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- Title
Hexokinase II overexpression improves exercise-stimulated but not insulin-stimulated muscle glucose uptake in high-fat-fed C57BL/6J mice.
- Authors
Fueger, Patrick T.; Bracy, Deanna P.; Malabanan, Carlo M.; Pencek, R. Richard; Granner, Daryl K.; Wasserman, David H.
- 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 ± 2 and 20 ± 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-fatfed mice. Exercise-stimulated Rg was impaired by highfat feeding in WT mice, but this impairment was largely rectified in HKTg mice. In conclusion, high-fat feeding impairs both insulin- and exercise-stimulated MGU, but only exercise-stimulated MGU was corrected by HK II overexpression.
- Subjects
GLUCOKINASE; GLUCOSE; INSULIN resistance; EDIBLE fats &; oils; DIET; EXERCISE
- Publication
Diabetes, 2004, Vol 53, Issue 2, p306
- ISSN
0012-1797
- Publication type
journal article
- DOI
10.2337/diabetes.53.2.306