-AKT levels in liver	Mice, KKAy	[110]
	Enhances peripheral insulin signaling in diabetic mice in association with PTBP1 inhibition	Mice deficient in IRS2 (Irs2 -/-) and injected with STZ	[111]
	Reduces stress on the endoplasmic reticulum, thus improving insulin sensitivity and glucose levels	Mice C57BL/6J on a HFD	[112]
	Regulates protein expression of insulin receptor and GLUT4	Rat, Goto-Kakizaki	[113]
	Counteracts insulin resistance caused by hyperinsulinemia by activating AMPK and regulating GLUT4 translocation in muscle cells	L6 cell line	[114]
	Reduces insulin levels and the HOMA-IR index	Patients with T2DM	[115]
Curcumin	As a pretreatment, it protects pancreatic islets from cytokine-induced death	Mice, C57BL/6J	[116]
	Protects pancreatic islets from glycolipotoxicity by inhibiting oxidative stress and NADPH oxidase activity	Rats, Sprague-Dawley	[117]
	Improves insulin sensitivity and energy metabolism through the FNDC5/p38 MAPK/ERK pathways	Mice, C57BL/6J	[118]
	HOMA-IR index decreases	Patients with T2DM	[119]
Garlic	Decreases serum insulin level, HOMA-IR index and appetite	Patients with metabolic syndrome	[120]
Rhizoma polygonati odorati extract	Regulates serum insulin, adiponectin and leptin levels in mice on an HFD	Mice, C57BL/6	[121]
Diospyros kaki (persimmon) extract	Increases the number of pancreatic islets, decreases the expression of TNFα and IL-6, which interferes with insulin action	Zebra fish	[122]
Morus alba leaves	Decreases in the fasting insulin level and the HOMA-IR index, resulting in decrease of insulin resistance	Mice, C57BL/6 with HFD and STZ	[123]
Hydrolyzed pea protein	Enhances insulin-stimulated phosphorylation of AKT and FOXO1, increases IRS1 expression	Cells AML-12	[124]
Avocado oil	Improves insulin and glucose sensitivity	Mice, C57BL/6J	[125]
Eugenol	Improves glucose uptake in muscle, by insulin-independent pathway CaMKKβ/AMPK/GLUT4.	Mice, C57BL/6N with HFD and STZ	[126]
Okra leaf extract (Abelmoschus esculentus)	Regulates blood glucose level, food intake and changes in body weight	Wistar rats with STZ	[127]

AKT: Protein kinase B; AML-12: Alpha mouse liver 12 cells; AMPK: Adenosine monophosphate-activated protein kinase; CaMKKβ: Ca2+/calmodulin-dependent kinase β; FNDC5: fibronectin type III domain containing 5; ERK: Extracellular signal-regulated kinase; FOXO1: Forkhead box protein O1; GLUT4: Glucose transporter 4; HFD: High-fat diet; HOMA-IR: Homeostatic Model Assessment of Insulin Resistance; IL-6: Interleukin-6; IRS1: Insulin receptor substrate 1; MAPK: Mitogen-activated protein kinases; NADPH: Nicotinamide adenine dinucleotide phosphate reduced; PTBP1: Polypyrimidine tract-binding protein 1; Sirt1: Sirtuin 1; STZ: Streptozotocin; T2DM: Type 2 diabetes mellitus; TNFα: Tumoral necrosis factor alpha.