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 Citations (Scopus)

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 2004
Externally publishedYes

Fingerprint

Hexokinase
Inbred C57BL Mouse
Fats
Insulin
Glucose
Muscles
Diet
Glucose Clamp Technique
Jugular Veins
Hyperinsulinism
High Fat Diet
Carotid Arteries
Blood Glucose
Fasting
Catheters
Genotype

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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

Hexokinase II Overexpression Improves Exercise-Stimulated but Not Insulin-Stimulated Muscle Glucose Uptake in High-Fat-Fed C57BL/6J Mice. / Fueger, Patrick T.; Bracy, Deanna P.; Malabanan, Carlo M.; Pencek, R. Richard; Granner, Daryl K.; Wasserman, David H.

In: Diabetes, Vol. 53, No. 2, 02.2004, p. 306-314.

Research output: Contribution to journalArticle

Fueger, Patrick T. ; Bracy, Deanna P. ; Malabanan, Carlo M. ; Pencek, R. Richard ; Granner, Daryl K. ; Wasserman, David H. / Hexokinase II Overexpression Improves Exercise-Stimulated but Not Insulin-Stimulated Muscle Glucose Uptake in High-Fat-Fed C57BL/6J Mice. In: Diabetes. 2004 ; Vol. 53, No. 2. pp. 306-314.
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