Insulin increases the rate of degradation of 2-deoxy-glucose-6-phosphate in the perfused rat heart: a 31P NMR study.
The effect of insulin on the production and degradation of 2-deoxyglucose-6-phosphate (2DG6P) from 2-deoxyglucose (2DG) in the Langendorff-perfused rat heart was studied by 31P NMR. The 2DG concentrations ranged from 0.25 to 20 mM in the 5 mM acetate perfusion medium, and from 2 to 4 mM in the 12 mM glucose medium. With acetate as the carbon source, the apparent Km for the production of 2DG6P was 7 mM and Vmax was 1.8 mumols/min/mg prot. Insulin enhanced Vmax 7-fold without change in Km of the transporter. With glucose perfusion, insulin had no effect on the initial rate of production of 2DG6P. The interpretation is that glucose phosphorylation is regulated by work when glucose is the energy substrate. In acetate-perfused hearts, in the conditions where the 2DG6P content reached a plateau, the rate of production of 2DG6P (equal to the measured degradation rate, see below) was eight times smaller than the initial rate, both with and without insulin. In glucose-perfused hearts, it was the same as the initial rate. The degradation of 2DG6P upon interruption of 2DG perfusion was exponential. The time constant was the same in acetate or glucose. It was strongly affected by insulin, being 225 +/- 60 min without, and 92 +/- 13 min with insulin. The observation that 2DG6P degradation is sensitive to insulin in the heart shows that its rate may vary. This possibility should be kept in mind in the analysis of PET studies of glucose metabolism.
Hoerter
J
J
U-241 INSERM, Université Paris XI, Orsay, France.
Dormont
D
D
Girault
M
M
Guéron
M
M
Syrota
A
A
D000085:Acetates / Q000378:metabolism; D000818:Animals; D003847:Deoxyglucose / Q000737:chemistry / Q000378:metabolism*; D005629:Frozen Sections; D005947:Glucose / Q000378:metabolism; D019298:Glucose-6-Phosphate / Q000031:analogs & derivatives*; D005958:Glucosephosphates / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D051381:Rats; D011919:Rats, Inbred Strains
D000085:Acetates; D005958:Glucosephosphates; D007328:Insulin; C015785:2-deoxyglucose-6-phosphate; D019298:Glucose-6-Phosphate; D003847:Deoxyglucose; D005947:Glucose