The HMG-CoA reductase inhibitor pravastatin stimulates insulin secretion through organic anion transporter polypeptides.
The HMG-CoA reductase inhibitor pravastatin stimulates insulin secretion through organic anion transporter polypeptides.
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DOI：
10.2133/dmpk.25.274
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发表时间：
2010
影响因子：
2.1
通讯作者：
Michiaki Abe;T. Toyohara;A. Ishii;Takehiro Suzuki;N. Noguchi;Yasutoshi Akiyama;H. Shiwaku;Rie Nakagomi-Hagihara;Guodong Zheng;E. Shibata;Tomokazu Souma;Tomohiko Shindo;H. Shima;Yoichi Takeuchi;Eikan Mishima;M. Tanemoto;T. Terasaki;T. Onogawa;M. Unno;S. Ito;S. Takasawa;T. Abe
中科院分区：
文献类型：
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作者：
Michiaki Abe;T. Toyohara;A. Ishii;Takehiro Suzuki;N. Noguchi;Yasutoshi Akiyama;H. Shiwaku;Rie Nakagomi-Hagihara;Guodong Zheng;E. Shibata;Tomokazu Souma;Tomohiko Shindo;H. Shima;Yoichi Takeuchi;Eikan Mishima;M. Tanemoto;T. Terasaki;T. Onogawa;M. Unno;S. Ito;S. Takasawa;T. Abe
据报道，3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂普伐他汀对减少新发糖尿病以及降低血脂具有有益作用。由于普伐他汀是一种水溶性有机阴离子，它不能轻易穿透细胞膜的脂双层。由于普伐他汀对糖代谢和糖尿病的确切作用机制尚未阐明，我们研究了有机阴离子转运蛋白家族对普伐他汀处理的胰岛和脂肪细胞功能的作用。Oatp 1/slco 1a 1、Oatp 2/slco 1a 4和Oatp 3/slco 1a 5在胰腺中表达，Oatp 3/slco 1a 5在大鼠胰岛素瘤细胞系INS-1 e中也有表达。普伐他汀不仅通过oatp 1/slco 1a 1和oatp 2/slco 1a 4转运，而且还通过大鼠oatp 3/slco 1a 5转运。检测到INS-1 e细胞中的普伐他汀摄取，并且这种转运被磺溴酞和利福平抑制，已知这两种物质都抑制oatp家族介导的摄取。此外，普伐他汀增强葡萄糖刺激的INS-1 e细胞的胰岛素分泌。当用普伐他汀治疗脂肪负荷的db/db小鼠时，葡萄糖耐受不良和胰岛素抵抗被预防。此外，普伐他汀还能促进胰岛分泌胰岛素。这些数据表明，普伐他汀具有多效性的影响，通过膜转运胰岛高脂/葡萄糖条件下。
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.