Insulin stimulation of glucose uptake in skeletal muscles and
adipose tissues in vivo is nitric oxide-dependent.
Roy, Denis, Myl[grave]ene Perreault, and Andr[acute]e Marette.
Department of Physiology and Lipid Research Unit, Laval University
Hospital Research Center, Qu[acute]ebec, G1V 4G2, Canada.
APStracts 4:0288E, 1997.
The purpose of this study was to investigate whether in vivo nitric
oxide (NO) synthase inhibition influences insulin-mediated glucose
disposal in rat peripheral tissues. The NO synthase (NOS) inhibitor
NG-nitro-L-arginine methyl ester (L-NAME) or saline were infused
constantly during an euglycemic hyperinsulinemic clamp (HIC) in
normal rats. Glucose utilization rates of insulin-sensitive tissues
(individual muscles, heart and adipose tissues) were simultaneously
determined using tracer infusion of 2-[3H]-deoxy-D-glucose. NOS
blockade with L-NAME resulted in significant (p < 0.05) reduction
in both whole-body glucose disposal (-16%, p < 0.01) and plasma 2
-[3H]-deoxy-D-glucose disappearance rate (-30%, p < 0.05) during
HIC. L-NAME significantly decreased insulin-stimulated glucose uptake
in heart (-62%, p = 0.01), soleus (-42%, p = 0.05), red (-53%, p <
0.001) and white (-62%, p < 0.001) gastrocnemius, tibialis (-57%, p
< 0.01), and quadriceps (-33%, p < 0.05) muscles. The NOS
inhibitor also decreased insulin action in brown interscapular (-47%,
p < 0.01), retroperitoneal (-52%, p = 0.07), and gonadal (-66%, p =
0.06) adipose tissues. In contrast with in vivo NOS blockade, L-NAME
failed to affect basal or insulin-stimulated 2-[3H]-deoxy-D-glucose
transport in isolated soleus or extensor digitorum longus muscles in
vitro. These results support the hypothesis that the action of
insulin to augment glucose uptake by skeletal muscles and other
peripheral insulin-sensitive tissues in vivo is NO-dependent.
Received 3 September 1997; accepted in final form 16 December
1997.
APS Manuscript Number E417-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 7 January 1998