Cellular regulation of islet hormone secretion by the incretin hormone glucagon-like peptide 1

Pflugers Arch. 1998 Apr;435(5):583-94. doi: 10.1007/s004240050558.

Abstract

Glucagon-like peptide 1 is a gastrointestinally derived hormone with profound effects on nutrient-induced pancreatic hormone release. GLP-1 modulates insulin, glucagon and somatostatin secretion by binding to guanine nucleotide binding protein-coupled receptors resulting in the activation of adenylate cyclase and generation of cyclic adenosine monophosphate (cAMP). In the B-cell, cAMP, via activation of protein kinase A, interacts with a plethora of signal transduction processes including ion channel activity, intracellular Ca2+ handling and exocytosis of the insulin-containing granules. The stimulatory action of GLP-1 on insulin secretion, contrary to that of the currently used hypoglycaemic sulphonylureas, is glucose dependent and requires the presence of normal or elevated concentrations of the sugar. For this reason, GLP-1 attracts much interest as a possible novel principle for the treatment of human type-2 diabetes. Here we review the actions of GLP-1 on islet cell function and attempt to integrate current knowledge into a working model for the control of pancreatic hormone secretion.

Publication types

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

MeSH terms

  • Animals
  • Calcium / metabolism
  • Calcium / physiology
  • Diabetes Mellitus, Type 2 / drug therapy
  • Diabetes Mellitus, Type 2 / physiopathology
  • Exocytosis / physiology
  • Glucagon / metabolism
  • Glucagon / physiology*
  • Glucagon / therapeutic use
  • Glucagon-Like Peptide 1
  • Glucagon-Like Peptide-1 Receptor
  • Glucagon-Like Peptides
  • Humans
  • Ion Channels / metabolism
  • Ion Channels / physiology
  • Islets of Langerhans / metabolism*
  • Pancreatic Hormones / metabolism*
  • Peptide Fragments / physiology*
  • Peptide Fragments / therapeutic use
  • Protein Precursors / physiology*
  • Protein Precursors / therapeutic use
  • Receptors, Glucagon / metabolism

Substances

  • GLP1R protein, human
  • Glucagon-Like Peptide-1 Receptor
  • Ion Channels
  • Pancreatic Hormones
  • Peptide Fragments
  • Protein Precursors
  • Receptors, Glucagon
  • glucagon-like peptide 1 (7-36)amide
  • Glucagon-Like Peptides
  • Glucagon-Like Peptide 1
  • Glucagon
  • Calcium