Cited by 45Metabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and LipoproteinsMuscle metabolism and nutrition

Regulation of hexokinase II expression in human skeletal muscle in vivo

Vogt, Christoph, Ardehali, Hossein, Iozzo, Patricia, Yki-Järvinen, Hannele, Koval, Janice, Maezono, Katsumi, Pendergrass, Merri, Printz, Richard +3 more·2000·Metabolism

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.

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Crossref · 10.1053/meta.2000.6245

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  • 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]

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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

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