Chronic exercise compensates for insulin resistance induced by a high-fat diet in rats.

We examined whether chronic exercise prevents insulin resistance developing in the high-fat-fed (HFF) rat, a model that otherwise develops profound peripheral insulin resistance. Insulin action (euglycemic clamp plus 2-[3H]deoxy-D-glucose-[14C]glucose tracer technique) was examined after 3 wk in sedentary control and sedentary or wheel cage exercise-trained HFF rats. At the whole body level, a reduction in peripheral insulin potency in HFF rats was prevented by concomitant chronic exercise; the 30-40% reduction in insulin-stimulated whole body net glucose utilization in sedentary HFF rats was abolished. Responses in individual muscles, however, suggested that the chronic exercise effect may be a compensation for, rather than a correction of insulin resistance induced by a high-fat diet; in six of eight muscles examined it produced an upward additive shift rather than a left shift in insulin dose response. Chronic exercise increased both muscle glycolytic flux and glycogen storage rates in the HFF rats, suggesting that glucose transport may be involved. We conclude that increased physical activity is beneficial in counteracting high-fat diet-induced insulin resistance. Different processes appear to be involved in the development of diet-induced insulin resistance in muscle and its amelioration by regular exercise.