Hexokinase II Overexpression Improves Exercise-Stimulated but Not Insulin-Stimulated Muscle Glucose Uptake in High-Fat-Fed C57BL/6J Mice

Patrick T. Fueger, Deanna P. Bracy, Carlo M. Malabanan, R. Richard Pencek, Daryl K. Granner, David H. Wasserman

Research output: Contribution to journalArticle

54 Scopus citations

Abstract

The aim of the present study was to determine the specific sites of impairment to muscle glucose uptake (MGU) in the insulin-resistant high-fat-fed, conscious C57BL/6J mouse. Wild type (WT) and hexokinase II overexpressing (HKTg) mice were fed either a standard diet or high-fat diet and studied at 4 months of age. A carotid artery and jugular veins had catheters chronically implanted for sampling and infusions, respectively, and mice were allowed to recovery for at least 5 days. Mice were fasted for 5 h and underwent a hyperinsulinemic-euglycemic clamp or saline infusion for 120 min. Separate groups of mice were studied during 30-min sedentary or treadmill exercise periods. A bolus of 2-deoxy[3H]glucose was administered 25 min before the end of each study for determination of Rg, an index of tissue-specific glucose uptake. Fasting blood glucose was increased in high-fat compared with standard dietfed WT (194 ± 4 vs. 171 ± 4 mg/dl) but not HKTg (179 ± 5 vs. 171 ± 3 mg/dl) mice. High-fat feeding created hyperinsulinemia in both WT and HKTg mice (58 ± 8 and 77 ± 15 μU/ml) compared with standard diet-fed mice (21 ± 1 μU/ml). Rg was not affected by genotype or diet during either saline infusion or sedentary conditions. HK II overexpression augmented insulin-stimulated Rg in standard diet-fed but not high-fat-fed mice. Exercise-stimulated Rg was impaired by high-fat feeding in WT mice, but this impairment was largely rectified in HK Tg mice. In conclusion, high-fat feeding impairs both insulin- and exercise-stimulated MGU, but only exercise-stimulated MGU was corrected by HK II overexpression.

Original languageEnglish (US)
Pages (from-to)306-314
Number of pages9
JournalDiabetes
Volume53
Issue number2
DOIs
StatePublished - Feb 1 2004

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

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    Fueger, P. T., Bracy, D. P., Malabanan, C. M., Pencek, R. R., Granner, D. K., & Wasserman, D. H. (2004). Hexokinase II Overexpression Improves Exercise-Stimulated but Not Insulin-Stimulated Muscle Glucose Uptake in High-Fat-Fed C57BL/6J Mice. Diabetes, 53(2), 306-314. https://doi.org/10.2337/diabetes.53.2.306