In:
American Journal of Physiology-Endocrinology and Metabolism, American Physiological Society, Vol. 298, No. 5 ( 2010-05), p. E920-E929
Abstract:
Low birth weight (LBW) is associated with type 2 diabetes and depression, which may be related to prenatal stress and insulin resistance as a result of chronic hypothalamic-pituitary-adrenal (HPA) axis hyperactivity. We examined whether treatment with a selective serotonin reuptake inhibitor [escitalopram (ESC)] could downregulate HPA axis activity and restore insulin sensitivity in LBW rats. After 4–5 wk of treatment, ESC-exposed LBW (SSRI-LBW) and saline-treated control and LBW rats (Cx and LBW) underwent an oral glucose tolerance test or a hyperinsulinemic euglycemic clamp to assess whole body insulin sensitivity. Hepatic phospho enolpyruvate carboxykinase (PEPCK) mRNA expression and red skeletal muscle PKB Ser 473 phosphorylation were used to assess tissue-specific insulin sensitivity. mRNA expression of the hypothalamic mineralocorticoid receptor was fivefold upregulated in LBW ( P 〈 0.05 vs. Cx), accompanied by increased corticosterone release during restraint stress and total 24-h urinary excretion ( P 〈 0.05 vs. Cx), whole body insulin resistance ( P 〈 0.001 vs. Cx), and impaired insulin suppression of hepatic PEPCK mRNA expression ( P 〈 0.05 vs. Cx). Additionally, there was a tendency for reduced red muscle PKB Ser 473 phosphorylation. The ESC treatment normalized corticosterone secretion ( P 〈 0.05 vs. LBW), whole body insulin sensitivity ( P 〈 0.01) as well as postprandial suppression of hepatic mRNA PEPCK expression ( P 〈 0.05), and red muscle PKB Ser 473 phosphorylation ( P 〈 0.01 vs. LBW). We conclude that these data suggest that the insulin resistance and chronic HPA axis hyperactivity in LBW rats can be reversed by treatment with an ESC, which downregulates HPA axis activity, lowers glucocorticoid exposure, and restores insulin sensitivity in LBW rats.
Type of Medium:
Online Resource
ISSN:
0193-1849
,
1522-1555
DOI:
10.1152/ajpendo.00606.2009
Language:
English
Publisher:
American Physiological Society
Publication Date:
2010
detail.hit.zdb_id:
1477331-4
detail.hit.zdb_id:
603841-4
SSG:
12
