Troxerutin attenuates insulin resistance via pancreatic IL-22/JAK1/STAT3 signaling activation in dihydrotestosterone-induced polycystic ovary syndrome rats
Polycystic ovary syndrome (PCOS) is an extremely common endocrine-metabolic disorder and the main cause of infertility in premenopausal women, thus targeted treatments are sorely needed. Accumulative evidence showed that exogenous supplementation of IL-22 in PCOS mice may be of significant positive effect on insulin resistance (IR), a root causative factor for this condition, but much remained unknown about its mechanism. According to our previous study, troxerutin, a common anticoagulant and thrombolytic agent in clinic, alleviated various PCOS-like phenotypes in dihydrotestosterone (DHT)-treated rat model with unclear mechanism. Here, glucose tolerance tests (GTTs), insulin tolerance tests (ITTs), and homeostatic model assessment of insulin resistance (HOMA-IR) analyses revealed that troxerutin treatment in DHT-treated rats also significantly improved insulin resistance and enhanced serum IL-22 levels, which thereby activated IL-22R1/Janus kinase 1 (JAK1)/signal transducer and activator of transcription-3 (STAT3) signaling pathway in pancreatic islet. This protective effect of troxerutin on insulin resistance improvement was blocked by an inhibitor of p-STAT3, S3I-201. Troxerutin administration to DHT rats decreased the relative abundance of Bifidobacterium and enhanced secondary bile acid profiles, which were positively correlated with serum IL-22 concentration. Conclusively, the present study reported that troxerutin is an endogenous enhancer of IL-22 and the effect of troxerutin on insulin resistance improvement was via IL-22R1/JAK1/STAT3 signaling activation in a DHT-induced PCOS rat model. These insights may be translated into a primary therapeutic agent for PCOS with insulin resistance and hyperandrogenism.NEW & NOTEWORTHY Troxerutin decreased the relative abundance of Bifidobacterium, along with enhancement of secondary bile acids/IL-22 system, which thereby activated its downstream IL-22R1/JAK1/STAT3 signaling pathway in pancreatic β cells, subsequently attenuated insulin resistance (IR), hyperandrogenism and PCOS-like phenotypes in DHT-induced PCOS rat models. Troxerutin is an endogenous IL-22 enhancer and may be of therapeutic value for PCOS with insulin resistance.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2022 |
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| Erschienen: |
2022 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:323 |
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| Enthalten in: |
American journal of physiology. Endocrinology and metabolism - 323(2022), 5 vom: 01. Nov., Seite E405-E417 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Gao, Zixuan [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 24.10.2022 Date Revised 13.12.2023 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1152/ajpendo.00150.2022 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| 245 | 1 | 0 | |a Troxerutin attenuates insulin resistance via pancreatic IL-22/JAK1/STAT3 signaling activation in dihydrotestosterone-induced polycystic ovary syndrome rats |
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| 500 | |a Date Revised 13.12.2023 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Polycystic ovary syndrome (PCOS) is an extremely common endocrine-metabolic disorder and the main cause of infertility in premenopausal women, thus targeted treatments are sorely needed. Accumulative evidence showed that exogenous supplementation of IL-22 in PCOS mice may be of significant positive effect on insulin resistance (IR), a root causative factor for this condition, but much remained unknown about its mechanism. According to our previous study, troxerutin, a common anticoagulant and thrombolytic agent in clinic, alleviated various PCOS-like phenotypes in dihydrotestosterone (DHT)-treated rat model with unclear mechanism. Here, glucose tolerance tests (GTTs), insulin tolerance tests (ITTs), and homeostatic model assessment of insulin resistance (HOMA-IR) analyses revealed that troxerutin treatment in DHT-treated rats also significantly improved insulin resistance and enhanced serum IL-22 levels, which thereby activated IL-22R1/Janus kinase 1 (JAK1)/signal transducer and activator of transcription-3 (STAT3) signaling pathway in pancreatic islet. This protective effect of troxerutin on insulin resistance improvement was blocked by an inhibitor of p-STAT3, S3I-201. Troxerutin administration to DHT rats decreased the relative abundance of Bifidobacterium and enhanced secondary bile acid profiles, which were positively correlated with serum IL-22 concentration. Conclusively, the present study reported that troxerutin is an endogenous enhancer of IL-22 and the effect of troxerutin on insulin resistance improvement was via IL-22R1/JAK1/STAT3 signaling activation in a DHT-induced PCOS rat model. These insights may be translated into a primary therapeutic agent for PCOS with insulin resistance and hyperandrogenism.NEW & NOTEWORTHY Troxerutin decreased the relative abundance of Bifidobacterium, along with enhancement of secondary bile acids/IL-22 system, which thereby activated its downstream IL-22R1/JAK1/STAT3 signaling pathway in pancreatic β cells, subsequently attenuated insulin resistance (IR), hyperandrogenism and PCOS-like phenotypes in DHT-induced PCOS rat models. Troxerutin is an endogenous IL-22 enhancer and may be of therapeutic value for PCOS with insulin resistance | ||
| 650 | 4 | |a Journal Article | |
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| 700 | 1 | |a Wang, Gui |e verfasserin |4 aut | |
| 700 | 1 | |a Ma, Xiaochen |e verfasserin |4 aut | |
| 700 | 1 | |a Tan, Huihui |e verfasserin |4 aut | |
| 700 | 1 | |a Zhang, Chu |e verfasserin |4 aut | |
| 700 | 1 | |a Yin, Xin |e verfasserin |4 aut | |
| 700 | 1 | |a Suo, Feng |e verfasserin |4 aut | |
| 700 | 1 | |a Yao, Ruiqin |e verfasserin |4 aut | |
| 700 | 1 | |a Yan, Xiaonan |e verfasserin |4 aut | |
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