title: miR-101a and miR-30b contribute to inflammatory cytokine-mediated β-cell dysfunction.
abstract: Inflammatory cytokines have a critical role in the progressive deterioration of pancreatic β-cell function and development of type 1 diabetes. Prolonged exposure of β-cells to inflammatory cytokines results in gene expression modifications, leading to loss of β-cell function. MicroRNAs (miRNAs) are small non-coding RNAs acting as key regulators of gene expression. Here, we demonstrate that miR-101a and miR-30b are key players in cytokine-mediated β-cell dysfunction. We found that IL-1β induces an increase in miR-101a and miR-30b in MIN6 cells, and that the two miRNAs participate in β-cell dysfunction, including decreased insulin content, gene expression, and increased β-cell death. miR-101a and miR-30b reduce proinsulin expression and insulin content by directly targeting the transcriptional factor Neurod1. In addition, β-cell apoptosis mediated by miR-101a and miR-30b is associated with diminished expression level of the antiapoptotic protein Bcl2. Moreover, we show that miR-101a causes an impairment in glucose-induced insulin secretion by decreasing the expression of the transcription factor Onecut2. Taken together, our findings suggest that changes in the levels of miR-101a and miR-30b contribute to cytokine-mediated β-cell dysfunction occurring during the development and progression of type 1 diabetes.
authors.affiliation: Center for Medical Research, 2nd Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan, China.
authors.forename: Yiting
authors.initials: Y
authors.lastname: Tu
authors.affiliation: Center for Medical Research, 2nd Xiangya Hospital, Central South University, Changsha, Hunan, China.
authors.forename: Hongwei
authors.initials: H
authors.lastname: Shen
authors.affiliation: Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan, China.
authors.forename: Zhijie
authors.initials: Z
authors.lastname: Dai
authors.affiliation: Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Lin
authors.affiliation: Diabetes Center, 2nd Xiangya Hospital, and Institute of Metabolism and Endocrinology, Key Laboratory of Diabetes Immunology, Ministry of Education, Central South University, Changsha, Hunan, China.
authors.forename: Zhiguang
authors.initials: Z
authors.lastname: Zhou
mesh_terms: D000818:Animals; D017209:Apoptosis; D051792:Basic Helix-Loop-Helix Proteins / Q000378:metabolism; D016207:Cytokines; D003922:Diabetes Mellitus, Type 1 / Q000209:etiology*; D057809:HEK293 Cells; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000096:biosynthesis; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D035683:MicroRNAs / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D016207:Cytokines; D018398:Homeodomain Proteins; D007328:Insulin; D035683:MicroRNAs; D019253:Proto-Oncogene Proteins c-bcl-2; D014157:Transcription Factors; C534072:MIRN101 microRNA, human; C546086:MIRN30b microRNA, human; C093970:NEUROD1 protein, human; C117354:ONECUT2 protein, human