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

In our lab, we investigate how the liver responds to common, as well as rare liver diseases, and how these adaptation may predispose to a pre-diabetogenic state. The liver responds to changes in nutrient availability and concentrations of hormones with increased transcription of relevant genes, but importantly also, with acute and non-transcriptional regulation. With the perfused liver, we can quantify all aspects of metabolism, including the release of metabolites in a minute to minute resolution.

Advantages of this technique compared to other in vitro models are that the liver is left in situ with an intact hepatic architecture. And that the liver is viable for at least three hours, allowing each mouse liver to be its own control. Lastly, increasing the translational relevance.

Using the mouse perfused liver system, we are able to identify and characterize novel signaling cascade of the hormone glucagon. This may be important as glucagon, as well as other hormone, may play a vital role in the dysmetabolic conditions of the liver in patients with fatty liver disease and diabetes.