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

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.

Biochemical Investigation of Therapeutic Efficacy of Berberine-Enriched Extract in Streptozotocin-Induced Metabolic Impairment

“…The pronounced effects of BEE on gene expression indicate its ability to enhance insulin signaling pathways and improve insulin sensitivity, making it a promising agent for addressing insulin resistance. The study of our result was affirmed by the previously published papers . The upregulation of genes, particularly GCK, IGF-1, and GLUT2, is pivotal in understanding the molecular mechanisms underlying the therapeutic effects of BEE in our study.…”

“…The study of our result was affirmed by the previously published papers. 28 The upregulation of genes, particularly GCK, IGF-1, and GLUT2, is pivotal in understanding the molecular mechanisms underlying the therapeutic effects of BEE in our study. The increased expression of these genes suggests a positive impact on carbohydrate metabolism and insulin sensitivity.…”

Chemicolome and Metabolome Profiling of Xieriga-4 Decoction, A Traditional Mongolian Medicine, Using the UPLC-QTOF/MS Approach

“…It efectively reduces fasting plasma glucose, postprandial blood glucose, and glycosylated hemoglobin by participating in insulin resistance, antiinfammatory, antioxidation, regulating lipid metabolism disorders and intestinal fora, and other methods. Berberine is mainly used in the treatment of type 2 diabetes, obesity, and metabolic diseases [21][22][23][24][25][26][27]. We detected berberine in plasma, feces, and biological samples, indicating that the prototype and metabolites of berberine are involved in the hypoglycemic mechanism.…”

Preliminary Study on the Protective Effects and Molecular Mechanism of Procyanidins against PFOS-Induced Glucose-Stimulated Insulin Secretion Impairment in INS-1 Cells

“…Insulinoma β-cells express glucose transporter-2 (Glut2), which can be used as a sensor molecule to regulate insulin secretion. Glut2 imbalance is one of the early signs of NIDDM [ 20 ]. Glucokinase (GCK) is a key regulatory enzyme in insulinoma β-cells, which can phosphorylate glucose to glucose-6-phosphate.…”