Document Detail


Genetic evidence of the programming of beta cell mass and function by glucocorticoids in mice.
MedLine Citation:
PMID:  20857084     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
AIMS/HYPOTHESIS: Prenatal exposure to excess glucocorticoids associates with low birthweight in rodents, primates and humans and its involvement in programming glucose homeostasis is suspected. Our aim was to further dissect the role of glucocorticoids on beta cell development and function in mice.
METHODS: Using the model of maternal general food restriction during the last week of pregnancy, we thoroughly studied in the CD1 mouse-mothers and fetal and adult offspring-the pancreatic, metabolic and molecular consequences of maternal undernutrition associated with excess glucocorticoids. The specific involvement of the glucocorticoid receptor (GR) was studied in mutant fetuses lacking GR in pancreatic precursors or mature beta cells.
RESULTS: Maternal general food restriction in the mouse is associated with decreased maternal glucose and increased corticosterone levels. Fetuses from underfed dams had increased corticosterone levels, decreased pancreatic endocrine gene expression but increased exocrine gene expression and a lower beta cell mass. The offspring of these dams had a low birthweight, permanent postnatal growth retardation and, as adults, impaired glucose tolerance, decreased beta cell mass (-50%) and massively reduced islet expression (-80%) of most of the genes involved in beta cell function (e.g. Pdx1, Sur1 [also known as Abcc8], insulin). Moreover, using mutant fetuses lacking GR in pancreatic precursors or beta cells we show that the deleterious effect of undernutrition on fetal beta cell development requires the presence of the GR in pancreatic precursor cells.
CONCLUSIONS/INTERPRETATION: These results demonstrate the crucial role of excess fetal glucocorticoids and the importance of GR signalling in progenitor cells to programme beta cell mass and dysfunction.
Authors:
B Valtat; C Dupuis; D Zenaty; A Singh-Estivalet; F Tronche; B Bréant; B Blondeau
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Publication Detail:
Type:  Journal Article     Date:  2010-09-21
Journal Detail:
Title:  Diabetologia     Volume:  54     ISSN:  1432-0428     ISO Abbreviation:  Diabetologia     Publication Date:  2011 Feb 
Date Detail:
Created Date:  2011-01-07     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0006777     Medline TA:  Diabetologia     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  350-9     Citation Subset:  IM    
Affiliation:
INSERM UMR-S 872, Centre de Recherche des Cordeliers, 15 rue de l'Ecole de Médecine, 75006, Paris, France.
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Comment In:
Diabetologia. 2011 Feb;54(2):223-6   [PMID:  21072627 ]

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