title: Differentially Expressed MicroRNA-483 Confers Distinct Functions in Pancreatic β- and α-Cells.
abstract: Insulin secreted from pancreatic β-cells and glucagon secreted from pancreatic α-cells are the two major hormones working in the pancreas in an opposing manner to regulate and maintain a normal glucose homeostasis. How microRNAs (miRNAs), a population of non-coding RNAs so far demonstrated to be differentially expressed in various types of cells, regulate gene expression in pancreatic β-cells and its closely associated α-cells is not completely clear. In this study, miRNA profiling was performed and compared between pancreatic β-cells and their partner α-cells. One novel miRNA, miR-483, was identified for its highly differential expression in pancreatic β-cells when compared to its expression in α-cells. Overexpression of miR-483 in β-cells increased insulin transcription and secretion by targeting SOCS3, a member of suppressor of cytokine signaling family. In contrast, overexpression of miR-483 decreased glucagon transcription and secretion in α-cells. Moreover, overexpressed miR-483 protected against proinflammatory cytokine-induced apoptosis in β-cells. This correlates with a higher expression level of miR-483 and the expanded β-cell mass observed in the islets of prediabetic db/db mice. Together, our data suggest that miR-483 has opposite effects in α- and β-cells by targeting SOCS3, and the imbalance of miR-483 and its targets may play a crucial role in diabetes pathogenesis.
authors.affiliation: From the Department of Biological Sciences, Michigan Technological University, Houghton, Michigan 49931.
authors.forename: Ramkumar
authors.initials: R
authors.lastname: Mohan
authors.affiliation: From the Department of Biological Sciences, Michigan Technological University, Houghton, Michigan 49931.
authors.forename: Yiping
authors.initials: Y
authors.lastname: Mao
authors.affiliation: From the Department of Biological Sciences, Michigan Technological University, Houghton, Michigan 49931.
authors.forename: Shungang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: the College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China, and.
authors.forename: Yu-Wei
authors.initials: YW
authors.lastname: Zhang
authors.affiliation: the College of Life Sciences, Peking-Tsinghua Center for Life Sciences, Peking University, Beijing 100871, China, and.
authors.forename: Cheng-Ran
authors.initials: CR
authors.lastname: Xu
authors.affiliation: the Institute of Genetics and Molecular and Cellular Biology, Department of Development and Stem cells, University of Strasbourg, 67404 Illkirch, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Gradwohl
authors.affiliation: From the Department of Biological Sciences, Michigan Technological University, Houghton, Michigan 49931, xtang2@mtu.edu.
authors.forename: Xiaoqing
authors.initials: X
authors.lastname: Tang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D002460:Cell Line; D005786:Gene Expression Regulation; D005934:Glucagon / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050416:Glucagon-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D006706:Homeostasis / Q000235:genetics; D007328:Insulin / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D007371:Interferon-gamma / Q000494:pharmacology; D053583:Interleukin-1beta / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008969:Molecular Sequence Data; D009928:Organ Specificity; D011236:Prediabetic State / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D054411:Receptors, Leptin / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
chemical_list: D007328:Insulin; D053583:Interleukin-1beta; D035683:MicroRNAs; C548913:Mirn483 microRNA, mouse; D054411:Receptors, Leptin; C491411:Socs3 protein, mouse; D000071223:Suppressor of Cytokine Signaling 3 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D014409:Tumor Necrosis Factor-alpha; C515447:leptin receptor, mouse; D007371:Interferon-gamma; D005934:Glucagon
keywords: alpha cells; beta cell (B-cell); diabetes; glucagon; insulin; miR-483; microRNA (miRNA)