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Mar. Drugs 2019, 17(1), 49; https://doi.org/10.3390/md17010049

CYC27 Synthetic Derivative of Bromophenol from Red Alga Rhodomela confervoides: Anti-Diabetic Effects of Sensitizing Insulin Signaling Pathways and Modulating RNA Splicing-Associated RBPs

1,2,†
,
2,†
,
2
,
2
and
3,*
1
School of Public Health, Qingdao University, Qingdao 266071, China
2
CAS Key Laboratory of Experimental Marine Biology, Institute of Oceanology, Chinese Academy of Sciences, Qingdao 266071, China
3
State Key Laboratory of Microbial Technology, Shandong University, Jinan 250100, China
These two authors contribute equally to this manuscript.
*
Author to whom correspondence should be addressed.
Received: 12 December 2018 / Revised: 7 January 2019 / Accepted: 7 January 2019 / Published: 11 January 2019
(This article belongs to the Collection Marine Drugs in the Management of Metabolic Diseases)
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Abstract

RNA-binding proteins (RBPs) lie at the center of posttranscriptional regulation and the dysregulation of RBPs contributes to diabetes. Therefore, the modulation of RBPs is anticipated to become a potential therapeutic approach to diabetes. CYC27 is a synthetic derivative of marine bromophenol BDB, which is isolated from red alga Rhodomela confervoides. In this study, we found that CYC27 significantly lowered the blood glucose levels of diabetic BKS db mice. Moreover, CYC27 effectively ameliorated dyslipidemia in BKS db mice by reducing their total serum cholesterol (TC) and triglyceride (TG) levels. Furthermore, CYC27 was an insulin-sensitizing agent with increased insulin-stimulated phosphorylation of insulin receptors and relevant downstream factors. Finally, to systemically study the mechanisms of CYC27, label-free quantitative phosphoproteomic analysis was performed to investigate global changes in phosphorylation. Enriched GO annotation showed that most regulated phosphoproteins were related to RNA splicing and RNA processing. Enriched KEGG analysis showed that a spliceosome-associated pathway was the predominant pathway after CYC27 treatment. Protein-protein interaction (PPI) analysis showed that CYC27 modulated the process of mRNA splicing via phosphorylation of the relevant RBPs, including upregulated Cstf3 and Srrt. Our results suggested that CYC27 treatment exerted promising anti-diabetic effects by sensitizing the insulin signaling pathways and modulating RNA splicing-associated RBPs. View Full-Text
Keywords: brominated organic compounds; hypoglycemic activity; insulin-sensitizing effect; RBPs; RNA splicing brominated organic compounds; hypoglycemic activity; insulin-sensitizing effect; RBPs; RNA splicing
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Luo, J.; Jiang, B.; Li, C.; Jia, X.; Shi, D. CYC27 Synthetic Derivative of Bromophenol from Red Alga Rhodomela confervoides: Anti-Diabetic Effects of Sensitizing Insulin Signaling Pathways and Modulating RNA Splicing-Associated RBPs. Mar. Drugs 2019, 17, 49.

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