Mechanisms involved in diabetes-induced cardiomyopathy and nephropathy in the Zucker diabetic Sprague-Dawley rats

Abstract: Diabetes mellitus is a group of metabolic disorders that is characterized by elevated glucose levels. It has been suggested that obesity is the main link to the development of diabetes mellitus type 2 due to the adipose tissue in these patients secreting abnormally large amounts of pro-inflammatory cytokines. Diabetic nephropathy can be defined as injury and inflammation in kidneys. Its incidence is mainly characterised by the presence of high urinary albumin excretion. The direct toxic effect of hyperglycaemia has been implicated in recent studies which were seen in both types of diabetes mellitus, i.e., type 1 and type 2. Overtime, there is production of advanced glycosylation end-products which accumulate to enhance the atherosclerosis formation by activating the adhesion molecules, growth factors as well as inflammatory cytokines. The current study was therefore designed to investigate mechanisms that are involved in diabetes induced cardiomyopathy and nephropathy in the Zucker diabetic Sprague-Dawley rats, a rodent model that has an intact leptin signalling pathway. From the beginning of week 15, ZDSD rats were given a high fat diet for 5 weeks. Glucose handling was also monitored every four weeks through oral glucose tolerance tests with the blood glucose levels collected from the tail vein at 15, 30, 60 and 120 min after the glucose load. Sections were stained using Haematoxylin and eosin (H&E) as well as with Masson’s trichrome. Both the heart and kidney sections were semi-quantitatively and quantitatively analysed. All statistical analyses were done using Graphpad prism software for windows (Version 7.0) and measurements for each variable was expressed as mean± standard error. At the end of the experiment, the ZDSD rats showed classical features of diabetes, and these are obesity, hyperglycaemia, and weight loss. In conclusion, this study successfully demonstrated T2DM in the ZDSD rat by monitoring and evaluating alterations in the body mass, lipid profiles, insulin resistance as well as fasting blood glucose. Furthermore, diabetic-related structural changes were noted, and these included the RCA and CMA alterations. Oxidative stress could be credited as a possible mechanism for the changes that were observed in this animal model.M.Tech. (Biomedical Technology