Glucose and amino acid uptake by exercising muscles in vivo: effect of insulin, fiber population, and denervation.

The first series of experiments was performed on control rats. The animals were injected iv with trace amounts of 2-deoxy-D-[1-14C]glucose [( 14C]DG) or alpha-[1-14C] aminoisobutyric acid with or without 0.1 U insulin/rat, and calf muscles of the right hindlimb were electrically stimulated to induce 1 contraction/sec. The exercise was discontinued 25 min after the injection, and cellular uptakes of DG or aminoisobutyric acid by soleus, plantaris, and gastrocnemius muscles in disintegrations per min/mg dry tissue weight were determined. The results of these experiments demonstrated that basal, insulin-induced, and exercise-induced uptakes of glucose and amino acids by muscles are dependent on muscle fiber population, and the stimulatory effects of exercise and insulin on soleus and plantaris muscles, but not gastrocnemius muscles, are synergistic rather than merely additive when both stimuli act together. The second series of experiments was performed in the same manner as the first series, except that the right hindlimb of each rat was denervated 3 days before the experiment. Cellular DG uptakes were determined in soleus, plantaris, and gastrocnemius muscles of the left (sham) hindlimb, which was always resting, and in corresponding muscles of the right (denervated) limb, which was either resting or exercising. In the resting state, the denervated soleus muscle had normal basal DG uptake, but, unlike sham soleus muscle, did not respond to insulin stimulation. Denervated plantaris and gastrocnemius muscles exhibited 264% and 150% elevations in basal glucose uptake, respectively, compared with corresponding sham muscles. The latter two denervated muscles did respond to insulin, but the hormone-induced increments in DG uptake were 68% and 45%, respectively, lower than in corresponding contralateral sham muscles. Under basal conditions, exercise had no effect on DG uptake by the denervated soleus muscle, but increased uptake by denervated plantaris and gastrocnemius muscles 207% and 778%, respectively. Stimulation of exercising denervated muscles with exogenous insulin did not increase DG uptake by any muscle above the level observed with exercise alone. The results show that manifestations of insulin resistance in denervated muscles depend on muscle fiber population; denervated muscles, which still retain some ability to respond to insulin, increase DG uptake during exercise, whereas such an increase is absent in denervated muscles completely unresponsive to insulin; and exercise does not improve or restore the ability of denervated muscles to respond to insulin.