Manell Elin, Hedenqvist Patricia, Svensson Anna, Jensen-Waern Marianne
Department of Clinical Sciences, Faculty of Veterinary Medicine and Animal Science, Swedish University of Agricultural Sciences, Uppsala, Sweden.
PLoS One. 2016 Feb 9;11(2):e0148896. doi: 10.1371/journal.pone.0148896. eCollection 2016.
Diabetes mellitus is increasing worldwide and reliable animal models are important for progression of the research field. The pig is a commonly used large animal model in diabetes research and the present study aimed to refine a model for oral glucose tolerance test (OGTT) in young growing pigs, as well as describing intravenous glucose tolerance test (IVGTT) in the same age group. The refined porcine OGTT will reflect that used in children and adolescents. Eighteen pigs were obtained one week after weaning and trained for two weeks to bottle-feed glucose solution, mimicking the human OGTT. The pigs subsequently underwent OGTT (1.75 g/kg BW) and IVGTT (0.5 g/kg BW). Blood samples were collected from indwelling vein catheters for measurements of glucose and the diabetes related hormones insulin, glucagon and active glucagon-like peptide-1. The study confirmed that pigs can be trained to bottle-feed glucose dissolved in water and thereby undergo an OGTT more similar to the human standard OGTT than previously described methods in pigs. With the refined method for OGTT, oral intake only consists of glucose and water, which is an advantage over previously described methods in pigs where glucose is given together with feed which will affect glucose absorption. Patterns of hormonal secretion in response to oral and intravenous glucose were similar to those in humans; however, the pigs were more glucose tolerant with lower insulin levels than humans. In translational medicine, this refined OGTT and IVGTT methods provide important tools in diabetes research when pigs are used as models for children and adolescents in diabetes research.
糖尿病在全球范围内呈上升趋势,可靠的动物模型对该研究领域的进展至关重要。猪是糖尿病研究中常用的大型动物模型,本研究旨在优化幼龄生长猪口服葡萄糖耐量试验(OGTT)模型,并描述同一年龄组的静脉葡萄糖耐量试验(IVGTT)。优化后的猪OGTT将反映儿童和青少年所采用的试验。18头仔猪在断奶一周后获取,并经过两周训练用奶瓶喂食葡萄糖溶液,模拟人类OGTT。随后这些猪接受了OGTT(1.75 g/kg体重)和IVGTT(0.5 g/kg体重)。从留置的静脉导管采集血样,用于测量葡萄糖以及与糖尿病相关的激素胰岛素、胰高血糖素和活性胰高血糖素样肽-1。该研究证实,猪可以训练用奶瓶喂食溶于水的葡萄糖,从而进行比之前猪的描述方法更接近人类标准OGTT的试验。采用优化后的OGTT方法,口服摄入仅包含葡萄糖和水,这比之前猪的描述方法更具优势,之前的方法中葡萄糖与饲料一起给予,会影响葡萄糖吸收。口服和静脉注射葡萄糖后激素分泌模式与人类相似;然而,猪比人类更耐葡萄糖,胰岛素水平更低。在转化医学中,当猪用作糖尿病研究中儿童和青少年的模型时,这种优化后的OGTT和IVGTT方法为糖尿病研究提供了重要工具。