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Hyperlipidemia-Induced MicroRNA-155-5p Improves β-Cell Function by Targeting Mafb.

Authors: Zhu, Mengyu  Wei, Yuanyuan  Geißler, Claudia  Abschlag, Kathrin  Corbalán Campos, Judit  Hristov, Michael  Möllmann, Julia  Lehrke, Michael  Karshovska, Ela  Schober, Andreas 
Citation: Zhu M, etal., Diabetes. 2017 Dec;66(12):3072-3084. doi: 10.2337/db17-0313. Epub 2017 Sep 29.
Pubmed: (View Article at PubMed) PMID:28970282
DOI: Full-text: DOI:10.2337/db17-0313

A high-fat diet increases bacterial lipopolysaccharide (LPS) in the circulation and thereby stimulates glucagon-like peptide 1 (GLP-1)-mediated insulin secretion by upregulating interleukin-6 (IL-6). Although microRNA-155-5p (miR-155-5p), which increases IL-6 expression, is upregulated by LPS and hyperlipidemia and patients with familial hypercholesterolemia less frequently develop diabetes, the role of miR-155-5p in the islet stress response to hyperlipidemia is unclear. In this study, we demonstrate that hyperlipidemia-associated endotoxemia upregulates miR-155-5p in murine pancreatic β-cells, which improved glucose metabolism and the adaptation of β-cells to obesity-induced insulin resistance. This effect of miR-155-5p is because of suppression of v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B, which promotes β-cell function through IL-6-induced GLP-1 production in α-cells. Moreover, reduced GLP-1 levels are associated with increased obesity progression, dyslipidemia, and atherosclerosis in hyperlipidemic Mir155 knockout mice. Hence, induction of miR-155-5p expression in β-cells by hyperlipidemia-associated endotoxemia improves the adaptation of β-cells to insulin resistance and represents a protective mechanism in the islet stress response.

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RGD Object Information
RGD ID: 21079445
Created: 2020-02-17
Species: All species
Last Modified: 2020-02-17
Status: ACTIVE



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