The HMG-CoA Reductase Inhibitor Pravastatin Stimulates Insulin Secretion through Organic Anion Transporter Polypeptides
| Autor: | Takehiro Suzuki, Michiaki Abe, Tomokazu Souma, Hirohito Shima, Takafumi Toyohara, Shin Takasawa, Sadayoshi Ito, Tomohiko Shindo, Eisuke Shibata, Yoichi Takeuchi, Yasutoshi Akiyama, Hiromi O. Shiwaku, Tohru Onogawa, Eikan Mishima, Michiaki Unno, Tetsuya Terasaki, Takaaki Abe, Naoya Noguchi, Guodong Zheng, Akiko Ishii, Masayuki Tanemoto, Rie Nakagomi-Hagihara |
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| Rok vydání: | 2010 |
| Předmět: |
Male
medicine.medical_specialty Organic anion transporter 1 medicine.medical_treatment Pharmaceutical Science Mice Inbred Strains Organic Anion Transporters Sodium-Independent Sulfobromophthalein Islets of Langerhans Mice chemistry.chemical_compound Insulin resistance Cell Line Tumor Internal medicine Adipocyte Insulin Secretion Diabetes Mellitus polycyclic compounds medicine Animals Insulin Pharmacology (medical) Pancreas Pravastatin Pharmacology biology nutritional and metabolic diseases Biological Transport Membrane transport medicine.disease Immunohistochemistry Hydroxymethylglutaryl-CoA reductase Rats Endocrinology chemistry Models Animal HMG-CoA reductase biology.protein Hydroxymethylglutaryl CoA Reductases lipids (amino acids peptides and proteins) Adiponectin Rifampin medicine.drug |
| Zdroj: | Drug Metabolism and Pharmacokinetics. 25:274-282 |
| ISSN: | 1347-4367 |
| DOI: | 10.2133/dmpk.25.274 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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