Purpose: Glucagon-like peptide-1 (GLP-1) is originally identified in the gut as an incretin hormone, and it is potent in stimulating insulin secretion in the pancreas. However, increasing evidence suggests that GLP-1 is also produced locally within pancreatic islets. This review focuses on the past and current discoveries regarding intra-islet GLP-1 production and its functions.
Main Findings: There has been a long-standing debate with regard to whether GLP-1 is produced in the pancreatic α cells. Early controversies lead to the widely accepted conclusion that the vast majority of proglucagon is processed to form glucagon in the pancreas, whereas an insignificant amount is cleaved to produce GLP-1. With technological advancements, recent studies have shown that bioactive GLP-1 is produced locally in the pancreas, and the expression and secretion of GLP-1 within islets are regulated by various factors such as cytokines, hyperglycemia, and β cell injury.
Conclusions: GLP-1 is produced by the pancreatic α cells, and it is fully functional as an incretin. Therefore, intra-islet GLP-1 may exert insulinotropic and glucagonostatic effects locally via paracrine and/or autocrine actions, under both normal and diabetic conditions.
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http://dx.doi.org/10.1016/j.jdiacomp.2016.05.016 | DOI Listing |
Nutrition
November 2024
Department of Integrated Applied Life Science, Integrated Graduate School of Medicine, Engineering, and Agricultural Sciences, University of Yamanashi, Kofu, Yamanashi, Japan; Department of Local Produce and Food Sciences, Laboratory of Food and Nutritional Sciences, Faculty of Life and Environmental Sciences, University of Yamanashi, Kofu, Yamanashi, Japan. Electronic address:
Objectives: Gastrointestinal hormones, such as glucagon-like peptide 1 (GLP-1), gastric inhibitory polypeptide, and peptide YY (PYY) are important for reducing malnutrition at older ages because they are related to assimilation and feeding behavior. Medium-chain triacylglycerol (MCT) ameliorates metabolic symptoms and frailty in adults; however, whether it has the same effect in old age is unknown. To address this, we examined the changes in insulin and gastrointestinal hormones in aged Brd4 (+/-) mice exhibiting symptoms of old age.
View Article and Find Full Text PDFBMC Endocr Disord
December 2024
Department of Veterans Affairs, Tennessee Valley Health Authority, Nashville, TN, USA.
Background: Medications targeting the glucagon-like peptide-1 (GLP-1) pathway are an important therapeutic class currently used for the treatment of Type 2 diabetes (T2D). However, there is not enough known about which subgroups of patients would receive the most benefit from these medications.
Objective: The goal of this study was to develop a predictive model for patient responsiveness to medications, here collectively called GLP-1 M, that include GLP-1 receptor agonists and dipeptidyl peptidase-4 (DPP4) inhibitors (that normally degrade endogenously-produced GLP-1).
Int J Mol Sci
November 2024
Unit of Pharmacology and Therapeutics, Department of Biomedicine, Faculty of Medicine, University of Porto (FMUP), 4200-450 Porto, Portugal.
Immune-mediated inflammatory diseases (IMIDs) are characterized by dysregulated immune responses and chronic tissue inflammation. In the setting of inflammatory bowel disease (IBD), dipeptidyl peptidase 4 (DPP4) and gut microorganisms have been proved to interplay, potentially influenced by dietary factors. This rapid review aimed to study the DPP4-gut microbiome link in IBD.
View Article and Find Full Text PDFExpert Opin Investig Drugs
December 2024
Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.
Introduction: Type 1 diabetes is a chronic autoimmune condition characterized by the selective destruction of insulin-producing beta cells in the pancreas. The etiology of T1D is multifactorial, with a combination of genetic susceptibility and environmental triggers believed to underlie beta-cell destruction. Preserving and prolonging beta-cell function in T1D is a pivotal therapeutic objective that can mitigate disease progression and improve glycemic control.
View Article and Find Full Text PDFJ Physiol
December 2024
Institute of Metabolic Science and MRC Metabolic Diseases Unit, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.
Gut hormones control intestinal function, metabolism and appetite, and have been harnessed therapeutically to treat type 2 diabetes and obesity. Our understanding of the enteroendocrine axis arises largely from animal studies, but intestinal organoid models make it possible to identify, genetically modify and purify human enteroendocrine cells (EECs). This study aimed to map human EECs using single-cell RNA sequencing.
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