This Article Full Text Full Text (PDF) Submit a related Letter to the 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 Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Vogt, C. Articles by Mandarino, L. Search for Related Content PubMed PubMed Citation Articles by Vogt, C. Articles by Mandarino, L.

Effects of Insulin on Subcellular Localization of Hexokinase II in Human Skeletal Muscle in Vivo ¹

The Diabetes Division, Department of Medicine (C.V., H.Y-J., P.I., R.Pi., M.P., J.K., R.D., L.M.) and Biochemistry (L.M.), the University of Texas Health Science Center at San Antonio, San Antonio, Texas 78284; The Department of Molecular Physiology (H.A., R.Pr. D.G.), Vanderbilt University School of Medicine, Nashville, Tennessee 373232-0615

Address correspondence and requests for reprints to: Lawrence J. Mandarino, Ph.D., The University of Texas Health Science Center, Department of Medicine/Diabetes Division, 7703 Floyd Curl Drive, San Antonio, Texas 78284-7886.

The phosphorylation of glucose to glucose-6-phosphate, catalyzed by hexokinase, is the first committed step in glucose uptake into skeletal muscle. Two isoforms of hexokinase, HKI and HKII, are expressed in human skeletal muscle, but only HKII expression is regulated by insulin. HKII messenger RNA, protein, and activity are increased after 4 h of insulin infusion; however, glucose uptake is stimulated much more rapidly, occurring within minutes. Studies in rat muscle suggest that changes in the subcellular distribution of HKII may be an important regulatory factor for glucose uptake. The present studies were undertaken to determine if insulin causes an acute redistribution of HKII activity in human skeletal muscle in vivo. Muscle biopsies (vastus lateralis muscle) were performed before and at the end of 30 min insulin infusion, performed using the euglycemic clamp technique. Muscle biopsies were subfractionated into soluble and particulate fractions to determine if insulin acutely changes the subcellular distribution of HKII. Insulin decreased HKII activity in the soluble fraction from 2.20 ± 0.31 to 1.40 ± 0.18 pmoles/(min[chempt]µg) and increased HKII activity in the particulate fraction from 3.02 ± 0.46 to 3.45 ± 0.46 pmoles/(min[chempt]µg) (P < 0.01 for both). These changes in HKII activity were correlated with changes in HKII protein, as determined by immunoblot analysis (r = 0.53, P = 0.05). Insulin had no effect on the subcellular distribution of HKI activity, which was primarily restricted to the soluble fraction. These studies are consistent with the conclusion that, in vivo in human skeletal muscle, insulin changes the subcellular distribution of HKII within 30 min.

This article has been cited by other articles:

				R. A. DeFronzo From the Triumvirate to the Ominous Octet: A New Paradigm for the Treatment of Type 2 Diabetes Mellitus Diabetes, April 1, 2009; 58(4): 773 - 795. [Full Text] [PDF]

				M. Pendergrass, A. Bertoldo, R. Bonadonna, G. Nucci, L. Mandarino, C. Cobelli, and R. A. DeFronzo Muscle glucose transport and phosphorylation in type 2 diabetic, obese nondiabetic, and genetically predisposed individuals Am J Physiol Endocrinol Metab, January 1, 2007; 292(1): E92 - E100. [Abstract] [Full Text] [PDF]

				R. Southworth, K. A. B. Davey, A. Warley, and P. B. Garlick A reevaluation of the roles of hexokinase I and II in the heart Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H378 - H386. [Abstract] [Full Text] [PDF]

				K. V. Williams, J. C. Price, and D. E. Kelley Interactions of Impaired Glucose Transport and Phosphorylation in Skeletal Muscle Insulin Resistance: A Dose-Response Assessment Using Positron Emission Tomography Diabetes, September 1, 2001; 50(9): 2069 - 2079. [Abstract] [Full Text] [PDF]

				V. B. Ritov and D. E. Kelley Hexokinase Isozyme Distribution in Human Skeletal Muscle Diabetes, June 1, 2001; 50(6): 1253 - 1262. [Abstract] [Full Text]

				K. Gottlob, N. Majewski, S. Kennedy, E. Kandel, R. B. Robey, and N. Hay Inhibition of early apoptotic events by Akt/PKB is dependent on the first committed step of glycolysis and mitochondrial hexokinase Genes & Dev., June 1, 2001; 15(11): 1406 - 1418. [Abstract] [Full Text] [PDF]

				T. Utriainen, S. Lovisatti, S. Makimattila, A. Bertoldo, S. Weintraub, R. DeFronzo, C. Cobelli, and H. Yki-Jarvinen Direct measurement of the lumped constant for 2-deoxy-[1-14C]glucose in vivo in human skeletal muscle Am J Physiol Endocrinol Metab, July 1, 2000; 279(1): E228 - E233. [Abstract] [Full Text] [PDF]

				T. P. Ciaraldi, L. Carter, S. Nikoulina, S. Mudaliar, D. A. McClain, and R. R. Henry Glucosamine Regulation of Glucose Metabolism in Cultured Human Skeletal Muscle Cells: Divergent Effects on Glucose Transport/Phosphorylation and Glycogen Synthase in Non-Diabetic and Type 2 Diabetic Subjects Endocrinology, September 1, 1999; 140(9): 3971 - 3980. [Abstract] [Full Text]