| First Author | Healy JA | Year | 2010 |
| Journal | Sci Signal | Volume | 3 |
| Issue | 113 | Pages | ra19 |
| PubMed ID | 20234002 | Mgi Jnum | J:185415 |
| Mgi Id | MGI:5428410 | Doi | 10.1126/scisignal.2000771 |
| Citation | Healy JA, et al. (2010) Cholinergic augmentation of insulin release requires ankyrin-B. Sci Signal 3(113):ra19 |
| abstractText | 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. |
