MONDAY, March 16 (HealthDay News) -- Mice that overexpress a protein that normally increases in muscle after exercise have improved glucose tolerance and insulin sensitivity and do not become obese even after eating a high-fat diet, according to a study published online March 5 in Endocrinology.

Yasuhide Fukatsu, from Kobe University Graduate School of Medicine in Japan, and colleagues analyzed changes in gene expression in the skeletal muscle of mice in response to exercise. After finding a twofold to threefold increase in heparin-binding epidermal growth factor-like growth factor (HB-EGF, also known as diphtheria toxin receptor) expression, they generated mice overexpressing HB-EGF specifically in skeletal muscle.

The researchers found that the mice had a higher respiratory quotient, indicating a preference for carbohydrate rather than fat as an energy source. They also had improved glucose tolerance, insulin sensitivity, and glucose uptake by skeletal muscle. When fed a high-fat diet, the mice were largely resistant to developing obesity, hepatic steatosis and insulin resistance.

"In the present study, we have revealed a potential role for HB-EGF in energy homeostasis by showing that its overexpression in muscle of transgenic mice increases whole-body carbohydrate utilization, glucose tolerance, and insulin sensitivity," Fukatsu and colleagues conclude. "Given that this growth factor is a key bioactive molecule up-regulated in contracting muscle, which handles a large proportion of incoming glucose, our results might provide important insight into the molecular basis of exercise treatment for various pathological conditions associated with insulin resistance."

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