Regulation of hexokinase II expression in human skeletal muscle in vivo
Abstract
The phosphorylation of glucose to glucose-6-phosphate (G-6-P) is the first committed step in glucose uptake in skeletal muscle. This reaction is catalyzed by hexokinase (HK). Two HK isoforms, HKI and HKII, are expressed in human skeletal muscle, but only HKII is regulated by insulin. The present study was undertaken to determine the time course for the regulation of HK activity and expression by physiological plasma insulin concentrations in human skeletal muscle in vivo. A hyperinsulinemic-euglycemic glucose clamp and percutaneous muscle biopsy were performed in separate groups of healthy subjects after 60, 120, 180, and 360 minutes of euglycemic hyperinsulinemia. Muscle biopsies were subfractionated into soluble and particulate fractions to determine HKI and HKII activities. RNA was extracted from a separate portion of the muscle biopsy, and HKI and HKII mRNA content was determined using an RNase protection assay. Glycogen synthase (GS) activity and fractional velocity were also determined. HKII mRNA was increased 2-fold by 120 minutes and remained high versus the basal value for up to 360 minutes. HKI mRNA was unchanged throughout the study. HKII activity increased after 360 minutes of insulin infusion, and this increase was limited to the soluble fraction. In contrast, insulin induced a 1.5- to 2-fold increase in GS fractional velocity that was sustained for 360 minutes. The time course of the ability of hyperinsulinemia to increase HKII mRNA indicates that insulin is likely a physiological regulator of HKII expression in human skeletal muscle in vivo.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In lean type 2 diabetics, the ability of insulin to augment HK-II activity and mRNA levels is markedly reduced compared with controls.
“In lean type 2 diabetics, the ability of insulin to augment HK-II activity and mRNA levels are markedly reduced compared with controls [199].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [199]
In human skeletal muscle, HK-II transcription is regulated by insulin, whereas HK-I mRNA and protein levels are not affected by insulin.
“In human skeletal muscle, HK-II transcription is regulated by insulin, whereas HK-I mRNA and protein levels are not affected by insulin [199, 200].”
From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [199]
Cites
Cushman, S. W., & Wardzala, L. J. (1980) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)85561-8 · Cited by 1,092 · see citing works
Wardzala, L. J., & Jeanrenaud, B. (1981) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)68926-x · Cited by 839 · see citing works
Multiple Hexokinases of Rat Tissues
Grossbard, L., & SCHIMKE, R. T. (1966) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)99866-2 · Cited by 483 · see citing works
Correlation between muscle glycogen synthase activity and in vivo insulin action in man
Bogardus, C., Lillioja, S., Stone, K., & Mott, D. (1984) · Journal of Clinical Investigation · doi:10.1172/jci111304 · Cited by 335 · see citing works
Rothman, D. L., Shulman, R. G., & Shulman, G. I. (1992) · Journal of Clinical Investigation · doi:10.1172/jci115686 · Cited by 328 · see citing works
Control of glycogen synthase by hierarchal protein phosphorylation
Roach, P. J. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.12.2168324 · Cited by 270 · see citing works
Kelley, D. E., Mintun, M. A., Watkins, S. C., Simoneau, J. A., Jadali, F., Fredrickson, A., Beattie, J., & Thériault, R. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118724 · Cited by 228 · see citing works
Damsbo, P., Vaag, A., Hother-Nielsen, O., & Beck-Nielsen, H. (1991) · Diabetologia · doi:10.1007/bf00405082 · Cited by 203 · see citing works
Mandarino, L. J., Wright, K. S., Verity, L. S., Nichols, J., Bell, J. M., Kolterman, O. G., & Beck-Nielsen, H. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113118 · Cited by 194 · see citing works
Self-citationRoles of Glucose Transport and Glucose Phosphorylation in Muscle Insulin Resistance of NIDDM
Bonadonna, R. C., Bonora, E., Prato, S. D., Saccomani, M. P., Cobelli, C., Natali, A., Frascerra, S., Pecori, N., Ferrannini, E., Bier, D., et al. (1996) · Diabetes · doi:10.2337/diab.45.7.915 · Cited by 191 · see citing works
Self-citationThorburn, A. W., Gumbiner, B., Bulacan, F., Wallace, P., & Henry, R. R. (1990) · Journal of Clinical Investigation · doi:10.1172/jci114468 · Cited by 185 · see citing works
Hexokinase II mRNA and gene structure, regulation by insulin, and evolution.
Printz, R. L., Koch, S. R., Potter, L. R., O'Doherty, R. M., Tiesinga, J. J., Moritz, S., & Granner, D. K. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)53521-3 · Cited by 179 · see citing works
Self-citationTransmembrane glucose transport in skeletal muscle of patients with non-insulin-dependent diabetes.
