Hepatic Glucose Production, Ureagenesis, and Lipolysis Quantified using the Perfused Mouse Liver Model

Marie Winther-S&#248;rensen; Ida Marie Kemp; Hanne Cathrine Bisgaard; Jens Juul Holst; Nicolai J. Wewer Albrechtsen

doi:10.3791/65596

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JoVE Journal Medicine

Hepatic Glucose Production, Ureagenesis, and Lipolysis Quantified using the Perfused Mouse Liver Model

使用灌注小鼠肝脏模型量化肝葡萄糖生成、尿素生成和脂肪分解

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06:21 min

October 6, 2023

DOI: 10.3791/65596-v

Marie Winther-Sørensen^1,2,3, Ida Marie Kemp^1,3, Hanne Cathrine Bisgaard⁴, Jens Juul Holst^1,5, Nicolai J. Wewer Albrechtsen^2,3

¹Department of Biomedical Sciences, Faculty of Health and Medical Sciences,University of Copenhagen, ²NNF Center for Protein Research, Faculty of Health and Medical Sciences,University of Copenhagen, ³Department for Clinical Biochemistry,Copenhagen University Hospital - Bispebjerg and Frederiksberg, ⁴Department of Cellular and Molecular Medicine, Faculty of Health and Medical Sciences,University of Copenhagen, ⁵NNF Center for Basic Metabolic Research, Faculty of Health and Medical Sciences,University of Copenhagen

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在这里，我们提出了一种用于小鼠肝脏原位灌注的稳健方法，以研究肝脏代谢的急性和直接调节，而不会干扰肝脏结构，但不存在肝外因素。

在我们的实验室中，我们研究了肝脏如何对常见和罕见的肝脏疾病做出反应，以及这些适应如何导致糖尿病前期状态。肝脏对营养可用性和激素浓度的变化做出反应，增加相关基因的转录，但重要的是，也具有急性和非转录调节。通过灌注肝脏，我们可以量化新陈代谢的各个方面，包括代谢物的释放，以分钟到分钟的分辨率。

与其他体外模型相比，该技术的优点是肝脏原位保留，具有完整的肝脏结构。肝脏至少存活三个小时，使每个小鼠肝脏成为自己的对照。最后，增加翻译相关性。

使用小鼠灌注的肝脏系统，我们能够识别和表征激素胰高血糖素的新型信号级联。这可能很重要，因为胰高血糖素以及其他激素可能在脂肪肝和糖尿病患者的肝脏代谢异常中起着至关重要的作用。

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