Description and evaluation of a diabetic dyslipidemia model in Gottingen Minipigs

摘要

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