Human hepatic insulin resistance. [ 2003 - 2005 ]

Research Grant

Researchers: A/Pr Graeme Macdonald (Principal investigator) ,  A/Pr Jonathan Whitehead ,  Prof Johannes Prins

Brief description Obesity is an important cause of disease, including liver disease. Obesity-associated liver disease occurs when the liver becoming resistance to the effects of insulin, the hormone that controls blood sugar (glucose). In muscle and fat, insulin causes glucose to be taken into the tissues and stored. Glucose is made in the liver and the actions of insulin here are to turn off the release of glucose into the circulation and increase uptake and storage of glucose. Insulin resistance occurs in a number of situations but the most important of these is obesity, particularly when there is accumulation of fat inside the abdominal cavity. Although the liver has a central role in co-ordinating the bodies response to insulin, the mechanisms of insulin resistance in human liver are unknown. One prominent hypothesis is that fat molecules released by intra-abdominal fat deposits are responsible. Intra-abdominal fat stores are important because fatty acids from these deposits can travel directly to the liver with the blood supply from the gut. However the precise effects of these on insulin action in the liver are unknown. Fat tissue is actively involved in the regulation of metabolism and releases a number of regulatory proteins. One of these, adiponectin, appears to have an important role in improving insulin sensitivity in the liver. The production of adiponectin decreases as obesity increases, providing another link between obesity and insulin resistance in the liver. This project will examine insulin action and the signalling molecules responsible for this in human liver tissue. The project aims to determine the effect of obesity, particularly intra-abdominal fat deposits, on insulin responses in liver tissue. The studies also aim to confirm (or otherwise) the role of free fatty acids and adiponectin on insulin action in human liver. The data from these studies will contribute to our understanding of insulin resistance and obesity-related liver disease.

Funding Amount $AUD 220,500.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant