MicroRNAs in islet hormone secretion

Abstract

Pancreatic islet hormone secretion is central in the maintenance of blood glucose homeostasis. During development of hyperglycaemia, the β-cell is under pressure to release more insulin to compensate for increased insulin resistance. Failure of the β-cells to secrete enough insulin results in type 2 diabetes (T2D). MicroRNAs (miRNAs) are short non-coding RNA molecules suitable for rapid regulation of the changes in target gene expression needed in β-cell adaptations. Moreover, miRNAs are involved in the maintenance of α-cell and β-cell phenotypic identities via cell-specific, or cell-enriched expression. Although many of the abundant miRNAs are highly expressed in both cell types, recent research has focused on the role of miRNAs in β-cells. It has been shown that highly abundant miRNAs, such as miR-375, are involved in several cellular functions indispensable in maintaining β-cell phenotypic identity, almost acting as "housekeeping genes" in the context of hormone secretion. Despite the abundance and importance of miR-375, it has not been shown to be differentially expressed in T2D islets. On the contrary, the less abundant miRNAs such as miR-212/miR-132, miR-335, miR-130a/b and miR-152 are deregulated in T2D islets, wherein the latter three miRNAs were shown to play key roles in regulating β-cell metabolism. In this review, we focus on β-cell function and describe miRNAs involved in insulin biosynthesis and processing, glucose uptake and metabolism, electrical activity and Ca²⁺ -influx and exocytosis of the insulin granules. We present current status on miRNA regulation in α-cells, and finally we discuss the involvement of miRNAs in β-cell dysfunction underlying T2D pathogenesis.

Keywords: exocytosis; glucagon; insulin; metabolism; microRNA; α-cell; β-cell.