α-Glucosidase inhibitor: identifying key targets and mechanisms in type 2 diabetes

Acarbose is an α-glucosidase inhibitor that helps lower blood sugar after meals by stopping complex carbohydrates from turning into simple sugars; however, its role other than α-glucosidase inhibition is not yet fully understood. In this study, we used bioinformatics to explore the molecular targets and mechanisms of acarbose in type 2 diabetes (T2D). We found one hundred and twenty-seven shared targets between proteins linked to acarbose and genes related to T2D. Analysis showed these targets are mainly involved in insulin signaling, glucose metabolism, PI3K/Akt pathway, and inflammation. Network analysis highlighted 10 important genes: AKT1, ALB, EGFR, ESR1, GSK3B, HSP90AA1, PPARG, STAT3, SRC, and TNF. Expression profiling showed these genes have different patterns in various tissues from diabetic samples. Molecular docking results indicated a binding affinity of acarbose with the key proteins, with EGFR showing the lowest binding energy of - 7.8 kcal/mol. Molecular dynamics (MD) simulations confirmed that the acarbose-protein complexes, especially with EGFR, STAT3, PPARG, and HSP90AA1, are stable. Overall, these results provide a detailed information on how acarbose may act on multiple targets other than inhibiting α-glucosidase in T2D.

The online version contains supplementary material available at 10.1007/s13205-026-04772-5.