Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
Islet Cell and Regenerative Biology, Joslin Diabetes Center, Boston, MA, USA; Department of Medicine, Brigham and Women's Hospital, Boston, MA, USA; Harvard Stem Cell Institute, Harvard Medical School, Boston, MA, USA.
Curr Opin Pharmacol. 2020 Dec;55:125-131. doi: 10.1016/j.coph.2020.10.008. Epub 2020 Nov 21.
Healthy pancreatic β-cells adapt to systemic insulin resistance to maintain normal blood glucose levels, and a failure of this adaptation leads to type 2 diabetes in humans. While genome-wide association studies have uncovered genetic variants that are associated with type 2 diabetes, it is still insufficient to explain the high prevalence of this disease. Epigenetics is the study of gene expression changes that do not involve DNA sequence alterations such as DNA methylation, histone modification, and non-coding RNAs. Over the last decade, a large number of studies have reported on the role of epigenetics in β-cell biology. In this review, we summarize the epigenetic mechanisms in β-cell adaptation and type 2 diabetes, including alterations in three-dimensional chromatin structure and RNA modifications.
健康的胰腺β细胞能够适应全身胰岛素抵抗以维持正常的血糖水平，而这种适应性的失败会导致人类患上 2 型糖尿病。虽然全基因组关联研究已经揭示了与 2 型糖尿病相关的遗传变异，但这仍然不足以解释这种疾病的高发病率。表观遗传学是研究基因表达变化的学科，这些变化不涉及 DNA 序列改变，如 DNA 甲基化、组蛋白修饰和非编码 RNA。在过去的十年中，大量研究报告了表观遗传学在β细胞生物学中的作用。在这篇综述中，我们总结了β细胞适应和 2 型糖尿病中的表观遗传机制，包括三维染色质结构和 RNA 修饰的改变。
