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) |
|---|---|
| Journal | Science Signaling |
| Volume | 3 |
| Issue number | 113 |
| DOIs | |
| State | Published - Mar 16 2010 |
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ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Cell Biology
Cite this
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 journal › Article
}
TY - JOUR
T1 - Cholinergic augmentation of insulin release requires ankyrin-B
AU - Healy, Jane A.
AU - Nilsson, Kent R
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.
AB - 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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U2 - 10.1126/scisignal.2000771
DO - 10.1126/scisignal.2000771
M3 - Article
C2 - 20234002
AN - SCOPUS:77953844541
VL - 3
JO - Science Signaling
JF - Science Signaling
SN - 1937-9145
IS - 113
ER -