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

doi:10.1126/scisignal.2000771

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 journal › Article › peer-review

36 Scopus citations

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)
Pages (from-to)	ra19
Journal	Science Signaling
Volume	3
Issue number	113
DOIs	https://doi.org/10.1126/scisignal.2000771
State	Published - Mar 16 2010
Externally published	Yes

ASJC Scopus subject areas

Biochemistry
Molecular Biology
Cell Biology

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title = "Cholinergic augmentation of insulin release requires ankyrin-B",

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.",

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AU - Hohmeier, Hans E.

AU - Berglund, Jelena

AU - Davis, Jonathan

AU - Hoffman, Janis

AU - Kohler, Martin

AU - Li, Luo Sheng

AU - Berggren, Per Olof

AU - Newgard, Christopher B.

AU - Bennett, Vann

PY - 2010/3/16

Y1 - 2010/3/16

N2 - 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.

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Cholinergic augmentation of insulin release requires ankyrin-B

Abstract

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