| Cholinergic augmentation of insulin release requires ankyrin-B. | |
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MedLine Citation:
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PMID: 20234002 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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 |
Publication Detail:
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Type: Journal Article Date: 2010-03-16 |
Journal Detail:
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Title: Science signaling Volume: 3 ISSN: 1937-9145 ISO Abbreviation: Sci Signal Publication Date: 2010 |
Date Detail:
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Created Date: 2010-03-17 Completed Date: 2010-07-15 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101465400 Medline TA: Sci Signal Country: United States |
Other Details:
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Languages: eng Pagination: ra19 Citation Subset: IM |
Affiliation:
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1Howard Hughes Medical Institute, Duke University Medical Center, Durham, NC 27710, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Ankyrins / deficiency, genetics, metabolism* Calcium / metabolism Carbachol / metabolism Diabetes Mellitus, Type 2 / metabolism* Glucose / metabolism Immunoblotting Inositol 1,4,5-Trisphosphate Receptors / metabolism* Insulin / secretion* Insulin-Secreting Cells / secretion* Mice Microscopy, Fluorescence Mutation, Missense Parasympathetic Nervous System / metabolism* Polymorphism, Single Nucleotide / genetics RNA, Small Interfering / genetics Reverse Transcriptase Polymerase Chain Reaction Risk Factors |
| Chemical | |
Reg. No./Substance:
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0/Ank2 protein, mouse; 0/Ankyrins; 0/Inositol 1,4,5-Trisphosphate Receptors; 0/RNA, Small Interfering; 11061-68-0/Insulin; 50-99-7/Glucose; 51-83-2/Carbachol; 7440-70-2/Calcium |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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