Overexpression of Micro Ribonucleic Acid 29, Highly Up-Regulated in Diabetic Rats, Leads to Insulin Resistance in 3T3-L1 Adipocytes

Micro-RNAs (miRNAs) have been suggested to play pivotal roles in multifarious diseases associated with the posttranscriptional regulation of protein-coding genes. In this study, we aimed to investigate the function of miRNAs in type 2 diabetes mellitus. The miRNAs expression profiles were examined b...

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Bibliographic Details
Published in:Molecular endocrinology (Baltimore, Md.) Md.), 2007-11, Vol.21 (11), p.2785-2794
Main Authors: He, Aibin, Zhu, Liuluan, Gupta, Nishith, Chang, Yongsheng, Fang, Fude
Format: Article
Language:English
Subjects:
3T3-L1 Cells
Adipocytes - metabolism
Animals
Diabetes Mellitus - genetics
Gene Expression Regulation
Humans
Insulin - metabolism
Male
Mice
MicroRNAs - biosynthesis
MicroRNAs - genetics
Muscle, Skeletal - metabolism
Phosphorylation
Proto-Oncogene Proteins c-akt - metabolism
Rats
Rats, Wistar
RNA Processing, Post-Transcriptional
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Summary:Micro-RNAs (miRNAs) have been suggested to play pivotal roles in multifarious diseases associated with the posttranscriptional regulation of protein-coding genes. In this study, we aimed to investigate the function of miRNAs in type 2 diabetes mellitus. The miRNAs expression profiles were examined by miRNA microarray analysis of skeletal muscles from healthy and Goto-Kakizaki rats. We identified four up-regulated miRNAs, and 11 miRNAs that were down-regulated relative to normal individuals. Among induced miRNAs were three paralogs of miR-29, miR-29a, miR-29b, and miR-29c. Northern blotting further confirmed their elevated expression in three important target tissues of insulin action: muscle, fat, and liver of diabetic rats. Adenovirus-mediated overexpression of miR-29a/b/c in 3T3-L1 adipocytes could largely repress insulin-stimulated glucose uptake, presumably through inhibiting Akt activation. The increase in miR-29 level caused insulin resistance, similar to that of incubation with high glucose and insulin in combination, which, in turn, induced miR-29a and miR-29b expression. In this paper, we demonstrate that Akt is not the direct target gene of miR-29 and that the negative effects of miR-29 on insulin signaling might be mediated by other unknown intermediates. Taken together, these data reveal the crucial role of miR-29 in type 2 diabetes.
ISSN:0888-8809
1944-9917
DOI:10.1210/me.2007-0167