Roles of cAMP signalling in insulin granule exocytosis.
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.
Seino
S
S
Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, Hyogo, Japan. seino@med.kobe-u.ac.jp
Takahashi
H
H
Fujimoto
W
W
Shibasaki
T
T
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000187:drug effects / Q000502:physiology*; D005089:Exocytosis / Q000187:drug effects / Q000502:physiology*; D007328:Insulin / Q000378:metabolism / Q000494:pharmacology*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D009544:Niflumic Acid / Q000494:pharmacology*; D015398:Signal Transduction
D007328:Insulin; D009544:Niflumic Acid; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium