Using U-14C-glucose as tracer the rates of 12C-glucose appearance (Ra), disappearance (Rd) and metabolic clearance (M) were determined in fasting dogs trained to horizontal running (100m/min): 1) before pancreatectomy, 2) 2 weeks after pancreatectomy, 1 day off insulin, and 3) the next day in the depancreatized dog on intraportal (215 μU/kg-min) or intracardial (120 μU/kg-min) insulin infusion. In each case Ra, Rd and M were determined by tracer injecton during (a) initial rest, (b) running, and (c) postrun rest. In the normal dog the average increase in Ra of 49% was accompanied by a 73% increase in Rd. In the depancreatized dog, both off insulin and on portal or intracardial insulin, Rd and M did not match the increased Ra and therefore glucose concentration rose in plasma. A rise in the concentration of free fatty acids in plasma accompanied running in each experiment. It is speculated that the adverse effect of exercise on glucose homeostasis in the depancreatized dog is associated with an excess of inhibiting factors, possibly free fatty acids. As glucose utilization did not increase during exercise in depancreatized dogs on insulin, a need for extra insulin in such running dogs is postulated. A factor, independent of insulin and pancreatic glucagon, which promotes glucose production is thought to be released during exercise. (Endocrinology85: 165, 1969)

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