Abstract
Increased blood glucose after a meal is countered by the subsequent increased release of the hypoglycemic hormone insulin from the pancreatic beta cells. The cascade of molecular events encompassing the initial sensing and transport of glucose into the beta cell, culminating with the exocytosis of the insulin large dense core granules (LDCVs) is termed “stimulus-secretion coupling.” Impairment in any of the relevant processes leads to insufficient insulin release, which contributes to the development of type 2 diabetes (T2D). The fate of the beta cell, when exposed to environmental triggers of the disease, is determined by the possibility to adapt to the new situation by regulation of gene expression. As established factors of post-transcriptional regulation, microRNAs (miRNAs) are well-recognized mediators of beta cell plasticity and adaptation. Here, we put focus on the importance of comprehending the transcriptional regulation of miRNAs, and how miRNAs are implicated in stimulus-secretion coupling, specifically those influencing the late stages of insulin secretion. We suggest that efficient beta cell adaptation requires an optimal balance between transcriptional regulation of miRNAs themselves, and miRNA-dependent gene regulation. The increased knowledge of the beta cell transcriptional network inclusive of non-coding RNAs such as miRNAs is essential in identifying novel targets for the treatment of T2D.
Highlights
Deregulated miRNA expression is thought to be implicated in the pathogenesis of many diseases [1], including metabolic disorders such as type 2 diabetes (T2D) [2]
Insulin secretion is a key feature in glucose metabolism, and impairment in the beta cell capacity to release enough of the hormone is central to the development of T2D
We have in this review listed the miRNAs controlling beta cell stimulus-secretion coupling and exocytosis
Summary
Deregulated miRNA expression is thought to be implicated in the pathogenesis of many diseases [1], including metabolic disorders such as type 2 diabetes (T2D) [2]. Recent studies have pointed out large differences between mouse and human beta cells regarding different channel sub-types involved [9] These species’ differences might be explained by species-specific non-coding. Genetic variations only explain a small part of the increased risk and other factors beyond the genome have been suggested to be involved, e.g., epigenetic regulation and miRNAs. It is obvious from recent studies that epigenetic marks and miRNAs play crucial roles in the regulation of human insulin secretion [29,30,31,32,33]. The balance between these two processes is essential for healthy beta cells; increased understanding of the interplay between them will most likely improve our possibilities of identifying new therapeutic approaches against beta cell impairment in T2D
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