Protective efficacy of melatonin and insulin against LPS caused toxicity in diabetic mice

Context: Deregulated glucose homeostasis leads to a life-threatening metabolic disorder known as diabetes. The insulin deficiency and hyperglycaemic condition related to diabetes cause dysregulation of the immune system. Objective: This study evaluated the combined efficacy of melatonin and insulin in attenuation of lipopolysaccharide (LPS) caused inflammation, macrophage functional impairment, and oxidative stress in the spleen of diabetic mice. Materials and Methods: Multiple low doses of streptozotocin (50mg/kg B. wt.) were administered intraperitoneally to induce diabetes. Diabetes mice were divided into two sets. Set-1 contained control, diabetes, diabetes insulin (2IU/100g B.wt.) treated, diabetes melatonin (100 mu g/100g. B.wt.) treated, and diabetes melatonin and insulin treated groups of mice. In set II, the same number of groups as those of set I were given a single dose of LPS (50 mu g/mice) 24 hours before euthanization. Results and Discussion: LPS caused a significant increase in oxidative stress, circulatory proinflammatory cytokines, significant suppression of antioxidant defense system, and phagocytic index in diabetic mice. Melatonin and insulin significantly improved the adverse effects caused by LPS treatment in diabetic mice. The present study noted that combined treatment of melatonin and insulin was more effective in attenuating LPS-induced devastating effects in laboratory mice. Conclusions: The present study may suggest a combinatorial approach in the therapeutic use of melatonin and insulin to improve such devastating conditions.