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Original Research
Hyperlipidemia-Induced MicroRNA-155-5p Improves β-cell Function by Targeting Mafb
Mengyu Zhu, Yuanyuan Wei, Claudia Geißler, Kathrin Abschlag, Judit Corbalán Campos, Michael Hristov, Julia Möllmann, Michael Lehrke, Ela Karshovska and Andreas Schober
Diabetes 2017 Sep; db170313. https://doi.org/10.2337/db17-0313
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Abstract

A high-fat diet increases bacterial lipopolysaccharide (LPS) in the circulation, and thereby stimulates glucagon-like peptide-1 (GLP-1)-mediated insulin secretion by up-regulating interleukin (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. Here, we demonstrate that hyperlipidemia-associated endotoxemia up-regulates 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 due to suppression of v-maf musculoaponeurotic fibrosarcoma oncogene family, protein B (Mafb), 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.

Footnotes

  • This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db17-0313/-/DC1.

  • Received March 13, 2017.
  • Accepted September 19, 2017.
  • © 2017 by the American Diabetes Association.
http://www.diabetesjournals.org/content/license

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.

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Hyperlipidemia-Induced MicroRNA-155-5p Improves β-cell Function by Targeting Mafb
Mengyu Zhu, Yuanyuan Wei, Claudia Geißler, Kathrin Abschlag, Judit Corbalán Campos, Michael Hristov, Julia Möllmann, Michael Lehrke, Ela Karshovska, Andreas Schober
Diabetes Sep 2017, db170313; DOI: 10.2337/db17-0313

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Hyperlipidemia-Induced MicroRNA-155-5p Improves β-cell Function by Targeting Mafb
Mengyu Zhu, Yuanyuan Wei, Claudia Geißler, Kathrin Abschlag, Judit Corbalán Campos, Michael Hristov, Julia Möllmann, Michael Lehrke, Ela Karshovska, Andreas Schober
Diabetes Sep 2017, db170313; DOI: 10.2337/db17-0313
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© 2019 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.