Research ArticlePhysiology

Cholinergic Augmentation of Insulin Release Requires Ankyrin-B

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

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Risk Factor for Diabetes

In addition to the glucose that enters the bloodstream, the parasympathetic nervous system also stimulates the pancreas to secrete insulin in response to eating a meal. Healy et al. show that loss of a single copy of the gene encoding ankyrin-B (ankB) in mice impaired insulin secretion in response to ingested glucose, causing glucose intolerance. In isolated pancreatic islets, ankB haploinsufficiency resulted in reduced abundance of the inositol trisphosphate receptor (IP3R), a calcium channel localized to the endoplasmic reticulum, and impaired calcium signaling in response to cholinergic stimulation. Although islets secrete insulin in response to glucose, the addition of a cholinergic agonist (to mimic parasympathetic stimulation) enhances the amount of insulin released. Islets from the ankB haploinsufficient mice failed to show this potentiation of insulin secretion. Healy et al. also found that, in humans, a loss-of-function mutation in AnkB, which is associated with heart disease, was also associated with diabetes. Thus, mutations in this scaffolding protein that cause aberrant calcium signaling may be a risk factor in multiple diseases.