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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Main Authors: Min Zhang, Hongyan Yang, Erwan Yang, Jia Li, Ling Dong
Format: Article
Language:English
Published: MDPI AG 2021-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/23/1/327
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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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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
work_keys_str_mv AT minzhang berberinedecreasesintestinalglut2translocationandreducesintestinalglucoseabsorptioninmice
AT hongyanyang berberinedecreasesintestinalglut2translocationandreducesintestinalglucoseabsorptioninmice
AT erwanyang berberinedecreasesintestinalglut2translocationandreducesintestinalglucoseabsorptioninmice
AT jiali berberinedecreasesintestinalglut2translocationandreducesintestinalglucoseabsorptioninmice
AT lingdong berberinedecreasesintestinalglut2translocationandreducesintestinalglucoseabsorptioninmice