A cholesterol-controlling drug could strike a blow against insulin resistance

April 09, 2003

April 9, 2003 (San Diego, CA) -- In industrialized countries insulin resistance/diabetes have become major public health concerns because of their epidemic growth and their association with major cardiovascular risk factors that are responsible for excess morbidity and mortality. In 1999, Americans had a six percent increase in new patients with Type 2 diabetes; growing obesity rates and sedentary lifestyles are also taking their toll across the Atlantic where Type 2 diabetes currently afflicts 22.5 million Europeans -- a staggering five percent of the population -- with another six million cases expected by 2025.

Researchers are looking for underlying mechanisms and new ways to combat this epidemic. 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 Stéphane 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.

Methodology

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.

Results

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.

Conclusions

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.
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The American Physiological Society (APS) is one of the world's most prestigious organizations for physiological scientists. These researchers specialize in understanding the processes and functions underlying human health and disease. Founded in 1887 the Bethesda, MD-based Society has more than 10,000 members and publishes 3,800 articles in its 14 peer-reviewed journals each year.

Contact: Donna Krupa @ 703-527-7357 (vm) Or 703-967-2751 (cell) or djkrupa1@aol.com Through April 10th, 2003.

NEWSROOM OPENS FRIDAY APRIL 11th, 2003 @ 7:00 AM PST

APS Newsroom: April 11-15, 2003
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