MicroRNAs in islet hormone secretion

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 Ca 2+ ‐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.