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 journalArticle

31 Citations (Scopus)

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)
JournalScience Signaling
Volume3
Issue number113
DOIs
StatePublished - Mar 16 2010

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Ankyrins
Cholinergic Agents
Insulin
Medical problems
Islets of Langerhans
Glucose
Type 2 Diabetes Mellitus
Muscarinic Agonists
Insulin-Secreting Cells
Carbachol
Inositol
Intraperitoneal Injections
Hispanic Americans
Hyperglycemia
Stabilization
Eating
Ions
Calcium
Mutation

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Healy, J. A., Nilsson, K. R., Hohmeier, H. E., Berglund, J., Davis, J., Hoffman, J., ... Bennett, V. (2010). Cholinergic augmentation of insulin release requires ankyrin-B. Science Signaling, 3(113). https://doi.org/10.1126/scisignal.2000771

Cholinergic augmentation of insulin release requires ankyrin-B. / Healy, Jane A.; Nilsson, Kent R; Hohmeier, Hans E.; Berglund, Jelena; Davis, Jonathan; Hoffman, Janis; Kohler, Martin; Li, Luo Sheng; Berggren, Per Olof; Newgard, Christopher B.; Bennett, Vann.

In: Science Signaling, Vol. 3, No. 113, 16.03.2010.

Research output: Contribution to journalArticle

Healy, JA, Nilsson, KR, Hohmeier, HE, Berglund, J, Davis, J, Hoffman, J, Kohler, M, Li, LS, Berggren, PO, Newgard, CB & Bennett, V 2010, 'Cholinergic augmentation of insulin release requires ankyrin-B', Science Signaling, vol. 3, no. 113. https://doi.org/10.1126/scisignal.2000771
Healy, Jane A. ; Nilsson, Kent R ; Hohmeier, Hans E. ; Berglund, Jelena ; Davis, Jonathan ; Hoffman, Janis ; Kohler, Martin ; Li, Luo Sheng ; Berggren, Per Olof ; Newgard, Christopher B. ; Bennett, Vann. / Cholinergic augmentation of insulin release requires ankyrin-B. In: Science Signaling. 2010 ; Vol. 3, No. 113.
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