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Sibthorpe PEM, Fitzgerald DM, Sillence MN, de Laat MA. Studies in vitro of equine intestinal glucagon-like peptide-2 secretion. J Equine Vet Sci 2024; 142:105179. [PMID: 39197558 DOI: 10.1016/j.jevs.2024.105179] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/28/2024] [Revised: 05/29/2024] [Accepted: 08/25/2024] [Indexed: 09/01/2024]
Abstract
Equine insulin dysregulation (ID) is a significant metabolic problem because the hyperinsulinaemia that develops increases the animal's risk of developing laminitis, a debilitating foot condition. The role of gastrointestinal factors, such as incretin hormones, in the pathogenesis of ID and hyperinsulinaemia in horses is poorly understood, particularly in comparison to other species. Glucagon-like peptide-2 (GLP-2) is an intestinotrophic peptide released from L cells in the gastrointestinal tract and is implicated in metabolic dysfunction in other species. The aim of this study in vitro was to establish basic physiological understanding about intestinal secretion of GLP-2 in horses. Basal and glucose-stimulated GLP-2 secretion was measured in post-mortem tissue samples from the duodenum, jejunum, and ileum. We observed that GLP-2 secretion was minimal in samples from the duodenum compared to the jejunum and ileum (5-9-fold higher; P < 0.05). Furthermore, GLP-2 secretion was not responsive to glucose stimulation in the ileum or duodenum but was responsive to glucose in the jejunum. This effect in the jejunum was inhibited by 30 % (P = 0.02) using phlorizin, a selective sodium-glucose cotransporter-1 (SGLT-1) inhibitor, and by 38 % (P = 0.04) using phloretin, a non-selective SGLT-1/GLUT-2 inhibitor. The localisation of glucose-responsive GLP-2 secretion in the jejunum might be relevant to the development of post-prandial hyperinsulinaemia. This study has provided data on GLP-2 secretion from the equine small intestine that will enable more complex and dynamic studies on the pathogenesis of ID.
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Affiliation(s)
- P E M Sibthorpe
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia
| | - D M Fitzgerald
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia
| | - M N Sillence
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia
| | - M A de Laat
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia.
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Sibthorpe PEM, Fitzgerald DM, Sillence MN, de Laat MA. Associations between feeding and glucagon-like peptide-2 in healthy ponies. Equine Vet J 2024; 56:309-317. [PMID: 37705248 DOI: 10.1111/evj.14004] [Citation(s) in RCA: 1] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/21/2023] [Accepted: 08/25/2023] [Indexed: 09/15/2023]
Abstract
BACKGROUND Gastrointestinal peptides, such as glucagon-like peptide-2 (GLP-2), could play a direct role in the development of equine hyperinsulinaemia. OBJECTIVES To describe the secretory pattern of endogenous GLP-2 over 24 h in healthy ponies and determine whether oral administration of a synthetic GLP-2 peptide increases blood glucose or insulin responses to feeding. STUDY DESIGN A cohort study followed by a randomised, controlled, cross-over study. METHODS In the cohort study, blood samples were collected every 2 h for 24 h in seven healthy ponies and plasma [GLP-2] was measured. In the cross-over study, 75 μg/kg bodyweight of synthetic GLP-2, or carrier only, was orally administered to 10 ponies twice daily for 10 days. The area under the curve (AUC0-3h ) of post-prandial blood glucose and insulin were determined before and after each treatment. RESULTS Endogenous [GLP-2] ranged from <0.55 to 1.95 ± 0.29 [CI 0.27] ng/mL with similar peak concentrations in response to meals containing 88-180 g of non-structural carbohydrate, that were ~4-fold higher (P < 0.001) than the overnight nadir. After GLP-2 treatment peak plasma [GLP-2] increased from 1.1 [0.63-1.37] ng/mL to 1.54 [1.1-2.31] ng/mL (28.6%; P = 0.002), and AUC0-3h was larger (P = 0.01) than before treatment. The peptide decreased (7%; P = 0.003) peak blood glucose responses to feeding from 5.33 ± 0.45 mmol/L to 5.0 ± 0.21 mmol/L, but not AUC0-3h (P = 0.07). There was no effect on insulin secretion. MAIN LIMITATIONS The study only included healthy ponies and administration of a single dose of GLP-2. CONCLUSIONS The diurnal pattern of GLP-2 secretion in ponies was similar to other species with no apparent effect of daylight. Although GLP-2 treatment did not increase post-prandial glucose or insulin responses to eating, studies using alternative dosing strategies for GLP-2 are required.
