| The HMG-CoA reductase inhibitor pravastatin stimulates insulin secretion through organic anion transporter polypeptides. | |
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MedLine Citation:
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PMID: 20610886 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor pravastatin has been reported to have a beneficial effect on reducing the new onset of diabetes as well as lowering plasma lipids. Because pravastatin is a water-soluble organic anion, it cannot easily penetrate the lipid bilayer of the cell membrane. As the precise mechanisms of the effect of pravastatin on glucose metabolism and diabetes have not been clarified, we examined the roles of the organic anion transporter family on pravastatin-treated islet and adipocyte functions. Rat oatp1/slco1a1, oatp2/slco1a4 and oatp3/slco1a5 were expressed in the pancreas, and rat oatp3/slco1a5 was also detected in rat insulinoma cell line INS-1e. Pravastatin was transported not only by oatp1/slco1a1 and oatp2/slco1a4, but also by rat oatp3/slco1a5. Pravastatin uptake into INS-1e cells was detected and this transport was inhibited by sulfobromophthalein and rifampicin, both of which are known to inhibit oatp family-mediated uptake. In addition, pravastatin enhanced the glucose-stimulated insulin secretion from INS-1e cells. When fat-loaded db/db mice were treated with pravastatin, glucose intolerance and insulin resistance were prevented. In addition, insulin secretion from isolated islets was enhanced by pravastatin. These data suggest that pravastatin has pleiotropic effects on islets through membrane transport under high fat/glucose conditions. |
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Authors:
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Michiaki Abe; Takafumi Toyohara; Akiko Ishii; Takehiro Suzuki; Naoya Noguchi; Yasutoshi Akiyama; Hiromi O Shiwaku; Rie Nakagomi-Hagihara; Guodong Zheng; Eisuke Shibata; Tomokazu Souma; Tomohiko Shindo; Hirohito Shima; Yoichi Takeuchi; Eikan Mishima; Masayuki Tanemoto; Tetsuya Terasaki; Tohru Onogawa; Michiaki Unno; Sadayoshi Ito; Shin Takasawa; Takaaki Abe |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Drug metabolism and pharmacokinetics Volume: 25 ISSN: 1880-0920 ISO Abbreviation: Drug Metab. Pharmacokinet. Publication Date: 2010 |
Date Detail:
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Created Date: 2010-07-08 Completed Date: 2010-10-12 Revised Date: 2012-04-09 |
Medline Journal Info:
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Nlm Unique ID: 101164773 Medline TA: Drug Metab Pharmacokinet Country: Japan |
Other Details:
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Languages: eng Pagination: 274-82 Citation Subset: IM |
Affiliation:
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Division of Nephrology, Endocrinology, and Vascular Medicine, Tohoku University Graduate School of Medicine, 1-1 Seiryo-cho, Aoba-ku, Sendai, Japan. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adiponectin
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blood Animals Biological Transport / drug effects Cell Line, Tumor Diabetes Mellitus / drug therapy Hydroxymethylglutaryl CoA Reductases Immunohistochemistry Insulin / agonists, secretion* Islets of Langerhans / cytology*, drug effects Male Mice Mice, Inbred Strains Models, Animal Organic Anion Transporters, Sodium-Independent / analysis, metabolism* Pancreas / cytology, drug effects Pravastatin / pharmacokinetics*, pharmacology* Rats Rifampin / pharmacology Sulfobromophthalein / pharmacology |
| Chemical | |
Reg. No./Substance:
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0/Adiponectin; 0/Adipoq protein, mouse; 0/Insulin; 0/Organic Anion Transporters, Sodium-Independent; 13292-46-1/Rifampin; 297-83-6/Sulfobromophthalein; 81093-37-0/Pravastatin; EC 1.1.1.-/Hydroxymethylglutaryl CoA Reductases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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