Analysis of insulin-stimulated skeletal muscle glucose uptake in
the conscious rat using isotopic glucose analogues.
O'doherty, Robert M., Amy E. Halseth, Daryl K. Granner, Deanna P.
Bracy, and David H. Wasserman.
Department of Molecular Physiology and Biophysics, Vanderbilt
University School of Medicine, Nashville, TN 37232
APStracts 4:0242E, 1997.
An isotopic method was used in conscious rats to determine the roles
of glucose transport and the trans-sarcolemmal glucose gradient
(TSGG) in control of basal and insulin-stimulated muscle glucose
uptake. Rats received an intravenous 3-0- [3H]methyl-glucose (3-0
-[3H]MG) infusion from -100 to 40 min and a 2-deoxy- [3H]glucose ([2
-3H]DG) infusion from 0 to 40 min to calculate a glucose metabolic
index (Rg). Insulin was infused from -100 to 40 min at rates of 0.0,
0.6, 1.0 and 4.0 mU/(kg x min) and glucose was clamped at basal
concentrations. The ratio of soleus intracellular to extracellular 3
-0-[3H]MG concentration and soleus glucose concentrations were used to
estimate the TSGG using principles of glucose countertransport.
Tissue glucose concentrations were compared in well-perfused, slow
twitch muscle (soleus) and poorly-perfused, fast twitch muscle
(vastus lateralis, gastrocnemius). Data show: (a) small increases in
insulin increase soleus Rg without decreasing TSGG, suggesting that
muscle glucose delivery and phosphorylation can accommodate the
increased flux; (b) due to a limitation in soleus glucose
phosphorylation and possibly delivery, insulin at high physiological
levels decreases TSGG, and at supraphysiological insulin levels the
TSGG is not significantly different from 0; (c) maximum Rg is
maintained even though TSGG decreases with increasing insulin levels,
indicating that glucose transport continues to increase and is not
rate limiting for maximal insulin-stimulated glucose uptake; (d)
muscle consisting of fast-twitch fibers that are poorly perfused
exhibit a 35 to 45% fall in tissue glucose with insulin, suggesting
that glucose delivery is a major limitation in sustaining the TSGG.
In conclusion, control of glucose uptake is distributed between
glucose transport and factors that determine the TSGG. Insulin-
stimulation of glucose transport increases the demands on the factors
that maintain glucose delivery to the muscle membrane and glucose
phosphorylation inside the muscle.
Received 20 August 1997; accepted in final form 28 October 1997.
APS Manuscript Number E390-7.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 14 November 1997