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Affiliation(s)
- Poppy E M Sibthorpe
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia
| | - Danielle M Fitzgerald
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia
| | - Martin N Sillence
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia
| | - Melody A de Laat
- School of Biology and Environmental Science, Queensland University of Technology, Brisbane, Queensland, Australia
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Skarbaliene J, Mathiesen JM, Larsen BD, Thorkildsen C, Petersen YM. Glepaglutide, a novel glucagon-like peptide-2 agonist, has anti-inflammatory and mucosal regenerative effects in an experimental model of inflammatory bowel disease in rats. BMC Gastroenterol 2023; 23:79. [PMID: 36944922 PMCID: PMC10029296 DOI: 10.1186/s12876-023-02716-4] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/11/2022] [Accepted: 03/10/2023] [Indexed: 03/23/2023] Open
Abstract
BACKGROUND Glucagon-like peptide-2 (GLP-2) enhances intestinal repair and attenuates inflammation in preclinical inflammatory bowel disease (IBD) models, making GLP-2 analogues attractive candidates for IBD therapy. Glepaglutide is a long-acting GLP-2 receptor agonist in clinical development for treatment of short bowel syndrome. Here, we investigated if glepaglutide is therapeutically beneficial in rats with small intestinal inflammation. METHODS Small intestinal inflammation was induced with indomethacin in naive Wistar rats, followed by glepaglutide administration at different disease stages. Glepaglutide was administered in co-treatment and post-treatment regimens. Small intestinal length and concentrations of inflammatory markers α-1-acid glycoprotein and myeloperoxidase were used to assess anti-inflammatory effects. Small intestinal mass was evaluated to determine intestinotrophic effects. RESULTS Glepaglutide co- and post-treatment significantly reduced severity of small intestinal inflammation, evidenced by reversed small intestinal shortening and decreased α-1-acid glycoprotein and/or myeloperoxidase concentration(s). Co- and post-treatment with glepaglutide also significantly increased small intestinal mass, indicating intestinal regenerative effects. Similar effects were observed in naive rats after glepaglutide treatment. CONCLUSION Glepaglutide has anti-inflammatory and intestinotrophic effects without the need for pre-treatment in a rat model of small intestinal inflammation. Thus, glepaglutide is of potential clinical interest for patients with IBD.
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Affiliation(s)
- Jolanta Skarbaliene
- Research and Development, Zealand Pharma A/S, Sydmarken 11, 2860, Søborg, Denmark
- Pharvaris GmbH, 6300, Grafenauweg 8, Zug, Switzerland
| | | | - Bjarne Due Larsen
- Research and Development, Zealand Pharma A/S, Sydmarken 11, 2860, Søborg, Denmark
| | | | - Yvette Miata Petersen
- Research and Development, Zealand Pharma A/S, Sydmarken 11, 2860, Søborg, Denmark
- Hoffmann-La Roche, Grenzacherstrasse 124, 4070, Basel, Switzerland
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Abstract
The ultimate goal of treatment of short bowel syndrome/intestinal failure patients is to achieve enteral autonomy by eliminating parenteral nutrition (PN)/intravenous fluids (IV). After optimization of diet, oral hydration and anti-diarrheal medications, attempt should be made to eliminate PN/IV. Weaning from PN/IV should be individualized for each patient. Although teduglutide is the preferred agent for PN/IV volume reduction or successful weaning, optimal patient selection and long-term safety need further evaluation. Following PN/IV elimination, patients need long-term monitoring for nutritional deficiencies. This article will address clinical considerations before, during, and after PN/IV weaning to facilitate safe and successful PN/IV weaning process.
