Department of Pathology and Laboratory Medicine, University of Cincinnati, Metabolic Diseases Institute, Cincinnati, Ohio, USA.
Vitam Horm. 2010;84:221-49. doi: 10.1016/B978-0-12-381517-0.00008-4.
The past several decades have witnessed a flourish of interest in the field of incretin biology. The importance of the two incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), in health and disease is becoming more apparent as the prevalence of type 2 diabetes and other metabolic disorders escalates. Rodent models have become indispensable in the study of the physiological function of GIP and GLP-1; however, investigators have run into several roadblocks when untangling the regulation of incretin secretion in these systems. The low circulating levels of the incretin hormones combined with sensitivity of the currently available assays require substantial amounts of blood to be removed from an animal if the hormones are to be analyzed over a period of time. Because of these limitations, continuous monitoring of GIP and GLP-1 secretion becomes difficult. A more effective means of studying incretin secretion in small animal models is therefore desirable. This chapter evaluates the use of the lymph fistula rat as a model to study the secretion of incretins. Lymph fistula models, in a variety of animals, have been used for decades to study the absorption and transport of lipid and lipophilic compounds; however, only recently has the value of this model been appreciated as a tool to explore incretin secretion.
过去几十年见证了人们对肠降血糖素生物学领域的浓厚兴趣。随着 2 型糖尿病和其他代谢紊乱的流行率不断上升,两种肠降血糖素激素——葡萄糖依赖性胰岛素释放肽(GIP)和胰高血糖素样肽-1(GLP-1)——在健康和疾病中的重要性变得越来越明显。啮齿动物模型在研究 GIP 和 GLP-1 的生理功能方面变得不可或缺;然而,研究人员在梳理这些系统中肠降血糖素分泌的调节时遇到了几个障碍。由于肠降血糖素激素的循环水平较低,而且目前可用的检测方法非常敏感,如果要在一段时间内分析这些激素,就需要从动物体内提取大量的血液。由于这些限制,对 GIP 和 GLP-1 分泌的连续监测变得困难。因此,需要一种更有效的方法来研究小型动物模型中的肠降血糖素分泌。本章评估了将淋巴瘘大鼠用作研究肠降血糖素分泌的模型的用途。淋巴瘘模型在各种动物中已被使用了几十年,用于研究脂质和脂溶性化合物的吸收和转运;然而,直到最近,人们才认识到这种模型作为探索肠降血糖素分泌的工具的价值。