31 Buhl, E. S. Neschen, S. Yonemitsu, S. Rossbacher, J. Zhang, D. Morino, K. Flyvbjerg, A. Perret, P. Samuel, V. Kim, J. Cline, G. W. Petersen, K. F. 2007 Am J Physiol Endocrinol Metab 293 5 E1451-8 Nov 0193-1849 (Print) 17895287 Triglycerides/blood Reverse Transcriptase Polymerase Chain Reaction Restraint, Physical/physiology Receptors, Glucocorticoid/genetics/metabolism Rats, Sprague-Dawley Rats Random Allocation Pregnancy Pituitary-Adrenal System/*metabolism Phosphoenolpyruvate Carboxykinase (ATP)/genetics/metabolism Liver/enzymology/*metabolism Insulin-Like Growth Factor I/genetics/metabolism Insulin-Like Growth Factor Binding Protein 1/genetics/metabolism Insulin Resistance/*physiology Insulin/blood Hypothalamo-Hypophyseal System/*metabolism Glucose/metabolism Female Fasting/blood Corticosterone/blood/urine Cholesterol/blood Animals, Newborn Animals Adrenocorticotropic Hormone/blood Receptors Newborn Restraint Physical/physiology Glucocorticoid/genetics/metabolism Sprague-Dawley 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. P01 DK068229/DK/NIDDK NIH HHS/United StatesP30 DK45735/DK/NIDDK NIH HHS/United StatesR01 AG23686/AG/NIA NIH HHS/United StatesR01 DK40936/DK/NIDDK NIH HHS/United StatesJournal ArticleResearch Support, N.I.H., ExtramuralResearch Support, Non-U.S. Gov'tUnited States http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17895287