title: Regulation of glucose homeostasis by GLP-1.
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.
authors.affiliation: Department of Medicine, State University of New York (SUNY), Upstate Medical University, Syracuse, New York, USA; Joslin Diabetes Center, State University of New York (SUNY), Upstate Medical University, Syracuse, New York, USA.
authors.forename: Prashant
authors.initials: P
authors.lastname: Nadkarni
authors.affiliation: Department of Medicine, State University of New York (SUNY), Upstate Medical University, Syracuse, New York, USA.
authors.forename: Oleg G
authors.initials: OG
authors.lastname: Chepurny
authors.affiliation: Department of Medicine, State University of New York (SUNY), Upstate Medical University, Syracuse, New York, USA; Department of Pharmacology, State University of New York (SUNY), Upstate Medical University, Syracuse, New York, USA. Electronic address: holzg@upstate.edu.
authors.forename: George G
authors.initials: GG
authors.lastname: Holz
mesh_terms: D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000378:metabolism; D052216:Glucagon-Like Peptide 1 / Q000096:biosynthesis / Q000378:metabolism*; D000067757:Glucagon-Like Peptide-1 Receptor; D005947:Glucose / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D050417:Insulin-Secreting Cells / Q000378:metabolism; D018027:Receptors, Glucagon / Q000819:agonists / Q000378:metabolism
chemical_list: C000593833:GLP1R protein, human; D000067757:Glucagon-Like Peptide-1 Receptor; D018027:Receptors, Glucagon; D052216:Glucagon-Like Peptide 1; D005947:Glucose
keywords: Diabetes; GLP-1; Glucagon; Glucose; Hyperglycemia; Incretin hormone; Insulin