MicroRNA-182-5p contributes to the protective effects of thrombospondin 1 against lipotoxicity in INS-1 cells.

The dysfunction of beta cells serves an important role in the pathogenesis of type 2 diabetes mellitus (T2DM). An improved understanding of the molecular mechanisms underlying beta cell mass and failure will be useful for identifying novel approaches toward preventing and treating this disease. Recent studies have indicated that free fatty acids (FFAs) can cause beta cell dysfunction. In the present study, palmitate (Pal) was used as a FFA and its functions on cell viability and apoptosis were detected. MTT assay and flow cytometry were used and the results revealed that incubation of INS-1 cells with Pal significantly decreased cell viability and increased cell apoptosis. However, a co-incubation with thrombospondin 1 (THBS-1) protected the cells against Pal-induced toxicity. Numerous studies have demonstrated that microRNAs (miRs) are involved in fatty acid-induced beta cell dysfunction. Various studies have reported that miR-182-5p is associated with a number of diseases, including cancer, heart disease, and leukemia. However, to the best of our knowledge miR-182-5p has never been reported to be associated with diabetes. In the present study, miR-182-5p, which is predicted to target the 3'-untranslated region (UTR) of THBS-1, was detected using reverse transcription-quantitative polymerase chain reaction in INS-1 cells in response to Pal. miR-182-5p was significantly increased in Pal-treated cells compared with the control cells. Furthermore, miR-182-5p mimics significantly decreased cell viability and increased Pal-induced apoptosis in INS-1 cells. However, cell viability was increased and Pal-induced apoptosis was decreased in cells that were treated with miR-182-5p inhibitors. The present findings also revealed that overexpression of THBS-1 counteracted the effect of miR-182-5p on cell viability and apoptosis. These results suggested that miR-182-5p is involved in the mechanism of THBS 1 on the modulation of beta cell survival.