Genevieve E Fava1, Emily W Dong1, Hongju Wu2. 1. Endocrinology Section, Department of Medicine, Tulane University Health Science Center, New Orleans, LA, United States. 2. Endocrinology Section, Department of Medicine, Tulane University Health Science Center, New Orleans, LA, United States. Electronic address: hwu3@tulane.edu.
Abstract
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.
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.
Authors: Y Nie; M Nakashima; P L Brubaker; Q L Li; R Perfetti; E Jansen; Y Zambre; D Pipeleers; T C Friedman Journal: J Clin Invest Date: 2000-04 Impact factor: 14.808
Authors: Juris J Meier; Baptist Gallwitz; Stefan Salmen; Oliver Goetze; Jens J Holst; Wolfgang E Schmidt; Michael A Nauck Journal: J Clin Endocrinol Metab Date: 2003-06 Impact factor: 5.958
Authors: Corinna Lebherz; Florian Kahles; Katja Piotrowski; Michael Vogeser; Ann Christina Foldenauer; Kirsten Nassau; Erich Kilger; Nikolaus Marx; Klaus G Parhofer; Michael Lehrke Journal: Cardiovasc Diabetol Date: 2016-02-03 Impact factor: 9.951
Authors: Joshua Wollam; Matthew Riopel; Yong-Jiang Xu; Andrew M F Johnson; Jachelle M Ofrecio; Wei Ying; Dalila El Ouarrat; Luisa S Chan; Andrew W Han; Nadir A Mahmood; Caitlin N Ryan; Yun Sok Lee; Jeramie D Watrous; Mahendra D Chordia; Dongfeng Pan; Mohit Jain; Jerrold M Olefsky Journal: Diabetes Date: 2019-04-22 Impact factor: 9.461
Authors: Scott A Campbell; Dominic P Golec; Matt Hubert; Janyne Johnson; Nicole Salamon; Amy Barr; Patrick E MacDonald; Koenraad Philippaert; Peter E Light Journal: Mol Metab Date: 2020-05-12 Impact factor: 7.422