详细记录  
题名:miRNA-30a-5p-mediated silencing of Beta2/NeuroD expression is an important initial event of glucotoxicity-induced beta cell dysfunction in rodent models.
作者:KIM JW; YOU YH; JUNG S; SUH-KIM H; LEE IK; CHO JH; YOON KH;
来源:Diabetologia. 2013 Apr;56(4):847-55. doi: 10.1007/s00125-012-2812-x. Epub 2013 [ IF= 6.81 ] ]
URL :10.1007/s00125-012-2812-x
日期:20130131
摘要: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.

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