A malonyl-CoA fuel-sensing mechanism in muscle: effects of insulin, glucose, and denervation.
Increases in the concentration of malonyl-CoA in skeletal muscle have been observed in the KKAy mouse, an obese rodent with high plasma insulin and glucose levels [Saha et al. Am. J. Physiol. 267 (Endocrinol. Metab. 30): E95-E101, 1994]. To assess whether insulin and glucose directly regulate malonyl-CoA in muscle, soleus muscles from young rats were incubated with insulin and glucose at various concentrations, and their content of malonyl-CoA was determined. In addition, the effect on malonyl-CoA of denervation and electrically induced muscle contractions was assessed. The concentration of malonyl-CoA in the soleus, taken directly from a rat fed ad libitum, was 2.0 +/- 0.2 nmol/g. In muscles incubated for 20 min in a medium devoid of added insulin and glucose, the concentration was decreased to 0.8 +/- 0.2 nmol/g. When the medium contained 0.5, 7.5, or 30 mM glucose, malonyl-CoA levels were 1.3 +/- 0.1, 1.8 +/- 0.1, or 2.4 +/- 0.2 nmol/g, respectively, in the absence of insulin and 1.7 +/- 0.1, 4.6 +/- 0.3, or 5.5 +/- 0.6 nmol/g in its presence (10 mU/ml). Compared with its level in a control muscle, the concentration of malonyl-CoA was increased threefold in the soleus 6-8 h after denervation and remained twofold higher for > or = 48 h. In contrast, muscle contractions induced by sciatic nerve stimulation, in vivo, acutely decreased the concentration of malonyl-CoA by 30-35%. The results indicate that insulin and glucose, and probably contractile activity, regulate the concentration of malonyl-CoA in muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
Saha
A K
AK
Diabetes and Metabolism Unit, Boston University Medical Center, Massachusetts 02118, USA.
Kurowski
T G
TG
Ruderman
N B
NB
D000818:Animals; D004338:Drug Combinations; D004558:Electric Stimulation; D005947:Glucose / Q000494:pharmacology*; D006614:Hindlimb; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D008316:Malonyl Coenzyme A / Q000378:metabolism*; D009119:Muscle Contraction; D009121:Muscle Denervation; D009132:Muscles / Q000294:innervation / Q000502:physiology*; D009994:Osmolar Concentration; D051381:Rats; D017207:Rats, Sprague-Dawley
D004338:Drug Combinations; D007328:Insulin; D008316:Malonyl Coenzyme A; D005947:Glucose