Research ArticlePhysiology

Cholinergic Augmentation of Insulin Release Requires Ankyrin-B

See allHide authors and affiliations

Sci. Signal.  16 Mar 2010:
Vol. 3, Issue 113, pp. ra19
DOI: 10.1126/scisignal.2000771

You are currently viewing the abstract.

View Full Text


Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP3R)–mediated calcium ion (Ca2+) release. Ankyrin-B binds to the IP3R and is enriched in pancreatic beta cells. We found that ankyrin-B–deficient islets displayed impaired potentiation of insulin secretion by the muscarinic agonist carbachol, blunted carbachol-mediated intracellular Ca2+ release, and reduced the abundance of IP3R. Ankyrin-B–haploinsufficient mice exhibited hyperglycemia after oral ingestion but not after intraperitoneal injection of glucose, consistent with impaired parasympathetic potentiation of glucose-stimulated insulin secretion. The R1788W mutation of ankyrin-B impaired its function in pancreatic islets and is associated with type 2 diabetes in Caucasians and Hispanics. Thus, defective glycemic regulation through loss of ankyrin-B–dependent stabilization of IP3R is a potential risk factor for type 2 diabetes.

View Full Text