Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats |
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Authors: | Buhl Esben S Neschen Susanne Yonemitsu Shin Rossbacher Joerg Zhang Dongyan Morino Katsutaro Flyvbjerg Allan Perret Pascale Samuel Varman Kim Jung Cline Gary W Petersen Kitt Falk |
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Institution: | Department of Pharmacology, Faculty of Health Sciences, Medical Department M, University of Aarhus, Aarhus, Denmark. |
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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. |
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