Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells
We have previously reported that Agriophyllum oligosaccharides (AOS) significantly enhance glycemic control by increasing the activation of insulin receptor (INS-R), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), peroxisome proliferator-activated...
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Frontiers Media S.A.
2021-08-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2021.656220/full |
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| author | Shuyin Bao Shuyin Bao Xiuzhi Wang Xiuzhi Wang Sung Bo Cho Yan-Ling Wu Chengxi Wei Shuying Han Liming Bao Qiong Wu Wuliji Ao Wuliji Ao Ji-Xing Nan Ji-Xing Nan |
| author_facet | Shuyin Bao Shuyin Bao Xiuzhi Wang Xiuzhi Wang Sung Bo Cho Yan-Ling Wu Chengxi Wei Shuying Han Liming Bao Qiong Wu Wuliji Ao Wuliji Ao Ji-Xing Nan Ji-Xing Nan |
| author_sort | Shuyin Bao |
| collection | DOAJ |
| description | We have previously reported that Agriophyllum oligosaccharides (AOS) significantly enhance glycemic control by increasing the activation of insulin receptor (INS-R), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), peroxisome proliferator-activated receptor (PPAR)-γ, and glucose transporter 4 (Glut4) proteins in hepatic tissues. However, the effect of glucose control by AOS on the regulation of pancreatic tissues in db/db mice and MIN6 cells remains to be determined. An oral dose of AOS (380 or 750 mg/kg) was administered to type-2 diabetic db/db mice for 8 weeks to determine whether AOS regulates glucose by the INS-R/IRS/Glut4-mediated insulin pathway. Meanwhile, the effects of AOS on glucose uptake and its related signaling pathway in MIN6 cells were also investigated. The results showed that the random blood glucose (RBG) level in the AOS-treated group was lower than that in the control group. AOS reduced the levels of glycated hemoglobin (HbA1c) and free fatty acid (FFA) and significantly improved the pathological changes in the pancreatic tissues in db/db mice. Moreover, immunohistochemical analysis revealed that the expression of INS-R, IRS-1, IRS-2, and Glut4 was increased in the AOS-treated group than in the model group. Further, in vitro experiments using MIN6 cells showed that AOS regulated INS-R, IRS-1, IRS-2, and Glut4 protein and mRNA levels and attenuated insulin resistance and cell apoptosis. The results of both in vitro and in vivo experiments were comparable. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometric analysis of AOS with precolumn derivatization with 3-amino-9-ethylcarbazole (AEC) tentatively identified five types of sugars: glucose, lactose, rutinose, glucuronic acid, and maltotriose. Our present study clearly showed that AOS is efficacious in preventing hyperglycemia, possibly by increasing insulin sensitivity and improving IR by regulating the INS-R/IRS/Glut4 insulin signal pathway. Therefore, AOS may be considered as a potential drug for diabetes treatment. |
| first_indexed | 2024-12-21T16:03:14Z |
| format | Article |
| id | doaj.art-f54bf527774f4408abafbcbec91daacd |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-12-21T16:03:14Z |
| publishDate | 2021-08-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-f54bf527774f4408abafbcbec91daacd2022-12-21T18:57:58ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122021-08-011210.3389/fphar.2021.656220656220Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 CellsShuyin Bao0Shuyin Bao1Xiuzhi Wang2Xiuzhi Wang3Sung Bo Cho4Yan-Ling Wu5Chengxi Wei6Shuying Han7Liming Bao8Qiong Wu9Wuliji Ao10Wuliji Ao11Ji-Xing Nan12Ji-Xing Nan13Key Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, ChinaMedical College, Inner Mongolia University for Nationalities, Tongliao, ChinaDepartment of Medicines and Foods, Tongliao Vocational College, Tongliao, ChinaThe Research Institute of Traditional Mongolian Medicine Engineering Technology, Tongliao, ChinaCollege of Traditional Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao, ChinaKey Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, ChinaMedical College, Inner Mongolia University for Nationalities, Tongliao, ChinaBasic