Bonadonna, R. C., Del Prato, S., Saccomani, M. P., Bonora, E., Gulli, G., Ferrannini, E., Bier, D., Cobelli, C., & DeFronzo, R. A. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116592 · Cited by 149 · see citing works
Self-citationRegulation of hexokinase II and glycogen synthase mRNA, protein, and activity in human muscle
Mandarino, L. J., Printz, R. L., Cusi, K. A., Kinchington, P., O'Doherty, R. M., Osawa, H., Sewell, C., Consoli, A., Granner, D. K., & DeFronzo, R. A. (1995) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1995.269.4.e701 · Cited by 124 · see citing works
Self-citationYki-Järvinen, H., Mott, D., Young, A. A., Stone, K., & Bogardus, C. (1987) · Journal of Clinical Investigation · doi:10.1172/jci113069 · Cited by 123 · see citing works
Self-citationRat skeletal muscle hexokinase II mRNA and activity are increased by a single bout of acute exercise
O'Doherty, R. M., Bracy, D. P., Osawa, H., Wasserman, D. H., & Granner, D. K. (1994) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1994.266.2.e171 · Cited by 98 · see citing works
Self-citationPostic, C., Leturque, A., Rencurel, F., Printz, R. L., Forest, C. D., Granner, D. K., & Girard, J. R. (1993) · Diabetes · doi:10.2337/diab.42.6.922 · Cited by 95 · see citing works
Self-citationHuman Hexokinase II mRNA and Gene Structure
Printz, R. L., Ardehali, H., Koch, S., & Granner, D. K. (1995) · Diabetes · doi:10.2337/diab.44.3.290 · Cited by 50 · see citing works
Self-citationRoles of glucose transport and glucose phosphorylation in muscle insulin resistance of NIDDM
Bonadonna, R. C., Prato, S. D., Bonora, E., et al. (1996) · Diabetes · doi:10.2337/diabetes.45.7.915 · Cited by 46 · see citing works
Glycogen synthase: activation by insulin and effect of transgenic overexpression in skeletal muscle
Lawrence, J. C., Skurat, A. V., Roach, P. J., et al. (1997) · Biochemical Society Transactions · doi:10.1042/bst0250014 · Cited by 19 · see citing works
Human hexokinase II mRNA and gene structure
Printz, R. L., Ardehali, H., Koch, S. R., et al. (1995) · Diabetes · doi:10.2337/diabetes.44.3.290 · Cited by 12 · see citing works
Self-citationPostic, C., Leturque, A., Rencurel, F., et al. (1993) · Diabetes · doi:10.2337/diabetes.42.6.922 · Cited by 11 · see citing works
Thompson, D. B., de Gregorio, M., & Sommercorn, J. (1996) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jcem.81.2.8636261 · Cited by 9 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Pathogenesis of type 2 diabetes mellitus
DeFronzo, R. A. (2004) · Medical Clinics of North America · doi:10.1016/j.mcna.2004.04.013 · Cited by 1,342 · see citing works
Self-citationPathogenesis of insulin resistance in skeletal muscle
Abdul-Ghani, M. A., & DeFronzo, R. A. (2010) · Journal of Biomedicine and Biotechnology · doi:10.1155/2010/476279 · Cited by 670 · see citing works
Self-citationSkeletal muscle insulin resistance: role of mitochondria and other ROS sources
Di Meo, S., Iossa, S., & Venditti, P. (2017) · Journal of Endocrinology · doi:10.1530/joe-16-0598 · Cited by 282 · see citing works
- Authors
- Vogt, C., Ardehali, H., Iozzo, P., Yki-Järvinen, H., Koval, J., Maezono, K., Pendergrass, M., Printz, R., Granner, D., DeFronzo, R., & Mandarino, L.
- Affiliations
- The University of Texas at San Antonio Health Science Center (US)
- Corresponding author
- Mandarino, Lawrence
- Venue
- Metabolism
- Publisher
- Elsevier BV
- Published
- 2000-06
- Volume
- 49
- Issue
- 6
- Pages
- 814-818
- ISSN
- 0026-0495 (ISSN-L)
- OpenAlex
- W1971359775
- Cited by
- 45
- References
- 23
- Citations by year
- 2025: 2 · 2024: 3 · 2023: 1 · 2022: 3 · 2021: 4 · 2019: 1 · 2018: 2 · 2017: 4 · 2016: 3 · 2015: 2 · 2014: 2 · 2012: 1
- FWCI
- 0.24
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health (5r01dk046867-09)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK47936, DK-46867, DK 24092, R01DK047936)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Keywords
- hexokinase 2, hexokinase 1, skeletal muscle, insulin regulation, gene expression, hyperinsulinemic-euglycemic clamp, glycogen synthase, glucose phosphorylation, glucose uptake
- MeSH terms
- Adult, Female, Glucose, Glycogen Synthase, Hexokinase, Humans, Hyperinsulinism, Insulin, Isoenzymes, Male, RNA, Messenger, Time Factors, Glucose Clamp Technique, Gene Expression Regulation, Enzymologic, Muscle, Skeletal
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review