使用口服葡萄糖耐量试验（OGTT）和胰岛素耐量试验（ITT）研究高脂饮食喂养小鼠的体内葡萄糖代谢。,Journal of Visualized Experiments

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使用口服葡萄糖耐量试验（OGTT）和胰岛素耐量试验（ITT）研究高脂饮食喂养小鼠的体内葡萄糖代谢。
Journal of Visualized Experiments Pub Date : 2018-01-07 , DOI: 10.3791/56672
Csörsz Nagy ₁ , Elisa Einwallner ₂

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肥胖症是2型糖尿病发病机理中最重要的单一危险因素，该疾病的特征是对胰岛素刺激的葡萄糖摄取具有抵抗力，并且全身性葡萄糖代谢严重失代偿。尽管人们对葡萄糖代谢的理解取得了长足的进步，但其在健康和疾病中调节其分子机制的研究仍很不足，同时迫切需要预防和治疗糖尿病的新方法。饮食来源的葡萄糖刺激胰岛素的胰腺分泌，胰岛素在进食状态期间充当细胞合成代谢过程的主要调节者，因此平衡血糖水平以维持全身能量状态。长期过量喂食会引发元炎症，这导致周围胰岛素受体相关信号的改变，从而降低了对胰岛素介导的葡萄糖处置的敏感性。这些事件最终导致空腹血糖和胰岛素水平升高，以及葡萄糖耐量降低，这反过来又成为胰岛素抵抗的重要指标。在这里，我们提出了高脂饮食（HFD）喂养的小鼠的生成和代谢特征的协议，作为饮食诱导的胰岛素抵抗的常用模型。我们详细说明了口服葡萄糖耐量试验（OGTT），该试验监测随时间推移口服给药的葡萄糖负荷和胰岛素分泌的周边情况。此外，我们提出了胰岛素耐受性测试（ITT）的协议，以监测全身胰岛素的作用。一起，这些方法及其下游应用代表了表征小鼠一般代谢表型以及特异性评估葡萄糖代谢变化的强大工具。它们在胰岛素抵抗，糖尿病和肥胖症的广泛研究领域中可能特别有用，以提供对发病机理的更好理解以及测试治疗干预的效果。

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Study of In Vivo Glucose Metabolism in High-fat Diet-fed Mice Using Oral Glucose Tolerance Test (OGTT) and Insulin Tolerance Test (ITT).

Obesity represents the most important single risk factor in the pathogenesis of type 2 diabetes, a disease which is characterized by a resistance to insulin-stimulated glucose uptake and a gross decompensation of systemic glucose metabolism. Despite considerable progress in the understanding of glucose metabolism, the molecular mechanisms of its regulation in health and disease remain under-investigated, while novel approaches to prevent and treat diabetes are urgently needed. Diet derived glucose stimulates the pancreatic secretion of insulin, which serves as the principal regulator of cellular anabolic processes during the fed-state and thus balances blood glucose levels to maintain systemic energy status. Chronic overfeeding triggers meta-inflammation, which leads to alterations in peripheral insulin receptor-associated signaling and thus reduces the sensitivity to insulin-mediated glucose disposal. These events ultimately result in elevated fasting glucose and insulin levels as well as a reduction in glucose tolerance, which in turn serve as important indicators of insulin resistance. Here, we present a protocol for the generation and metabolic characterization of high-fat diet (HFD)-fed mice as a frequently used model of diet-induced insulin resistance. We illustrate in detail the oral glucose tolerance test (OGTT), which monitors the peripheral disposal of an orally administered glucose load and insulin secretion over time. Additionally, we present a protocol for the insulin tolerance test (ITT) to monitor whole-body insulin action. Together, these methods and their downstream applications represent powerful tools to characterize the general metabolic phenotype of mice as well as to specifically assess alterations in glucose metabolism. They may be especially useful in the broad research field of insulin resistance, diabetes and obesity to provide a better understanding of pathogenesis as well as to test the effects of therapeutic interventions.

更新日期：2019-11-01

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