Pharmacological Evaluation of Tyrosine Kinase Inhibitors in Combination with Retinoic Acid for Treatment of Diabetes Mellitus

Abstract

Aim and objective: Tyrosine kinase inhibitors (TKIs) exert anti hyperglycaemic effects that can reverse or prevent type 1 and 2 diabetes mellitus by correcting insulin resistance and beta cell dysfunction. Recent studies on retinoid metabolism have shown association with glucose metabolism in addition to insulin resistance. Therefore, present study focuses on Pharmacological Evaluation of Tyrosine Kinase Inhibitor in the combination with Retinoic Acid for the treatment of Diabetes Mellitus. Materials & methods: For this study we used six to ten weeks old Wistar rats of either sex. Induction was done by administration of 20 % w/v fructose solution for 4 weeks. Erlotinib was administered at dose 2.5mg/kg, Tretinoin was also administered at dose 2.5 mg/kg. Pioglitazone was administered at dose 2.5mg/kg for 7 days. The body weight gain, food intake and water intake was measured through-out the treatment period. At the end of treatment, blood glucose levels, lipid profile were monitored before and after treatment. Effect on glucose homeostasis was measured by oral glucose tolerance test. Liver was subjected to antioxidant study. Histopathology of Liver and Pancreas were assessed by using H & E staining. Results: A statistically significant improvement was observed in blood glucose levels after the treatment of 7-days by Erlotinib in combination with Tretinoin as compared to monotherapy. The combination also showed significant reduction in weight gain after giving the treatment. The glucose and lipid levels showed significant decrease as compared to diseased control group. AUC glucose resulted in reduction in glucose tolerance. Thee anti-oxidant parameters were significantly improved by treatment. Histological analysis resulted in presence of sinusoids and beta cell was obtained to be undamaged which proved the treatment of induced diabetes in the treated group by comparing it with diseased control group. Conclusion: Thus, the present study Erlotinib in combination with Tretinoin showed beneficial effect in treatment of Diabetes Mellitus.