Epigenetic mechanisms in the development of type 2 diabetes.
Type 2 diabetes (T2D) is a disorder of complex genetics influenced by interactions between susceptible genetic loci and environmental perturbations. Intrauterine growth retardation is one such environmental perturbation linked to the development of T2D in adulthood. An abnormal metabolic intrauterine milieu affects fetal development by permanently modifying expression of key genes regulating beta-cell development (Pdx1) and glucose transport (Glut4) in muscle. Epigenetic regulation of gene expression is one mechanism by which genetic susceptibility and environmental insults can lead to T2D. Therefore, therapeutic agents targeting epigenetic gene regulation can ultimately be used to treat T2D; however, there is much to be learned about genome-wide epigenetic programming of health and disease before these therapies can be used in patient care.
Pinney
Sara E
SE
Department of Pediatrics, The Children's Hospital Philadelphia, Philadelphia, PA 19104, USA.
Simmons
Rebecca A
RA
D042002:Chromatin Assembly and Disassembly / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000235:genetics*; D044127:Epigenesis, Genetic; D005317:Fetal Growth Retardation / Q000235:genetics; D005786:Gene Expression Regulation; D051275:Glucose Transporter Type 4 / Q000235:genetics; D006657:Histones / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D018384:Oxidative Stress; D015534:Trans-Activators / Q000235:genetics
D051275:Glucose Transporter Type 4; D006657:Histones; D018398:Homeodomain Proteins; C495692:SLC2A4 protein, human; D015534:Trans-Activators; C084010:pancreatic and duodenal homeobox 1 protein