Elevated hexokinase increases cardiac glycolysis in transgenic mice.
OBJECTIVE
Cardiac glucose metabolism is critical to normal and pathological function. The significance of the first committed metabolic step, glucose phosphorylation, has not been established. In this study a new transgenic model was developed in order to investigate the importance of this enzymatic step in cardiac glycolysis.


METHODS
Transgenic mice were produced that overexpress yeast hexokinase B under the control of a cardiac specific promoter. Yeast hexokinase B is a high affinity enzyme that is not inhibited by glucose-6-phosphate. Hexokinase enzyme activity was measured by a modified radiometric procedure. Cardiac glucose metabolism and contractility were measured in the Langendorff mode. Cardiac glycogen content and glucose-6-phosphate independent glycogen synthase activity were also determined.


RESULTS
In transgenic hearts hexokinase activity was significantly elevated and increased glucose metabolism, particularly in the presence of insulin and during cardiac reperfusion. However during ischemic perfusion the effect of the transgene on glycolysis was minimal. Under all conditions tested there was no effect of hexokinase on contractility. Glycogen content of transgenic hearts was elevated 2-fold and glucose-6-phosphate independent glycogen synthase was also increased.


CONCLUSIONS
These results demonstrate that glucose phosphorylation is a key step in determining cardiac glucose metabolism under oxidative conditions.
Liang
Qiangrong
Q
Department of Pharmacology, University of North Dakota, Grand Forks, ND 58202, USA.
Donthi
Rajakumar V
RV
Kralik
Patricia M
PM
Epstein
Paul N
PN
D000704:Analysis of Variance; D000818:Animals; D015152:Blotting, Northern; D005947:Glucose / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000032:analysis; D006006:Glycogen Synthase / Q000032:analysis; D006019:Glycolysis; D006593:Hexokinase / Q000032:analysis / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D019344:Lactic Acid / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009206:Myocardium / Q000737:chemistry / Q000378:metabolism*; D010477:Perfusion; D010766:Phosphorylation
D007328:Insulin; D019344:Lactic Acid; D019298:Glucose-6-Phosphate; D006006:Glycogen Synthase; D006593:Hexokinase; D005947:Glucose