Opposite effects of pravastatin and atorvastatin on insulin sensitivity in the rat: Role of vitamin D metabolites

作者：Beltowski Jerzy^*; Atanassova Pepa; Chaldakov George N; Jamroz Wisniewska Anna; Kula Wojciech; Rusek Marta

来源：Atherosclerosis, 2011, 219(2): 526-531.

DOI：10.1016/j.atherosclerosis.2011.08.009

• Statins
• Insulin sensitivity
• Vitamin D
• Adiponectin
• Adipokines
• Nitric oxide

Objective: Recent studies indicate that pravastatin improves whereas other statins impair glucose homeostasis in humans, but the underlying mechanisms are not clear. We examined the effect of pravastatin and atorvastatin on insulin sensitivity in a rat model.
Methods: Pravastatin (40 mg/kg/day) or atorvastatin (20 mg/kg/day) were administered for 3 weeks and insulin sensitivity was assessed by measuring fasting plasma insulin, HOMA-IR, non-esterified fatty acids (NEFA) and glycerol levels, as well as by the hyperinsulinemic euglycemic clamp.
Results: Pravastatin had no effect on fasting insulin and HOMA-IR but significantly reduced plasma NEFA and glycerol levels and increased glucose infusion rate (GIR) during the hyperinsulinemic clamp. Increase in GIR induced by pravastatin was not abolished by NO synthase inhibitor, L-NAME, indicating that this effect did not result from the improvement of endothelial function. Atorvastatin increased fasting insulin, HOM-IR, NEFA and glycerol levels as well as reduced GIR. Statins had no effect on leptin, HMW adiponectin, resistin, visfatin, interleukin-6 and TNF-alpha. Pravastatin increased plasma concentrations of 25-hydroxy- and 1,25-dyhydroxyvitamin D-3 (25-OH-D-3 and 1,25-(OH)(2)-D-3), and its effect on insulin sensitivity was mimicked by exogenous 1,25-(OH)(2)-D-3. Atorvastatin reduced plasma 25-OH-D-3 but had no effect on 1,25-(OH)(2)-D-3. Decrease in insulin sensitivity induced by atorvastatin was not corrected by supplementation of vitamin D-3 despite normalization of plasma 25-OH-D-3 level.
Conclusions: Pravastatin and atorvastatin have opposite effects on insulin sensitivity and vitamin D-3 status. Pravastatin-induced increase in insulin sensitivity is mediated by elevation of 1,25-(OH)(2)-D-3. In contrast, atorvastatin-induced decrease in insulin sensitivity is independent of lowering 25-OH-D-3.

• 出版日期2011-12