Melatonin and insulin modulates the cellular biochemistry, histoarchitecture and receptor expression during hepatic injury in diabetic rats

Aims; The present study was designed to ameliorate the integrated efficacy of exogenous melatonin and insulin on tissue biochemical, serological, histopathological architecture and receptor expression of melatonin (MT1, MT2) and insulin receptor (IR) expression against the hepatic injury in diabetic rats. Materials and Method; the rats were randomly allocated into nine different experimental groups. Diabetes was induced by streptozotocin (15 mg/kg) for 6 days. Rats having blood glucose level above 250 mg/dl were considered as diabetic. Animals euthanized after 4 weeks, blood and liver samples were collected to perform various biochemical, serological, histopathological and receptor expression of melatonin (MT1, MT2) and insulin receptor (IR). Key findings; Diabetic rats revealed significant increase in lipid peroxidation (LPO) of liver tissue, liver function tests (ALT, AST and ALP), increase in serum cholesterol, LDL, VLD, but decrease in HDL level. Further, diabetic rats exhibited significant decrement in antioxidative enzymatic system (GSH, SOD, CAT, GR, GPX, G6PDH and GST), total tissue protein and glycogen content. Histomicrograph of liver of diabetic rats resulted in vacuolization indicating cellular damages as well as upregulation in liver MT1, MT2 and IR protein expression. However, the combined therapy (Melatonin and insulin treatment) revealed significant recovery and restoration in biochemical, cellular architecture of liver cells and receptor expression pattern of MT1, MT2 and IR. Significance; It may establish a synergistic action of melatonin and insulin, which might be a novel evidence for clinicians to combat the hepatic complication along with controlling diabetes.