Roles of cAMP signalling in insulin granule exocytosis

Diabetes Obes Metab. 2009 Nov;11 Suppl 4:180-8. doi: 10.1111/j.1463-1326.2009.01108.x.

Abstract

Insulin secretion is regulated by a series of complex events generated by various intracellular signals including Ca(2+), ATP, cAMP and phospholipid-derived signals. Glucose-stimulated insulin secretion is the principal mode of insulin secretion, and the mechanism potentiating the secretion is critical for physiological responses. Among the various intracellular signals involved, cAMP is particularly important for amplifying insulin secretion. Recently, glucagon-like peptide-1 (GLP-1) analogues and dipeptidyl peptidase-IV (DPP-IV) inhibitors have been developed as new antidiabetic drugs. These drugs all act through cAMP signalling in pancreatic beta-cells. Until recently, cAMP was generally thought to potentiate insulin secretion through protein kinase A (PKA) phosphorylation of proteins associated with the secretory process. However, it is now known that in addition to PKA, cAMP has other targets such as Epac (also referred to as cAMP-GEF). The variety of the effects mediated by cAMP signalling may be linked to cAMP compartmentation in the pancreatic beta-cells.

Publication types

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

MeSH terms

  • Animals
  • Calcium / pharmacology*
  • Cyclic AMP-Dependent Protein Kinases / drug effects
  • Cyclic AMP-Dependent Protein Kinases / physiology*
  • Exocytosis / drug effects
  • Exocytosis / physiology*
  • Insulin / metabolism
  • Insulin / pharmacology*
  • Insulin Secretion
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / physiology*
  • Mice
  • Niflumic Acid / pharmacology*
  • Signal Transduction

Substances

  • Insulin
  • Niflumic Acid
  • Cyclic AMP-Dependent Protein Kinases
  • Calcium