Mechanisms of the insulin-sensitising effects of AMPK activation in liver and muscle.

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). Insulin resistance is closely associated with obesity, dyslipidemia, hypertension and cardiovascular diseases (Syndrome X) as well as diabetes. A high caloric intake (particularly with a high fat content) and a sedentary lifestyle are extremely important environmental contributors to Syndrome X and diabetes. One of the most exciting developments in the past few years has been the discovery that an enzyme, AMP kinase (AMPK), normally activated by exercise, may be involved in its beneficial effects. We have contributed to this exciting field by showing in an animal model that one dose of AICAR, a chemical agent which can activate AMPK, ameliorates the effects of insulin resistance in muscle and liver. Further very recent work has linked AMPK with various drugs (particularly glitazones and metformin) and hormones which can enhance insulin sensitivity. The goal of the experiments in this project is to determine the overall mechanism by which AMPK has ameliorating effects on counteracting insulin resistance. We hypothesize that the mechanism for this involves an effect of AMPK to reduce fat molecules accumulating within muscle and liver cells, and our studies will examine this hypothesis. Our studies should lead to a better understanding of how exercise and pharmacological activators of AMPK help in management of diabetes and insulin resistant states. In addition because AMPK activation enhances glucose metabolism by a separate pathway to insulin, it offers promise of developing compounds able to bypass metabolic steps impaired by insulin resistance. Our studies should help in the design of new therapeutic agents which can counteract insulin resistance.

Funded Activity Details

Start Date: 01-01-2005

End Date: 01-01-2007

Funding Scheme: NHMRC Project Grants

Funding Amount: $454,500.00

Funder: National Health and Medical Research Council

Research Topics

ANZSRC Field of Research (FoR)

Endocrinology

ANZSRC Socio-Economic Objective (SEO)

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Other Keywords

AMP-activated protein kinase | Dyslipidaemia | Liver steatosis | Obesity | Syndrome X or Metabolic Syndrome | Thiazolidinediones and adiponectin | Type 2 diabetes | in vivo metabolism | lipid metabolism | muscle and liver insulin resistance

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