Loureirin B activates GLP-1R and promotes insulin secretion in Ins-1 cells

J Cell Mol Med. 2021 Jan;25(2):855-866. doi: 10.1111/jcmm.16138. Epub 2020 Dec 10.

Abstract

Loureirin B (LB) is a natural product derived from Sanguis draconis, which has hypoglycaemic effects. In order to research the possible target of LB in the treatment of diabetes, molecular docking was used to simulate the interaction between LB and potential targets, and among them, glucagon-like peptide-1 receptor (GLP-1R) had the optimal results. Further, spectroscopy and surface plasmon resonance (SPR) experiments were applied to detect the interaction between LB and GLP-1R. Ultimately, after GLP-1R siRNA interfering the expression of GLP-1R in Ins-1 cell, the promoting insulin secretion of LB was weaken, which directly proved that GLP-1R plays an important role. These results show that LB promotes insulin secretion of Ins-1 cells through GLP-1R. Hence, the strategy of LB as a prodrug will provide a potential approach for non-peptide GLP-1R agonist.

Keywords: agonist; anti-diabetic drugs; glucagon-like peptide-1 receptor; insulin; natural product.

MeSH terms

  • Animals
  • Biological Products
  • Blotting, Western
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Glucagon-Like Peptide-1 Receptor / metabolism*
  • Hypoglycemic Agents / pharmacology
  • Insulin / metabolism
  • Insulin Secretion / drug effects
  • Insulin-Secreting Cells / drug effects
  • Insulin-Secreting Cells / metabolism
  • Rats
  • Resins, Plant / pharmacology*

Substances

  • Biological Products
  • Glucagon-Like Peptide-1 Receptor
  • Hypoglycemic Agents
  • Insulin
  • Resins, Plant
  • loureirin B