PPARα/γ, adiponectin, and GLUT4 overexpression induced by moronic acid methyl ester influenced glucose and triglyceride levels of experimental diabetic mice.

Abstract

The current study aimed to determine the antidiabetic and antidyslipidemic activities of moronic acid methyl ester (1) (compound 1) by in vivo, in vitro, in silico, and molecular biology studies. Compound 1 was evaluated to establish its dose-dependent antidiabetic and antihyperglycemic (50mg/kg) activities, in diabetic and normoglycemic male CD1 mice, respectively. Also, compound 1 was subjected to a subacute study (50mg/kg per day for 8 days) to determine blood biochemical profiles and the expression of protein tyrosine phosphatase 1B (PTP-1B), glucose transporter type 4 (GLUT4), peroxisome proliferator-activated receptor α (PPAR-α), PPAR-γ, adiponectin, interleukin-1β (IL-1β), and monocyte chemoattractant protein 1 (MCP-1) in adipose tissue of animals after treatment. Different doses in acute administration of compound 1 decreased glycemia (p< 0.05) compared with vehicle, showing greater effectiveness in the range 50-160mg/kg. Also, the oral glucose tolerance test showed that compound 1 induced a significant antihyperglycemic action by opposing the hyperglycemic peak (p< 0.05). Moreover, compound 1 subacute administration decreased glucose and triglyceride levels after treatment (p< 0.05); while the expression of PPAR-α and PPAR-γ, adiponectin, and GLUT4 displayed an increase (p< 0.05) compared with the diabetic control group. In conclusion, compound 1 showed antihyperglycemic, antidiabetic, and antidyslipidemic effects in normal and diabetic mice, probably due to insulin sensitization through increased mRNA expression of GLUT4, PPAR-α, PPAR-γ, and adiponectin genes.