Numerous epidemiological studies have related an increased risk of adult-onset cardiovascular and metabolic disease to an adverse intra-uterine environment at critical periods. We have shown that fetal sheep exposed to dexamethasone for only 2 days at 27 days of gestation (term ≈ 150 days) became hypertensive adults, whereas those exposed at 64 days of gestation remained normotensive, as did controls. In the same sheep, now nearly 5 years old, we performed glucose tolerance tests and hyperinsulinaemic euglycaemic clamps to study the insulin sensitivity of glucose, amino acid and non-esterified fatty acid metabolism. Glucose tolerance, calculated as the area under the curve, after intravenous administration of bolus glucose and insulin secretion in response to a glucose challenge were not altered in any group. There were no significant differences in the insulin sensitivity of net whole-body glucose or amino acid uptake. However, suppression of lipolysis by insulin, measured as the proportional decrease in the circulating concentration of non-esterified fatty acids during the hyperinsulinaemic clamp, was 69±1.2% at steady-state plasma insulin levels (≈ 1000 m-units/l) in the group exposed to dexamethasone at 27 days of gestation, but only 50.8±6.5% in the controls (P < 0.05). In the group exposed to dexamethasone at 64 days of gestation, the decrease was 66.4±5.1%, which did not reach significance compared with the controls (P = 0.10). Thus brief dexamethasone exposure during early gestation programmed hypertension independently of insulin resistance of glucose or amino acid metabolism; however, it did lead to increased insulin sensitivity of the inhibition of lipolysis, which may increase susceptibility to the development of obesity postnatally.
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Research Article|
April 03 2000
Differential timing for programming of glucose homoeostasis, sensitivity to insulin and blood pressure by in utero exposure to dexamethasone in sheep
Kathryn L. GATFORD;
Kathryn L. GATFORD
*Department of Physiology, University of Adelaide, Adelaide, SA 5005, Australia
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E. Marelyn WINTOUR;
E. Marelyn WINTOUR
†Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3052, Australia
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Miles J. DE BLASIO;
Miles J. DE BLASIO
*Department of Physiology, University of Adelaide, Adelaide, SA 5005, Australia
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Julie A. OWENS;
Julie A. OWENS
*Department of Physiology, University of Adelaide, Adelaide, SA 5005, Australia
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Miodrag DODIC
†Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria 3052, Australia
Correspondence: Dr Miodrag Dodic (e-mail m.dodic@hfi.unimelb.edu.au).
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Publisher: Portland Press Ltd
Received:
July 15 1999
Revision Received:
November 19 1999
Accepted:
January 13 2000
Online ISSN: 1470-8736
Print ISSN: 0143-5221
The Biochemical Society and the Medical Research Society © 2000
2000
Clin Sci (Lond) (2000) 98 (5): 553–560.
Article history
Received:
July 15 1999
Revision Received:
November 19 1999
Accepted:
January 13 2000
Citation
Kathryn L. GATFORD, E. Marelyn WINTOUR, Miles J. DE BLASIO, Julie A. OWENS, Miodrag DODIC; Differential timing for programming of glucose homoeostasis, sensitivity to insulin and blood pressure by in utero exposure to dexamethasone in sheep. Clin Sci (Lond) 1 May 2000; 98 (5): 553–560. doi: https://doi.org/10.1042/cs0980553
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