Regulation of Pancreatic beta-Cell Mass by Gene-Environment Interaction

The main pathogenic mechanism of diabetes consists of an increase in insulin resistance and a decrease in insulin secretion from pancreatic beta-cells. The number of diabetic patients has been increasing dramatically worldwide, especially in Asian people whose capacity for insulin secretion is inherently lower than that of other ethnic populations. Causally, changes of environmental factors in addition to intrinsic genetic factors have been considered to have an influence on the increased prevalence of diabetes. Particular focus has been placed on "gene-environment interactions" in the development of a reduced pancreatic beta-cell mass, as well as type 1 and type 2 diabetes mellitus. Changes in the intrauterine environment, such as intrauterine growth restriction, contribute to alterations of gene expression in pancreatic beta-cells, ultimately resulting in the development of pancreatic beta-cell failure and diabetes. As a molecular mechanism underlying the effect of the intrauterine environment, epigenetic modifications have been widely investigated. The association of diabetes susceptibility genes or dietary habits with gene-environment interactions has been reported. In this review, we provide an overview of the role of gene-environment interactions in pancreatic beta-cell failure as revealed by previous reports and data from experiments.