Overexpression of hexokinase II increases insulin- and exercise-stimulatedmuscle glucose uptake in vivo

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.