Role of microRNAs in the regulation of insulin secretion and during the development of type 2 diabetes

Abstract

Insulin released from β-cells within the pancreatic islet of Langerhans is central in the control of blood glucose homeostasis. A combination of environmental and genetic factors can lead to defects in this regulation and lead to type 2 diabetes (T2D). Hyperglycaemia due to reduced glucose uptake in target tissues needs to be compensated by the β-cell through increased insulin secretion. Failure of the β-cells to secrete enough insulin results in T2D. MicroRNAs are small non-coding RNAs post-transcriptionally regulating gene expression. Their ability for rapid regulation of alterations in target gene expression make microRNAs ideal in the β-cell adaptations needed during development of T2D. However, whereas changes in the expression of some microRNAs occur as a compensatory mechanism for insulin resistance others are part of the etiology of T2D. MicroRNAs are also involved in the maintenance of β-cell phenotypic identities via cell-specific, or cell-enriched expression, and some microRNAs, such as e.g., miR-29, reduce the expression of beta-cell disallowed genes. One of the most highly abundant microRNAs in the β-cell is miR-375. MiR-375 is highly involved in several cellular processes essential for maintaining the β-cell phenotypic identity. Despite the importance of miR-375, it has not been shown to be differentially expressed in T2D islets. On the contrary, other microRNAs such as miR-200, miR-335, miR-130a/b and miR-152 are deregulated in T2D islets. I will discuss the involvement of microRNAs in β-cell dysfunction underlying T2D pathogenesis, introduce how microRNAs can be involved in future treatment, and present how microRNAs can be used as potential biomarkers of disease.