Cholinergic augmentation of insulin release requires ankyrin-B.

Published online

Journal Article

Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP(3)R)-mediated calcium ion (Ca2+) release. Ankyrin-B binds to the IP(3)R 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.

Full Text

Duke Authors

Cited Authors

  • Healy, JA; Nilsson, KR; Hohmeier, HE; Berglund, J; Davis, J; Hoffman, J; Kohler, M; Li, L-S; Berggren, P-O; Newgard, CB; Bennett, V

Published Date

  • March 16, 2010

Published In

Volume / Issue

  • 3 / 113

Start / End Page

  • ra19 -

PubMed ID

  • 20234002

Pubmed Central ID

  • 20234002

Electronic International Standard Serial Number (EISSN)

  • 1937-9145

Digital Object Identifier (DOI)

  • 10.1126/scisignal.2000771

Language

  • eng

Conference Location

  • United States