Role of Akt in insulin resistance [ 2007 - 2008 ]

Research Grant

Researchers: Dr Mark Cleasby (Principal investigator) ,  Prof Edward Kraegen

Brief description Type 2 diabetes represents an escalating global health problem. In Australia 7.2% of the population has diabetes but an additional 16% have difficulty handling glucose, a problem which frequently precedes the development of diabetes. Resistance of tissues to the action of insulin is an essential pre-requisite for type 2 diabetes but is also closely associated with the syndrome of obesity, dyslipidaemia, hypertension and cardiovascular diseases (Syndrome X). Genetic factors combined with a high caloric intake and a sedentary lifestyle are together responsible for the development of insulin resistance. From evidence that we and others have obtained in recent years it is evident that an important mediator of insulin resistance is the amount of fat which accumulates in muscle and liver. One way in which this abnormality seems to cause insulin resistance is through interference with the normal signalling mechanism which causes increased glucose metabolism in response to insulin. While experiments in cell systems have identified some candidate molecules that may be involved, a need exists to demonstrate whether their dysregulation actually causes the insulin resistance in the whole animal or human, or are merely associated with it. We will use novel techniques to manipulate the levels of one of these candidate genes, protein kinase B-Akt, and its regulators in the muscle of rodents. We will then examine the effects of these manipulations on insulin resistance using a combination of metabolic and molecular tests. Building upon earlier work we will also determine how important different subtypes of this molecule are for both normal and abnormal insulin-glucose metabolism, and whether these molecules or others in the pathway are more important in insulin resistance. This knowledge will be invaluable in tailoring specific novel treatment strategies or drugs for prevention or treatment of insulin resistance, and thus reducing the burden of type 2 diabetes and Syndrome X.

Funding Amount $AUD 340,399.70

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant