Increased Metabolic Stress in Zucker Diabetic Fatty Rat Kidney and Pancreas

Abstract

Background/Aims: Obesity and diabetes (hereafter termed diabesity) are among the most challenging global health problems. Since the main pathophysiological complications in diabesity are hyperglycemia, hyperlipidemia, insulin resistance, cardiomyopathy, nephropathy, and urinary infections, the kidney and pancreas are the potential target organs affected in the above conditions. However, the precise molecular mechanisms of disease progression and complications are still unclear. The Zucker homozygous (FA/FA) diabetic fatty (ZDF) rat is a genetic model for obesity and type 2 diabetes. Our previous studies, using cardiac muscles have demonstrated metabolic and oxidative stress in ZDF rats. In the present study, our aim was to investigate oxidative stress associated metabolic complications in ZDF rat kidney and pancreas. Methods: Here we have measured oxidative stress, glutathione (GSH)-dependent metabolism and mitochondrial respiratory functions in the kidney and pancreas of ZDF and Zucker lean (ZL, +/FA) control rats. Results: Our results showed an increase in reactive oxygen species, NO production, lipid and protein peroxidation in ZDF rat kidney and pancreas accompanied by alterations in GSH-dependent metabolism and mitochondrial function. Western blot analysis has also confirmed increased expression of oxidative stress marker proteins in ZDF rats. Conclusion: We have demonstrated that ZDF rats develop metabolic complications associated with oxidative stress and mitochondrial dysfunction. Thus, these results might have implications in understanding the etiology and pathology of diabesity.