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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2008-6-2
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pubmed:databankReference |
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pubmed:abstractText |
Cyclic ADP-ribose (cADPR), accumulated in pancreatic beta-cells in response to elevated ATP levels after glucose stimulation, mobilizes Ca(2+) from the endoplasmic reticulum through the ryanodine receptor (RyR) and thereby induces insulin secretion. We have recently demonstrated in an in vitro study that cADPR activates RyR through binding to FK506-binding protein 12.6 (FKBP12.6), an accessory protein of RyR. Here we generated FKBP12.6-deficient (FKBP12.6(-/-)) mice by homologous recombination. FKBP12.6(-/-) mice showed glucose intolerance coupled to insufficient insulin secretion upon a glucose challenge. Insulin secretion in response to glucose was markedly impaired in FKBP12.6(-/-) islets, while sulfonylurea- or KCl-induced insulin secretion was unaffected. No difference was found in the glucose oxidation rate between FKBP12.6(-/-) and wild-type islets. These results indicate that FKBP12.6 plays a role in glucose-induced insulin secretion downstream of ATP production, independently of ATP-sensitive K(+) channels, in pancreatic beta-cells.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
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pubmed:status |
MEDLINE
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pubmed:month |
Jul
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pubmed:issn |
1090-2104
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pubmed:author |
pubmed-author:IkedaTakayukiT,
pubmed-author:NataKojiK,
pubmed-author:NoguchiNaoyaN,
pubmed-author:OkamotoHiroshiH,
pubmed-author:ShervaniNausheen JamalNJ,
pubmed-author:SugawaraAkiraA,
pubmed-author:TakahashiIwaoI,
pubmed-author:TakasawaShinS,
pubmed-author:UrunoAkiraA,
pubmed-author:YamauchiAkiyoA,
pubmed-author:YoshikawaTakeoT
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pubmed:issnType |
Electronic
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pubmed:day |
11
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pubmed:volume |
371
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
735-40
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pubmed:dateRevised |
2011-11-17
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pubmed:meshHeading |
pubmed-meshheading:18466757-Amino Acid Sequence,
pubmed-meshheading:18466757-Animals,
pubmed-meshheading:18466757-Base Sequence,
pubmed-meshheading:18466757-Gene Expression,
pubmed-meshheading:18466757-Glucose,
pubmed-meshheading:18466757-Glucose Intolerance,
pubmed-meshheading:18466757-Glucose Tolerance Test,
pubmed-meshheading:18466757-Insulin,
pubmed-meshheading:18466757-Islets of Langerhans,
pubmed-meshheading:18466757-KATP Channels,
pubmed-meshheading:18466757-Mice,
pubmed-meshheading:18466757-Mice, Knockout,
pubmed-meshheading:18466757-Molecular Sequence Data,
pubmed-meshheading:18466757-Oxidation-Reduction,
pubmed-meshheading:18466757-Potassium Chloride,
pubmed-meshheading:18466757-RNA, Messenger,
pubmed-meshheading:18466757-Sulfonylurea Compounds,
pubmed-meshheading:18466757-Tacrolimus Binding Proteins
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pubmed:year |
2008
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pubmed:articleTitle |
FKBP12.6 disruption impairs glucose-induced insulin secretion.
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pubmed:affiliation |
Department of Advanced Biological Sciences for Regeneration (Kotobiken Medical Laboratories), Tohoku University Graduate School of Medicine, 2-1 Seiryo-machi, Sendai 980-8575, Japan.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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