Developmental origins of adult disease.
Intrauterine growth retardation (IUGR) has been linked to development of type 2 diabetes in adulthood. Using a rat model, we tested the hypothesis that uteroplacental insufficiency disrupts the function of the electron transport chain in the fetal beta-cell and leads to a debilitating cascade of events. The net result is progressive loss of beta-cell function and eventual development of type 2 diabetes in the adult. Studies in the IUGR rat demonstrate that an abnormal intrauterine environment induces epigenetic modifications of key genes regulating beta-cell development; experiments directly link chromatin remodeling with suppression of transcription. Future research will be directed at elucidating the mechanisms underlying epigenetic modifications in offspring.
Simmons
Rebecca A
RA
Department of Pediatrics, Children's Hospital, Philadelphia, PA, USA. rsimmons@mail.med.upenn.edu
D000328:Adult; D000818:Animals; D001402:B-Lymphocytes / Q000502:physiology*; D001724:Birth Weight / Q000502:physiology; D042002:Chromatin Assembly and Disassembly; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D004195:Disease Models, Animal; D044127:Epigenesis, Genetic; D005260:Female; D005317:Fetal Growth Retardation / Q000235:genetics* / Q000276:immunology; D015870:Gene Expression; D006801:Humans; D050417:Insulin-Secreting Cells / Q000473:pathology*; D008297:Male; D008928:Mitochondria / Q000502:physiology; D018384:Oxidative Stress; D051381:Rats