14747279

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2

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 (HK(Tg)) 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[(3)H]glucose was administered 25 min before the end of each study for determination of R(g), an index of tissue-specific glucose uptake. Fasting blood glucose was increased in high-fat compared with standard diet-fed WT (194 +/- 4 vs. 171 +/- 4 mg/dl) but not HK(Tg) (179 +/- 5 vs. 171 +/- 3 mg/dl) mice. High-fat feeding created hyperinsulinemia in both WT and HK(Tg) mice (58 +/- 8 and 77 +/- 15 micro U/ml) compared with standard diet-fed mice (21 +/- 2 and 20 +/- 1 micro U/ml). R(g) was not affected by genotype or diet during either saline infusion or sedentary conditions. HK II overexpression augmented insulin-stimulated R(g) in standard diet-fed but not high-fat-fed mice. Exercise-stimulated R(g) 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.

eng

AIM

MEDLINE

0012-1797

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NLM

306-14

pubmed-meshheading:14747279-Animals, pubmed-meshheading:14747279-Biological Transport, pubmed-meshheading:14747279-Blood Glucose, pubmed-meshheading:14747279-Crosses, Genetic, pubmed-meshheading:14747279-Deoxyglucose, pubmed-meshheading:14747279-Dietary Fats, pubmed-meshheading:14747279-Fasting, pubmed-meshheading:14747279-Female, pubmed-meshheading:14747279-Gene Expression Regulation, Enzymologic, pubmed-meshheading:14747279-Glucose, pubmed-meshheading:14747279-Glucose Clamp Technique, pubmed-meshheading:14747279-Hexokinase, pubmed-meshheading:14747279-Humans, pubmed-meshheading:14747279-Hyperinsulinism, pubmed-meshheading:14747279-Insulin, pubmed-meshheading:14747279-Kinetics, pubmed-meshheading:14747279-Male, pubmed-meshheading:14747279-Mice, pubmed-meshheading:14747279-Mice, Inbred C57BL, pubmed-meshheading:14747279-Mice, Transgenic, pubmed-meshheading:14747279-Physical Conditioning, Animal, pubmed-meshheading:14747279-Physical Exertion, pubmed-meshheading:14747279-Sodium Chloride

Hexokinase II overexpression improves exercise-stimulated but not insulin-stimulated muscle glucose uptake in high-fat-fed C57BL/6J mice.

Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.