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Affiliation(s)
- Andrew Ukleja
- Division of Gastroenterology and Hepatology, Beth Israel Deaconess Medical Center/Beth Israel Lahey Health, 330 Brookline Ave., Boston, MA 02215, USA.
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de Laat MA, Fitzgerald DM, Sillence MN, Spence RJ. Glucagon‐like peptide‐2: A potential role in equine insulin dysregulation. Equine Vet J 2018; 50:842-847. [DOI: 10.1111/evj.12825] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/26/2017] [Accepted: 02/23/2018] [Indexed: 12/19/2022]
Affiliation(s)
- M. A. de Laat
- Science and Engineering Faculty Queensland University of Technology (QUT) Brisbane Queensland Australia
| | - D. M. Fitzgerald
- Science and Engineering Faculty Queensland University of Technology (QUT) Brisbane Queensland Australia
| | - M. N. Sillence
- Science and Engineering Faculty Queensland University of Technology (QUT) Brisbane Queensland Australia
| | - R. J. Spence
- Science and Engineering Faculty Queensland University of Technology (QUT) Brisbane Queensland Australia
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Wagner L, Klemann C, Stephan M, von Hörsten S. Unravelling the immunological roles of dipeptidyl peptidase 4 (DPP4) activity and/or structure homologue (DASH) proteins. Clin Exp Immunol 2016; 184:265-83. [PMID: 26671446 DOI: 10.1111/cei.12757] [Citation(s) in RCA: 78] [Impact Index Per Article: 8.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/01/2015] [Revised: 12/01/2015] [Accepted: 12/14/2015] [Indexed: 12/31/2022] Open
Abstract
Dipeptidyl peptidase (DPP) 4 (CD26, DPP4) is a multi-functional protein involved in T cell activation by co-stimulation via its association with adenosine deaminase (ADA), caveolin-1, CARMA-1, CD45, mannose-6-phosphate/insulin growth factor-II receptor (M6P/IGFII-R) and C-X-C motif receptor 4 (CXC-R4). The proline-specific dipeptidyl peptidase also modulates the bioactivity of several chemokines. However, a number of enzymes displaying either DPP4-like activities or representing structural homologues have been discovered in the past two decades and are referred to as DPP4 activity and/or structure homologue (DASH) proteins. Apart from DPP4, DASH proteins include fibroblast activation protein alpha (FAP), DPP8, DPP9, DPP4-like protein 1 (DPL1, DPP6, DPPX L, DPPX S), DPP4-like protein 2 (DPL2, DPP10) from the DPP4-gene family S9b and structurally unrelated enzyme DPP2, displaying DPP4-like activity. In contrast, DPP6 and DPP10 lack enzymatic DPP4-like activity. These DASH proteins play important roles in the immune system involving quiescence (DPP2), proliferation (DPP8/DPP9), antigen-presenting (DPP9), co-stimulation (DPP4), T cell activation (DPP4), signal transduction (DPP4, DPP8 and DPP9), differentiation (DPP4, DPP8) and tissue remodelling (DPP4, FAP). Thus, they are involved in many pathophysiological processes and have therefore been proposed for potential biomarkers or even drug targets in various cancers (DPP4 and FAP) and inflammatory diseases (DPP4, DPP8/DPP9). However, they also pose the challenge of drug selectivity concerning other DASH members for better efficacy and/or avoidance of unwanted side effects. Therefore, this review unravels the complex roles of DASH proteins in immunology.
