Preliminary report: The effects of phospholipase C inhibition on insulin-stimulated glucose transport in skeletal muscle

Abstract

Previous research has demonstrated that phospholipase C (PLC) is involved in insulin-stimulated glucose transport in 3T3-L1 adipocytes. The purpose of the current investigation was to determine if PLC is also involved in insulin-stimulated glucose uptake in rat skeletal muscle. To that end, we used an in vitro muscle preparation of the rat soleus muscle to test the effects of the PLC inhibitor, U73122, on glucose transport. The PLC inhibitor, U73122, led to a concentration-dependent inhibition of insulin (0.6 nmol/L)-stimulated glucose transport, whereas it had no effect on basal glucose transport. Specifically 10, 20, 50, and 150 [mu ]mol/L U73122 inhibited insulin (0.6 nmol/L)-stimulated glucose transport approximately 17%, 20%, 26%, and 38%, respectively, while an equal molar concentration of U73343 (inactive form of U73122) and/or carrier media (dimethyl sulfoxide [DMSO]) did not influence glucose uptake. A secondary aim of this investigation was to determine if increasing the concentration of insulin from a physiologic concentration (0.6 nmol/L) to a supraphysiologic concentration (6.0 nmol/L) could ameliorate the inhibitory effects of U73122. A 10-fold increase in insulin eliminated the inhibitory effects of U73122 on insulin-stimulated glucose uptake in soleus muscle. In summary, this preliminary report provides evidence to suggest that a PLC signaling mechanism modifies insulin-stimulated glucose uptake in skeletal muscle via its influence on insulin sensitivity.