| Raldh3 expression in diabetic islets reciprocally regulates secretion of insulin and glucagon from pancreatic islets. | |
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MedLine Citation:
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PMID: 20833146 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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We have previously reported that obesity-induced diabetes developed in high-fat diet (HFD)-fed BDF1 mice. This is caused by insufficient insulin response to an excess glucose load. In this study, we have shown that the enhanced expression of retinaldehyde dehydrogenase 3 (Raldh3) causes functional disorders of pancreatic islets in diabetic mouse models. In the pancreatic islets of HFD-induced diabetic BDF1 mice and spontaneously diabetic C57BL/KsJ(db/db) mice, gene expression analysis with oligonucleotide microarray revealed a significant increase in Raldh3 expression. Exposure to a culture medium containing a higher glucose concentration (25 mM) significantly increased Raldh3 expression in murine MIN6 and alphaTC1 clone 9 cells, which derived from the α and β-cells of pancreatic islets, respectively. Overexpression of Raldh3 reduced the insulin secretion in MIN6 cells, and surprisingly, increased the glucagon secretion in alphaTC1 clone 9 cells. Furthermore, the knockdown of Raldh3 expression with siRNA decreased the glucagon secretion in alphaTC1 clone 9 cells. Raldh3 catalyzes the conversion of 13-cis retinal to 13-cis retinoic acid and we revealed that 13-cis retinoic acid significantly reduces cell viability in MIN6 and alphaTC1 clone 9 cells, but not in cells of H4IIEC3, 3T3-L1, and COS-1 cell lines. These findings suggest that an increasing expression of Raldh3 deregulates the balanced mechanisms of insulin and glucagon secretion in the pancreatic islets and may induce β-cell dysfunction leading to the development of type 2 diabetes. |
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Authors:
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Mitsuru Shimamura; Hiroshi Karasawa; Sachiko Sakakibara; Akira Shinagawa |
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Publication Detail:
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Type: Journal Article Date: 2010-09-15 |
Journal Detail:
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Title: Biochemical and biophysical research communications Volume: 401 ISSN: 1090-2104 ISO Abbreviation: Biochem. Biophys. Res. Commun. Publication Date: 2010 Oct |
Date Detail:
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Created Date: 2010-10-11 Completed Date: 2010-11-30 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0372516 Medline TA: Biochem Biophys Res Commun Country: United States |
Other Details:
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Languages: eng Pagination: 79-84 Citation Subset: IM |
Copyright Information:
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Copyright © 2010 Elsevier Inc. All rights reserved. |
Affiliation:
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Research and Development Planning Division, Daiichi Sankyo Co., Ltd., 1-2-58 Hiromachi, Shinagawa-ku, Tokyo 140-8710, Japan. shimamura.mitsuru.f2@daiichisankyo.co.jp |
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| MeSH Terms | |
Descriptor/Qualifier:
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3T3-L1 Cells Animals COS Cells Cercopithecus aethiops Diabetes Mellitus, Experimental / enzymology* Diabetes Mellitus, Type 2 / enzymology* Glucagon / secretion* Insulin / secretion* Insulin-Secreting Cells / drug effects, enzymology, secretion Islets of Langerhans / drug effects, enzymology, secretion* Isotretinoin / pharmacology Mice Mice, Inbred C57BL Retinal Dehydrogenase / biosynthesis*, genetics |
| Chemical | |
Reg. No./Substance:
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11061-68-0/Insulin; 4759-48-2/Isotretinoin; 9007-92-5/Glucagon; EC 1.2.1.36/Retinal Dehydrogenase; EC 1.2.1.36/retinaldehyde dehydrogenase 3, mouse |
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