| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232
An isotopic method
was used in conscious rats to determine the roles of glucose transport
and the transsarcolemmal glucose gradient (TSGG) in control of basal
and insulin-stimulated muscle glucose uptake. Rats received an
intravenous
3-O-[3H]methylglucose
(3-O-[3H]MG)
infusion from 
100 to 40 min and a
2-deoxy-[3H]glucose
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
1 · min1,
and glucose was clamped at basal concentrations. The ratios of soleus
intracellular to extracellular
3-O-[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 that 1)
small increases in insulin increase soleus
Rg without decreasing TSGG,
suggesting that muscle glucose delivery and phosphorylation can
accommodate the increased flux; 2)
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; 3) 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; and
4) muscle consisting of fast-twitch
fibers that are poorly perfused exhibits a 35-45% 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.
countertransport; 3-O-methylglucose; 2-deoxyglucose
This article has been cited by other articles:
|
|
 |
|
  D. H. Wasserman and P. T. Fueger Point-Counterpoint: Glucose phosphorylation is/is not a significant barrier to muscle glucose uptake by the working muscle J Appl Physiol, December 1, 2006; 101(6): 1803 - 1805. [Full Text] [PDF]
|
|
|
|
 |
|
 R. R. Pencek, A. Bertoldo, J. Price, C. Kelley, C. Cobelli, and D. E. Kelley Dose-responsive insulin regulation of glucose transport in human skeletal muscle Am J Physiol Endocrinol Metab, June 1, 2006; 290(6): E1124 - E1130. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. A. Bhatt, J. J. Dube, N. Dedousis, J. A. Reider, and R. M. O'Doherty Diet-induced obesity and acute hyperlipidemia reduce I{kappa}B{alpha} levels in rat skeletal muscle in a fiber-type dependent manner Am J Physiol Regulatory Integrative Comp Physiol, January 1, 2006; 290(1): R233 - R240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. T. Fueger, D. P. Bracy, C. M. Malabanan, R. R. Pencek, and D. H. Wasserman Distributed control of glucose uptake by working muscles of conscious mice: roles of transport and phosphorylation Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E77 - E84. [Abstract] [Full Text]
|
|
|
|
|
|
C. L. Brand, J. Sturis, C. F. Gotfredsen, J. Fleckner, C. Fledelius, B. F. Hansen, B. Andersen, J.-M. Ye, P. Sauerberg, and K. Wassermann Dual PPARalpha /gamma activation provides enhanced improvement of insulin sensitivity and glycemic control in ZDF rats Am J Physiol Endocrinol Metab, April 1, 2003; 284(4): E841 - E854. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. A. Petersen, P. T. Fueger, D. P. Bracy, D. H. Wasserman, and A. E. Halseth Fiber type-specific determinants of Vmax for insulin-stimulated muscle glucose uptake in vivo Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E541 - E548. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Halseth, D. P. Bracy, and D. H. Wasserman Functional limitations to glucose uptake in muscles comprised of different fiber types Am J Physiol Endocrinol Metab, June 1, 2001; 280(6): E994 - E999. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. A. MacLean, S. M. Ettinger, L. I. Sinoway, and K. F. Lanoue Determination of muscle-specific glucose flux using radioactive stereoisomers and microdialysis Am J Physiol Endocrinol Metab, January 1, 2001; 280(1): E187 - E192. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Halseth, D. P. Bracy, and D. H. Wasserman Limitations to basal and insulin-stimulated skeletal muscle glucose uptake in the high-fat-fed rat Am J Physiol Endocrinol Metab, November 1, 2000; 279(5): E1064 - E1071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Halseth, D. P. Bracy, and D. H. Wasserman Overexpression of hexokinase II increases insulinand exercise-stimulated muscle glucose uptake in vivo Am J Physiol Endocrinol Metab, January 1, 1999; 276(1): E70 - E77. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. E. Halseth, D. P. Bracy, and D. H. Wasserman Limitations to exercise- and maximal insulin-stimulated muscle glucose uptake J Appl Physiol, December 1, 1998; 85(6): 2305 - 2313. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 G. H. Crist, B. Xu, K. F. Lanoue, and C. H. Lang Tissue-specific effects of in vivo adenosine receptor blockade on glucose uptake in Zucker rats FASEB J, October 1, 1998; 12(13): 1301 - 1308. [Abstract] [Full Text]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
