Abstract
MicroRNAs (miRNAs) have been implicated in β cells dysfunction. Previous studies indicated that miR-127 was specifically abundant in β cells and one of its target genes, Kif3b, promoted cell proliferation. However, the impact of the miR-127-Kif3b axis on β cells remains unknown. In this study, we revealed that miR-127 level was declined both in islets from the mice with a high-fat diet and in MIN6 cells with elevated glucose treatment. The elevated level of miR-127 attenuated β cell proliferation by repressing Kif3b expression without affecting apoptosis and cell cycle, and it dampened insulin secretion. Moreover, β cell-derived miR-127 could also affect the islet endothelial cell-line, MS1, in vitro via the transfer of extracellular vesicles (EVs). Treating MS1 cells with the EVs secreted by MIN6 cells exhibited a higher ability in cell migration and tube formation. However, this effect was abolished by the miR-127 inhibitor co-cultured with EVs-treated MS1 cells. Thus, we define that miR-127 is a crucial regulator of insulin secretion and cell proliferation in pancreatic β cells as well as a potential functional regulation factor in islet endothelial cells.
Highlights
Diabetes mellitus is characterized by elevated blood glucose and it affects more than 400 million people worldwide; it has been recognized as one of the global public health issues [1]
To investigate the role of miR-127 in the pathogenesis of type 2 diabetes (T2D), we examined its level in the islets from high fat diet (HFD) mice
Www.aging-us.com expression was regulated by glucose, MIN6 cells were exposed to different concentration of glucose from 5.5mM to 33.3mM for 24 h
Summary
Diabetes mellitus is characterized by elevated blood glucose and it affects more than 400 million people worldwide; it has been recognized as one of the global public health issues [1]. Beta cell dysfunction and loss of β cell identity lead to insufficient insulin secretion and contribute to the pathogenesis of type 2 diabetes (T2D) [2]. Previous studies demonstrated that the aberrant expression of certain transcription factors was related to β cell dysfunction [3]. Emerging studies have highlighted the key roles of miRNA in β cell function including apoptosis, insulin secretion, etc. Several miRNAs play an important role in mouse pancreas development, insulin gene expression and insulin secretion [8]. It was demonstrated that miR-375 and miR-15a positively regulated insulin secretion by targeting MTPN and UCP-2, respectively [9, 10], whereas miR-133a acted as a negative regulator in insulin production [11]
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