HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 275, Issue 29, 22381-22386, July 21, 2000

This Article Full Text Full Text (PDF) All Versions of this Article: 275/29/22381    most recent M001946200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hansen, P. A. Articles by Mueckler, M. Search for Related Content PubMed PubMed Citation Articles by Hansen, P. A. Articles by Mueckler, M. Social Bookmarking                      What's this?

Transgenic Overexpression of Hexokinase II in Skeletal Muscle Does Not Increase Glucose Disposal in Wild-type or Glut1-overexpressing Mice^*

Polly A. Hansen^§, Bess Adkins Marshall^§¶, May Chen, John O. Holloszy, and Mike Mueckler^**

From the Departments of  Medicine, ^¶ Pediatrics, and  Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110

Glut1 transgenic mice were bred with transgenic mice that overexpress hexokinase II in skeletal muscle in order to determine whether whole-body glucose disposal could be further augmented in mice overexpressing glucose transporters. Overexpression of hexokinase alone in skeletal muscle had no effect on glucose transport or metabolism in isolated muscles, nor did it alter blood glucose levels or the rate of whole-body glucose disposal. Expression of the hexokinase transgene in the context of the Glut1 transgenic background did not alter glucose transport in isolated muscles but did cause additional increases in steady-state glucose 6-phosphate (3.2-fold) and glycogen (7.5-fold) levels compared with muscles that overexpress the Glut1 transporter alone. Surprisingly, however, these increases were not accompanied by a change in basal or insulin-stimulated whole-body glucose disposal in the doubly transgenic mice compared with Glut1 transgenic mice, probably due to an inhibition of de novo glycogen synthesis as a result of the high levels of steady-state glycogen in the muscles of doubly transgenic mice (430 µmol/g versus 10 µmol/g in wild-type mice). We conclude that the hexokinase gene may not be a good target for therapies designed to counteract insulin resistance or hyperglycemia.

CiteULike

Complore

Connotea

Del.icio.us

Digg

Reddit

Technorati

This article has been cited by other articles:

				P. T Fueger, J. Shearer, D. P Bracy, K. A Posey, R. R. Pencek, O. P McGuinness, and D. H Wasserman Control of muscle glucose uptake: test of the rate-limiting step paradigm in conscious, unrestrained mice J. Physiol., February 1, 2005; 562(3): 925 - 935. [Abstract] [Full Text] [PDF]

				P. T. Fueger, H. S. Hess, K. A. Posey, D. P. Bracy, R. R. Pencek, M. J. Charron, and D. H. Wasserman Control of Exercise-stimulated Muscle Glucose Uptake by GLUT4 Is Dependent on Glucose Phosphorylation Capacity in the Conscious Mouse J. Biol. Chem., December 3, 2004; 279(49): 50956 - 50961. [Abstract] [Full Text] [PDF]

				P. T. Fueger, H. S. Hess, D. P. Bracy, R. R. Pencek, K. A. Posey, M. J. Charron, and D. H. Wasserman Regulation of Insulin-Stimulated Muscle Glucose Uptake in the Conscious Mouse: Role of Glucose Transport Is Dependent on Glucose Phosphorylation Capacity Endocrinology, November 1, 2004; 145(11): 4912 - 4916. [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]

				P. T. Fueger, S. Heikkinen, D. P. Bracy, C. M. Malabanan, R. R. Pencek, M. Laakso, and D. H. Wasserman Hexokinase II partial knockout impairs exercise-stimulated glucose uptake in oxidative muscles of mice Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E958 - E963. [Abstract] [Full Text] [PDF]

				P. M. Garcia-Roves, D.-H. Han, Z. Song, T. E. Jones, K. A. Hucker, and J. O. Holloszy Prevention of glycogen supercompensation prolongs the increase in muscle GLUT4 after exercise Am J Physiol Endocrinol Metab, October 1, 2003; 285(4): E729 - E736. [Abstract] [Full Text] [PDF]

				J. O. Holloszy A forty-year memoir of research on the regulation of glucose transport into muscle Am J Physiol Endocrinol Metab, March 1, 2003; 284(3): E453 - E467. [Abstract] [Full Text] [PDF]

				A. Ahmad, S. Ahmad, B. K. Schneider, C. B. Allen, L.-Y. Chang, and C. W. White Elevated expression of hexokinase II protects human lung epithelial-like A549 cells against oxidative injury Am J Physiol Lung Cell Mol Physiol, September 1, 2002; 283(3): L573 - L584. [Abstract] [Full Text] [PDF]

				Q. Liang, R. V Donthi, P. M Kralik, and P. N Epstein Elevated hexokinase increases cardiac glycolysis in transgenic mice Cardiovasc Res, February 1, 2002; 53(2): 423 - 430. [Abstract] [Full Text] [PDF]