The Effect of OATP2B1-Mediated Statin Transport on Beta Cell Dysfunction
Abstract
Statins are a class of cholesterol-lowering drugs which work by inhibiting the mevalonate pathway. Statin treatment has been linked to an increase in the risk of new-onset diabetes mellitus, and previous studies have suggested impairment in insulin secretion following statin treatment. Recent work from our laboratory confirmed the expression of organic anion transporting polypeptide 2B1 (OATP2B1), an important statin uptake transporter, in human pancreatic beta cells. Our study examined the role of OATP2B1 in statin-associated beta cell toxicity using INS-1 cells as a beta cell model. We showed that OATP2B1 augments cellular accumulation of rosuvastatin and atorvastatin, but not pravastatin. While rosuvastatin and atorvastatin led to a dose-dependent reduction in insulin secretion, OATP2B1 had no effect. However, OATP2B1 was found to facilitate statin-induced mitochondrial toxicity, apoptosis and ATP level reduction. In conclusion, our findings support an important role of OATP2B1-mediated statin uptake on beta cell toxicity but not insulin secretion.