Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs

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Serval ID
serval:BIB_3D99E2CF7027
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs
Journal
Biological Chemistry
Author(s)
Lovis P., Gattesco S., Regazzi R.
ISSN
1431-6730
Publication state
Published
Issued date
2008
Peer-reviewed
Oui
Volume
389
Number
3
Pages
305-312
Language
english
Abstract
Fine-tuning of insulin secretion from pancreatic beta-cells participates in blood glucose homeostasis. Defects in this process can lead to chronic hyperglycemia and diabetes mellitus. Several proteins controlling insulin exocytosis have been identified, but the mechanisms regulating their expression remain poorly understood. Here, we show that two non-coding microRNAs, miR124a and miR96, modulate the expression of proteins involved in insulin exocytosis and affect secretion of the beta-cell line MIN6B1. miR124a increases the levels of SNAP25, Rab3A and synapsin-1A and decreases those of Rab27A and Noc2. Inhibition of Rab27A expression is mediated by direct binding to the 3'-untranslated region of Rab27A mRNA. The effect on the other genes is indirect and linked to changes in mRNA levels. Over-expression of miR124a leads to exaggerated hormone release under basal conditions and a reduction in glucose-induced secretion. miR96 increases mRNA and protein levels of granuphilin, a negative modulator of insulin exocytosis, and decreases the expression of Noc2, resulting in lower capacity of MIN6B1 cells to respond to secretagogues. Our data identify miR124a and miR96 as novel regulators of the expression of proteins playing a critical role in insulin exocytosis and in the release of other hormones and neurotransmitters
Keywords
1-Methyl-3-isobutylxanthine , Affect , Animals , blood , Blood Glucose , Cell Line , Diabetes Mellitus , drug effects , Exocytosis , Forskolin , Glucose , Homeostasis , Hyperglycemia , Insulin , Insulin-Secreting Cells , metabolism , Mice , MicroRNAs , pharmacology , physiology , Proteins , rab GTP-Binding Proteins , rab3A GTP-Binding Protein , Role , secretion , Switzerland , Synapsins , Synaptosomal-Associated Protein 25 , Vesicular Transport Proteins
Pubmed
Web of science
Open Access
Yes
Create date
29/01/2009 23:13
Last modification date
01/10/2019 7:17
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