Involvement of MicroRNAs in the Cytotoxic Effects Exerted by Proinflammatory Cytokines on Pancreatic β-Cells

• DOI: 10.2337/db09-0881
• Publication Date: 2010-01-20T05:23:53Z
• Authors: Elodie Roggli; Aurore Britan; Sonia Gattesco; Nathalie Lin-Marq; Amar Abderrahmani; Paolo Meda; Romano Regazzi
• Keywords: Proinflammatory cytokine; Insulitis; Pancreatic Islets; NOD mice

OBJECTIVE Pancreatic β-cells exposed to proinflammatory cytokines display alterations in gene expression resulting defective insulin secretion and apoptosis. MicroRNAs are small noncoding RNAs emerging as key regulators of expression. Here, we evaluated the contribution microRNAs cytokine-mediated β-cell cytotoxicity. RESEARCH DESIGN AND METHODS We used global microarray profiling real-time PCR analysis detect changes microRNA islets pre-diabetic NOD mice. assessed involvement affected failure by modifying their insulin-secreting MIN6 cells. RESULTS found that IL-1β TNF-α induce miR-21, miR-34a, miR-146a both cells human pancreatic islets. further show an increase these mice during development insulitis. Blocking or function using antisense molecules did not restore insulin-promoter activity but prevented reduction glucose-induced observed upon exposure. Moreover, anti–miR-34a anti–miR-146a treatment protected from cytokine-triggered cell death. CONCLUSIONS Our data identify novel players elicited vitro vivo cytokines, notably peri-insulitis precedes overt diabetes