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Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats.

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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https://www.hal.inserm.fr/inserm-00379890
Contributor : Pascale Perret <>
Submitted on : Thursday, September 10, 2009 - 4:31:17 PM
Last modification on : Friday, July 26, 2019 - 3:22:31 PM
Long-term archiving on: : Thursday, June 10, 2010 - 7:09:00 PM

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Esben Buhl, Susanne Neschen, Shin Yonemitsu, Joerg Rossbacher, Dongyan Zhang, et al.. Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats.. AJP - Endocrinology and Metabolism, American Physiological Society, 2007, 293 (5), pp.E1451-8. ⟨10.1152/ajpendo.00356.2007⟩. ⟨inserm-00379890⟩

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