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MEG3是一种长链非编码RNA。已有研究证明,鼠源Meg3参与小鼠诱导多能干细胞、神经元和视网膜的分化过程。最新报道,MEG3在人胰岛β细胞中高表达,但其对维持成年胰岛β细胞的功能尚不清楚。本研究旨在探讨Meg3在小鼠胰岛细胞胰岛素分泌功能中的作用。实时定量PCR揭示,与Balb/c小鼠心、肝、脾、肺、肌、肾等组织/器官比较,Meg3在胰腺组织中高表达。在非糖尿病小鼠发生自发性糖尿病的第8、12周,Meg3在胰岛中的表达水平分别下调24%±8%和29%±9%(P<0.01);而当血糖升高20 mmol/L,小鼠胰岛中Meg3表达下调72%±16%(P<0.01)。在MIN6细胞中采用RNA干扰敲减Meg3的表达,在高糖浓度(20 mmol/L)刺激条件下,胰岛素分泌显著减少。小鼠静脉注射si RNA,结合血糖测定或葡萄糖耐受试验(IPGTT)显示,si-Meg3小鼠血清胰岛素水平显著下降。注射葡萄糖前血糖升高,注射葡萄糖后耐受能力降低;免疫组化分析显示,si-Meg3小鼠胰岛素阳性细胞的面积减少。实验结果提示,Meg3通过参与胰岛素的合成和分泌维持成年小鼠胰岛功能。Meg3表达失调可能参与I型糖尿病(T1DM)发病过程。
MEG3 is a long-chain, non-coding RNA. Studies have shown that mouse-derived Meg3 is involved in the induction of pluripotent stem cells, neuronal and retinal differentiation in mice. Recently, MEG3 is overexpressed in human islet beta cells, but its function in maintaining adult pancreatic islet beta cells remains unclear. This study aimed to investigate the role of Meg3 in insulin secretion in mouse islet cells. Real-time quantitative PCR revealed that Meg3 was overexpressed in pancreatic tissues compared with the tissues / organs such as heart, liver, spleen, lung, muscle and kidney of Balb / c mice. At the 8th and 12th week of spontaneous diabetes in non-diabetic mice, the expression of Meg3 in islets was down-regulated by 24% ± 8% and 29% ± 9%, respectively (P <0.01) L, Meg3 expression was down-regulated by 72% ± 16% in mouse islets (P <0.01). Meg3 expression was knocked down by RNA interference in MIN6 cells, and insulin secretion was significantly reduced under high glucose (20 mmol / L) stimulation. Mice were intravenously injected with si RNA and combined with a blood glucose test or glucose tolerance test (IPGTT) showed a significant decrease in serum insulin levels in si-Meg3 mice. The glucose level increased before injection of glucose, and the tolerance of glucose decreased after injection of glucose. Immunohistochemical analysis showed that the area of insulin-positive cells in si-Meg3 mice decreased. The experimental results suggest that Meg3 maintains the islet function of adult mice by participating in the synthesis and secretion of insulin. Meg3 dysregulation may be involved in the pathogenesis of type 1 diabetes mellitus (T1DM).