INSULIN-INDEPENDENT ACUTE RESTORATION OF EUGLYCEMIA NORMALIZES THE IMPAIRED GLUCOSE CLEARANCE DURING EXERCISE IN DIABETIC DOGS

At rest and during exercise, chronic hyperglycemia, high free fatty ac id (FFA) oxidation, and insulin deficiency in diabetes are well known to impair glucose clearance (metabolic clearance rate [MCR]), The effe ct of acute restoration of glycemia per se on MCR has been less well c haracterized, We therefore studied normal and alloxan-diabetic dogs bo th at rest and during exercise, as diabetic hyperglycemic or after acu tely induced euglycemia (<160 min) generated by infusion of either ins ulin or phlorizin, Glucose uptake was similar under hyperglycemic and normoglycemic conditions both at rest and during exercise, indicating a precise balance between the mass effect of glucose and decreased MCR . Rest and exercise MCR was fourfold lower under conditions of hypergl ycemia, but insulin-independent restoration of euglycemia improved bas al MCR threefold and normalized MCR during exercise, High FFA turnover did not affect glucose uptake but was correlated with plasma lactate concentrations (r = 0.72, P < 0.001), suggesting that muscle fuel requ irements are controlled by glucose oxidation and not uptake, We conclu de that in alloxan-diabetic dogs, the impaired MCR may be an adaptive phenomenon because correction of hyperglycemia corrects MCR despite pa rtial insulin deficiency and high FFA turnover, We speculate that cons tant glucose uptake despite hyperglycemia in diabetes may protect the muscle from excessive exposure to glucose.