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 language | English (US) |
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Pages (from-to) | ra19 |
Journal | Science Signaling |
Volume | 3 |
Issue number | 113 |
DOIs | |
State | Published - Mar 16 2010 |
Externally published | Yes |
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology