| Development of type 2 diabetes caused by a deficiency of a tRNAlys modification. | |
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MedLine Citation:
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PMID: 22157242 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Genetic variations in the cdk5 regulator associated protein 1-like 1 (cdkal1) gene have been identified in whole-genome association studies as a risk factor for the development of type 2 diabetes (T2D). A recent study showed that Cdkal1 was a mammalian methythiotransferase, which specifically synthesizes 2-methylthio-N6-threonylcarbamoyladenosine (ms2t6A) at position 37 of tRNAlys(UUU). The ms2t6A modification in tRNAlys(UUU) was important for the accurate decoding of its cognate codon. In pancreatic, β-cell-specific, Cdkal1 knockout (Cdkal1 KO) mice, a deficiency of ms2t6A caused the mistranslation of a Lys codon in proinsulin, resulting in improper processing. The mice showed a decrease in insulin secretion and glucose intolerance. In addition, the mistranslation contributed to the expression of the endoplasmic reticulum (ER) stress response in Cdkal1-deficient β-cells. Furthermore, Cdkal1 KO mice were hypersensitive to high-fat diet-induced glucose intolerance, as well as the ER stress response. These findings might potentially explain the molecular pathogenesis of T2D in patients carrying Cdkal1 variations. |
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Authors:
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Fan-Yan Wei; Kazuhito Tomizawa |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-1-01 |
Journal Detail:
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Title: Islets Volume: 4 ISSN: 1938-2022 ISO Abbreviation: - Publication Date: 2012 Jan |
Date Detail:
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Created Date: 2011-12-13 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101495366 Medline TA: Islets Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Affiliation:
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Department of Molecular Physiology; Faculty of Life Sciences; Kumamoto University; Kumamoto, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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