A malonyl-coa fuel sensing mechanism in muscle: effects of insulin,
glucose and denervation.
Saha, Asish K., Theodore G. Kurowski, and Neil B. Ruderman.
Diabetes and Metabolism Unit, Boston University Medical Center,
Boston, MA 02118
APStracts 2:0062E, 1995.
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: 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 determined. In addition, the effect on malonyl CoA of
denervation, and of electrically-induced muscle contractions were
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 minutes in a medium devoid of added insulin and
glucose it 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 and 2.4+0.2 nmol/g respectively in the absence of
insulin and 1.7+0.1, 4.6+0.3 and 5.5+ 0.6 nmol/g in its presence (10
mU/ml). In comparison to its level in a control muscle, the
concentration of malonyl CoA was increased 3-fold in the soleus 6-8
hours after denervation and remained 2-fold higher for at least 48
hours. 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. They suggest that malonyl CoA is a component of a fuel
sensing and signalling mechanism that responds to changes in the fuel
milieu and possibly the energy expenditure of the muscle cell.
Received 31 January 1995; accepted in final form 31 March 1995.
APS Manuscript Number E40-5.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 19 April 1995.