Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice
Postprandial hyperglycemia is an important causative factor of type 2 diabetes mellitus, and permanent localization of intestinal GLUT2 in the brush border membrane is an important reason of postprandial hyperglycemia. Berberine, a small molecule derived from Coptidis rhizome, has been found to be p...
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MDPI AG
2021-12-01
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author | Min Zhang Hongyan Yang Erwan Yang Jia Li Ling Dong |
author_facet | Min Zhang Hongyan Yang Erwan Yang Jia Li Ling Dong |
author_sort | Min Zhang |
collection | DOAJ |
description | Postprandial hyperglycemia is an important causative factor of type 2 diabetes mellitus, and permanent localization of intestinal GLUT2 in the brush border membrane is an important reason of postprandial hyperglycemia. Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose, but how berberine lowers postprandial blood glucose is still elusive. Here, we investigated the effect of berberine on intestinal glucose transporter 2 (GLUT2) translocation and intestinal glucose absorption in type 2 diabetes mouse model. Type 2 diabetes was induced by feeding of a high-fat diet and injection of streptozotocin and diabetic mice were treated with berberine for 6 weeks. The effects of berberine on intestinal glucose transport and GLUT2 translocation were accessed in isolated intestines and intestinal epithelial cells (IEC-6), respectively. We found that berberine treatment improved glucose tolerance and systemic insulin sensitivity in diabetic mice. Furthermore, berberine decreased intestinal glucose transport and inhibited GLUT2 translocation from cytoplasm to brush border membrane in intestinal epithelial cells. Mechanistically, berberine inhibited intestinal insulin-like growth factor 1 (IGF-1R) phosphorylation and thus reduced localization of PLC-β2 in the membrane, leading to decreased GLUT2 translocation. These results suggest that berberine reduces intestinal glucose absorption through inhibiting IGF-1R-PLC-β2-GLUT2 signal pathway. |
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issn | 1661-6596 1422-0067 |
language | English |
last_indexed | 2024-03-10T03:38:25Z |
publishDate | 2021-12-01 |
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series | International Journal of Molecular Sciences |
spelling | doaj.art-3766a0f0d0c54adf915b52ff24e883b62023-11-23T11:38:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-12-0123132710.3390/ijms23010327Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in MiceMin Zhang0Hongyan Yang1Erwan Yang2Jia Li3Ling Dong4Key Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Air Force Military Medical University, Xi’an 710032, ChinaKey Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Air Force Military Medical University, Xi’an 710032, ChinaKey Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Air Force Military Medical University, Xi’an 710032, ChinaKey Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Air Force Military Medical University, Xi’an 710032, ChinaKey Laboratory of Aerospace Medicine of the Ministry of Education, School of Aerospace Medicine, Air Force Military Medical University, Xi’an 710032, ChinaPostprandial hyperglycemia is an important causative factor of type 2 diabetes mellitus, and permanent localization of intestinal GLUT2 in the brush border membrane is an important reason of postprandial hyperglycemia. Berberine, a small molecule derived from Coptidis rhizome, has been found to be potent at lowering blood glucose, but how berberine lowers postprandial blood glucose is still elusive. Here, we investigated the effect of berberine on intestinal glucose transporter 2 (GLUT2) translocation and intestinal glucose absorption in type 2 diabetes mouse model. Type 2 diabetes was induced by feeding of a high-fat diet and injection of streptozotocin and diabetic mice were treated with berberine for 6 weeks. The effects of berberine on intestinal glucose transport and GLUT2 translocation were accessed in isolated intestines and intestinal epithelial cells (IEC-6), respectively. We found that berberine treatment improved glucose tolerance and systemic insulin sensitivity in diabetic mice. Furthermore, berberine decreased intestinal glucose transport and inhibited GLUT2 translocation from cytoplasm to brush border membrane in intestinal epithelial cells. Mechanistically, berberine inhibited intestinal insulin-like growth factor 1 (IGF-1R) phosphorylation and thus reduced localization of PLC-β2 in the membrane, leading to decreased GLUT2 translocation. These results suggest that berberine reduces intestinal glucose absorption through inhibiting IGF-1R-PLC-β2-GLUT2 signal pathway.https://www.mdpi.com/1422-0067/23/1/327berberineintestinal epithelial cellsglucose absorptionGLUT2 |
spellingShingle | Min Zhang Hongyan Yang Erwan Yang Jia Li Ling Dong Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice International Journal of Molecular Sciences berberine intestinal epithelial cells glucose absorption GLUT2 |
title | Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice |
title_full | Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice |
title_fullStr | Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice |
title_full_unstemmed | Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice |
title_short | Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice |
title_sort | berberine decreases intestinal glut2 translocation and reduces intestinal glucose absorption in mice |
topic | berberine intestinal epithelial cells glucose absorption GLUT2 |
url | https://www.mdpi.com/1422-0067/23/1/327 |
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