Abstract
Individuals born with a low birth weight (LBW) have an increased prevalence of type 2 diabetes, but the mechanisms responsible for this association are unknown. Given the important role of insulin resistance in the pathogenesis of type 2 diabetes, we examined insulin sensitivity in a rat model of LBW due to intrauterine fetal stress. During the last 7 days of gestation, rat dams were treated with dexamethasone and insulin sensitivity was assessed in the LBW offspring by a hyperinsulinemic euglycemic clamp. The LBW group had liver-specific insulin resistance associated with increased levels of PEPCK expression. These changes were associated with pituitary hyperplasia of the ACTH-secreting cells, increased morning plasma ACTH concentrations, elevated corticosterone secretion during restraint stress, and an approximately 70% increase in 24-h urine corticosterone excretion. These data support the hypothesis that prenatal stress can result in chronic hyperactivity of the hypothalamic-pituitary-adrenal axis, resulting in increased plasma corticosterone concentrations, upregulation of hepatic gluconeogenesis, and hepatic insulin resistance.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adrenocorticotropic Hormone / blood
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Animals
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Animals, Newborn
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Cholesterol / blood
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Corticosterone / blood
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Corticosterone / urine
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Fasting / blood
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Female
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Glucose / metabolism
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Hypothalamo-Hypophyseal System / metabolism*
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Insulin / blood
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Insulin Resistance / physiology*
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Insulin-Like Growth Factor Binding Protein 1 / genetics
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Insulin-Like Growth Factor Binding Protein 1 / metabolism
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Insulin-Like Growth Factor I / genetics
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Insulin-Like Growth Factor I / metabolism
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Liver / enzymology
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Liver / metabolism*
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Phosphoenolpyruvate Carboxykinase (ATP) / genetics
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Phosphoenolpyruvate Carboxykinase (ATP) / metabolism
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Pituitary-Adrenal System / metabolism*
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Pregnancy
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Random Allocation
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Rats
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Rats, Sprague-Dawley
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Receptors, Glucocorticoid / genetics
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Receptors, Glucocorticoid / metabolism
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Restraint, Physical / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Triglycerides / blood
Substances
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Insulin
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Insulin-Like Growth Factor Binding Protein 1
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Receptors, Glucocorticoid
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Triglycerides
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Insulin-Like Growth Factor I
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Adrenocorticotropic Hormone
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Cholesterol
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Phosphoenolpyruvate Carboxykinase (ATP)
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Glucose
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Corticosterone