Chromatin Switching and Gene Dynamics Associated with Type 2 Diabetes

摘要: Type 2 diabetes (T2DM) is a chronic disease with rapidly increasing global burden. An early event in the deregulation of glycaemic control resulting periods hyperglycaemia. Large-scale clinical studies have shown that complications from this hyperglycaemia can be manifest long after has been restored (UKPDS, Intensive blood-glucose sulphonylureas or insulin compared conventional treatment and risk patients type (UKPDS 33) UK Prospective Diabetes Study (UKPDS) Group. Lancet 352:837–852, 1998; Chalmers J, Cooper ME, UKPDS legacy effect. N Engl J Med 359:1618–1620, 2008), phenomenon known as “legacy effect” (Holman RR et al., 10-year follow-up intensive glucose diabetes. 359:1577–1589, 2008). Such continued development cardiovascular complications, which result prior exposure to hyperglycaemia, led proposal “metabolic memory” (Cooper Metabolic memory: implications for diabetic vascular complications. Pediatr 10:343–346, 2009). hypothesis suggests transient results persistent changes gene expression are not reversed merely by restoring control. Support early, came Control Complications Trial (DCCT) revealed sustained benefits better outcomes 2009), it recently proposed minimising paramount (Aizawa T, Funase Y, Intervention at very stage Diabetologia 54:703–704; author reply 707–708, 2011). Currently, most attractive potential mechanism responsible epigenetic, manifested DNA methylation and/or posttranslational modifications on histones. Over last decade, numerous identified correlations specific epigenetic marks diabetes, more mechanisms these lead alterations levels interrogated.