LEW.1WR1 rats have altered hepatic metabolism during their type 1 diabetes susceptibility window
Date of Award
Master of Science (MS)
Glucose -- Metabolism., Lipids -- Metabolism., Diabetes -- Animal models.
LEW.1WR1 (1WR1) rats have increased type 1 diabetes (T1D) onset with the administration of polyinosinic-polycytidylic acid (PIC). The objective of this study was to compare the insulitis status and liver gene expression in both control and treated 1WR1 rats during disease induction with a T1D-resistant strain of rat, the LEW/SsNHsd (SsNHsd). Using immunohistochemistry we observed higher T cell infiltration in the 1WR1 treated rats compared to the control strain, the SsNHsd PIC-treated rat. Yet we confirmed that the 1WR1 rats were not undergoing significant insulitis at the time point we selected. Interestingly the 1WR1 treated rat had significantly increased insulin levels compared to the SsNHsd rats, both groups of the 1WR1 rats also had increased liver FAT10 gene expression compared to the SsNHsd. We observed 1WR1 rats have increased expression of genes related to lipid catabolism and lower expression of glucose metabolism-related genes. In conclusion, 1WR1 rats have reduced insulin sensitivity in the context of increased inflammation due to PIC injection which increases beta-cell sensitivity to eventual T-cell mediated destruction.
Wimalarathne, Madushika, "LEW.1WR1 rats have altered hepatic metabolism during their type 1 diabetes susceptibility window" (2020). Theses. 361.