代谢状态的表征非人灵长类动物与静脉葡萄糖耐量试验
Summary
该协议的目的是提出一种标准方法来执行静脉内葡萄糖耐量试验（IVGTTs）评估在非人灵长类动物的血糖控制和从健康评估dysmetabolic其代谢状态。
Abstract
静脉内葡萄糖耐量试验（IVGTT）起着葡萄糖稳态的表征了关键作用。当与血清生化型材，包括在这两个馈血糖水平和禁食状态，糖化血红蛋白，胰岛素水平，饮食的临床病史，身体组成和体重状态，正常和异常的血糖控制的评估一起可以制成。一个IVGTT的解释是通过在葡萄糖和胰岛素水平的变化的测量随时间的关系做了葡萄糖挑战。要考虑的关键组成部分是：在关系达到T0（葡萄糖输注结束），葡萄糖清除率ķ从快速葡萄糖清除的斜率在第20分钟，衍生（T1至T20），时间峰的葡萄糖和胰岛素水平返回到葡萄糖基线和曲线（AUC）下的面积。这些IVGTT措施将显示来自健康t特性变化的葡萄糖稳态举动OA患病代谢状态5。这里我们将描述非人灵长类动物（猕猴和食蟹猕猴），这是在人类中II型糖尿病（T2D）的最相关的动物模型和IVGTT和这些动物的临床概况从表征贫健康，肥胖dysmetabolic，和T2D状态8，10，11。
Introduction
的IVGTT是常规用于确定在人类中的β细胞功能在不同的代谢状态5,7的便利功能测定法。在T2D中的动物模型中，它被公认为表征的动物，显示从代谢疾病进展的工具一个健康的一个dysmetabolic高血糖状态8,9。T2D的最接近动物模型是表现在非人灵长类动物（NHPS），其中恒河猴和食蟹猴是显着的例子。这些动物自然发展随着年龄和肥胖促进其发生率相同的风险因素，如2型糖尿病的人类10。此外，还有一个类似的疾病进展和胰腺病理表示作为dysmetabolic疾病进展11淀粉样蛋白沉积物。
在这里，我们对我们在执行的NHPS作为IVGTT我们对这些动物代谢状态的殖民地特征的一部分的标准方法报告。此方法是容易进行相对于其它更耗时且昂贵的技术2。该IVGTT是一个用于快速和频繁的表征大群动物是有用的。当与糖化血红蛋白（HbA1c）的电平考虑在内的动物的饮食和食物摄取的历史，以及他们的百分之瘦体重和体脂肪，所述IVGTT通常足以用于向显性糖尿病6表征动物的代谢状态和进展8。
糖化血红蛋白代表了一个红血细胞的寿命的平均血糖水平，过去6周〜3个月，只要葡萄糖水平的可靠量度。当从IVGTT的禁食基线血样测定，该值在提供程序之间的几个月一个窗口，血糖控制。如果动物已经从dysmetabolic转变自上次IVGTT糖尿病，比前值高得多的糖化血红蛋白数值表明该过渡即将开始他们的最后IVGTT后，而，糖化血红蛋白值更接近其先前的数值表明，他们最近才转移。在一般情况下，在恒河猴，糖化血红蛋白值大于6％的被认为是不正常的，并指示血糖控制不佳10,23。
血糖水平应的动物作为一个整体的行为和一般健康状况的范围内进行解释。糖尿病猕猴 – 人一样 – 展览亢进，多饮，多尿。动物群的住房提供了这些指标和个人护理dysmetabolic和糖尿病的猴子所需的测量显著的挑战。我们建议单独容纳动物，以便可以提供更个性化的服务，并且更容易的猴的健康行为标记物来监测8。此外，糖尿病猕猴将表现出体重下降，以及升高的脂质分布（增加的胆固醇，高甘油三酯血症）和血清化学干扰矿物质代谢。它测量肝脏和血清化学肾功能的标志物是重要的，因为这些器官损伤往往前进代谢紊乱/糖尿病的并发症，并且可以是血糖，脂质和矿物质失衡9，11，18的共同决定因素，24 。
使用此方法时，来自多个，经常刻画产生的历史价值在猴子的生活中具有特殊的价值。如果其他程序，如葡萄糖钳夹或分级葡萄糖输注（GGI），需要充分评估动物的健康，这是常用于初步鉴定时，他们的历史是不可用。每三个月的频率。然而，一旦一个基线已经建立，重复IVGTTs通常足以跟踪动物的进展。当动物被注册到整个多项研究，这是特别重要历年的代谢状态为主。而他们的健康可能在一个时间数年保持相对稳定，当动物的代谢状况恶化，在胰岛素抵抗和葡萄糖不耐症的显着增加可以非常迅速地发生。糖化血红蛋白值允许的预定相隔3个月的程序之间的动物的健康状况的下降或改善一些插值。由于这个原因，这种方法是理想的特征在多个纵向研究对其自然寿命的过程中使用的动物。
Protocol
Representative Results
Discussion
的IVGTT评估葡萄糖刺激的胰岛素释放的基于体重5，12，13的单一的葡萄糖输注的能力。从测定中，空腹血糖和胰岛素水平达到，并且它允许动物的能力来评估释放胰岛素和朝基线返回升高的血糖水平。这提供了信息来表征动物作为一个正常的血糖和胰岛素水平健康对照，具有正常血糖高胰岛素dysmetabolic动物，或高血糖的胰岛素抵抗性糖尿病动物的用户。
重要的是血液?…
Divulgazioni
The authors have nothing to disclose.
