Regardless of socioeconomic or demographic background, the prevalence of type 2 diabetes mellitus, which affects more than half a billion people worldwide, has been steadily increasing over time. The health, emotional, sociological, and economic well-being of people would suffer if this number is not successfully handled. The liver is one of the key organs accountable for sustaining metabolic balance. Elevated levels of reactive oxygen species inhibit the recruitment and activation of IRS-1, IRS-2, and PI3K-Akt downstream signaling cascade. These signaling mechanisms reduce hepatic glucose absorption and glycogenesis while increasing hepatic glucose output and glycogenolysis. In our work, an analysis of the molecular mechanism of Carica papaya in mitigating hepatic insulin resistance in vivo and in silico was carried out. The gluconeogenic enzymes, glycolytic enzymes, hepatic glycogen tissue concentration, oxidative stress markers, enzymatic antioxidants, protein expression of IRS-2, PI3K, SREBP-1C, and GLUT-2 were evaluated in the liver tissues of high-fat-diet streptozotocin-induced type 2 diabetic rats using q-RT-PCR as well as immunohistochemistry and histopathology. Upon treatment, C. papaya restored the protein and gene expression in the liver. In the docking analysis, quercetin, kaempferol, caffeic acid, and p-coumaric acid present in the extract were found to have high binding affinities against IRS-2, PI3K, SREBP-1c, and GLUT-2, which may have contributed much to the antidiabetic property of C. papaya. Thus, C. papaya was capable of restoring the altered levels in the hepatic tissues of T2DM rats, reversing hepatic insulin resistance.
Chitin is most abundantly found non-digestible carbohydrate similar to cellulose. It has gained a lot of interest in last few years due to its wide range of applications. They are used as an alternative, dietary supplement. Chitin on deacetylation forms chitosan, an active component of chitin. The degree of deacetylation and molecular weight are the factors that elucidate varying degree of biological property of chitosan. The ability of chitosan in fat and lipid excretion has obtained keen eye among various researchers. This property of chitosan is made use in enhancing the elimination of various harmful environmental lipophilic xenobiotics. Endocrine disruptors are a group of environmental pollutants causing various hazardous effects in living system. They are highly lipophilic, persistent and can accumulate in various tissues. Thus correlating the ability of chitosan to increase excretion of fats and lipophilic xenobiotics showed a promising positive outcome.
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