Regulation of the expression of components of the exocytotic machinery of insulin-secreting cells by microRNAs
| Autor: | Pascal Lovis, Romano Regazzi, Sonia Gattesco |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Synaptosomal-Associated Protein 25
medicine.medical_treatment Clinical Biochemistry Vesicular Transport Proteins Biochemistry Exocytosis rab27 GTP-Binding Proteins Cell Line Mice 1-Methyl-3-isobutylxanthine Insulin-Secreting Cells Insulin Secretion microRNA medicine Animals Insulin Glucose homeostasis Secretion Molecular Biology Adaptor Proteins Signal Transducing Chemistry Colforsin Intracellular Signaling Peptides and Proteins Proteins Synapsin Rab3A GTP-Binding Protein Affect blood Blood Glucose Diabetes Mellitus drug effects Forskolin Glucose Homeostasis Hyperglycemia metabolism MicroRNAs pharmacology physiology rab GTP-Binding Proteins rab3A GTP-Binding Protein Role secretion Switzerland Synapsins Cell biology Hormone |
| Zdroj: | Biological Chemistry, vol. 389, no. 3, pp. 305-312 |
| Popis: | Fine-tuning of insulin secretion from pancreatic β-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 β-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. |
| Databáze: | OpenAIRE |
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