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1-adrenergic blockade reduces insulin
sensitivity
1 Geriatric Research, Education and Clinical Center, Veterans Affairs Health Care System, and 2 Department of Endocrinology, Gerontology, and Metabolism, Stanford University School of Medicine, Palo Alto, California 94304; 3 Thermal and Mountain Division, US Army Research Institute of Environmental Medicine, Natick, Massachusetts 01460; 4 Womens Health Research, University of Colorado Health Sciences Center, Denver 80262; and 5 Department of Kinesiology and Applied Physiology, University of Colorado, Boulder, Colorado 80309
After short-term exposure to high
altitude (HA), men appear to be less sensitive to insulin than at sea
level (SL). We hypothesized that the same would be true in
women, that reduced insulin sensitivity would be directly related to
the rise in plasma epinephrine concentrations at altitude, and that the
addition of 
-adrenergic blockade would potentiate the reduction. To
test the hypotheses, 12 women consumed a high-carbohydrate meal at SL
and after 16 h at simulated 4,300-m elevation (HA). Subjects were
studied twice at each elevation: once with prazosin (Prz), an
1-adrenergic antagonist, and once with placebo (Pla).
Mathematical models were used to assess insulin resistance based on
fasting [homeostasis model assessment of insulin resistance
(HOMA-IR)] and postprandial [composite model insulin sensitivity
index (C-ISI)] glucose and insulin concentrations. Relative to SL-Pla
(HOMA-IR: 1.86 ± 0.35), insulin resistance was greater in HA-Pla
(3.00 ± 0.45; P < 0.05), SL-Prz (3.46 ± 0.51; P < 0.01), and HA-Prz (2.82 ± 0.43;
P < 0.05). Insulin sensitivity was reduced in
HA-Pla (C-ISI: 4.41 ± 1.03; P < 0.01), SL-Prz
(5.73 ± 1.01; P < 0.05), and HA-Prz (4.18 ± 0.99; P < 0.01) relative to SL-Pla (8.02 ± 0.92). Plasma epinephrine was significantly elevated in HA-Pla
(0.57 ± 0.08 ng/ml; P < 0.01), SL-Prz (0.42 ± 0.07; P < 0.05), and HA-Prz (0.82 ± 0.07;
P < 0.01) relative to SL-Pla (0.28 ± 0.04), but
correlations with HOMA-IR, HOMA-
-cell function, and C-ISI were weak.
In women, short-term exposure to simulated HA reduced insulin
sensitivity compared with SL. The change does not appear to be directly
mediated by a concurrent rise in plasma epinephrine concentrations.
homeostatic model; glucose tolerance; insulin resistance; epinephrine; prazosin
Deceased December 27, 1999
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