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Differential timing for programming of glucose homoeostasis, sensitivity to insulin and blood pressure by in utero exposure to dexamethasone in sheep
journal contribution
posted on 2000-05-01, 00:00 authored by K L Gatford, E M Wintour, M J De Blasio, Julie OwensJulie Owens, M DodicNumerous 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 approximately 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 ( approximately 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.
History
Journal
Clinical scienceVolume
98Issue
5Pagination
553 - 560Publisher
Portland PressLocation
London, Eng.Publisher DOI
ISSN
0143-5221Language
engPublication classification
C1.1 Refereed article in a scholarly journalCopyright notice
2000, The Biochemical Society and the Medical Research SocietyUsage metrics
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No categories selectedKeywords
Amino AcidsAnimalsBlood GlucoseDexamethasoneFemaleGestational AgeGlucocorticoidsGlucose Tolerance TestHomeostasisHypertensionInsulin ResistanceMaternal-Fetal ExchangePregnancyPrenatal Exposure Delayed EffectsSheepScience & TechnologyLife Sciences & BiomedicineMedicine, Research & ExperimentalResearch & Experimental MedicineinsulinLOW-PROTEIN DIETSPRENATAL EXPOSURE11-BETA-HYDROXYSTEROID DEHYDROGENASEGLUCOCORTICOID EXPOSUREBIRTH-WEIGHTIN-UTERORATSDISEASEMALNUTRITION
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