Background: Diabetes mellitus is a chronic metabolic disorder characterized by persistent hyperglycemia due to impaired insulin secretion, reduced insulin sensitivity, or both. Its pathogenesis is associated with pancreatic β-cell dysfunction, oxidative stress, inflammation, and structural tissue injury. Recent evidence suggests that abnormal activation of the aryl hydrocarbon receptor (AhR) pathway may contribute to diabetic disturbances through upregulation of downstream genes such as CYP1A1 and CYP1B1, thereby aggravating metabolic and pancreatic dysfunction.
Aim: This study aimed to investigate the involvement of AhR signaling in alloxan-induced diabetic pancreatic injury and to evaluate the modulatory and protective effects of metformin in rats.
Methods: Thirty adult male rats were divided into five groups; Sham, diabetic control, diabetic vehicle control, metformin-treated, and AhR blocker-treated. By alloxan the diabetes was induced, and treatments continued for 3 weeks. Pancreatic CYP1A1, CYP1B1, PPAR-Gamma (PPARG), and SLC2A4 expression was assessed by RT-qPCR. C-peptide, TNF-alpha, and malondialdehyde (MDA) levels were measured by ELISA, and pancreatic histology was examined using H&E staining.
Results: CYP1A1 and CYP1B1 expression increased in diabetes and PPARG and SLC2A4 reduced, with decreased C-peptide and elevated TNF-alpha and MDA. Metformin improved these molecular and biochemical changes and partially restored pancreatic architecture. AhR blockade produced similar improvement.
Conclusion: Metformin palliated diabetic pancreatic injury, possibly through indirect modulation of the AhR–CYP1A1/CYP1B1 pathway, supporting the role of AhR signaling in diabetic pancreatic damage.