A Propolis‐Derived Small Molecule Tectochrysin Ameliorates Type 2 Diabetes in Mice by Activating Insulin Receptor β

Scope Propolis has been found to decrease glucose levels and increase insulin sensitivity in type 2 diabetes. However, the active ingredient responsible for these effects and its regulating mechanism are not fully understood. Methods and results To address this, molecular docking screening is used to screen the effective hypoglycemic ingredient in propolis and found that tectochrysin (TEC) has a high affinity to the insulin receptor (IR), highlighting its potential for glycemic control. In vivo tests show that TEC decreases glucose levels and enhances insulin sensitivity in db/db mice. By hyperinsulinemic euglycemic clamp test, this study further finds that TEC promotes glucose uptake in adipose tissue and skeletal muscle, as well as inhibits hepatic gluconeogenesis. Moreover, it finds that TEC promotes glucose uptake and adipocytes differentiation in 3T3‐L1 cells like insulin, suggesting that TEC exerts an insulin mimetic effect. Mechanistically, pharmacology inhibition of IRβ abolishes the effects of TEC on glucose uptake and the phosphorylation of IR. The study further demonstrates that TEC binds to and activates IRβ by targeting its E1077 and M1079. Conclusion Therefore, this study sheds light on the mechanism underlying propolis’ potential for ameliorating type 2 diabetes, offering a natural food‐derived compound as a promising therapeutic option.