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Hexokinase II protein content is a determinant of exercise endurance capacity in the mouse
Author(s) -
Fueger Patrick T.,
Shearer Jane,
Krueger Tess M.,
Posey Kelly A.,
Bracy Deanna P.,
Heikkinen Sami,
Laakso Markku,
Rottman Jeffrey N.,
Wasserman David H.
Publication year - 2005
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2005.085043
Subject(s) - medicine , glycogen , treadmill , endocrinology , chemistry , vo2 max , respiratory exchange ratio , hexokinase , endurance training , heart rate , glycolysis , metabolism , blood pressure
Hexokinase (HK) II content is elevated in fatigue resistant muscle fibres and exercise trained muscle. The aim of this study was to determine if exercise capacity is dependent on muscle HK protein content. C57Bl/6 mice with a 50% HK knockout (HK +/− ), no genetic manipulation (wild‐type, WT) and an ∼3‐fold HK overexpression (HK Tg ) were tested. Mice ( n = 12/group) completed both a maximal oxygen consumption test and an endurance capacity test (run at ∼75%) on an enclosed treadmill equipped to measure gas exchange. Arterial and venous catheters were surgically implanted into separate groups of mice ( n = 9–11/group) in order to measure an index of muscle glucose uptake ( R g ) during 30 min of treadmill exercise. Maximum work rate (0.95 ± 0.05, 1.00 ± 0.04 and 1.06 ± 0.07 kg m min −1 ), (137 ± 3, 141 ± 4 and 141 ± 5 ml kg −1 min −1 ) and maximal respiratory exchange ratio (1.04 ± 0.02, 1.00 ± 0.03 and 1.04 ± 0.04) were similar in HK +/− , WT and HK Tg , respectively. Exercise endurance capacity (measured as time to exhaustion) increased as HK content increased (55 ± 11, 77 ± 5 and 98 ± 9 min) and this was related to R g measured in mice during 30 min of exercise (13 ± 2, 24 ± 5 and 42 ± 5 μmol (100 g) −1 min −1 ). Muscle glycogen in sedentary HK +/− mice and HK +/− mice following 30 min of exercise were significantly lower than in HK Tg and WT mice. However, the net exercise‐induced muscle glycogen breakdown was equal in the three genotypes. In summary, HK protein content within the range studied (a) was not associated with a difference in the capacity to perform maximal intensity exercise, (b) was a powerful determinant of the ability to sustain moderate intensity exercise, as reducing HK content impaired endurance and increasing HK content enhanced endurance, and (c) although directly related to exercise endurance, was not a determinant of net muscle glycogen usage during exercise. In conclusion, adaptations that increase HK protein content and/or functional activity such as regular exercise contribute to increased muscular endurance.