Importance of Both Imprinted Genes and Functional Heterogeneity in Pancreatic Beta Cells: Is There a Link?

Diabetes mellitus now affects more than 400 million individuals worldwide, with significant impacts on the lives of those affected and associated socio-economic costs. Although defects in insulin secretion underlie all forms of the disease, the molecular mechanisms which drive them are still poorly understood. Subsets of specialised beta cells have, in recent years, been suggested to play critical roles in pacing overall islet activity. The molecular nature of these cells, the means through which their identity is established and the changes which may contribute to their functional demise and loss of influence in both type 1 and type 2 diabetes are largely unknown. Genomic imprinting involves the selective silencing of one of the two parental alleles through DNA methylation and modified imprinted gene expression is involved in a number of diseases. Loss of expression, or loss of imprinting, can be shown in mouse models to lead to defects in beta cell function and abnormal insulin secretion. In the present review we survey the evidence that altered expression of imprinted genes contribute to loss of beta cell function, the importance of beta cell heterogeneity in normal and disease states, and hypothesise whether there is a direct link between the two.

Automated summary

This passage discusses the global impact of diabetes mellitus and the unclear molecular mechanisms underlying the disease. It also highlights the critical role of specialized beta cells in islet activity, the influence of genomic imprinting on beta cell function, and the defects in insulin secretion associated with loss of expression or imprinting in mouse models.