Role of impaired insulin signalling in fatty acid-induced muscle insulin resistance in vivo

Funded Activity Summary

Type 2 diabetes represents an escalating global health problem. In Australia 7.5% of the population has diabetes and another 16% insulin resistance (impaired action of insulin in tissues). As well as diabetes, insulin resistance is closely associated with obesity, dyslipidaemia, hypertension and cardiovascular diseases (Syndrome X). While genetic factors play a role, a high caloric intake (particularly with a high fat content) and a sedentary lifestyle are extremely important environmental contributors to Syndrome X and diabetes. From evidence that we and others have obtained over the last few years it is now evident that an important mediator of insulin resistance is the quantity of fat molecules which accumulate in muscle and liver. This project examines mechanisms whereby this fat accumulation can disrupt the signalling mechanism normally causing increased glucose metabolism in response to insulin. While basic experiments in cell systems have identified some candidates, a need exists to demonstrate whether they actually cause the insulin resistance in the whole animal or human, or are merely associated with it. We will combine metabolic-physiological studies with a novel technique we have recently established in our laboratory for introducing DNA into skeletal muscle of laboratory animal models. We now aim to exploit this approach to obtain more definitive data about the importance of insulin signalling changes to insulin resistance. Two major steps in insulin signalling will be investigated, involving the insulin receptor substrate proteins and the kinase Akt-PKB, both strongly implicated in lipid-induced insulin resistance. This knowledge will be invaluable in improving strategies to lessen or prevent lipid-associated insulin resistance, a major contributor to the metabolic derangement in Type 2 diabetes and Syndrome X.

Funded Activity Details

Start Date: 01-01-2004

End Date: 01-01-2006

Funding Scheme: NHMRC Project Grants

Funding Amount: $481,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Nutritional science

ANZSRC Socio-Economic Objective (SEO)

There are no SEO codes available for this funding activity

Other Keywords

Dyslipidemia | Obesity | Syndrome X or Metabolic Syndrome | Type 2 Diabetes | fatty acids | gene transfer in vivo | in vivo metabolism | insulin signalling in muscle | muscle insulin resistance

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