Acknowledgements
笔者想承认DHMRI CLAS照顾动物的工作人员的大力支持下，基金经理丹尼尔·佩拉尔塔先生和主治兽医，Glicerio伊格纳西奥博士，DVM MRCVS。
Materials
| Allegra X-15R Centrifuge | plasma: 4C @3000 rpm for 10 min | ||
| Sorvall ST16R Centrifuge | serum: 22C @3000 rpm for 10 min | ||
| Thermo Scientific -86C Freezer, Forma 88000 Series | Model: 88500A | ||
| Dextrose 50% (D50) | Webster | 07-8008986 | I.V. glucose infusate |
| 3mL Luer Lock Syringe | Midwest Veterinary Suppy | serial blood draws | |
| 5ml Luer Lock Syringe | Midwest Veterinary Suppy | heparinized saline flush | |
| 10mL Luer Lock Syringe | Midwest Veterinary Suppy | delivery of I.V. D50 | |
| Gauze sponges 2×2 | Midwest Veterinary Suppy | 366.23000.4 | Used Dry, w/ %70 Alcohol, and 2% Chlorohex Solution |
| 4 ml serum separator tubes | Midwest Veterinary Supply | 366.45000.4 | blood collection tube for superchem panel |
| K2EDTA, 2mL | VWR | 95057-239 | blood collection tubes |
| Aprotinin, 100mg | Sigma | A1153-100MG | blood collection tube protease additive |
| 22g x 1" Catheters | Midwest Veterinary Suppy | 193.75250.2 | I.V. catheter |
| Injection Plug W/ Cap | Midwest Veterinary Suppy | 001.11500.2 | %50 dextrose infusion port |
| Porus Tape, 1/2" x 10yd | Midwest Veterinary Suppy | 001.85000.2 | maintain adherance of catheters and hep. Locks |
| Chlorhexidine Solution 2% | Midwest Veterinary Suppy | 193.08855.3 | prep catheter site |
| 70% Ethanol | VWR | 71001-654 | prep catheter site |
| tourniquet | Webster | 07-8003432 | |
| 3 way stopcock | Midwest Veterinary Supply | 366.28510.4 | hep. lock |
| 37" extension set | Webster | 07-8454200 | hep. lock |
| Exel 50-60cc LL Syringes | Midwest Veterinary Suppy | 001.12250.2 | Heparinized saline flush |
| 250 ml bag 0.9% saline | Webster | 07-8365593 | flush |
| 1,000 U Heparin, 10 ml | Webster | 07-883-4916 | |
| Ketamine, (Ketaset) 100mg/mL | Fort Dodge | (AV ordered) | |
| Precision Xtra glucose test strips 50/bx | Abbott (American Diabetes Wholesale) | 9381599728K7 | test baseline/ T3 blood glucose levels |
| Masimo Rad 57 | DRE | 6052057V | pulse-oximeter |
| Pavia rectal thermometer | Patterson | 07-8391335 | |
| Precision Xtra Glucometer | Abbott | 9381599728K7 | Handheld glucometer |
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