Department of General Surgery, The Third Xiangya Hospital, Central South University, Changsha, China.
Front Endocrinol (Lausanne). 2021 Jul 28;12:695164. doi: 10.3389/fendo.2021.695164. eCollection 2021.
Diabetes is a metabolic disorder induced by the modulation of insulin on glucose metabolism, and the dysfunction and decreased number of islets β-cells are the main causes of T2DM (type 2 diabetes mellitus). Among multiple factors that might participate in T2DM pathogenesis, the critical roles of miRNAs in T2DM and β-cell dysfunction have been reported. Through bioinformatics analyses and literature review, we found that miR-344 might play a role in the occurrence and progression of diabetes in rats. The expression levels of miR-344-5p were dramatically decreased within cholesterol-stimulated and palmitic acid (PA)-induced rats' islet β-cells. In cholesterol-stimulated and PA-induced diabetic β-cell model, cholesterol-caused and PA-caused suppression on cell viability, increase in intracellular cholesterol level, decrease in GSIS, and increase in lip droplet deposition were dramatically attenuated the overexpression of miR-344-5p, whereas aggravated the inhibition of miR-344-5p. miR-344-5p also inhibited cholesterol-induced β-cell death affecting the apoptotic caspase 3/Bax signaling. Insulin receptor downstream MPAK/ERK signaling was involved in the protection of miR-344-5p against cholesterol-induced pancreatic β-cell dysfunction. Moreover, miR-344-5p directly targeted Cav1; Cav1 silencing could partially reverse the functions of miR-344-5p inhibition upon cholesterol-induced β-cell dysfunction, β-cell apoptosis, the apoptotic caspase 3/Bax signaling, and insulin receptor downstream MPAK/ERK signaling. In conclusion, the miR-344-5p/Cav1 axis modulates cholesterol-induced β-cell apoptosis and dysfunction. The apoptotic caspase 3/Bax signaling and MAPK/ERK signaling might be involved.
糖尿病是一种由胰岛素对葡萄糖代谢的调节引起的代谢紊乱，胰岛β细胞的功能障碍和数量减少是 T2DM（2 型糖尿病）的主要原因。在可能参与 T2DM 发病机制的多种因素中，miRNA 在 T2DM 和β细胞功能障碍中的关键作用已被报道。通过生物信息学分析和文献回顾，我们发现 miR-344 可能在大鼠糖尿病的发生和发展中起作用。胆固醇刺激和棕榈酸（PA）诱导的大鼠胰岛β细胞中 miR-344-5p 的表达水平显著降低。在胆固醇刺激和 PA 诱导的糖尿病β细胞模型中，miR-344-5p 的过表达显著减弱了胆固醇引起和 PA 引起的细胞活力抑制、细胞内胆固醇水平升高、GSIS 降低和脂滴沉积增加，而 miR-344-5p 的抑制则加剧了这些变化。miR-344-5p 还通过影响凋亡 caspase 3/Bax 信号抑制胆固醇诱导的β细胞死亡。胰岛素受体下游的 MPAK/ERK 信号参与了 miR-344-5p 对胆固醇诱导的胰腺β细胞功能障碍的保护作用。此外，miR-344-5p 直接靶向 Cav1；沉默 Cav1 可以部分逆转 miR-344-5p 抑制对胆固醇诱导的β细胞功能障碍、β细胞凋亡、凋亡 caspase 3/Bax 信号和胰岛素受体下游 MPAK/ERK 信号的作用。总之，miR-344-5p/Cav1 轴调节胆固醇诱导的β细胞凋亡和功能障碍。凋亡 caspase 3/Bax 信号和 MAPK/ERK 信号可能参与其中。
