PHOSPHATIDYLINOSITOL 3-KINASE AND DYNAMICS OF INSULIN-RESISTANCE IN DENERVATED SLOW AND FAST MUSCLES IN-VIVO

Regulation of glucose uptake by 1- and 3-day denervated soleus (slow-t witch) and plantaris (fast-twitch) muscles in vivo was investigated. O ne day after denervation, soleus and plantaris muscles exhibited 62 an d 65% decreases in insulin-stimulated 2-deoxyglucose uptake, respectiv ely, compared with corresponding control muscles. At this interval, de nervated muscles showed no alterations in insulin receptor binding and activity, amount and activity of phosphatidylinositol 3-kinase, and a mounts of GLUT-1 and GLUT-4. Three days after denervation, there was n o increase in X-deoxyglucose uptake in response to insulin in soleus m uscle, whereas plantaris muscle exhibited a 158% increase in basal and an almost normal absolute increment in insulin-stimulated uptake. Des pite these differences, denervated soleus and plantaris muscles exhibi ted comparable decreases in insulin-stimulated activities of the insul in receptor (similar to 40%) and phosphatidylinositol S-kinase (simila r to 50%) and a pronounced decrease in GLUT-4. An increase in GLUT-1 i n plantaris, but not soleus, muscle 3 days after denervation is consis tent with augmented basal 2-deoxyglucose uptake in plantaris muscle at this interval. These results demonstrate that, in denervated muscles, there is a clear dissociation between insulin-stimulated 2-deoxygluco se uptake and upstream events involved in insulin-stimulated glucose u ptake.