Effects of Insulin on Subcellular Localization of Hexokinase II in Human Skeletal Muscle in Vivo1 (original) (raw)

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1The Diabetes Division, Department of Medicine (C.V., H.Y-J., P.I., R.Pi., M.P., J.K., R.D., L.M.), San Antonio, Texas 78284;

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1The Diabetes Division, Department of Medicine (C.V., H.Y-J., P.I., R.Pi., M.P., J.K., R.D., L.M.), San Antonio, Texas 78284;

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1The Diabetes Division, Department of Medicine (C.V., H.Y-J., P.I., R.Pi., M.P., J.K., R.D., L.M.), San Antonio, Texas 78284;

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1The Diabetes Division, Department of Medicine (C.V., H.Y-J., P.I., R.Pi., M.P., J.K., R.D., L.M.), San Antonio, Texas 78284;

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1The Diabetes Division, Department of Medicine (C.V., H.Y-J., P.I., R.Pi., M.P., J.K., R.D., L.M.), San Antonio, Texas 78284;

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1The Diabetes Division, Department of Medicine (C.V., H.Y-J., P.I., R.Pi., M.P., J.K., R.D., L.M.), San Antonio, Texas 78284;

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3The Department of Molecular Physiology (H.A., R.Pr. D.G.), Vanderbilt University School of Medicine, Nashville, Tennessee 373232-0615

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3The Department of Molecular Physiology (H.A., R.Pr. D.G.), Vanderbilt University School of Medicine, Nashville, Tennessee 373232-0615

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3The Department of Molecular Physiology (H.A., R.Pr. D.G.), Vanderbilt University School of Medicine, Nashville, Tennessee 373232-0615

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1The Diabetes Division, Department of Medicine (C.V., H.Y-J., P.I., R.Pi., M.P., J.K., R.D., L.M.), San Antonio, Texas 78284;

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Revision received:

19 August 1997

Accepted:

24 September 1997

Published:

01 January 1998

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Christoph Vogt, Hannele Yki-Jarvinen, Patricia Iozzo, Ruben Pipek, Merri Pendergrass, Janice Koval, Hossein Ardehali, Richard Printz, Daryl Granner, Ralph DeFronzo, Lawrence Mandarino, Effects of Insulin on Subcellular Localization of Hexokinase II in Human Skeletal Muscle in Vivo, The Journal of Clinical Endocrinology & Metabolism, Volume 83, Issue 1, 1 January 1998, Pages 230–234, https://doi.org/10.1210/jcem.83.1.4476
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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.

Copyright © 1998 by The Endocrine Society

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