Cholinergic augmentation of insulin release requires ankyrin-B

Jane A. Healy, Kent R. Nilsson, Hans E. Hohmeier, Jelena Berglund, Jonathan Davis, Janis Hoffman, Martin Kohler, Luo Sheng Li, Per Olof Berggren, Christopher B. Newgard, Vann Bennett

Research output: Contribution to journalArticlepeer-review

33 Scopus citations

Abstract

Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP 3R)-mediated calcium ion (Ca 2+) release. Ankyrin-B binds to the IP 3R 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 carbacholmediated intracellular Ca 2+ release, and reduced the abundance of IP 3R. 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 IP 3R is a potential risk factor for type 2 diabetes.

Original languageEnglish (US)
Pages (from-to)ra19
JournalScience Signaling
Volume3
Issue number113
DOIs
StatePublished - Mar 16 2010
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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