title: 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.
authors: Department of Pharmacology, Faculty of Health Sciences, Medical Department M, University of Aarhus, Aarhus, Denmark.
authors: Esben S
authors: ES
authors: Buhl
authors: Susanne
authors: S
authors: Neschen
authors: Shin
authors: S
authors: Yonemitsu
authors: Joerg
authors: J
authors: Rossbacher
authors: Dongyan
authors: D
authors: Zhang
authors: Katsutaro
authors: K
authors: Morino
authors: Allan
authors: A
authors: Flyvbjerg
authors: Pascale
authors: P
authors: Perret
authors: Varman
authors: V
authors: Samuel
authors: Jung
authors: J
authors: Kim
authors: Gary W
authors: GW
authors: Cline
authors: Kitt Falk
authors: KF
authors: Petersen
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000818:Animals; D000831:Animals, Newborn; D002784:Cholesterol / Q000097:blood; D003345:Corticosterone / Q000097:blood / Q000652:urine; D005215:Fasting / Q000097:blood; D005260:Female; D005947:Glucose / Q000378:metabolism; D007030:Hypothalamo-Hypophyseal System / Q000378:metabolism*; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology*; D018970:Insulin-Like Growth Factor Binding Protein 1 / Q000235:genetics / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000235:genetics / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000378:metabolism*; D019764:Phosphoenolpyruvate Carboxykinase (ATP) / Q000235:genetics / Q000378:metabolism; D010913:Pituitary-Adrenal System / Q000378:metabolism*; D011247:Pregnancy; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011965:Receptors, Glucocorticoid / Q000235:genetics / Q000378:metabolism; D012149:Restraint, Physical / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000097:blood
chemical_list: D007328:Insulin; D018970:Insulin-Like Growth Factor Binding Protein 1; D011965:Receptors, Glucocorticoid; D014280:Triglycerides; D007334:Insulin-Like Growth Factor I; D000324:Adrenocorticotropic Hormone; D002784:Cholesterol; D019764:Phosphoenolpyruvate Carboxykinase (ATP); D005947:Glucose; D003345:Corticosterone