Upregulation of PPARγ by Aegle marmelos ameliorates insulin resistance and β-cell dysfunction in high fat diet fed-streptozotocin induced type 2 diabetic rats

Abstract

The global epidemic of type 2 diabetes demands the rapid evaluation of new and accessible interventions. This study investigated whether Aegle marmelos fruit aqueous extract (AMF; 250, 500 and 1000 mg/kg) improves insulin resistance, dyslipidemia and β-cell dysfunction in high fat diet fed-streptozotocin (HFD-STZ)-induced diabetic rats by modulating peroxisome proliferator-activated receptor-γ (PPARγ) expression. The serum levels of glucose, insulin, homeostasis model assessment of insulin resistance (HOMA-IR), homeostasis model assessment of β-cell function (HOMA-B), lipid profile, TNF-α and IL-6 were evaluated. Further, the TBARS level and SOD activity in pancreatic tissue and PPARγ protein expression in liver were assessed. In addition, histopathological and ultrastructural studies were performed to validate the effect of AMF on β-cells. The HFD-STZ treated rats showed a significant increase in the serum levels of glucose, insulin, HOMA-IR, TNF-α, IL-6, dyslipidemia with a concomitant decrease in HOMA-B and PPARγ expression. Treatment with AMF for 21 days in diabetic rats positively modulated the altered parameters in a dose-dependent manner. Furthermore, AMF prevented inflammatory changes and β-cell damage along with a reduction in mitochondrial and endoplasmic reticulum swelling. These findings suggest that the protective effect of AMF in type 2 diabetic rats is due to the preservation of β-cell function and insulin-sensitivity through increased PPARγ expression.