Suppression of Hyperglycemia-Induced Insulin Resistance by Rapanone Isolated from Connarus Ruber

Abstract

Although it would be ideal if insulin resistance due to a persistent hyperglycemic state could be prevented by consuming particular foods, to the best of our knowledge, no foods with such effects have as yet been reported. Connarus ruber (CR) extract, previously indicated to be effective against diabetes, was investigated in this study to ascertain whether it can inhibit the induction of insulin resistance in human hepatoma-derived HepG2 cells. Insulin resistance can be induced in cells by cultivating under hyperglycemic conditions. HepG2 cells were cultured for 24 and 48 h with 1.25 µg/mL of CR extract and its components, rapanone and embelin, at 1.25 and 5 µg/mL, followed by the induction of insulin resistance by hyperglycemic conditions. The results revealed a decrease over time in the glucose concentration of HepG2 cells, indicating that insulin resistance was inhibited in these cells. However, when HepG2 cells, already insulin resistant owing to previous exposure to hyperglycemic conditions, were cultured for 24 and 48 h with CR extract containing rapanone and embelin at <10 µg/mL, the glucose concentration creased over time, indicating that insulin resistance was not affected under these conditions. The results suggest that insulin resistance is inhibited only when CR extract exposure occurs before exposure to hyperglycemia conditions and CR cannot induce recovery from insulin resistance. Thus, this study indicates that CR extract, with rapanone and embelin as active ingredients, could be used as a functional food to reduce the risk of developing type 2 diabetes mellitus as a result of chronic hyperglycemia.