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Affiliation(s)
- L Wagner
- Deutschsprachige Selbsthilfegruppe für Alkaptonurie (DSAKU) e.V, Stuttgart.,Department for Experimental Therapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
| | - C Klemann
- Centre of Paediatric Surgery.,Centre for Paediatrics and Adolescent Medicine
| | - M Stephan
- Clinic for Psychosomatics and Psychotherapy, Hannover Medical School, Hannover
| | - S von Hörsten
- Department for Experimental Therapy, Friedrich-Alexander-Universität Erlangen-Nürnberg, Erlangen, Germany
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Villanueva SSM, Perdomo VG, Ruiz ML, Rigalli JP, Arias A, Luquita MG, Vore M, Catania VA, Mottino AD. Effect of glucagon-like peptide 2 on hepatic, renal, and intestinal disposition of 1-chloro-2,4-dinitrobenzene. Drug Metab Dispos 2012; 40:1252-8. [PMID: 22453052 PMCID: PMC3382840 DOI: 10.1124/dmd.111.044339] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2011] [Accepted: 03/27/2012] [Indexed: 12/13/2022] Open
Abstract
The ability of the liver, small intestine, and kidney to synthesize and subsequently eliminate dinitrophenyl-S-glutathione (DNP-SG), a substrate for multidrug resistance-associated protein 2 (Mrp2), was assessed in rats treated with glucagon-like peptide 2 (GLP-2, 12 μg/100 g b.wt. s.c. every 12 h for 5 consecutive days). An in vivo perfused jejunum model with simultaneous bile and urine collection was used. A single intravenous dose of 30 μmol/kg b.wt. 1-chloro-2,4-dinitrobenzene (CDNB) was administered, and its conjugate, DNP-SG, and dinitrophenyl cysteinyl glycine (DNP-CG), resulting from the action of γ-glutamyltransferase on DNP-SG, were determined in bile, intestinal perfusate, and urine by high-performance liquid chromatography. Tissue content of DNP-SG was also assessed in liver, intestine, and kidneys. Biliary excretion of DNP-SG+DNP-CG was decreased in GLP-2 rats with respect to controls. In contrast, their intestinal excretion was substantially increased, whereas urinary elimination was not affected. Western blot and real-time polymerase chain reaction studies revealed preserved levels of Mrp2 protein and mRNA in liver and renal cortex and a significant increase in intestine in response to GLP-2 treatment. Tissue content of DNP-SG detected 5 min after CDNB administration was decreased in liver, increased in intestine, and unchanged in kidney in GLP-2 versus control group, consistent with GLP-2-induced down-regulation of expression of glutathione transferase (GST) Mu in liver and up-regulation of GST-Alpha in intestine at both protein and mRNA levels. In conclusion, GLP-2 induced selective changes in hepatic and intestinal disposition of a common GST and Mrp2 substrate administered systemically that could be of pharmacological or toxicological relevance under therapeutic treatment conditions.
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Affiliation(s)
- Silvina S M Villanueva
- Instituto de Fisiología Experimental, Facultad de Ciencias Bioquímicas y Farmacéuticas, Suipacha 570, S2002LRL Rosario, Argentina
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Venneti KC, Hewage CM. Conformational and molecular interaction studies of glucagon-like peptide-2 with its N-terminal extracellular receptor domain. FEBS Lett 2010; 585:346-52. [DOI: 10.1016/j.febslet.2010.12.011] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/24/2010] [Revised: 12/08/2010] [Accepted: 12/08/2010] [Indexed: 10/18/2022]
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Martin GR, Beck PL, Sigalet DL. Gut hormones, and short bowel syndrome: The enigmatic role of glucagon-like peptide-2 in the regulation of intestinal adaptation. World J Gastroenterol 2006; 12:4117-29. [PMID: 16830359 PMCID: PMC4087358 DOI: 10.3748/wjg.v12.i26.4117] [Citation(s) in RCA: 56] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Short bowel syndrome (SBS) refers to the malabsorption of nutrients, water, and essential vitamins as a result of disease or surgical removal of parts of the small intestine. The most common reasons for removing part of the small intestine are due to surgical intervention for the treatment of either Crohn's disease or necrotizing enterocolitis. Intestinal adaptation following resection may take weeks to months to be achieved, thus nutritional support requires a variety of therapeutic measures, which include parenteral nutrition. Improper nutrition management can leave the SBS patient malnourished and/or dehydrated, which can be life threatening. The development of therapeutic strategies that reduce both the complications and medical costs associated with SBS/long-term parenteral nutrition while enhancing the intestinal adaptive response would be valuable.
