Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Antioxid Redox Signal ; 27(13): 913-930, 2017 Nov 01.
Article in English | MEDLINE | ID: mdl-28173719

ABSTRACT

AIMS: MicroRNAs (miRNAs), one type of noncoding RNA, modulate post-transcriptional gene expression in various pathogenic pathways in type 2 diabetes (T2D). Currently, little is known about how miRNAs influence disease pathogenesis by targeting cells at a distance. The purpose of this study was to investigate the role of exosomal miRNAs during T2D. RESULTS: We show that miR-15a is increased in the plasma of diabetic patients, correlating with disease severity. miR-15 plays an important role in insulin production in pancreatic ß-cells. By culturing rat pancreatic ß-cells (INS-1) cells in high-glucose media, we identified a source of increased miR-15a in the blood as exosomes secreted by pancreatic ß-cells. We postulate that miR-15a, produced in pancreatic ß-cells, can enter the bloodstream and contribute to retinal injury. miR-15a overexpression in Müller cells can be induced by exposing Müller cells to exosomes derived from INS-1 cells under high-glucose conditions and results in oxidative stress by targeting Akt3, which leads to apoptotic cell death. The in vivo relevance of these findings is supported by results from high-fat diet and pancreatic ß-cell-specific miR-15a-/- mice. INNOVATION: This study highlights an important and underappreciated mechanism of remote cell-cell communication (exosomal transfer of miRNA) and its influence on the development of T2D complications. CONCLUSION: Our findings suggest that circulating miR-15a contributes to the pathogenesis of diabetes and supports the concept that miRNAs released by one cell type can travel through the circulation and play a role in disease progression via their transfer to different cell types, inducing oxidative stress and cell injury. Antioxid. Redox Signal. 27, 913-930.


Subject(s)
Diabetes Mellitus, Type 2/genetics , Diabetic Retinopathy/genetics , Exosomes/metabolism , Insulin-Secreting Cells/metabolism , MicroRNAs/blood , Adult , Animals , Cell Line , Diabetes Mellitus, Type 2/blood , Diabetic Retinopathy/blood , Disease Models, Animal , Exosomes/genetics , Female , Humans , Male , Mice , Middle Aged , Oxidative Stress , Rats , Up-Regulation
SELECTION OF CITATIONS
SEARCH DETAIL
...