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Sci. Signal., 16 March 2010
Vol. 3, Issue 113, p. ra19
[DOI: 10.1126/scisignal.2000771]
RESEARCH ARTICLES
Cholinergic Augmentation of Insulin Release Requires Ankyrin-B
Jane A. Healy1,2,
Kent R. Nilsson1,3,
Hans E. Hohmeier3,4,5,
Jelena Berglund1,6,7,
Jonathan Davis1,
Janis Hoffman1,
Martin Kohler7,
Luo-Sheng Li7,
Per-Olof Berggren7,
Christopher B. Newgard3,4,5, and
Vann Bennett1,2,6*
1 Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. 2 Department of Biochemistry, Duke University Medical Center, Durham, NC 27710, USA. 3 Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA. 4 Department of Pharmacology and Cancer Biology, Duke University Medical Center, Durham, NC 27710, USA. 5 Sarah W. Stedman Nutrition and Metabolism Center, Duke University Medical Center, Durham, NC 27710, USA. 6 Department of Cell Biology, Duke University Medical Center, Durham, NC 27710, USA. 7 Rolf Luft Research Center for Diabetes and Endocrinology, Karolinska Institutet, S-17176 Stockholm, Sweden.
Abstract:
Parasympathetic stimulation of pancreatic islets augments glucose-stimulated insulin secretion by inducing inositol trisphosphate receptor (IP3R)–mediated calcium ion (Ca2+) release. Ankyrin-B binds to the IP3R 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.
* To whom correspondence should be addressed. E-mail: benne012{at}mc.duke.edu
Citation: J. A. Healy, K. R. Nilsson, H. E. Hohmeier, J. Berglund, J. Davis, J. Hoffman, M. Kohler, L.-S. Li, P.-O. Berggren, C. B. Newgard, V. Bennett, Cholinergic Augmentation of Insulin Release Requires Ankyrin-B. Sci. Signal.3, ra19 (2010).
Noninvasive in vivo model demonstrating the effects of autonomic innervation on pancreatic islet function.
R. Rodriguez-Diaz, S. Speier, R. D. Molano, A. Formoso, I. Gans, M. H. Abdulreda, O. Cabrera, J. Molina, A. Fachado, C. Ricordi, et al. (2012)
PNAS
109, 21456-21461
|Abstract »|Full Text »|PDF »
Ankyrin-B Protein in Heart Failure: IDENTIFICATION OF A NEW COMPONENT OF METAZOAN CARDIOPROTECTION.
F. Kashef, J. Li, P. Wright, J. Snyder, F. Suliman, A. Kilic, R. S. D. Higgins, M. E. Anderson, P. F. Binkley, T. J. Hund, et al. (2012)
J. Biol. Chem.
287, 30268-30281
|Abstract »|Full Text »|PDF »
