| First Author | Kim JW | Year | 2013 |
| Journal | Diabetologia | Volume | 56 |
| Issue | 4 | Pages | 847-55 |
| PubMed ID | 23338554 | Mgi Jnum | J:196417 |
| Mgi Id | MGI:5487896 | Doi | 10.1007/s00125-012-2812-x |
| Citation | Kim JW, et al. (2013) miRNA-30a-5p-mediated silencing of Beta2/NeuroD expression is an important initial event of glucotoxicity-induced beta cell dysfunction in rodent models. Diabetologia 56(4):847-55 |
| abstractText | AIMS/HYPOTHESIS: The loss of beta cell function is a critical factor in the development of type 2 diabetes. Glucotoxicity plays a major role in the progressive deterioration of beta cell function and development of type 2 diabetes mellitus. Here we demonstrate that microRNA (miR)-30a-5p is a key player in early-stage glucotoxicity-induced beta cell dysfunction. METHODS: We performed northern blots, RT-PCR and western blots in glucotoxicity-exposed primary rat islets and INS-1 cells. We also measured glucose-stimulated insulin secretion and insulin content. In vivo approaches were used to evaluate the role of miR-30a-5p in beta cell dysfunction. RESULTS: miR-30a-5p expression was increased in beta cells after exposure to glucotoxic conditions, and exogenous miR-30a-5p overexpression also induced beta cell dysfunction in vitro. miR-30a-5p directly suppressed expression of Beta2/NeuroD (also known as Neurod1) by binding to a specific binding site in its 3'-untranslated region. After restoration of Beta2/NeuroD expression by knockdown miR-30a-5p or transfection of the Beta2/NeuroD gene, beta cell dysfunction, including decreased insulin content, gene expression and glucose-stimulated insulin secretion, recovered. Glucose tolerance and beta cell dysfunction improved on direct injection of Ad-si30a-5p into the pancreas of diabetic mice. CONCLUSIONS/INTERPRETATION: Our data demonstrate that miR-30a-5p-mediated direct suppression of Beta2/NeuroD gene expression is an important initiation step of glucotoxicity-induced beta cell dysfunction. |
