| First Author | Zhu M | Year | 2017 |
| Journal | Diabetes | Volume | 66 |
| Issue | 12 | Pages | 3072-3084 |
| PubMed ID | 28970282 | Mgi Jnum | J:251558 |
| Mgi Id | MGI:5927673 | Doi | 10.2337/db17-0313 |
| Citation | Zhu M, et al. (2017) Hyperlipidemia-Induced MicroRNA-155-5p Improves beta-Cell Function by Targeting Mafb. Diabetes 66(12):3072-3084 |
| abstractText | 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 beta-cells, which improved glucose metabolism and the adaptation of beta-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 beta-cell function through IL-6-induced GLP-1 production in alpha-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 beta-cells by hyperlipidemia-associated endotoxemia improves the adaptation of beta-cells to insulin resistance and represents a protective mechanism in the islet stress response. |
