miR-33-5p Ameliorates β Cell Dysfunction and PI3K/AKT Signaling-Mediated Insulin Secretion in Diabetes via Targeting RND2

Shanshan Zhang, Fengjuan Yuan, Xiao Liu and Yali Liu

Background and Objective: As known, diabetes mellitus (DM) is a metabolic disorder that is highly correlated with the dysfunction of pancreatic β cells. Herein, the study aimed to investigate the potential role of miR-33-5p as a regulator of pancreatic β cells and the underlying mechanism in DM. Materials and Methods: The RNA and protein expression were analyzed by Quantitative Reverse Transcription-Polymerase Chain Reaction (qRT-PCR) and western blot, respectively. The target gene of miR-33-5p was identified and verified by TargetScan, dual-luciferase reporter and RNA immunoprecipitation (RIP) assays. The MTT, TUNEL, as well as ELISA analyses, were performed after streptozotocin (STZ)-induced INS-1 cells were transfected with miR-33-5p mimics/inhibitors and si-RND2 alone and in combination. Results: The miR-33-5p was lowly expressed in islet and serum of DM patients, STZ-induced mice and INS-1 cells. In vitro showed that the suppression of cell proliferation and insulin secretion and the increase of apoptosis induced by STZ was reversed by miR-33-5p overexpression in INS-1 cells, accompanied by the activation ofPI3K/AKT signalling pathway. Mechanically, RND2 was identified as the target of miR-33-5p in DM. Furthermore, the effects of miR-33-5p depletion on the cell proliferation, apoptosis and insulin secretion of STZ-induced INS-1 cells were restrained by RND2 knockdown. Conclusion: Overall, current findings proposed that miR-33-5p/RND2 were promising targets that regulated the balance of insulin secretion.

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