Identification Of Interlinked Signaling Pathways In Mouse Model Of Diabetes Mellitus And Hepatocellular Inflammation

Abstract

Diabetes Mellitus (DM), a metabolic disorder characterized by hyperglycemia and insulin resistance is the leading chronic disease and has emerged a big socio-economic burden in Pakistan. Chronic liver diseases on the other hand make Pakistan stand on 2nd position only after Egypt. Liver inflammation ranges from hepatic steatosis to progressive forms of diseases include liver injury, fibrosis, cirrhosis and carcinoma. Liver plays a central role in glucose and lipid metabolism and number of meta-analysis and observational studies shows a strong association between diabetes and chronic liver inflammation. The purpose of present study is to investigate the mutual factors between both pathological conditions. Variance in body weights, lipid profile, level of alanine aminotransferase (ALT), alkaline phosphatase (AST), Bilirubin, blood glucose and anti-oxidant activities were found more abnormal in balb/c model that developed both liver injury and diabetic condition. Histopathology of liver reveals a positive association between diabetic and liver insulted mice model. Western blot analysis revealed the presence of agents of pro-inflammatory pathways i.eNFκB, COX-2 and Akt. Level of these pro-inflammatory agents is found higher in mice group induced with both diabetes and liver injury than the group induced with either of the diseases. These investigations reveal the severity of pathogenesis in the presence of both diseases and also single out potential predictors of hepatic inflammation in diabetes mellitus.