3,4',5-Trimethoxy-trans-stilbene ameliorates hepatic insulin resistance and oxidative stress in diabetic obese mice through insulin and Nrf2 signaling pathways
Resveratrol has profound benefits against diabetes. However, whether its methylated derivative 3,4',5-trimethoxy-trans-stilbene (3,4',5-TMS) also plays a protective role in glucose metabolism is not characterized. We aimed to study the anti-diabetic effects of 3,4',5-TMS in vitro and in vivo. Insulin-resistant HepG2 cells (IR-HepG2) were induced by high glucose plus dexamethasone whilst six-week-old male C57BL/6J mice received a 60 kcal% fat diet for 14 weeks to establish an obese diabetic model. 3,4',5-TMS did not reduce the cell viability of IR-HepG2 cells at concentrations of 0.5 and 1 μM, which enhanced the capability of glycogen synthesis and glucose consumption in IR-HepG2 cells. Four-week oral administration of 3,4',5-TMS at 10 mg kg-1 day-1 ameliorated insulin sensitivity and glucose tolerance of diet-induced obese (DIO) mice. 3,4',5-TMS activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway by inhibiting phosphorylation of insulin receptor substrate (IRS)-1 at Ser307 and increasing the protein levels of IRS-1 and IRS-2 to restore the insulin signaling pathway in diabetes. 3,4',5-TMS also upregulated the phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at Ser9. 3,4',5-TMS suppressed oxidative stress by increasing the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H : quinone oxidoreductase 1 (NQO1) and antioxidant enzyme activity. In summary, 3,4',5-TMS alleviated hepatic insulin resistance in vitro and in vivo, by the activation of the insulin signaling pathway, accomplished by the suppression of oxidative stress.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:15 |
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| Enthalten in: |
Food & function - 15(2024), 6 vom: 18. März, Seite 2996-3007 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Tan, Yi [VerfasserIn] |
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| Links: |
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| Themen: |
3,4',5-trimethoxystilbene |
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| Anmerkungen: |
Date Completed 19.03.2024 Date Revised 19.03.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1039/d3fo04158a |
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| funding: |
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| Förderinstitution / Projekttitel: |
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NLM369011740 |
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| 245 | 1 | 0 | |a 3,4',5-Trimethoxy-trans-stilbene ameliorates hepatic insulin resistance and oxidative stress in diabetic obese mice through insulin and Nrf2 signaling pathways |
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| 520 | |a Resveratrol has profound benefits against diabetes. However, whether its methylated derivative 3,4',5-trimethoxy-trans-stilbene (3,4',5-TMS) also plays a protective role in glucose metabolism is not characterized. We aimed to study the anti-diabetic effects of 3,4',5-TMS in vitro and in vivo. Insulin-resistant HepG2 cells (IR-HepG2) were induced by high glucose plus dexamethasone whilst six-week-old male C57BL/6J mice received a 60 kcal% fat diet for 14 weeks to establish an obese diabetic model. 3,4',5-TMS did not reduce the cell viability of IR-HepG2 cells at concentrations of 0.5 and 1 μM, which enhanced the capability of glycogen synthesis and glucose consumption in IR-HepG2 cells. Four-week oral administration of 3,4',5-TMS at 10 mg kg-1 day-1 ameliorated insulin sensitivity and glucose tolerance of diet-induced obese (DIO) mice. 3,4',5-TMS activated the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) pathway by inhibiting phosphorylation of insulin receptor substrate (IRS)-1 at Ser307 and increasing the protein levels of IRS-1 and IRS-2 to restore the insulin signaling pathway in diabetes. 3,4',5-TMS also upregulated the phosphorylation of glycogen synthase kinase 3 beta (GSK3β) at Ser9. 3,4',5-TMS suppressed oxidative stress by increasing the protein levels of nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1) and NAD(P)H : quinone oxidoreductase 1 (NQO1) and antioxidant enzyme activity. In summary, 3,4',5-TMS alleviated hepatic insulin resistance in vitro and in vivo, by the activation of the insulin signaling pathway, accomplished by the suppression of oxidative stress | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Zhou, Chunxiu |e verfasserin |4 aut | |
| 700 | 1 | |a Miao, Lingchao |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Xutao |e verfasserin |4 aut | |
| 700 | 1 | |a Khan, Haroon |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Baojun |e verfasserin |4 aut | |
| 700 | 1 | |a Cheang, Wai San |e verfasserin |4 aut | |
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