Weixuan Wang , Dan Ma , Yong Chen , Rui Cheng , Ting Zhang , Qian Ge , Xi Li
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引用次数: 0
Abstract
We evaluated the potential mechanisms responsible for inducing beta-cell decline during the progression of obesity to type 2 diabetes mellitus (T2DM). Between February 2021 and February 2022, 25 subjects with non-diabetic obesity, 20 subjects with obesity and new-onset T2DM, and 25 healthy volunteers were recruited. Circulating exosome-contained miRNA expression profiling was performed by miRNA sequencing. The role of specific miRNA was analyzed by a gain-of-function approach in Min6 beta-cells, mouse islets, and human islets. Expression of 83 exosomal miRNAs was differently regulated in the circulation of subjects with non-diabetic obesity. We focused on miR-146b, which was mildly up-regulated in non-diabetic obesity and dramatically up-regulated in obese new-onset T2DM. Using an obese diabetic db/db mouse model, we found the expression of miR-146b to be mainly increased in islets. Overexpression of miR-146b in mouse beta-cells, mouse islets, and human islets in vitro facilitated beta-cell apoptosis yet inhibited its proliferation and insulin synthesis, leading to impaired insulin secretion. Eventually, miR-146b directly targeted the B cell translocation gene 2 (Btg2), an antiapoptotic transcriptional factor. Overexpression of Btg2 reversed miR-146b-induced apoptosis and -suppressed proliferation in beta-cells. miR-146b that targets Btg2 might be a predictive biomarker and an inducer of beta-cell decline.
期刊介绍:
Genes & Diseases is an international journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch.
Aims and Scopes
Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis will be placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.