Effect of simvastatin on burn-induced alterations in tissue specific glucose metabolism: implications for burn associated insulin resistance

Abstract

Abstract. In addition to their primary role in lowering plasma cholesterol, statins have a variety of other actions. We studied the effect of simvastatin treatment on burn injuryinduced changes in regional glucose metabolism. Groups of six CD-1 mice (male, ~25 g) were subjected to full thickness 30% total body surface area (TBSA) burn injury. The animals were treated with simvastatin at various doses (0.02, 0.2 and 2.0 μg/kg, i.p.) for seven days. The following morning, mice were injected with 18 F labeled 2-fluoro-2-deoxy-Dglucose ( 18 FDG) (50 μCi) via the tail vein. Approximately 60 min after tracer injection, the animals were sacrificed and biodistribution was measured. A sub-set of burned mice with and without statin treatment and sham controls was injected with ~1.0 mCi of FDG and tracer distribution was evaluated by μPET. In addition, oral glucose tolerance tests (OGTT) were performed in other groups of burned mice with and without statin treatment and sham controls. In the heart and brown adipose tissue (BAT), burn injury produced a highly significant increase in 18 FDG accumulation (p<0.01), whereas tracer accumulation in brain was markedly reduced (p<0.01). In the heart and BAT, simvastatin treatment produced dosedependent reductions in 18 FDG accumulation. In contrast, simvastatin did not affect 18 FDG accumulation in the brain. There was no effect of simvastatin treatment on 18 FDG accumulation in the heart, BAT or brain of sham-treated mice. Less pronounced effects were detected in other tissues that were studied. All animals had normal plasma glucose levels (~90 mg/dl). The OGTTs demonstrated insulin resistance in burn injured mice which was reversed by statin treatment. Our results indicate that simvastatin reverses burn-induced increases in 18 FDG accumulation by the heart and BAT in a dose-dependent manner but does not affect burn-induced reductions of 18 FDG accumulation by the brain. These findings suggest that statins exert some of their effects by tissue specific modulation of glucose metabolism.