Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice
Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying m...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/15938 |
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| author | Yaxin Fu Wenming Ji Quan Liu Lin Zhang Caina Li Yi Huan Lei Lei Xuefeng Gao Leilei Chen Cunyu Feng Liran Lei Jiayu Zhai Pingping Li Hui Cao Shuainan Liu Zhufang Shen |
| author_facet | Yaxin Fu Wenming Ji Quan Liu Lin Zhang Caina Li Yi Huan Lei Lei Xuefeng Gao Leilei Chen Cunyu Feng Liran Lei Jiayu Zhai Pingping Li Hui Cao Shuainan Liu Zhufang Shen |
| author_sort | Yaxin Fu |
| collection | DOAJ |
| description | Voglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors. |
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| language | English |
| last_indexed | 2024-03-09T03:32:19Z |
| publishDate | 2022-12-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-48a6e76853ba45869a3a0070cce4957a2023-12-03T14:53:10ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241593810.3390/ijms232415938Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy MiceYaxin Fu0Wenming Ji1Quan Liu2Lin Zhang3Caina Li4Yi Huan5Lei Lei6Xuefeng Gao7Leilei Chen8Cunyu Feng9Liran Lei10Jiayu Zhai11Pingping Li12Hui Cao13Shuainan Liu14Zhufang Shen15State Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaDepartment of Endocrinology, Beijing Tongren Hospital, Capital Medical University, Beijing 100730, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaState Key Laboratory of Bioactive Substances and Functions of Natural Medicines, Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, ChinaVoglibose is an α-glycosidase inhibitor that improves postprandial hyperglycemia and increases glucagon-like peptide-1 (GLP-1) secretion in patients with type 2 diabetes. Recently, there has been increasing interest in the anti-inflammatory effects of voglibose on the intestine, but the underlying mechanism is not clear. This study evaluated the effects and mechanisms of voglibose on glycemic control and intestinal inflammation. Type 2 diabetic KKAy mice were treated with voglibose (1 mg/kg) by oral gavage once daily. After 8 weeks, glucose metabolism, levels of short-chain fatty acids (SCFAs), systematic inflammatory factors, intestinal integrity and inflammation were evaluated using hematoxylin and eosin staining, immunohistochemistry, immunofluorescence and Western blot analysis. Voglibose ameliorated glucose metabolism by enhancing basal- and glucose-dependent GLP-1 secretion. Several beneficial SCFAs, such as acetic acid and propionic acid, were increased by voglibose in the fecal sample. Additionally, voglibose notably decreased the proportion of pro-inflammatory macrophages and the expression of nuclear factor kappa B but increased the expression of tight junction proteins in the ileum, thus markedly improving intestinal inflammatory damage and reducing the systematic inflammatory factors. Ileal genomics and protein validation suggested that voglibose attenuated inositol-requiring protein 1α-X-box binding protein 1-mediated endoplasmic reticulum stress (ERS). Together, these results showed that voglibose enhanced the secretion of GLP-1, which contributed to the glycemic control in KKAy mice at least in part by regulating intestinal inflammation and the expression of ERS factors.https://www.mdpi.com/1422-0067/23/24/15938voglibosetype 2 diabetesinflammationileal macrophagesendoplasmic reticulum stress |
| spellingShingle | Yaxin Fu Wenming Ji Quan Liu Lin Zhang Caina Li Yi Huan Lei Lei Xuefeng Gao Leilei Chen Cunyu Feng Liran Lei Jiayu Zhai Pingping Li Hui Cao Shuainan Liu Zhufang Shen Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice International Journal of Molecular Sciences voglibose type 2 diabetes inflammation ileal macrophages endoplasmic reticulum stress |
| title | Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice |
| title_full | Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice |
| title_fullStr | Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice |
| title_full_unstemmed | Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice |
| title_short | Voglibose Regulates the Secretion of GLP-1 Accompanied by Amelioration of Ileal Inflammatory Damage and Endoplasmic Reticulum Stress in Diabetic KKAy Mice |
| title_sort | voglibose regulates the secretion of glp 1 accompanied by amelioration of ileal inflammatory damage and endoplasmic reticulum stress in diabetic kkay mice |
| topic | voglibose type 2 diabetes inflammation ileal macrophages endoplasmic reticulum stress |
| url | https://www.mdpi.com/1422-0067/23/24/15938 |
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