Dynamics of insulin resistance in denervated slow and fast muscles in vivo

Abstract

Sciatic nerve in one hindlimb of rats was sectioned, and animals were investigated 3, 6, 9, and 24 h and 3, 8, and 17 days after surgery. Cellular uptakes of 2-deoxy-D-glucose (DG) and alpha-aminoisobutyric acid (AIB) by soleus, plantaris, and gastrocnemius muscles of the denervated and contralateral sham hindlimb were compared in vivo. Effects of insulin on DG and AIB uptakes by soleus and plantaris muscles, but not gastrocnemius muscles, were reduced 20-58% as early as 3-6 h after denervation. Three to 17 days after denervation, soleus muscle did not respond to insulin stimulation of DG uptake, whereas plantaris and gastrocnemius muscles responded, but the insulin-induced increment in DG uptake was reduced 24-68% compared with the sham muscles. In contrast, none of the denervated muscles increased AIB uptake in response to insulin stimulation 3-17 days after surgery. The levels of creatine phosphate and ATP in calf muscles frozen in situ 3 days after denervation were increased 7 and 9%, respectively, and those of ADP, AMP, glucose-6-phosphate, and lactate were unchanged compared with sham muscles. It is concluded that muscle denervation results in a rapid development of insulin resistance, the effect of denervation depends on muscle fiber population, and insulin resistance of denervated muscles is not due to a cellular energy deficit.