Effects of insulin and phospholipase C in control and denervated rat skeletal muscle

Phospholipase C (PLC), an enzyme that increases endogenous 1,2-diacylglycerol (DAG), caused dose-dependent stimulation of 2-deoxy-D-glucose (2-DG) uptake in rat soleus muscles; the maximal effect was less than that of insulin. In denervated muscles the effect of insulin on 2-DG uptake was markedly reduced, whereas the response to PLC was identical to that of control muscles. Both PLC and insulin stimulated glucose incorporation into glycogen in control but not in denervated solei. Amino acid transport was unaffected by PLC; however, the enzyme completely inhibited the stimulation of amino acid transport by insulin. PLC did not activate the insulin receptor tyrosine kinase but decreased activation of the receptor by insulin in vivo. Basal muscle DAG content increased after denervation. Incubation with PLC markedly increased DAG in control and in denervated muscle. Insulin increased total DAG mass less than PLC in control muscles and did not affect DAG in denervated muscles. In media without added Ca2+, PLC stimulation of DAG production was impaired, and 2-DG uptake was unresponsive to PLC. The data are consistent with, but do not prove, that a subpopulation of DAGs may participate in insulin-mediated stimulation of glucose transport. They also suggest that the denervation-induced insulin resistance of glucose transport may reflect impaired generation of certain DAGs involved in the signaling cascade.