Evodiamine may inhibit insulin resistance in type 2 diabetes through IRS-1/PI3K/AKT/GLUT4 pathway

In a study aimed at understanding how evodiamine (Evo) could help combat insulin resistance (IR) in type 2 diabetes mellitus (T2DM), researchers examined the impact of Evo on the IRS-1/PI3K/AKT/GLUT4 signaling pathway. Evo, extracted from a traditional Chinese medicine, is an alkaloid with potential therapeutic benefits. Researchers identified 122 targets related to Evo and found that 37 overlapped with IR-related targets, focusing on key proteins such as AKT1, STAT3, SRC, and PTGS2.

By analyzing the PI3K/AKT signaling pathway using KEGG pathway analysis, they discovered that Evo significantly enhanced glucose consumption and reduced glucose production in HepG2 cells, mirroring the effects of the positive control metformin. Evo treatment also restored p-AKT and p-PI3K levels to normal in IR-HepG2 cells, similar to metformin's action.

Moreover, Evo reduced p-IRS-1 in IR-HepG2 cells, a finding that metformin did not achieve. The study suggests that Evo's potential as a treatment for IR may stem from its ability to modulate the IRS-1/PI3K/AKT signaling pathway and boost GLUT4 expression.