Currently, therapeutic options available for the treatment of SBS are limited. There are many potential stimulators of intestinal adaptation including peptide hormones, growth factors, and neuronally-derived components. Glucagon-like peptide-2 (GLP-2) is one potential treatment for gastrointestinal disorders associated with insufficient mucosal function. A significant body of evidence demonstrates that GLP-2 is a trophic hormone that plays an important role in controlling intestinal adaptation. Recent data from clinical trials demonstrate that GLP-2 is safe, well-tolerated, and promotes intestinal growth in SBS patients. However, the mechanism of action and the localization of the glucagon-like peptide-2 receptor (GLP-2R) remains an enigma. This review summarizes the role of a number of mucosal-derived factors that might be involved with intestinal adaptation processes; however, this discussion primarily examines the physiology, mechanism of action, and utility of GLP-2 in the regulation of intestinal mucosal growth.
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Affiliation(s)
- G-R Martin
- Department of Gastrointestinal Sciences, Faculty of Medicine, University of Calgary, 3330 Hospital Drive NW., Calgary, Alberta T2N 4N1, Canada.
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10
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Abstract
Despite dramatic fluctuations in calorie intake, animals maintain a very stable body weight. The reason is that energy intake and expenditure are precisely matched. Long-term regulation of energy balance is dependent on the coordination and interpretation of signals such as those given by insulin and leptin indicating sufficient long-term energy stores as well as short-term, meal-related signals such as those given by cholecystokinin (CCK). Within the last 30 years, our knowledge of short-term signals has increased dramatically. Throughout the cephalo-caudal axis of the gastrointestinal system, discrete enteroendocrine cells respond to both mechanical and chemical stimulation. Meal-associated hormone release is dependent on the concentration and composition of the nutrients ingested. Released signals are transmitted neurally through vagal afferents or humorally as circulating ligands for specific receptor populations in the periphery and central nervous system. These signals are interpreted by the CNS and manifested as a behavioral modification of feeding. This review will present past and recent literature in support of gut hormones and their roles as mediators of satiety. Evidence from pharmacologic and physiologic studies involving both humans and rodents will be presented, along with a short section outlining the knowledge gained through the use of murine knockout models. Last, the contribution of satiety hormones as likely mediators of the effectiveness seen following obesity surgery will be reviewed. Although traditionally thought of as short-term, meal-related signals, enhanced, chronic hormone secretion and signaling resulting from gut reconstruction as seen with gastric bypass surgery most likely contributes to the superior efficacy of surgery as a treatment for obesity.
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Affiliation(s)
- April D Strader
- Genome Research Institute, University of Cincinnati Medical Center, 2170 E. Galbraith Road, Cincinnati, OH 45237, USA
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Niinikoski H, Stoll B, Guan X, Kansagra K, Lambert BD, Stephens J, Hartmann B, Holst JJ, Burrin DG. Onset of small intestinal atrophy is associated with reduced intestinal blood flow in TPN-fed neonatal piglets. J Nutr 2004; 134:1467-74. [PMID: 15173413 DOI: 10.1093/jn/134.6.1467] [Citation(s) in RCA: 90] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
Our aim was to determine the speed of onset of total parenteral nutrition (TPN)-induced mucosal atrophy, and whether this is associated with changes in intestinal blood flow and tissue metabolism in neonatal piglets. Piglets were implanted with jugular venous and duodenal catheters and either a portal venous or superior mesenteric artery (SMA) blood flow probe. At 3 wk of age, piglets were randomly assigned to receive continuous enteral formula feeding (n = 8) or TPN (n = 17) for 24 or 48 h. Blood flow was recorded continuously and piglets were given an i.v. bolus of bromodeoxyuridine and (13)C-phenylalanine to measure crypt cell proliferation and protein synthesis, respectively. After 8 h of TPN, portal and SMA blood flow decreased 30% compared with enteral feeding (P < 0.01), and remained near levels of food-deprived piglets for the remaining 48 h of TPN. After 24 h, TPN reduced jejunal inducible nitric oxide synthase (iNOS) activity and protein abundance (P < 0.05), small intestinal weight, and villous height (P < 0.01) compared with enterally fed piglets. Cell proliferation and DNA mass were decreased (P < 0.05) and apoptosis increased (P < 0.05) after 48 h of TPN. Protein synthesis was lower (P < 0.05) after 24 h of TPN, and protein mass was lower (P < 0.05) after 48 h of TPN, compared with enteral feeding. These data indicate that the transition from enteral to parenteral nutrition induced a rapid (<8 h) decrease in intestinal blood flow, and this likely precedes villous atrophy and the suppression of protein synthesis at 24 h, and of cell proliferation and survival at 48 h.
