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Gestational chronic intermittent hypoxia alters glucose homeostasis in rat male offspring (1072.3)
Author(s) -
Iqbal Waseem,
Hardy Daniel,
Ciriello John
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.1072.3
Subject(s) - endocrinology , medicine , offspring , gluconeogenesis , glucose homeostasis , biology , phosphoenolpyruvate carboxykinase , glucocorticoid , gestation , fetus , glucocorticoid receptor , pregnancy , insulin resistance , insulin , metabolism , enzyme , biochemistry , genetics
We have shown that exposure to chronic intermittent hypoxia (CIH) during pregnancy results in offspring with increased fat deposition that are hyperglycemic, hyperinsulinemic, and have impaired early‐stage glucose tolerance in adulthood, but the underlying mechanisms are unknown. This study was done to examine changes in the glucoregulatory function of the liver as a result of CIH exposure during gestational development. Female Sprague‐Dawley rats were mated and exposed daily to CIH throughout gestation. Offspring were sacrificed at postnatal day‐1 or 6‐wks of age to determine immediate and long‐term changes in liver function. By 6 wks of age, male CIH offspring had higher plasma corticosterone concomitant with higher liver protein expression of 11β‐hydroxysteroid dehydrogenase type I and glucocorticoid receptor (GR). These were associated with lower liver X receptor (LXR) protein expression. Analysis of GR and LXR‐direct target genes in gluconeogenesis showed that glucose‐6‐phosphatase expression was higher in CIH offspring, while no changes in phosphoenolpyruvate carboxykinase protein levels were observed. Taken together, these data suggest that gestational exposure to CIH results in long‐term alteration of hepatic glucose homeostasis via increased glucocorticoid signaling and decreased regulation of gluconeogenic enzymes by LXR. Supported by HSF of Ontario and CIHR. Grant Funding Source : Heart and Stroke Foundation of Ontario and Canadian Institutes of Health Research