Ae. Halseth et al., Overexpression of hexokinase II increases insulin- and exercise-stimulatedmuscle glucose uptake in vivo, AM J P-ENDO, 39(1), 1999, pp. E70-E77
Citations number
33
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM
The hypothesis of this investigation was that glucose uptake would be incre
ased in skeletal muscle of transgenic mice (TG) overexpressing hexokinase I
I (HK II) compared with their nontransgenic littermates (NTG) during euglyc
emic hyperinsulinemia and treadmill exercise. For insulin experiments, cath
eters were surgically implanted in the jugular vein and carotid artery for
infusions and sampling, respectively. Conscious mice underwent experiments
similar to 5 days later in which 4 mU.kg(-1).min(-1) insulin and variable g
lucose (n = 7 TG and n = 7 NTG) or saline (n = 5 TG and n = 4 NTG;) was inf
used for 140 min. Over the last 40 min of the experiments, 2-deoxy-[H-3]glu
cose ([2-H-3]DG) was infused, after which muscles were removed. For the exe
rcise experiments, jugular vein catheters were surgically implanted. Five d
ays later, mice received a bolus of [2-H-3]DG and then remained sedentary(n
= 6 TG and n = 8 NTG) or ran on a motorized treadmill(n = 12 TG and n = 8
NTG) for 30 min. TG and NTG had similar muscle [2-H-3]DG B-phosphate ([2-H-
3]DGP) accumulation in the basal state (P > 0.05). In the hyperinsulinemic
experiments, TG required similar to 25% more glucose to maintain euglycemia
(P < 0.05), and muscle [2-H-3]DGP accumulation normalized to infusate [2-H
-3]DG was similarly increased (P < 0.05). In the exercise experiments, musc
le [2-H-3]DGP accumulation was significantly greater in TG than NTG (P < 0.
05). In conclusion, we did not detect an effect of HK II overexpression on
muscle [2-H-3]DGP accumulation under basal conditions. Hyperinsulinemia and
exercise shift the control of muscle glucose uptake so that phosphorylatio
n is a more important determinant of the rate of this process.