2. Academic Validation
  3. Berberine protects mice against type 2 diabetes by promoting PPARγ-FGF21-GLUT2-regulated insulin sensitivity and glucose/lipid homeostasis

Berberine protects mice against type 2 diabetes by promoting PPARγ-FGF21-GLUT2-regulated insulin sensitivity and glucose/lipid homeostasis

  • Biochem Pharmacol. 2023 Nov 17:218:115928. doi: 10.1016/j.bcp.2023.115928.
Yi Chen 1,  Qi Li 2,  Shiwei Zhao 2,  Lei Sun 2,  Zequn Yin 3,  Xiaolin Wang 2,  Xiaoju Li 2,  Yasuko Iwakiri 4,  Jihong Han 5,  Yajun Duan 6
Affiliations

Affiliations

  • 1 Department of Cell Biology, School of Basic Medical Sciences, Hangzhou Normal University, Hangzhou, China.
  • 2 College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China.
  • 3 Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China.
  • 4 Section of Digestive Diseases, Yale University School of Medicine, New Haven, CT, USA.
  • 5 College of Life Sciences, State Key Laboratory of Medicinal Chemical Biology, Key Laboratory of Bioactive Materials of Ministry of Education, Nankai University, Tianjin, China; Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China. Electronic address: jihonghan2008@nankai.edu.cn.
  • 6 Key Laboratory of Metabolism and Regulation for Major Diseases of Anhui Higher Education Institutes, College of Food and Biological Engineering, Hefei University of Technology, Hefei, China. Electronic address: yduan@hfut.edu.cn.
PMID: 37979703 DOI: 10.1016/j.bcp.2023.115928
Abstract

Type 2 diabetes (T2D) is a chronic, burdensome disease that is characterized by disordered Insulin sensitivity and disturbed glucose/lipid homeostasis. Berberine (BBR) has multiple therapeutic actions on T2D, including regulation of glucose and lipid metabolism, improvement of Insulin sensitivity and energy expenditure. Recently, the function of BBR on Fibroblast Growth Factor 21 (FGF21) has been identified. However, if BBR ameliorates T2D through FGF21, the underlying mechanisms remain unknown. Herein, we used T2D wild type (WT) and FGF21 global knockout (FKO) mice [mouse T2D model: established by high-fat diet (HFD) feeding plus streptozotocin (STZ) injection], and hepatocyte-specific peroxisome proliferator activated receptor γ (PPARγ) deficient (PPARγHepKO) mice, and cultured human liver carcinoma cells line, HepG2 cells, to characterize the role of BBR in glucose/lipid metabolism and Insulin sensitivity. We found that BBR activated FGF21 expression by up-regulating PPARγ expression at the cellular level. Meanwhile, BBR ameliorated glucosamine hydrochloride (Glcn)-induced Insulin resistance and increased glucose transporter 2 (GLUT2) expression in a PPARγ/FGF21-dependent manner. In T2D mice, BBR up-regulated the expression of PPARγ, FGF21 and GLUT2 in the liver, and GLUT2 in the pancreas. BBR also reversed T2D-induced Insulin resistance, liver lipid accumulation, and damage in liver and pancreas. However, FGF21 deficiency diminished these effects of BBR on diabetic mice. Altogether, our study demonstrates that the therapeutic effects of BBR on T2D were partly accomplished by activating PPARγ-FGF21-GLUT2 signaling pathway. The discovery of this new pathway provides a deeper understanding of the mechanism of BBR for T2D treatment.

Keywords

Berberine; FGF21; GLUT2; Insulin sensitivity; PPARγ; Type 2 diabetes.

Figures
Products