Developmental origins of diabetes: the role of epigenetic mechanisms

Abstract

Purpose of review: Intrauterine growth retardation has been linked to later development of type 2 diabetes. An abnormal intrauterine milieu affects the development of the fetus by permanently modifying gene expression of susceptible cells. Altered gene expression persists after birth suggesting that an epigenetic mechanism may be responsible for changes in transcription. The purpose of this article is to review basic epigenetic mechanisms and familiarize the reader with the latest research linking epigenetics, fetal programming, and the development of type 2 diabetes.

Recent findings: Intrauterine growth retardation causes hypomethylation and hyperacetylation of genomic DNA in brain and liver of rats. These findings are associated with zinc deficiency that often accompanies fetal growth retardation. Studies in the intrauterine growth retardation rat demonstrate that an abnormal intrauterine environment induces epigenetic modifications of key genes regulating beta-cell development and experiments directly link chromatin remodeling to suppression of transcription. Dietary protein restriction of pregnant rats induces hypomethylation of the glucocorticoid receptor and peroxisome proliferator-activated receptor gamma genes in liver of the offspring. It is postulated that these epigenetic changes result in the observed increase in expression of these genes.

Summary: Future research will be directed at elucidating the mechanisms underlying epigenetic modifications in offspring.