Clearance Rates of Metabolizable and Nonmetabolizable Sugars in Insulin-infused Dogs and in Exercising Dogs

Abstract

Dogs with indwelling arterial and venous catheters were trained to run on a treadmill (slope, 15% speed, 100 m/min). The clearance rates (CR) of 3H-inulin, 3-3Hglucose (G), 14C-L-arabinose (L-A), 14C-D-xylose (D-X), 14C-3-methyl-O-glucose (3-m-G) and 2-deoxy-glucose (2-d-G) were measured using the primed constant infusion tracer technics. With the exception of glucose, all substances were excreted in the urine; therefore the CR is the sum of the urinary clearance rate (UCR) plus the tissue clearance rate (tCR). By measuring CRinuMn and the concentration of 3H-inulin in the urine, the flow rate of urine and the UCR and tCR of the simultaneously infused 14C-sugars were calculated. Infusion of insulin (1.5 mU/kg min) and glucose (6 mg/kg min) into the resting dog raised plasma insulin to 60–40μU/ml at normoglycemia. The tCR of all sugars was increased: G>2-d-G>3-m-G>D-X>L-A. There was a great discrepancy between the phosphorylable (G, 2- d-G) and the nonmetabolizable sugars (3-m-G, D-X, LA). Insulin increased tCR of glucose almost threefold, and it was estimated that 27% of the increase could be ascribed to the unassisted direct effect of membrane- transport (3-m-G) and 55% if the glucose could be phosphorylated but not metabolized further (2-d-G). Exercise decreased plasma insulin by almost 50%, hepatic glucose production rose more than twofold, and the tCR-glucose more than 21/2-fold. The tCR of L-A remained unchanged and that of the other sugar derivatives was increased by the run in the following order G>2-d-G>3-m-G>D-X. It was estimated that only 16% of the increase of tCR-glucose could be ascribed to the effect of exercise on the membrane-transport if it was not assisted by the hexokinase, and 53% with the help of the enzyme but without the accelerated glycolysis. It is concluded that, under physiologic conditions, a relatively small fraction (16–20%) of the twoto threefold increase of glucose utilization can be ascribed to a direct membrane effect if the activity of flux-generating steps towards either glycogen formation (insulin) or glycolysis (exercise) is accelerated.