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Regulation of glucose homeostasis by GLP-1

  • SUNY Upstate Medical University

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

268 Scopus citations

Abstract

Glucagon-like peptide-1(7-36)amide (GLP-1) is a secreted peptide that acts as a key determinant of blood glucose homeostasis by virtue of its abilities to slow gastric emptying, to enhance pancreatic insulin secretion, and to suppress pancreatic glucagon secretion. GLP-1 is secreted from L cells of the gastrointestinal mucosa in response to a meal, and the blood glucose-lowering action of GLP-1 is terminated due to its enzymatic degradation by dipeptidyl-peptidase-IV (DPP-IV). Released GLP-1 activates enteric and autonomic reflexes while also circulating as an incretin hormone to control endocrine pancreas function. The GLP-1 receptor (GLP-1R) is a G protein-coupled receptor that is activated directly or indirectly by blood glucose-lowering agents currently in use for the treatment of type 2 diabetes mellitus (T2DM). These therapeutic agents include GLP-1R agonists (exenatide, liraglutide, lixisenatide, albiglutide, dulaglutide, and langlenatide) and DPP-IV inhibitors (sitagliptin, vildagliptin, saxagliptin, linagliptin, and alogliptin). Investigational agents for use in the treatment of T2DM include GPR119 and GPR40 receptor agonists that stimulate the release of GLP-1 from L cells. Summarized here is the role of GLP-1 to control blood glucose homeostasis, with special emphasis on the advantages and limitations of GLP-1-based therapeutics.

Original languageEnglish
Title of host publicationGlucose Homeostatis and the Pathogenesis of Diabetes Mellitus
PublisherElsevier B.V.
Pages23-65
Number of pages43
ISBN (Print)9780128001011
DOIs
StatePublished - 2014

Publication series

NameProgress in Molecular Biology and Translational Science
Volume121

Keywords

  • Diabetes
  • GLP-1
  • Glucagon
  • Glucose
  • Hyperglycemia
  • Incretin hormone
  • Insulin

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