Interaction of decreased arterial po2 and exercise on carbohydrate
metabolism in the dog.
Zinker, Bradley A., Robert D. Wilson, and David H. Wasserman.
Department of Molecular Physiology and Biophysics and Diabetes
Research and Training Center, Vanderbilt University School of
Medicine, Nashville, TN 37232-0615
APStracts 2:0059E, 1995.
The aim of these studies was to determine the mechanism by which low
arterial PO2 (PaO2) affects muscle carbohydrate (CHO) metabolism
during exercise. Chronically catheterized dogs were fit with a mask
allowing control of the fraction of inspired oxygen (FIO2). Dogs
inhaled gas consisting of 0.21 (NO; n=6) or 0.11 (LO; n=6) FIO2
during rest and 150 min of moderate treadmill exercise. Limb
arteriovenous difference and isotopic (3H- and 14C-glucose) methods
were used to assess muscle carbohydrate metabolism and
glycogenolysis. PaO2 was reduced by 50% in LO vs NO but limb O2
uptake was similar. Glucose disappearance was increased during rest
(13+/-2 vs 19+/-1 [mu]mol/kg-min) and exercise (23+/-4 vs 36+/-6
[mu]mol/kg-min at 150 min) in LO vs NO, but arterial glucose was
unchanged since hepatic glucose production was increased similarly.
Limb glucose and pyruvate oxidation (derived from vein 14C-lactate
specific activity) rates were elevated 2-fold during rest and
exercise in LO vs NO, while non-oxidative glucose metabolism was
unaffected. Estimated limb glycogenolysis increased at rest (21+/-9
vs 96+/-23 [mu]mol/min) and during exercise (70+/-21 vs 184+/-41
[mu]mol/min at 150 min) in LO vs NO. The % CO2 and % lactate from
glucose in LO were 2-fold the values in NO in rest and exercise. The
% CO2 from pyruvate was greater and FFA levels were lower, suggesting
reduced fat metabolism in LO. Arterial lactate and pyruvate levels
were elevated during rest and the initial 30 min of exercise in LO,
even though net limb outputs were no greater. Arterial and venous
lactate to pyruvate ratios and pH were similar in LO vs NO during
exercise. In conclusion, a reduction in FIO2 from 0.21 to 0.11 causes
a shift in the metabolism of the working limb so that both glucose
and total CHO oxidation are greater and fat metabolism is reduced. In
contrast to the added stimulation of CHO oxidation, non-oxidative
processes are unaffected. The greater demand for CHO is satisfied by
an increased release of glucose from the liver and mobilization of
intramuscular glycogen. These adaptations in muscle metabolism occur
without evidence of local tissue oxygen insufficiency.
Received 2 August 1994; accepted in final form 24 March 1995.
APS Manuscript Number E304-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 4 April 1995.