Regulation of glucose homeostasis by GLP-1

Prog Mol Biol Transl Sci. 2014;121:23-65. doi: 10.1016/B978-0-12-800101-1.00002-8.


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.

Keywords: Diabetes; GLP-1; Glucagon; Glucose; Hyperglycemia; Incretin hormone; Insulin.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / metabolism
  • Glucagon-Like Peptide 1 / biosynthesis
  • Glucagon-Like Peptide 1 / metabolism*
  • Glucagon-Like Peptide-1 Receptor
  • Glucose / metabolism*
  • Homeostasis*
  • Humans
  • Insulin-Secreting Cells / metabolism
  • Receptors, Glucagon / agonists
  • Receptors, Glucagon / metabolism


  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Receptors, Glucagon
  • Glucagon-Like Peptide 1
  • Glucose