Maternal exposure to dexamethasone or cortisol in early pregnancy differentially alters insulin secretion and glucose homeostasis in adult male sheep offspring
| Autor: | Miodrag Dodic, E. M. Wintour, Karen M. Moritz, M. J. De Blasio, Julie A. Owens, Andrew J. Jefferies |
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| Rok vydání: | 2007 |
| Předmět: |
Blood Glucose
Male medicine.medical_specialty Hydrocortisone Physiology Offspring Endocrinology Diabetes and Metabolism medicine.medical_treatment Gestational Age Carbohydrate metabolism Biology Dexamethasone Pregnancy Physiology (medical) Internal medicine Insulin Secretion medicine Animals Birth Weight Homeostasis Insulin Glucose homeostasis Sheep medicine.disease Glucose Endocrinology Maternal Exposure Prenatal Exposure Delayed Effects Drug Evaluation Pregnancy Animal Female Growth and Development Glucocorticoid medicine.drug |
| Zdroj: | American Journal of Physiology-Endocrinology and Metabolism. 293:E75-E82 |
| ISSN: | 1522-1555 0193-1849 |
| DOI: | 10.1152/ajpendo.00689.2006 |
| Popis: | An adverse intrauterine environment increases the risk of developing various adult-onset diseases, whose nature varies with the timing of exposure. Maternal undernutrition in humans can increase adiposity, and the risk of coronary heart disease and impaired glucose tolerance in adult life, which may be partly mediated by maternal or fetal endocrine stress responses. In sheep, dexamethasone in early pregnancy impairs cardiovascular function, but not glucose homeostasis in adult female offspring. However, male offspring are often more susceptible to early life “programming”. Pregnant sheep were infused intravenously with saline (0.19 ml/h), dexamethasone (0.48 mg/h), or cortisol (5 mg/h), for 2 days from 26 to 28 days of gestation. In male offspring, size at birth and postnatal growth were measured, and glucose tolerance [intravenous glucose tolerance test (IVGTT)], insulin secretion, and insulin sensitivity of glucose, α-amino nitrogen, and free fatty acid metabolism were assessed at 4 yr of age. We show that cortisol, but not dexamethasone, treatment of mothers causes fasting hyperglycemia in adult male offspring. Maternal cortisol induced a second-phase hyperinsulinemia during IVGTT, whereas maternal dexamethasone induced a first-phase hyperinsulinemia. Dexamethasone improved glucose tolerance, while cortisol had no impact, and neither affected insulin sensitivity. This suggests that maternal glucocorticoid exposure in early pregnancy alters glucose homeostasis and induces hyperinsulinemia in adult male offspring, but in a glucocorticoid-specific manner. These consequences of glucocorticoid exposure in early pregnancy may lead to pancreatic exhaustion and diabetes longer term and are consistent with stress during early pregnancy contributing to such outcomes in humans. |
| Databáze: | OpenAIRE |
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