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Doctoral thesis, 2020

Refinement of porcine models in diabetes and transplantation research

Manell, Elin;

Abstract

Animal models are widely used in biomedical research aiming to prevent and improve treatments of diseases. The 3Rs (replace, reduce, refine) are considered when working with laboratory animals. Socialisation and training of pigs in research are important to avoid stress responses that could potentially affect research data. Domestic pigs were subjected to a structured training programme before inclusion in renal transplantation studies. The training programme enabled blood and urine sampling, and ultrasound examinations in conscious pigs without restraint. The porcine diabetes model was further characterised with regards to hormonal responses to oral glucose, metabolic changes due to insulin deficiency, distribution of glucagon-like peptide-1 receptors (GLP-1R) in pancreas and gastrointestinal tract, and GLP-1R occupancy in vivo during oral glucose tolerance test (OGTT). Both similarities and differences between pigs and humans were identified, both of which are important to keep in mind when designing animal studies. Furthermore, a refined model for OGTT in pigs, which reduces experimental variation and facilitates comparisons between experiments, was established. An insulin treatment protocol for streptozotocin diabetic pigs was developed to enable long-term studies and minimise risk of serious complications. Well characterised animal models and calm animals are important to acquire relevant and reliable research data, and to minimise the number of animals needed. Using refined techniques to minimise stressful situations is also important from an animal welfare perspective. Results presented in this thesis contribute to the 3Rs.

Keywords

Pig; 3Rs; training; diabetes mellitus; streptozotocin; oral glucose tolerance test; insulin; glucagon-like peptide-1; glucagon-like peptide-1 receptor; fatty acid; triglyceride; amino acid; cystatin-C; renal transplantation

Published in

Acta Universitatis Agriculturae Sueciae

2020, number: 2020:72
ISBN: 978-91-7760-662-8, eISBN: 978-91-7760-663-5
Publisher: Department of Clinical Sciences, Swedish University of Agricultural Sciences

Authors' information

Swedish University of Agricultural Sciences, Department of Clinical Sciences

UKÄ Subject classification

Other Basic Medicine
Clinical Science

URI (permanent link to this page)

https://res.slu.se/id/publ/108716