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

doi:10.2337/diabetes.53.2.306

Back

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

Journal article

Open access

Peer reviewed

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 and David H Wasserman

Diabetes (New York, N.Y.), Vol.53(2), pp.306-314

02/2004

DOI: 10.2337/diabetes.53.2.306

PMID: 14747279

Files and links (1)

url

https://doi.org/10.2337/diabetes.53.2.306View

Published (Version of record) Open Access

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.

Physical Exertion - physiology

Sodium Chloride - pharmacology

Humans

Male

Dietary Fats - pharmacology

Female

Biological Transport - drug effects

Hexokinase - genetics

Hyperinsulinism

Physical Conditioning, Animal

Insulin - pharmacology

Fasting

Mice, Inbred C57BL

Deoxyglucose - blood

Insulin - administration & dosage

Mice, Transgenic

Blood Glucose - drug effects

Gene Expression Regulation, Enzymologic

Animals

Glucose - metabolism

Biological Transport - physiology

Mice

Glucose Clamp Technique

Kinetics

Blood Glucose - metabolism

Crosses, Genetic

Details

Title: Subtitle: Hexokinase II overexpression improves exercise-stimulated but not insulin-stimulated muscle glucose uptake in high-fat-fed C57BL/6J mice
Creators: Patrick T Fueger - Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee, USA. patrick.fueger@vanderbilt.edu
Deanna P Bracy
Carlo M Malabanan
R Richard Pencek
Daryl K Granner
David H Wasserman
Resource Type: Journal article
Publication Details: Diabetes (New York, N.Y.), Vol.53(2), pp.306-314
Publisher: United States
DOI: 10.2337/diabetes.53.2.306
PMID: 14747279
ISSN: 0012-1797
eISSN: 1939-327X
Grant note: R01 DK-54902 / NIDDK NIH HHS U24-DK-59637 / NIDDK NIH HHS DK-20593 / NIDDK NIH HHS
Language: English
Date published: 02/2004
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984020715902771

Metrics

21 Record Views

55 Times Cited - Web of Science