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Cited by 119Metabolism, Diabetes, and CancerDiabetes, Cardiovascular Risks, and LipoproteinsAdipokines, Inflammation, and Metabolic Diseases

Insulin-induced hexokinase II expression is reduced in obesity and NIDDM.

Pendergrass, M, Koval, J, Vogt, C, Yki-Jarvinen, H, Iozzo, P, Pipek, R, Ardehali, H, Printz, R +3 more·1998·Diabetes
DOI 10.2337/diabetes.47.3.387
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Abstract

NIDDM and obesity are characterized by decreased insulin-stimulated glucose uptake in muscle. It has been suggested that impaired glucose phosphorylation to glucose-6-phosphate, catalyzed in muscle by hexokinase (HK)II, may contribute to this insulin resistance. Insulin is known to increase HKII mRNA, protein, and activity in lean nondiabetic individuals. The purpose of this study was to determine whether defects in insulin-stimulated HKII expression and activity could contribute to the insulin resistance of obesity and NIDDM. Fifteen lean nondiabetic control subjects, 17 obese nondiabetic subjects, and 14 obese NIDDM patients were studied. Percutaneous muscle biopsies of the vastus lateralis were performed in conjunction with leg balance and local indirect calorimetry measurements before and at the end of a 3-h euglycemic-hyperinsulinemic clamp (40 or 240 mU x min(-1) x m[-2]). Leg glucose uptake in response to the 40-mU insulin infusion was higher in the lean control subjects (2.53 +/- 0.35 micromol x min(-1) per x 100 ml leg vol) than in obese (1.46 +/- 0.50) or NIDDM (0.53 +/- 0.25, P < 0.05) patients. In response to 240 mU insulin, leg glucose uptake was similar in all of the groups. In response to 40 mU insulin, HKII mRNA in lean control subjects was increased 1.48 +/- 0.18-fold (P < 0.05) but failed to increase significantly in the obese (1.12 +/- 0.24) or NIDDM (1.14 +/- 0.18) groups. In response to 240 mU insulin, HKII mRNA was increased in all groups (control subjects 1.48 +/- 0.18, P < 0.05 vs. basal, obese 1.30 +/- 0.16, P < 0.05, and NIDDM 1.25 +/- 0.14, P < 0.05). Under basal conditions, HKI and HKII activities did not differ significantly between groups. Neither the 40 mU nor the 240 mU insulin infusion affected HK activity. Total HKII activity was reduced in the obese subjects (4.33 +/- 0.08 pmol x min(-1) x g(-1) muscle protein) relative to the lean control subjects (5.00 +/- 0.08, P < 0.05). There was a further reduction in the diabetic patients (3.10 +/- 0.10, P < 0.01 vs. the control subjects, P < 0.01 vs. the obese subjects). Resistance to insulin's metabolic effects extends to its ability to induce HKII expression in obesity and NIDDM.

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Crossref · 10.2337/diabetes.47.3.387

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  • Glycogen synthase is the key insulin-regulated enzyme controlling the rate of muscle glycogen synthesis.

    “Glycogen synthase is the key insulin-regulated enzyme that controls the rate of muscle glycogen synthesis [148, 150, 200, 212–214].”

    From Pathogenesis of insulin resistance in skeletal muscle (2010) · cites this paper as [200]

  • 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 [200]

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Authors
Pendergrass, M., Koval, J., Vogt, C., Yki-Jarvinen, H., Iozzo, P., Pipek, R., Ardehali, H., Printz, R., Granner, D., DeFronzo, R. A., & Mandarino, L. J.
Affiliations
  • The University of Texas at San Antonio Health Science Center (US)
  • Department of Medicine, University of Texas Health Science Center at San Antonio, 78284-7886, USA.
ORCID
Venue
Diabetes
Publisher
American Diabetes Association
Published
1998-03-01
Volume
47
Issue
3
Pages
387-394
ISSN
  • 0012-1797 (ISSN-L)
  • 1939-327X
DOI
10.2337/diabetes.47.3.387
OpenAlex
W2109297349
Cited by
119
References
11
Citations by year
2025: 1 · 2024: 2 · 2023: 1 · 2022: 5 · 2021: 2 · 2018: 6 · 2017: 4 · 2016: 3 · 2015: 3 · 2014: 6 · 2013: 4 · 2012: 3
FWCI
2.80
Type
journal article
Language
en
Open access
closed
Locations
  • Diabetes (publishedVersion)
  • PubMed (publishedVersion)
Funders
National Institute of Diabetes and Digestive and Kidney Diseases (DK47936, DK 20593, 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
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
Keywords
hexokinase 2, insulin resistance, obesity, type 2 diabetes, skeletal muscle glucose uptake, glucose phosphorylation, hyperinsulinemic-euglycemic clamp, vastus lateralis, muscle glucose metabolism, indirect calorimetry
MeSH terms
Adult, Biopsy, Diabetes Mellitus, Type 2, Dose-Response Relationship, Drug, Female, Glucose, Glycogen Synthase, Hexokinase, Humans, Infusions, Intravenous, Insulin, Leg, Male, Obesity, Regional Blood Flow, RNA, Messenger, Glucose Clamp Technique, Cohort Studies, Gene Expression Regulation, Enzymologic, Muscle, Skeletal

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