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In search of new fangled therapeutic agents against type 2 diabetes mellitus (T2DM), an appropriate preclinical disease model is important to ensure the success of subsequent clinical trials. There is an increasing trend in the use of high-fat diet (HFD) fed streptozotocin (STZ)-induced rodent models in investigating novel therapeutic agents against T2DM. Though several studies have been conducted on the development of the aforementioned model they were mainly focused on biochemical characteristics. Only limited studies have focused on histopathological changes which is the gold standard in investigating the treatment-related changes of novel therapeutic agents. Therefore, the present study aimed at assessing the histopathological changes of the pancreas and liver, the two main organs involved in glucose homeostasis, in a newly developed HFD-fed STZ-induced Wistar rat model. For this study, Wistar rats were induced with T2DM by intraperitoneal injection of STZ (30, 40, and 50 mg/kg) which was given after feeding the rats with an HFD consisting of 60% calories from fat for four weeks duration. Diabetic rats were sacrificed after maintaining for further four weeks. The liver and pancreas were excised and hematoxylin and eosin-stained sections were observed using a light microscope. The major histopathological changes in the pancreas of HFD-fed STZ-induced diabetic rats were loss of pancreatic islets, pancreatic islet hypertrophy, and mild fatty change in the exocrine pancreas. In contrast, the liver did not show any degree of fatty change, but the majority showed prominent hydropic degeneration in the hepatocytes. In conclusion, prominent alterations were well noted in the pancreatic and liver tissues of the Wistar rats fed with HFD, followed by STZ (50 mg/kg), and the established model could be useful in investigating and elucidating antidiabetic mechanisms of novel pharmaceutical agents.
Wickramasinghe et al. (Tue,) studied this question.