Refinement of porcine models in diabetes and transplantation research

Elin Manell

Refinement of porcine models in diabetes and transplantation research

Bidragets översatta titel: Förbättringar av grismodeller för forskning kring diabetes och transplantation

Elin Manell

Publikation: Avhandling › Doktorsavhandling

4 Nedladdningar

Sammanfattning

Djurmodeller används ofta inom biomedicinsk forskning som syftar till att förebygga eller förbättra behandlingar av sjukdomar. När man använder försöksdjur tar man hänsyn till 3R (replace, reduce, refine). Socialisering och träning av grisar i forskning är viktigt för att undvika stress som kan påverka forskningsdata. Konventionella grisar genomgick ett strukturerat träningsprogram innan de gick in i njurtransplantationsstudier. Träningsprogrammet möjliggjorde blod- och urinprovstagning samt ultraljudundersökningar hos vakna grisar utan fasthållning. Grismodellen för diabetes karaktäriserades djupare med avseende på hormonellt svar till oral glukos, metabola förändringar på grund av insulinbrist, distribution av glucagon-like peptide-1 receptorer (GLP-1R) i pankreas och magtarmkanalen, och bindning till GLP-1R in vivo under oralt glukosbelastningstest (OGTT). Både skillnader och likheter mellan gris och människa identifierades, vilka båda är viktiga att beakta när man designar djurstudier. Vidare togs en förfinad modell för OGTT fram vilken minskar experimentell variation och underlättar jämförelser mellan studier. Ett insulinbehandlingsprotokoll för streptozotocin-diabetiska grisar etablerades vilket möjliggör långtidsstudier och minimerar risken för allvarliga komplikationer. Väl karaktäriserade djurmodeller och lugna djur är viktiga för att få relevant och tillförlitlig forskningsdata, och för att minimera antalet djur som behövs. Användandet av förfinade tekniker för att minimera stressande situationer är också viktigt ur djurvälfärdssynpunkt. Resultaten i avhandlingen bidrar till 3R.

Bidragets översatta titel	Förbättringar av grismodeller för forskning kring diabetes och transplantation
Originalspråk	Engelska
Kvalifikation	Doktor i filosofi
Förlag	Swedish University of Agricultural Sciences
Tryckta ISBN	978-91-7760-662-8
Elektroniska ISBN	978-91-7760-663-5
Status	Publicerad - 2020

Nyckelord

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

SLU-serie

Acta Universitatis Agriculturae Sueciae

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title = "Refinement of porcine models in diabetes and transplantation research",

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.",

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author = "Elin Manell",

year = "2020",

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isbn = "978-91-7760-662-8",

series = "Acta Universitatis Agriculturae Sueciae",

publisher = "Swedish University of Agricultural Sciences",

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TY - BOOK

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AU - Manell, Elin

PY - 2020

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AB - 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.

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KW - Pig

KW - amino acid

KW - cystatin-C

KW - diabetes mellitus

KW - fatty acid

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KW - glucagon-like peptide-1 receptor

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