Dual Molecular Actions of Aspirin on Pancreatic β-Cell Function and Hepatic Glucose Transport in Experimental Diabetes

Abstract

Background: Aspirin (acetylsalicylic acid), a nonsteroidal anti-inflammatory drug, has been shown to modulate inflammatory and metabolic pathways. Objectives: This study aimed to investigate the molecular effects of aspirin on pancreatic and hepatic gene expression associated with β-cell function and glucose regulation in alloxan-induced diabetic rats. Methods: Twenty-four male Wistar rats were allocated to the control, diabetic, and diabetic-aspirin groups. Rats in the diabetic-aspirin group received aspirin (100 mg/kg/day, intraperitoneally) for 35 days. Fasting blood glucose (FBG), body weight, and the mRNA expression of Pdx1, Ins1/2, Insr, and Tnfα in pancreatic tissue, as well as Glut1, Glut2, Insr, and Tnfα in hepatic tissue, were analyzed using quantitative real-time polymerase chain reaction. Results: Diabetes induction significantly increased FBG levels and dysregulated the expression of genes involved in insulin synthesis, glucose transport, and inflammation. Aspirin administration markedly reduced FBG by approximately 30% without affecting body weight, restored pancreatic Pdx1 and Ins1/2 expression, and downregulated Insr and Tnfα, indicating improved β-cell function and reduced local inflammation. In hepatic tissue, aspirin significantly suppressed the overexpression of Glut1, Glut2, Insr, and Tnfα, suggesting improved hepatic glucose handling and attenuated inflammatory signaling. These organ-specific transcriptional effects indicate that aspirin simultaneously supports β-cell regeneration and modulates hepatic glucose transport and inflammatory pathways. Mechanistically, these effects may be mediated through inhibition of the nuclear factor kappa B pathway, activation of AMP-activated protein kinase, and reduction of oxidative stress. Conclusions: Collectively, these findings provide molecular evidence that aspirin may exert beneficial antidiabetic and anti-inflammatory effects by restoring pancreatic β-cell gene expression and normalizing hepatic metabolic gene networks, thereby supporting its potential as an accessible adjunct therapy for diabetes management.