Abstract | OBJECTIVES: METHODS: RESULTS: The results showed that 250 µM PA for ≥2 days was optimal for inducing IR in HepG2 cells; 600 nM celastrol significantly attenuated the PA-induced IR in HepG2 cells. The PA-induced GLUT4 and IRS1 downregulation and Ser307 phosphorylation on IRS1 was reversed by subsequent treatment with 600 nM celastrol for 6 h. We next investigated which IR-related miRNAs were possible upstream regulators of celastrol-mediated reversal of PA-induced HepG2 IR. Two miRNAs, miR-150 and -223, were significantly downregulated by PA and were re-raised by subsequent celastrol treatment; and miR-223 was upstream of miR-150. Moreover, knocking down miR-223 abolished celastrol's anti-IR effects in the PA-induced model. CONCLUSIONS: Collectively, our results demonstrated that celastrol reverses PA-induced IR-related alterations, in part via miR-223 in HepG2 cells. Further investigation is warranted for establishing the clinical potential of celastrol in treating IR-related disorders.
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Authors | Xue Zhang, Xiao-Cheng Xue, Ying Wang, Fan-Fan Cao, Jun You, Georges Uzan, Bin Peng, Deng-Hai Zhang |
Journal | Canadian journal of diabetes
(Can J Diabetes)
Vol. 43
Issue 3
Pg. 165-172
(Apr 2019)
ISSN: 2352-3840 [Electronic] Canada |
PMID | 30287053
(Publication Type: Journal Article)
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Copyright | Copyright © 2019. Published by Elsevier Inc. |
Chemical References |
- Glucose Transporter Type 4
- MIRN223 microRNA, human
- MicroRNAs
- Pentacyclic Triterpenes
- Triterpenes
- Palmitic Acid
- celastrol
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Topics |
- Animals
- Down-Regulation
- Gene Expression Regulation
- Glucose Transporter Type 4
(genetics, metabolism)
- Hep G2 Cells
- Humans
- Insulin Resistance
(physiology)
- MicroRNAs
(metabolism)
- Palmitic Acid
(metabolism)
- Pentacyclic Triterpenes
- Phosphorylation
- Signal Transduction
- Triterpenes
(pharmacology)
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