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Long-term disruption of maternal glucose homeostasis induced by prenatal glucocorticoid treatment correlates with miR-29 upregulation.
MedLine Citation:
PMID:  24253049     Owner:  NLM     Status:  Publisher    
Excess of glucocorticoids (GCs) during pregnancy is strongly associated with the programming of glucose intolerance in the offspring. However, the impact of high GCs levels on maternal metabolism is not clearly documented. This study aimed to test the hypothesis that mothers exposed to elevated levels of GCs might also display long-term disturbances in glucose homeostasis. Dexamethasone (DEX) was administered noninvasively to the mothers via drinking water between the 14th and the 19th days of pregnancy. Mothers were subjected to glucose and insulin tolerance tests at 1, 2, 3, 6 and 12 months post-weaning. Pregnant rats not treated with DEX and age-matched virgin rats were used as control. Pancreatic islets were isolated at the 20th day of pregnancy and 12 months post-weaning in order to evaluate glucose-stimulated insulin secretion. The expression of the miR-29 family was also studied due to its responsiveness to GCs and its well-documented role in the regulation of pancreatic beta cell function. Rats treated with DEX during pregnancy presented long-term glucose intolerance and impaired insulin secretion. These changes correlated with: (i) increased expression of miR-29 and its regulator p53; (ii) reduced expression of Syntaxin-1a, a direct target of miR-29; and (iii) altered expression of genes related to cellular senescence. Our data demonstrate that the use of DEX during pregnancy results in deleterious outcomes to the maternal metabolism hallmarked by reduced insulin secretion and glucose intolerance. This maternal metabolic programming might be a consequence of time-sustained upregulation of miR-29s in maternal pancreatic islets.
Patricia R Gomes; Maria F Graciano; Lucas C Pantaleao; Andre L Renno; Sandra C Rodrigues; Licio A Velloso; Marcia Q Latorraca; Angelo R Carpinelli; Gabriel F Anhe; Silvana Bordin
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-11-19
Journal Detail:
Title:  American journal of physiology. Endocrinology and metabolism     Volume:  -     ISSN:  1522-1555     ISO Abbreviation:  Am. J. Physiol. Endocrinol. Metab.     Publication Date:  2013 Nov 
Date Detail:
Created Date:  2013-11-20     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100901226     Medline TA:  Am J Physiol Endocrinol Metab     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
1Institute of Biomedical Sciences, University of Sao Paulo.
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