MicroRNA Sequences Modulated by Beta Cell Lipid Metabolism: Implications for Type 2 Diabetes Mellitus

SIMPLE SUMMARY: At present, more than 450 million adults worldwide are living with diabetes, with a further 370 million individuals at risk of developing this condition. Diabetes is caused by loss of production of, or sensitivity to, insulin, the hormone which controls blood sugar levels. One key factor contributing to loss of insulin output from beta cells in pancreatic islets is the damaging effects of sugars and fats in the bloodstream. This review article sought to identify the changes in expression of small pieces of RNA (microRNA) which are reported to be caused in beta cells and islets by exposure to sugars and fats. These small RNA sequences alter the expression of networks of genes which can promote, or protect, against beta cell damage, and their levels in the bloodstream have also been used as markers of diabetes. The combined effects of these microRNA sequences in beta cells were predicted, and may help to inform drug discovery strategies. ABSTRACT: Alterations in lipid metabolism within beta cells and islets contributes to dysfunction and apoptosis of beta cells, leading to loss of insulin secretion and the onset of type 2 diabetes. Over the last decade, there has been an explosion of interest in understanding the landscape of gene expression which influences beta cell function, including the importance of small non-coding microRNA sequences in this context. This review sought to identify the microRNA sequences regulated by metabolic challenges in beta cells and islets, their targets, highlight their function and assess their possible relevance as biomarkers of disease progression in diabetic individuals. Predictive analysis was used to explore networks of genes targeted by these microRNA sequences, which may offer new therapeutic strategies to protect beta cell function and delay the onset of type 2 diabetes.