Roles of Epigenetic Modifications in the Differentiation and Function of Pancreatic β-Cells.

Fei Xu,Linjun Chen,Lixin Na,Jing Liu

doi:10.3389/fcell.2020.00748

Abstract

Diabetes, a metabolic disease with multiple causes characterized by high blood sugar, has become a public health problem. Hyperglycaemia is caused by deficiencies in insulin secretion, impairment of insulin function, or both. The insulin secreted by pancreatic β cells is the only hormone in the body that lowers blood glucose levels and plays vital roles in maintaining glucose homeostasis. Therefore, investigation of the molecular mechanisms of pancreatic β cell differentiation and function is necessary to elucidate the processes involved in the onset of diabetes. Although numerous studies have shown that transcriptional regulation is essential for the differentiation and function of pancreatic β cells, increasing evidence indicates that epigenetic mechanisms participate in controlling the fate and regulation of these cells. Epigenetics involves heritable alterations in gene expression caused by DNA methylation, histone modification and non-coding RNA activity that does not result in DNA nucleotide sequence alterations. Recent research has revealed that a variety of epigenetic modifications play an important role in the development of diabetes. Here, we review the mechanisms by which epigenetic regulation affects β cell differentiation and function.

Highlights

The global incidence of diabetes has risen sharply with societal progress and improvements in living standards, and the disease is showing a trend toward affecting younger individuals
Ling et al reported that the DNA methylation of the PPARGG1α promoter in the islets of T2DM patients was accompanied by decreased mRNA expression, suggesting that epigenetics can regulate the expression of the PPARGG1α gene and subsequently affect insulin secretion (Ling et al, 2008)
The results showed that F1 and F2 offspring which were exposed to intrauterine hyperglycemia had impaired insulin secretion from the islets, and both F1 and F2 offspring showed similar hypomethylation level at the−1952 site of the tumor necrosis factor (Tnf) gene (Su et al, 2016)

Summary

Introduction

The global incidence of diabetes has risen sharply with societal progress and improvements in living standards, and the disease is showing a trend toward affecting younger individuals. The methylation of the CpG island in the insulin promoter region may play a crucial role in the maturation and tissuespecific expression of insulin genes in pancreatic β cells. In vitro experiments confirmed that methylation of the CDKN1A and PDE7B promoter genes inhibited their transcriptional activity and led to a decrease in the exocytosis function of pancreatic β cells and reduced insulin secretion (Dayeh et al, 2014).

Results

Conclusion