Villeneuve Louisa M, Natarajan Rama
Division of Diabetes, Beckman Research Institute of City of Hope, 1500 E. Duarte Road, Duarte, CA-91010, USA.
Expert Rev Endocrinol Metab. 2010 Jan;5(1):137-148. doi: 10.1586/eem.09.54.
Type 1 and Type 2 diabetes are complex diseases associated with multiple complications, and both genetic and environmental factors have been implicated in these pathologies. While numerous studies have provided a wealth of knowledge regarding the genetics of diabetes, the mechanistic pathways leading to diabetes and its complications remain only partly understood. Studying the role of epigenetics in diabetic complications can provide valuable new insights to clarify the interplay between genes and the environment. DNA methylation and histone modifications in nuclear chromatin can generate epigenetic information as another layer of gene transcriptional regulation sensitive to environmental signals. Recent evidence shows that key biochemical pathways and epigenetic chromatin histone methylation patterns are altered in target cells under diabetic conditions and might also be involved in the metabolic memory phenomenon noted in clinical trials and animal studies. New therapeutic targets and treatment options could be uncovered from an in-depth study of the epigenetic mechanisms that might perpetuate diabetic complications despite glycemic control.
1型糖尿病和2型糖尿病是与多种并发症相关的复杂疾病，遗传因素和环境因素均与这些病理状况有关。尽管众多研究已提供了关于糖尿病遗传学的丰富知识，但导致糖尿病及其并发症的机制途径仍仅被部分理解。研究表观遗传学在糖尿病并发症中的作用可为阐明基因与环境之间的相互作用提供有价值的新见解。核染色质中的DNA甲基化和组蛋白修饰可产生表观遗传信息，作为对环境信号敏感的另一层基因转录调控。最近的证据表明，在糖尿病条件下，靶细胞中的关键生化途径和表观遗传染色质组蛋白甲基化模式会发生改变，并且可能也参与了临床试验和动物研究中所指出的代谢记忆现象。通过对表观遗传机制的深入研究，可能会发现新的治疗靶点和治疗选择，这些机制可能会使糖尿病并发症在血糖得到控制的情况下仍然持续存在。
