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Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats
| Title | Increased hypothalamic-pituitary-adrenal axis activity and hepatic insulin resistance in low-birth-weight rats |
| Publication Type | Journal Article |
| Year of Publication | 2007 |
| Authors | |
| Journal | Am J Physiol Endocrinol Metab |
| Volume | 293 |
| Issue | 5 |
| Pagination | E1451-8 |
| Date Published | Nov |
| Publication Language | eng |
| ISBN Number | 0193-1849 (Print) |
| Accession Number | 17895287 |
| Key Words | Receptors, Rats, Insulin/blood, Female, Animals, Newborn, Triglycerides/blood, Reverse Transcriptase Polymerase Chain Reaction, Restraint, Physical/physiology, Glucocorticoid/genetics/metabolism, Sprague-Dawley, 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, Hypothalamo-Hypophyseal System/*metabolism, Glucose/metabolism, Fasting/blood, Corticosterone/blood/urine, Cholesterol/blood, Adrenocorticotropic Hormone/blood |
| 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. |
| Notes | 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 |
| URL | http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&dopt=Citation&list_uids=17895287 |
| Citation Key | 307 |
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- Adrenocorticotropic Hormone/blood
- Animals
- Animals, Newborn
- Cholesterol/blood
- Corticosterone/blood/urine
- Fasting/blood
- Female
- Glucose/metabolism
- Hypothalamo-Hypophyseal System/*metabolism
- Insulin Resistance/*physiology
- Insulin-Like Growth Factor Binding Protein 1/genetics/metabolism
- Insulin-Like Growth Factor I/genetics/metabolism
- Insulin/blood
- Liver/enzymology/*metabolism
- Phosphoenolpyruvate Carboxykinase (ATP)/genetics/metabolism
- Pituitary-Adrenal System/*metabolism
- Pregnancy
- Random Allocation
- Rats
- Rats, Sprague-Dawley
- Receptors, Glucocorticoid/genetics/metabolism
- Restraint, Physical/physiology
- Reverse Transcriptase Polymerase Chain Reaction
- Triglycerides/blood