title: Hexokinase II overexpression improves exercise-stimulated but not insulin-stimulated muscle glucose uptake in high-fat-fed C57BL/6J mice.
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 (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.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. patrick.fueger@vanderbilt.edu
authors.forename: Patrick T
authors.initials: PT
authors.lastname: Fueger
authors.forename: Deanna P
authors.initials: DP
authors.lastname: Bracy
authors.forename: Carlo M
authors.initials: CM
authors.lastname: Malabanan
authors.forename: R Richard
authors.initials: RR
authors.lastname: Pencek
authors.forename: Daryl K
authors.initials: DK
authors.lastname: Granner
authors.forename: David H
authors.initials: DH
authors.lastname: Wasserman
mesh_terms: D000818:Animals; D001692:Biological Transport / Q000187:drug effects / Q000502:physiology; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D003433:Crosses, Genetic; D003847:Deoxyglucose / Q000097:blood; D004041:Dietary Fats / Q000494:pharmacology; D005215:Fasting; D005260:Female; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006593:Hexokinase / Q000235:genetics*; D006801:Humans; D006946:Hyperinsulinism; D007328:Insulin / Q000008:administration & dosage / Q000494:pharmacology*; D007700:Kinetics; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010805:Physical Conditioning, Animal; D005082:Physical Exertion / Q000502:physiology; D012965:Sodium Chloride / Q000494:pharmacology
chemical_list: D001786:Blood Glucose; D004041:Dietary Fats; D007328:Insulin; D012965:Sodium Chloride; D003847:Deoxyglucose; D006593:Hexokinase; D005947:Glucose