Diabetes mellitus (DM), a familiar disease, is characterized by high blood glucose levels owing to insulin deficiency. Researches have suggested that the incidence rate of diabetes is increasing and it has become an important global epidemic. The type 2 diabetes mellitus (T2DM) is featured with pancreatic β-cell loss and lack of insulin release. Nevertheless, the therapeutic methods that was helpful to improve pancreatic β-cell damage still unclear. Previous report have revealed that tensin homolog deleted on chromosome ten (PTEN) was remarkably enhanced in serum of patients with T2DM, and the lack of PTEN may prevent function deficiency of pancreatic β-cells in DM. However, the underlying mechanisms are rarely illustrated. Our purpose in this report was to illustrated the roles and potential mechanism of microRNA-296-3p (miR-296-3p) in uric acid (UA)-induced pancreatic β-cell injury. The direct target of miR-296-3p was predicted and verified by dual-luciferase reporter system and TargetScan assay. Moreover, Min6 cells were induced by 5 mg/dl UA and the cell proliferation, apoptosis, and insulin release were evaluated using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and glucose-stimulated insulin secretion (GSIS), respectively. Quantitative reverse transcription PCR (qRT-PCR) and western blot assay were adopted to analyze the levels of miR-296-3p, PTEN and apoptosis-related proteins. TargetScan and Dual-luciferase reporter system confirmed that PTEN directly target miR-296-3p. MiR-296-3p was downregulated in UA-induced Min6 cells and the serum of type 2 diabetes patients, while PTEN was upregulated in UA-induced Min6 cells. Upregulation of miR-296-3p by mimic dramatically promoted miR-296-3p level and decreased PTEN level. Besides, PTEN was over-expressed after PTEN-plasmid transfection. UA treatment prominently decreased cell viability, promoted apoptotic cells, enhanced Bax levels, declined Bcl-2 level as well as decreased insulin release in Min6 cells. MiR-296-3p mimic significantly alleviated UA-induced pancreatic β-cells dysfunction, and PTEN-plasmid eliminated the protective effect of miR-296-3p on insulin release, cell viability, and apoptosis of pancreatic β-cells in UA-stimulated Min6 cells. In summary, our findings revealed that upregulation of miR-296-3p protected pancreatic β-cells functions against UA-induced dysfunction by targeting PTEN, which provides a novel agent for type 2 diabetes treatment.

糖尿病（DM）是一种熟悉的疾病，其特征是由于胰岛素缺乏导致的高血糖水平。研究表明，糖尿病的发病率正在上升，已成为全球重要的流行病。2 型糖尿病 (T2DM) 的特点是胰腺 β 细胞丢失和胰岛素释放不足。然而，有助于改善胰腺β细胞损伤的治疗方法仍不清楚。先前的报道显示，T2DM 患者血清中 10 号染色体上缺失的张力蛋白同源物（PTEN）显着增强，而 PTEN 的缺乏可能会阻止 DM 中胰腺 β 细胞的功能缺陷。然而，基本机制很少被说明。我们在本报告中的目的是说明 microRNA-296-3p (miR-296-3p) 在尿酸 (UA) 诱导的胰腺 β 细胞损伤中的作用和潜在机制。通过双荧光素酶报告系统和TargetScan分析预测并验证了miR-296-3p的直接靶标。此外，Min6 细胞由 5 mg/dl UA 诱导，并使用 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) 测定法评估细胞增殖、凋亡和胰岛素释放，流式细胞术和葡萄糖刺激的胰岛素分泌（GSIS），分别。采用定量逆转录PCR（qRT-PCR）和蛋白质印迹法分析miR-296-3p、PTEN和凋亡相关蛋白的水平。TargetScan 和双荧光素酶报告系统证实 PTEN 直接靶向 miR-296-3p。MiR-296-3p 在 UA 诱导的 Min6 细胞和 2 型糖尿病患者的血清中下调，而 PTEN 在 UA 诱导的 Min6 细胞中上调。通过模拟上调 miR-296-3p 显着促进 miR-296-3p 水平并降低 PTEN 水平。此外，PTEN 质粒转染后 PTEN 过表达。UA 处理显着降低细胞活力，促进凋亡细胞，提高 Bax 水平，降低 Bcl-2 水平以及减少 Min6 细胞中的胰岛素释放。MiR-296-3p mimic 显着减轻 UA 诱导的胰腺 β 细胞功能障碍，PTEN 质粒消除了 miR-296-3p 对 UA 刺激的 Min6 中胰腺 β 细胞的胰岛素释放、细胞活力和凋亡的保护作用细胞。总之，