alexa miRNAs control insulin content in pancreatic β-cells via downregulation of transcriptional repressors.
Biomedical Sciences

Biomedical Sciences

Journal of Bioanalysis & Biomedicine

Author(s): MelkmanZehavi T, Oren R, KredoRusso S, Shapira T, Mandelbaum AD,

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Abstract MicroRNAs (miRNAs) were shown to be important for pancreas development, yet their roles in differentiated β-cells remain unclear. Here, we show that miRNA inactivation in β-cells of adult mice results in a striking diabetic phenotype. While islet architecture is intact and differentiation markers are maintained, Dicer1-deficient β-cells show a dramatic decrease in insulin content and insulin mRNA. As a consequence of the change in insulin content, the animals become diabetic. We provide evidence for involvement of a set of miRNAs in regulating insulin synthesis. The specific knockdown of miR-24, miR-26, miR-182 or miR-148 in cultured β-cells or in isolated primary islets downregulates insulin promoter activity and insulin mRNA levels. Further, miRNA-dependent regulation of insulin expression is associated with upregulation of transcriptional repressors, including Bhlhe22 and Sox6. Thus, miRNAs in the adult pancreas act in a new network that reinforces insulin expression by reducing the expression of insulin transcriptional repressors.
This article was published in EMBO J and referenced in Journal of Bioanalysis & Biomedicine

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