Diabetes, Vol 46, Issue 11 1805-1812, Copyright © 1997 by American Diabetes Association
Insulin-independent acute restoration of euglycemia normalizes the impaired glucose clearance during exercise in diabetic dogs
SJ Fisher, M Lekas, ZQ Shi, D Bilinski, G Carvalho, A Giacca and M Vranic
Department of Physiology, Faculty of Medicine, University of Toronto, Ontario, Canada.
At rest and during exercise, chronic hyperglycemia, high free fatty acid
(FFA) oxidation, and insulin deficiency in diabetes are well known to
impair glucose clearance (metabolic clearance rate [MCR]). The effect of
acute restoration of glycemia per se on MCR has been less well
characterized. We therefore studied normal and alloxan-diabetic dogs both
at rest and during exercise, as diabetic hyperglycemic or after acutely
induced euglycemia (<160 min) generated by infusion of either insulin 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 hyperglycemia, but
insulin-independent restoration of euglycemia improved basal 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 requirements are
controlled by glucose oxidation and not uptake. We conclude that in
alloxan-diabetic dogs, the impaired MCR may be an adaptive phenomenon
because correction of hyperglycemia corrects MCR despite partial insulin
deficiency and high FFA turnover. We speculate that constant glucose uptake
despite hyperglycemia in diabetes may protect the muscle from excessive
exposure to glucose.