The synergistic effect of fenretinide and metformin to achieve a decrease in insulin resistance and inflammatory mediators: an in vivo study

Abstract

Background: The effects of metformin and fenretinide on insulin resistance and inflammatory mediators were investigated to treat type 2 diabetes mellitus. Methods: Type 2 diabetes was induced in adult albino Wistar rats via the administration of streptozotocin and nicotinamide. Rats were divided as follows: Group I, control rats administered normal saline solution; Group II, diabetic rats; Group III, diabetic rats treated with metformin; Group IV, diabetic rats administered fenretinide; and Group V, diabetic rats administered both metformin and fenretinide. Results: Fasting blood glucose (FBG) was increased in diabetic rats compared to control rats (p<0.05). However, both FBG and glycated hemoglobin levels were decreased (p<0.05) in diabetic rats treated with fenretinide and metformin compared to diabetic untreated rats. A positive relationship was identified between RBP4 level and insulin resistance. Further, diabetic rats treated with fenretinide and metformin had decreased RBP4 levels. Conversely, GLUT4 mRNA was markedly increased (p<0.05) in diabetic rats administered fenretinide and metformin, thereby improving insulin sensitivity. TNF-α level showed a direct relationship with the insulin resistance. Evidently, metformin and fenretinide decreased plasma IL-6 level and increased IL-10 levels. Conclusion: Metformin and fenretinide exhibit individual and synergistic effects when administered to treat diabetes in a rat model. Abbreviations: RBP4: Retinol-binding protein 4; IL: Interleukin; TNF-α: tumor necrosis factor-alpha; STZ: Streptozotocin; NaF: sodium fluoride; cDNA: complementary DNA; ACTB: beta-actin; GLUT4: glucose transporter type 4; LDL: low-density lipoprotein; VLDL: very-low-density lipoprotein; TAG: triacylglycerol; HDL: high-density lipoprotein; FBG: fasting blood glucose; DIO: diet-induced obese; IR: insulin receptor; TG: triglyceride.