Scholars@Duke

Cholinergic augmentation of insulin release requires ankyrin-B.

Publication ,  Journal Article
Healy, JA; Nilsson, KR; Hohmeier, HE; Berglund, J; Davis, J; Hoffman, J; Kohler, M; Li, L-S; Berggren, P-O; Newgard, CB; Bennett, V
Published in: Sci Signal
March 16, 2010
Published version (DOI) Link to item

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.

Duke Scholars

Kent Ronald Nilsson Jr.
Author Kent Ronald Nilsson Jr. Medicine, Cardiology
Hans-Ewald Hohmeier
Author Hans-Ewald Hohmeier Medicine, Endocrinology, Metabolism, and Nutrition
Christopher Bang Newgard
Author Christopher Bang Newgard Pharmacology & Cancer Biology
Vann Bennett
Author Vann Bennett Biochemistry

Published In

Sci Signal

DOI

10.1126/scisignal.2000771

EISSN

1937-9145

Publication Date

March 16, 2010

Volume

3

Issue

113

Start / End Page

ra19

Location

United States

Related Subject Headings

  • Risk Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • Polymorphism, Single Nucleotide
  • Parasympathetic Nervous System
  • Mutation, Missense
  • Microscopy, Fluorescence
  • Mice
  • Insulin-Secreting Cells
  • Insulin Secretion
 

Citation

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ICMJE
MLA
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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. Sci Signal, 3(113), ra19. https://doi.org/10.1126/scisignal.2000771
Healy, Jane A., Kent R. Nilsson, Hans E. Hohmeier, Jelena Berglund, Jonathan Davis, Janis Hoffman, Martin Kohler, et al. “Cholinergic augmentation of insulin release requires ankyrin-B.” Sci Signal 3, no. 113 (March 16, 2010): ra19. https://doi.org/10.1126/scisignal.2000771.
Healy JA, Nilsson KR, Hohmeier HE, Berglund J, Davis J, Hoffman J, et al. Cholinergic augmentation of insulin release requires ankyrin-B. Sci Signal. 2010 Mar 16;3(113):ra19.
Healy, Jane A., et al. “Cholinergic augmentation of insulin release requires ankyrin-B.” Sci Signal, vol. 3, no. 113, Mar. 2010, p. ra19. Pubmed, doi:10.1126/scisignal.2000771.
Healy JA, Nilsson KR, Hohmeier HE, Berglund J, Davis J, Hoffman J, Kohler M, Li L-S, Berggren P-O, Newgard CB, Bennett V. Cholinergic augmentation of insulin release requires ankyrin-B. Sci Signal. 2010 Mar 16;3(113):ra19.

Published In

Sci Signal

DOI

10.1126/scisignal.2000771

EISSN

1937-9145

Publication Date

March 16, 2010

Volume

3

Issue

113

Start / End Page

ra19

Location

United States

Related Subject Headings

  • Risk Factors
  • Reverse Transcriptase Polymerase Chain Reaction
  • RNA, Small Interfering
  • Polymorphism, Single Nucleotide
  • Parasympathetic Nervous System
  • Mutation, Missense
  • Microscopy, Fluorescence
  • Mice
  • Insulin-Secreting Cells
  • Insulin Secretion