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Mol Endocrinol. 2007 Nov;21(11):2785-94. Epub 2007 Jul 24.

Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes.

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1
The National Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, The Chinese Academy of Medical Sciences and Peking Union Medical College, 5 Dong Dan San Tiao, Beijing 100005, China.

Abstract

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.

PMID:
17652184
DOI:
10.1210/me.2007-0167
[Indexed for MEDLINE]
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