Minimal effects of phorbol esters on glucose transport and insulin sensitivity of rat skeletal muscle.
Protein kinase C (PKC) has been suggested as a mediator of insulin's effect on glucose transport, and PKC-mediated modulation of tyrosine kinase activity in the insulin receptor has been implicated in regulating the insulin sensitivity of tissues. Because skeletal muscle is a major target of insulin action, we examined the effects of 12-O-tetradecanoylphorbol-13-acetate (TPA), 1-oleoyl-2-acetyl-rac-glycerol, and dioctanoyl diacylglycerol, known activators of PKC, on glucose metabolism in rat skeletal muscles. In contrast to results reported for other tissues, incubation of muscles with PKC activators produced only small increases in glucose transport and had minimal effects on the ability of insulin to stimulate transport. However, TPA treatment of muscles produced a significant decrease in basal glycogen synthesis. Incubation of muscles with TPA did not affect insulin binding or the tyrosine kinase activity of partially purified insulin receptors measured under basal conditions or after stimulation by insulin in situ or in vitro. Our findings do not support activation of PKC as a major mechanism for regulating glucose uptake or insulin receptor activity in skeletal muscle. However, the data do not rule out the possibility that glucose transport in skeletal muscle may respond to physiological activators of PKC.
Sowell
M O
MO
Department of Medicine, Medical University of South Carolina, Charleston 29425.
Treutelaar
M K
MK
Burant
C F
CF
Buse
M G
MG
D000818:Animals; D005947:Glucose / Q000378:metabolism*; D007328:Insulin / Q000502:physiology*; D008297:Male; D009132:Muscles / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010703:Phorbol Esters / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin / Q000187:drug effects
D007328:Insulin; D010703:Phorbol Esters; D011972:Receptor, Insulin; D011493:Protein Kinase C; D005947:Glucose