In Vitro: In human hepatoma-derived cells (HepG2), KY-226 (0.3-10 μM) increases the phosphorylated insulin receptor (pIR) produced by insulin. KY-226 (1 μM; 24 hours; bEnd.3 cells) treatment rescues lipopolysaccharide-induced reduction of mRNA and protein levels of ZO-1. KY-226 treatment restores phosphorylation of pAkt (T308) and its downstream target forkhead box protein O1 (FoxO1) (S256) in bEnd.3 cells.
In Vivo: KY-226 (10-30 mg/kg/day; oral administration; daily; for 4 weeks; male db/db mice) treatment significantly reduces plasma glucose and triglyceride levels as well as hemoglobin A1c values without increasing body weight gain. KY-226 attenuates plasma glucose elevations in the oral glucose tolerance test. KY-226 also increases pIR and phosphorylated Akt in the liver and femoral muscle.