US EPA

1987935 

Journal Article 

Description and evaluation of a diabetic dyslipidemia model in Gottingen Minipigs 

Celdran, D; Sanchez-Margallo, FM; Moreno, B; Martin-Cancho, MF 

2013 

207-213 

WOS:000322821600041 

The aim of this study is to provide data from a highly detailed protocol for the induction of diabetes and dyslipidemia in Gottingen minipigs, to contribute in the development of a safe and stable diabetes model mimicking as faithfully as possible the real clinical situation. Twenty-four Gottingen minipigs were used. Six animals were used as non treated controls while in the other eighteen diabetes induction was carried out by Streptozotocin intravenous administration (150 mg/kg). During the first three days after administration an anti-inflammatory / analgesic treatment was established (buprenorphine patch (35 mu g/h/72h) and flunixin meglumine (2 mg/kg/IM/12h). Metoclopramide (10 mg/kg/IM/12h) was also administered in order to prevent vomiting. After induction, if the fasting glucose exceeded 400 mg/dl, animals received a subcutaneous combination of short-acting insulin (3IU) and retard insulin (3IU). With the aim of establishing a dyslipidemia (hypertriglyceridemia and hypercholesterolemia) the maintenance feed was supplemented with animal fat, raising the fat level of the diet using animal fat, in order to reach a content of 15% of the daily ration. To assess the establishment of the diabetes and dyslipidemic states a weekly monitoring of glucose, total cholesterol, triglycerides, HDL cholesterol and LDL cholesterol was conducted during 35 weeks. At the end of this time all the animals, with the exemption of three from each group, were euthanized and tissue samples from the kidney, liver and coronary artery were taken and immediately fixed with 4% formaldehyde for histological examination. The thoracic aorta were also removed and fixed with 4% formaldehyde for the later Sudan IV staining for fatty steaks. The described diabetic induction protocol produces an intense and irreversible diabetic state, which needs to be controlled by insulin administration. However hyperlipidic diet used did not produce the expected results in our trial. This protocol and results contribute to the refinement of animals use by providing specific useful information that may allow diabetes research groups to reduce or even avoid initial studies to set up a reliable diabetic dyslipidemia model in Gottingen minipigs. 

Diabetes model refinement; Gottingen minipigs; Dyslipidemia model