Contribution of increased pancreatic hormone responses to the
acceleration in carbohydrate metabolism with decreased pao2.
Zinker, Bradley A., Robert 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 2:0026E, 1995.
Reduced O2 availability, such as might occur under some physiologic
and pathologic conditions, stimulates the release of insulin and
glucagon and increases glucose fluxes and muscle carbohydrate
metabolism. The aim of the present study was to determine the role of
reduced PO2, independent of changes in glucagon and insulin. Six dogs
were investigated in paired studies that were randomized in order and
separated by 2 wks. Glucagon and insulin levels were fixed throughout
by infusing somatostatin with basal intraportal glucagon and insulin
replacement. The studies consisted of a control period followed by 90
min of breathing either 21% (NO) or 8% (LO) O2. Isotopic (3H- and
14C-glucose) and arteriovenous (hepatic and hindlimb) methods were
used to assess carbohydrate metabolism. Measured variables were
constant over time in NO. Arterial PO2 was 100 mmHg in NO and
reduced to 30 mmHg in LO, resulting in a 50% fall in O2 content.
Insulin, glucagon, and catecholamine levels were similar in NO vs LO.
Cortisol was significantly increased in LO (200%). Arterial glucose
was unchanged in both groups. Results below reflect values from the
last 45 min of the experimental period in LO. Glucose production
(14+/-1 to 18+/-1 [mu]mol/kg-min), glucose disappearance (15+/-1 to17+/-1
[mu]mol/kg-min), and net hepatic glucose output (11+/-1 to 15+/-1 [mu]mol/kg
-min) rose in LO. Limb pyruvate oxidation (2.9+/-0.8 to 4.7+/-1.1
[mu]mol/min) and estimated glycogenolysis (9+/-3 to 42+/-9 [mu]mol/min)
increased. The percentages of CO2 from limb pyruvate and glucose
increased in LO, while the percentage of lactate from blood glucose
decreased. Arterial blood lactate was 100% more in LO, even though
net limb and hepatic lactate balances were unaltered. This suggests
that neither liver or muscle is the source of the increased blood
lactate. Comparison of these results with our previous study (Zinker
et al. Am. J. Physiol. 29(6): E921, 1994) shows that the response to
reduced PaO2, though present, is reduced when the glucagon and
insulin levels are fixed at basal. The majority of the stimulation of
glucose production by decreased PaO2 is still present when the
pancreatic hormones are clamped at basal, while the response by the
tissues of the hindlimb is greatly reduced.
Received 21 October 1994; accepted in final form 30 January 1995.
APS Manuscript Number E435-4.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 25 February 1995.