Characterizing Insulin Sensitivity in Adult LEW.1WR1 Rats

Abstract

Diabetes prevention is a large topic of research that is focused on nutritional and exercise‐based interventions with some genetic predisposition based interventions. FAT10 is a ubiquitin‐like protein and Type 1 Diabetes (T1D) susceptibility gene that may play a role in age‐related inflammation, adiposity, cancer, and kidney disease. The young T1D susceptible, LEW.1WR1 rat overexpresses FAT10 and has higher fasting concentrations of blood insulin. It is unclear how the overexpression of FAT10 effects directly affects insulin sensitivity, secretion, or production. It is also unclear if the initial insulin sensitivity of this animal model plays a role in disease susceptibility. Therefore we hypothesized that older LEW.1WR1 rats will have markers of increased insulin resistance like increased insulin and beta cell mass due to the poor regulation of FAT10 expression in this model. The objective of this study was to characterize insulin sensitivity, insulin levels, and characterize the relative beta cell size of adult LEW.1WR1 rats with or without dietary stress to understand if FAT10 expression plays a role in the regulation of inflammation and aging‐induced insulin resistance. To test this hypothesis we used LEW.1WR1 and LEW.SsNHsd rat and monitored weight gain and glucose tolerance over the course of 12 weeks on a high fat or control diet; we also isolated pancreata and used immunohistochemistry staining for insulin to analyze islet size and insulin staining. The LEW.ssNHsd rat served as a control rat because it does not have the alteration in the FAT10 promoter region. Glucose tolerance tests were performed prior to starting the diet as a baseline, and after 10 weeks on the diet to determine the effects of diet and aging on the rat groups in regards to Insulin Sensitivity. We observed that in the course of 10 weeks the control LEW.1WR1 rats became significantly more glucose intolerant and had increased insulin levels. The control LEW.1WR1 rats also gained weight at a rate similar to the high‐fat diet, a diet that is traditionally used to induce insulin resistance and glucose intolerance. This data suggests that FAT10 may be playing a role in age‐related adiposity, glucose intolerance, insulin sensitivity, and beta‐cell changes in the LEW.1WR1 rat. This study begins to lay the groundwork for understanding how alterations in FAT10 and metabolism increase T1D susceptibility.Support or Funding InformationThe University of Alabama in HuntsvilleLouis Stokes Alliance for Minority Participation (NSF)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.