Abstract
AbstractType 2 diabetes is a challenge in modern healthcare, and animal models are necessary to identify underlying mechanisms. The Nile rat (Arvicanthis niloticus) develops diet-induced diabetes rapidly on a conventional rodent chow diet without genetic or chemical manipulation. Unlike common laboratory models, the outbred Nile rat model is diurnal and has a wide range of overt diabetes onset and diabetes progression patterns in both sexes, better mimicking the heterogeneous diabetic phenotype in humans. While fasted blood glucose has historically been used to monitor diabetic progression, postprandial blood glucose is more sensitive to the initial stages of diabetes. However, there is a long-held assumption that ad libitum feeding in rodent models leads to increased variance, thus masking diabetes-related metabolic changes in the plasma. Here we compared repeatability within triplicates of non-fasted or fasted plasma samples and assessed metabolic changes relevant to glucose tolerance in fasted and non-fasted plasma of 8–10-week-old male Nile rats. We used liquid chromatography–mass spectrometry lipidomics and polar metabolomics to measure relative metabolite abundances in the plasma samples. We found that, compared to fasted metabolites, non-fasted plasma metabolites are not only more strongly associated with glucose tolerance on the basis of unsupervised clustering and elastic net regression model, but also have a lower replicate variance. Between the two sampling groups, we detected 66 non-fasted metabolites and 32 fasted metabolites that were associated with glucose tolerance using a combined approach with multivariable elastic net and individual metabolite linear models. Further, to test if metabolite replicate variance is affected by age and sex, we measured non-fasted replicate variance in a cohort of mature 30-week-old male and female Nile rats. Our results support using non-fasted plasma metabolomics to study glucose tolerance in Nile rats across the progression of diabetes.
Funder
The Garland Initiative
U.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences
U.S. Department of Health & Human Services | NIH | U.S. National Library of Medicine
Publisher
Springer Science and Business Media LLC
Subject
General Veterinary,Animal Science and Zoology
Reference54 articles.
1. International Diabetes Federation. IDF Diabetes Atlas 10th edn (International Diabetes Federation, 2021).
2. Suliman, S. M., Shumake, S. A. & Jackson, W. B. Food preference in the Nile rat Arvicanthis niloticus. Trop. Pest Manag. 30, 151–158 (1984).
3. Senzota, R. B. M. A case of rodent–ungulate resource partitioning. J. Mammal. 64, 326–329 (1983).
4. Toh, H., Thomson, J. A. & Jiang, P. Maternal high-fiber diet protects offspring against type 2 diabetes. Nutrients 13, E94 (2020).
5. King, A. & Bowe, J. Animal models for diabetes: understanding the pathogenesis and finding new treatments. Biochem. Pharmacol. 99, 1–10 (2016).
Cited by
1 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献