Let7b-5p 抑制小鼠胰岛素分泌并减少胰岛 β 细胞数量。

Let7b-5p inhibits insulin secretion and decreases pancreatic β-cell mass in mice.

机构信息

Department of Endocrine and Metabolic Diseases, Shanghai Institute of Endocrine and Metabolic Diseases, National Clinical Research Centre for Metabolic Diseases, Key Laboratory for Endocrine and Metabolic Diseases of the National Health Commission, Shanghai Key Laboratory for Endocrine Tumors, Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai, China; National Research Center for Translational Medicine, National Key Scientific Infrastructure for Translational Medicine (Shanghai), Shanghai Jiao Tong University, Shanghai, China.

出版信息

Mol Cell Endocrinol. 2022 Jan 15;540:111506. doi: 10.1016/j.mce.2021.111506. Epub 2021 Nov 18.

DOI:10.1016/j.mce.2021.111506

PMID:34801668

Abstract

MicroRNAs are crucial regulators for the development, mass and function of pancreatic β-cells. MiRNA dysregulation is associated with β-cell dysfunction and development of diabetes. The members of let7 family are important players in regulating cellular growth and metabolism. In this study we investigated the functional role of let7b-5p in the mouse pancreatic β-cells. We generated pancreatic β-cell-specific let7b-5p transgenic mouse model and analyzed the glucose metabolic phenotype, β-cells mass and insulin secretion in vivo. Luciferase reporter assay, immunofluorescence staining and western blot were carried out to study the target genes of let7b-5p in β-cells. Let7b-5p overexpression impaired the insulin production and secretion of β-cells and resulted impaired glucose tolerance in mice. The overexpressed let7b-5p inhibited pancreatic β-cell proliferation and decreased the expression of cyclin D1 and cyclin D2. Our findings demonstrated that let7b-5p was critical in regulating the proliferation and insulin secretion of pancreatic β-cells.

摘要

微小 RNA 是胰腺 β 细胞发育、质量和功能的重要调节因子。miRNA 失调与 β 细胞功能障碍和糖尿病的发生有关。let7 家族成员是调节细胞生长和代谢的重要参与者。在这项研究中，我们研究了 let7b-5p 在小鼠胰腺 β 细胞中的功能作用。我们生成了胰腺 β 细胞特异性 let7b-5p 转基因小鼠模型，并在体内分析了葡萄糖代谢表型、β 细胞质量和胰岛素分泌。通过荧光素酶报告基因检测、免疫荧光染色和 Western blot 检测，研究了 let7b-5p 在 β 细胞中的靶基因。let7b-5p 的过表达损害了 β 细胞的胰岛素产生和分泌，导致小鼠糖耐量受损。过表达的 let7b-5p 抑制胰腺 β 细胞增殖，并降低细胞周期蛋白 D1 和 D2 的表达。我们的研究结果表明，let7b-5p 对调节胰腺 β 细胞的增殖和胰岛素分泌至关重要。