ADDITIVE EFFECT OF CONTRACTIONS AND INSULIN ON GLUT-4 TRANSLOCATION INTO THE SARCOLEMMA

The maximal effects of insulin and muscle contractions on glucose tran sport are additive. GLUT-4 is the major glucose transporter isoform ex pressed in skeletal muscle. Muscle contraction and insulin each induce translocation of GLUT-4 from intracellular sites into the plasma memb rane. The purpose of this study was to test the hypothesis that the in cremental effect of contractions and insulin on glucose transport is m ediated by additivity of the maximal effects of these stimuli on GLUT- 4 translocation into the sarcolemma. Anesthetized rats were given insu lin by intravenous infusion to raise plasma insulin to 2,635 +/- 638 m u U/ml. The gastrocnemius-plantaris-soleus group was stimulated to con tract via the sciatic nerve by using a protocol that maximally activat es glucose transport. After treatment with insulin, contractions, or i nsulin plus contractions or no treatment, the gastrocnemius-plantaris- soleus muscle group was dissected out and was subjected to subcellular fractionation to separate the plasma membrane and intracellular membr ane fractions. Insulin induced a 70% increase and contractions induced a 113% increase in the GLUT-4 content of the plasma membrane fraction . The effects of insulin and contractions were additive, as evidenced by a 185% increase in the GLUT-4 content of the sarcolemmal fraction. This finding provides evidence that the incremental effect of maximall y effective insulin and contractile stimuli on glucose transport is me diated by additivity of their effects on GLUT-4 translocation into the sarcolemma.