Department of Clinical Sciences in Malmö, Unit of Islet Cell Exocytosis, Lund University Diabetes Centre, Lund University, Skåne University Hospital, 205 02 Malmö, Sweden.
Endocrinology. 2023 Mar 13;164(5). doi: 10.1210/endocr/bqad040.
Type 2 diabetes (T2D) develops due to insulin resistance and an inability of the pancreatic β-cells to increase secretion of insulin and reduce elevated blood glucose levels. Diminished β-cell function and mass have been implicated in impaired β-cell secretory capacity and several microRNAs (miRNAs) have been reported to be involved in regulating β-cell processes. We believe miRNAs are nodes in important miRNA-mRNA networks regulating β-cell function and that miRNAs therefore can be targets for the treatment of T2D. MicroRNAs are short (≈19-23 nucleotides [nt]) endogenous noncoding RNAs which regulate gene expression by directly binding to the mRNA of their target genes. Under normal circumstances, miRNAs act as rheostats to keep expression of their gene targets at optimal levels for different β-cell outputs. In T2D, levels of some miRNAs are altered as part of the compensatory mechanism to improve insulin secretion. Other miRNAs are differentially expressed as part of the process of T2D pathogenesis, which results in reduced insulin secretion and increased blood glucose. In this review, we present recent findings concerning miRNAs in islets and in insulin-secreting cells, and their differential expression in diabetes, with a specific focus on miRNAs involved in β-cell apoptosis/proliferation and glucose-stimulated insulin secretion. We present thoughts around miRNA-mRNA networks and miRNAs as both therapeutic targets to improve insulin secretion and as circulating biomarkers of diabetes. Overall, we hope to convince you that miRNAs in β-cells are essential for regulating β-cell function and can in the future be of clinical use in the treatment and/or prevention of diabetes.
2 型糖尿病（T2D）的发生是由于胰岛素抵抗以及胰岛β细胞不能增加胰岛素分泌和降低升高的血糖水平。β细胞功能和数量的下降与β细胞分泌能力受损有关，已有报道称几种 microRNAs（miRNAs）参与调节β细胞过程。我们认为 miRNAs 是调节β细胞功能的重要 miRNA-mRNA 网络中的节点，因此 miRNAs 可以成为 T2D 治疗的靶点。miRNAs 是短的（≈19-23 个核苷酸 [nt]）内源性非编码 RNA，通过直接与靶基因的 mRNA 结合来调节基因表达。在正常情况下，miRNAs 作为变阻器，将其靶基因的表达保持在不同β细胞输出的最佳水平。在 T2D 中，一些 miRNAs 的水平会发生变化，作为改善胰岛素分泌的代偿机制的一部分。其他 miRNAs 的表达水平存在差异，是 T2D 发病机制过程的一部分，导致胰岛素分泌减少和血糖升高。在这篇综述中，我们介绍了胰岛和胰岛素分泌细胞中 miRNAs 的最新发现，以及它们在糖尿病中的差异表达，特别关注涉及β细胞凋亡/增殖和葡萄糖刺激胰岛素分泌的 miRNAs。我们围绕 miRNA-mRNA 网络和 miRNAs 作为改善胰岛素分泌的治疗靶点以及糖尿病的循环生物标志物进行了思考。总的来说，我们希望能让你相信，β 细胞中的 miRNAs 对于调节β细胞功能至关重要，并且将来可能在糖尿病的治疗和/或预防中具有临床应用价值。