Medical College, North China University of Science and Technology, Tangshan, ChinaCollege of Traditional Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao, ChinaDepartment of Cardiology, Tongliao Second People’s Hospital, Tongliao, ChinaThe Research Institute of Traditional Mongolian Medicine Engineering Technology, Tongliao, ChinaCollege of Traditional Mongolian Medicine, Inner Mongolia University for Nationalities, Tongliao, ChinaKey Laboratory for Traditional Chinese Korean Medicine of Jilin Province, College of Pharmacy, Yanbian University, Yanji, ChinaClinical Research Center, Yanbian University Hospital, Yanji, ChinaWe have previously reported that Agriophyllum oligosaccharides (AOS) significantly enhance glycemic control by increasing the activation of insulin receptor (INS-R), insulin receptor substrate-2 (IRS-2), phosphatidylinositol 3 kinase (PI3K), protein kinase B (AKT), peroxisome proliferator-activated receptor (PPAR)-γ, and glucose transporter 4 (Glut4) proteins in hepatic tissues. However, the effect of glucose control by AOS on the regulation of pancreatic tissues in db/db mice and MIN6 cells remains to be determined. An oral dose of AOS (380 or 750 mg/kg) was administered to type-2 diabetic db/db mice for 8 weeks to determine whether AOS regulates glucose by the INS-R/IRS/Glut4-mediated insulin pathway. Meanwhile, the effects of AOS on glucose uptake and its related signaling pathway in MIN6 cells were also investigated. The results showed that the random blood glucose (RBG) level in the AOS-treated group was lower than that in the control group. AOS reduced the levels of glycated hemoglobin (HbA1c) and free fatty acid (FFA) and significantly improved the pathological changes in the pancreatic tissues in db/db mice. Moreover, immunohistochemical analysis revealed that the expression of INS-R, IRS-1, IRS-2, and Glut4 was increased in the AOS-treated group than in the model group. Further, in vitro experiments using MIN6 cells showed that AOS regulated INS-R, IRS-1, IRS-2, and Glut4 protein and mRNA levels and attenuated insulin resistance and cell apoptosis. The results of both in vitro and in vivo experiments were comparable. Ultra-performance liquid chromatography coupled with time-of-flight mass spectrometric analysis of AOS with precolumn derivatization with 3-amino-9-ethylcarbazole (AEC) tentatively identified five types of sugars: glucose, lactose, rutinose, glucuronic acid, and maltotriose. Our present study clearly showed that AOS is efficacious in preventing hyperglycemia, possibly by increasing insulin sensitivity and improving IR by regulating the INS-R/IRS/Glut4 insulin signal pathway. Therefore, AOS may be considered as a potential drug for diabetes treatment.https://www.frontiersin.org/articles/10.3389/fphar.2021.656220/fullAgriophyllum oligosaccharides (AOS)T2DMinsulin resistanceINS-R/IRS/Glut4 insulin pathwaydb/db mice |
| spellingShingle | Shuyin Bao Shuyin Bao Xiuzhi Wang Xiuzhi Wang Sung Bo Cho Yan-Ling Wu Chengxi Wei Shuying Han Liming Bao Qiong Wu Wuliji Ao Wuliji Ao Ji-Xing Nan Ji-Xing Nan Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells Frontiers in Pharmacology Agriophyllum oligosaccharides (AOS) T2DM insulin resistance INS-R/IRS/Glut4 insulin pathway db/db mice |
| title | Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells |
| title_full | Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells |
| title_fullStr | Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells |
| title_full_unstemmed | Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells |
| title_short | Agriophyllum Oligosaccharides Ameliorate Diabetic Insulin Resistance Through INS-R/IRS/Glut4-Mediated Insulin Pathway in db/db Mice and MIN6 Cells |
| title_sort | agriophyllum oligosaccharides ameliorate diabetic insulin resistance through ins r irs glut4 mediated insulin pathway in db db mice and min6 cells |
| topic | Agriophyllum oligosaccharides (AOS) T2DM insulin resistance INS-R/IRS/Glut4 insulin pathway db/db mice |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2021.656220/full |
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