Berberine Decreases Intestinal GLUT2 Translocation and Reduces Intestinal Glucose Absorption in Mice.

Min Zhang,Jia Li,Ling Dong,Erwan Yang,Hongyan Yang

doi:10.3390/ijms23010327

Abstract

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.

Highlights

Body weight and fasting blood glucose were increased in mice in the DM group compared to mice in the control group, while body weight and fasting blood glucose were decreased in the berberine treated diabetic mice compared to diabetic mice
We found that intestinal glucose absorption was enhanced in diabetic conditions, which was mainly evidenced by the increased ability of intestinal glucose transport in vitro and permanent localization of glucose transporter 2 (GLUT2) in the brush border membrane (BBM) of intestinal epithelium in diabetic mice
Using the method of 2-NBDG uptake, we found that berberine decreased intestinal glucose transport, which indicated that berberine decreased intestinal glucose absorption in diabetes

Summary

Introduction

The absorption of nutrients is the primary function of the small intestine, and abnormal intestinal absorption often leads to various metabolic diseases. As for type 2 diabetes mellitus (T2DM), pathological enhancement of intestinal glucose absorption has been considered as one of the major causal factors of postprandial hyperglycemia, which is closely related to complications and prognosis of T2DM [1]. There are hardly any highly recommended medications to rescue pathological changes of intestinal glucose absorption directly in T2DM management. Intestinal glucose absorption mainly depends on sodium-glucose cotransporter 1. (SGLT1) and glucose transporter 2 (GLUT2) in epithelial cells [2]. Luminal glucose is transported into epithelial cells through SGLT1 in the brush border membrane (BBM)

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