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Affiliation(s)
- Harri Niinikoski
- U.S. Department of Agriculture/ARS Children's Nutrition Research Center, Department of Pediatrics, Baylor College of Medicine, Houston, TX 77030, USA
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Mayo KE, Miller LJ, Bataille D, Dalle S, Göke B, Thorens B, Drucker DJ. International Union of Pharmacology. XXXV. The glucagon receptor family. Pharmacol Rev 2003; 55:167-94. [PMID: 12615957 DOI: 10.1124/pr.55.1.6] [Citation(s) in RCA: 335] [Impact Index Per Article: 15.2] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/27/2022] Open
Abstract
Peptide hormones within the secretin-glucagon family are expressed in endocrine cells of the pancreas and gastrointestinal epithelium and in specialized neurons in the brain, and subserve multiple biological functions, including regulation of growth, nutrient intake, and transit within the gut, and digestion, energy absorption, and energy assimilation. Glucagon, glucagon-like peptide-1, glucagon-like peptide-2, glucose-dependent insulinotropic peptide, growth hormone-releasing hormone and secretin are structurally related peptides that exert their actions through unique members of a structurally related G protein-coupled receptor class 2 family. This review discusses advances in our understanding of how these peptides exert their biological activities, with a focus on the biological actions and structural features of the cognate receptors. The receptors have been named after their parent and only physiologically relevant ligand, in line with the recommendations of the International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification (NC-IUPHAR).
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Affiliation(s)
- Kelly E Mayo
- Department of Biochemistry, Molecular Biology and Cell Biology, Northwestern University, Evanston, Illinois, USA
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Schwartz MZ, Kuenzler KA. Pharmacotherapy and growth factors in the treatment of short bowel syndrome. Semin Pediatr Surg 2001; 10:81-90. [PMID: 11329609 DOI: 10.1053/spsu.2001.22385] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/14/2023]
Abstract
A review of the pharmacologic substances and growth factors that have been studied experimentally and administered clinically for the management of short bowel syndrome is presented. The medical management of short bowel syndrome is multifaceted. In the acute phase, efforts focus on fluid and electrolyte management and the reduction of gastric acid output. As enteral feeding is initiated, antimotility and antisecretory agents may be effective in reducing gastrointestinal losses. Additional modalities of management, including nutrients and growth factors, may be directed at maximizing absorptive function beyond that which occurs with intestinal adaptation. Continued research aimed at further elucidating the process of intestinal adaptation may allow us to use the various peptides and hormones that act as growth factors for the bowel mucosa. Knowledge gained from these studies combined with gene therapy techniques will result in the permanent enhancement of intestinal function beyond the normal adaptation process, eliminate the dependence on total parenteral nutrition, and avoid the need for intestine transplantation.
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Affiliation(s)
- M Z Schwartz
- A.I. duPont Hospital for Children, Wilmington, Delaware 19803, USA
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Impaired meal stimulated glucagon-like peptide 2 response in ileal resected short bowel patients with intestinal failure. NUTR CLIN METAB 2000. [DOI: 10.1016/s0985-0562(00)80043-6] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.0] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/17/2022]
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