Issue 153 Item 3 Simvastatin Treats Insulin Resistance

Cholesterol controlling drug Simvastatin fighst insulin resistance Over the past decade, evidence has accumulated indicating that nitric oxide (NO) may play a key role in the control of metabolic and cardiovascular homeostasis, as evidenced by mice lacking the gene for endothelial nitric oxide synthase (eNOS) that are insulin resistant and hypertensive. An animal study now finds that stimulating NO bioavailability by lipid lowering statins may represent a new way to combat this epidemic. Statins are a group of compounds that have been used successfully to lower cholesterol and prevent myocardial infarction. A less well known effect of statins is that they augment NO bioavailability in circulation. Abnormalities in the body’s production of NO have been implicated in high blood pressure, atherosclerosis (narrowing of the arteries), diabetes, impotence, and stroke. One statin is the prescription drug Simvastatin, used with diet changes (restriction of cholesterol and fat intake) to reduce the amount of cholesterol and certain fatty substances in the blood. Accumulation of cholesterol and fats along the walls of the arteries (a process known as atherosclerosis) decreases blood flow and, therefore, the oxygen supply to the heart, brain, and other parts of the body. Lowering your blood level of cholesterol and fats may help to prevent heart disease, angina (chest pain), strokes, and heart attacks. Now this important drug could also be instrumental in the battle against insulin resistance. The role of stimulating NO bioavailability by statins in treating insulin resistance is addressed in a study from Switzerland. The authors of ” Simvastatin Prevents High-Fat Diet-Diet-Induced Arterial Hypertension and Metabolic Insulin Resistance in Partially eNOS Deficient Mice,” are Stephane Cook, MD, Peter Vollenweider, MD and Urs Scherrer, MD, all at the Centre Hospitalier Universitaire Vaudois, Lausanne, Switzerland. Their findings are being presented at the American Physiology Society sponsored conference, Experimental Biology 2003, being held April 11-15, 2003, at the San Diego Conference Center, San Diego, CA. Simvastatin or vehicle treated eNOS+/- and eNOS-/- mice were fed a high-fat diet or normal chow for eight weeks. Arterial pressure and insulin sensitivity (glucose infusion rate during euglycemic hyperinsulinemic clamp) were measured at the end of this eight week period. High-fat diet caused arterial hypertension and insulin resistance in eNOS+/- mice. Simvastatin prevented both the high-fat diet-induced insulin resistance and arterial hypertension in eNOS+/- mice. In contrast, simvastatin did not attenuate high-fat diet induced arterial hypertension and insulin resistance in eNOS-/- mice. These findings provide the first evidence that simvastatin prevents diet-induced arterial hypertension and insulin resistance in mice. This effect appears to be related to stimulation of vascular NO availability (as evidenced by the results in eNOS-/- mice). These data suggest that simvastatin may help to combat the epidemic of insulin resistance and hypertension in humans. ================================