Dual Effect of Rosuvastatin on Glucose Homeostasis Through Improved Insulin Sensitivity and Reduced Insulin Secretion

• Rosuvastatin lowered blood glucose in vivo most likely due to improved glucose uptake.
• Rosuvastatin reduced insulin content and impaired Ca2 + signaling in beta cells leading to reduced insulin secretion.
• Dual effects of rosuvastatin in HFD mice though decreased compensatory insulin secretion and increased glucose uptake.Statins are a group of drugs used to lower blood cholesterol in individuals with a risk of developing cardiovascular disease. It has been shown in several studies that statins increase the risk of developing type 2 diabetes. This increased risk has not yet been explained. We have investigated the effect of rosuvastatin on blood glucose regulation in mice. We found that rosuvastatin has a beneficial effect on glucose uptake in muscles which results in lowered blood glucose. However, in the insulin producing beta cells rosuvastatin altered normal cell function something that might increase the risk of developing type 2 diabetes.

Statins are beneficial in the treatment of cardiovascular disease (CVD), but these lipid-lowering drugs are associated with increased incidence of new on-set diabetes. The cellular mechanisms behind the development of diabetes by statins are elusive. Here we have treated mice on normal diet (ND) and high fat diet (HFD) with rosuvastatin. Under ND rosuvastatin lowered blood glucose through improved insulin sensitivity and increased glucose uptake in adipose tissue. In vitro rosuvastatin reduced insulin secretion and insulin content in islets. In the beta cell Ca2 + signaling was impaired and the density of granules at the plasma membrane was increased by rosuvastatin treatment. HFD mice developed insulin resistance and increased insulin secretion prior to administration of rosuvastatin. Treatment with rosuvastatin decreased the compensatory insulin secretion and increased glucose uptake. In conclusion, our data shows dual effects on glucose homeostasis by rosuvastatin where insulin sensitivity is improved, but beta cell function is impaired.