AJP - Endocrinology and Metabolism, Vol 268, Issue 6 E1174-E1183, Copyright © 1995 by American Physiological Society
Contribution of pancreatic hormone responses to the elevation in carbohydrate metabolism with reduced PaO2
B. A. Zinker, R. Wilson and D. H. Wasserman
Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232-0615, USA.
Reduced O2 availability, as might occur under some physiological and
pathological conditions, stimulates insulin and glucagon release and
increases glucose fluxes and muscle carbohydrate metabolism. The aim of
this study was to determine the role of reduced PO2, independent of changes
in glucagon and insulin. In six dogs, in paired studies separated by 2 wk,
glucagon and insulin levels were fixed throughout by infusion of
somatostatin with basal intraportal glucagon and insulin replacement. A
control period was followed by 90 min of breathing 21% (NO) or 8% (LO) O2.
Isotopic and arteriovenous methods were used to assess carbohydrate
metabolism. Measured variables were constant over time in NO. Arterial PO2
(Pao2) was approximately 100 mmHg in NO and approximately 30 mmHg in LO,
resulting in a 50% fall in O2 content. Insulin, glucagon, and catecholamine
levels were similar in NO and LO. Cortisol was significantly increased in
LO. Arterial glucose was unchanged in both groups. In the last 45 min of
the experimental period in LO, 1) glucose production (14 +/- 1 to 18 +/- 1
mumol.kg-1.min-1), glucose disappearance (15 +/- 1 to 17 +/- 1
mumol.kg-1.min-1), and net hepatic glucose output (11 +/- 1 to 15 +/- 1
mumol.kg-1.min-1) rose, 2) limb pyruvate oxidation (11 +/- 2 to 24 +/- 5
mumol/min) and estimated glycogenolysis (9 +/- 3 to 42 +/- 9 mumol/min)
increased, 3) percentages of CO2 from limb pyruvate and glucose increased,
and percentage of lactate from blood glucose decreased, and 4) arterial
blood lactate was approximately 100% more, although net limb and hepatic
lactate balances were unaltered, which suggests that neither liver nor
muscle is the source of increased blood lactate. Comparison of these
results with our previous study [Zinker et al. Am. J. Physiol. 266
(Endocrinol. Metab. 29): E921-E929, 1994] shows that the response to
reduced PaO2, although present, is reduced when glucagon and insulin levels
are fixed at basal. The majority of stimulation of glucose production by
decreased PaO2 is still present when pancreatic hormones are clamped at
basal, while the response by the hindlimb tissues is greatly reduced.
