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Research Topic : AMP activated protein kinase
Field of Research : Endocrinology
Status : Closed
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  • Funded Activity

    Cytokine Signalling And Insulin Resistance In Obesity.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $512,065.00
    Summary
    Western communities are experiencing an epidemic of obesity that is contributing to diabetes, heart disease, and premature death. This project is investigating why being overweight and obese causes diabetes. Improved understanding about how hormones regulates the body's storage and breakdown of fat and responsiveness to insulin will enable the development of new medicines for the treatment of obesity and the prevention of diabetes.
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    Mechanisms Of The Insulin-sensitising Effects Of AMPK Activation In Liver And Muscle.

    Funder
    National Health and Medical Research Council
    Funding Amount
    $454,500.00
    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 m .... 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.
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    Funded Activity

    Hormonal Regulation Of Vascular Muscle

    Funder
    National Health and Medical Research Council
    Funding Amount
    $519,036.00
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    Funded Activity

    Regulation Of Cell Signalling Processes

    Funder
    National Health and Medical Research Council
    Funding Amount
    $99,288.00
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    Funded Activity

    Omega 3 Polyunsaturated Fatty Acid Analogues In The Treatment Of Diabetic Complications

    Funder
    National Health and Medical Research Council
    Funding Amount
    $418,446.00
    Summary
    Treatment of diabetes has become an even greater challenge to our community today. The ill health from diabetes arises from the high blood sugar levels. Treatment of diabetic complications such as kidney damage has now become a major goal. This research addresses this problem by trying to find out if a group of novel polyunsaturated fatty acids can target the process initiated by high blood sugar responsible for kidney damage.
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    Funded Activity

    Mechanism Regulating Stress Hormone Release By The Pitu Itary

    Funder
    National Health and Medical Research Council
    Funding Amount
    $228,172.00
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    Funded Activity

    Role Of Macrophages In Lipotoxic Beta Cell Failure

    Funder
    National Health and Medical Research Council
    Funding Amount
    $612,736.00
    Summary
    Type 2 diabetes (T2D) affects 7% of Australians and is a major cause of morbidity and mortality. A failure of insulin secretion contributes to T2D, and this is linked to the inability of insulin producing ?-cells to use lipids appropriately (lipotoxicity). Here we will study the role of the immune system and how this inhibits insulin secretion in T2D
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    Analysis Of A Factor Controlling The Formation And Func Tion Of White Blood Cells

    Funder
    National Health and Medical Research Council
    Funding Amount
    $80,794.00
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    Funded Activity

    How A Pituitary Hormone (ACTH) Stimulates Production Of Cortisol

    Funder
    National Health and Medical Research Council
    Funding Amount
    $242,298.00
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    Funded Activity

    Therapeutic Strategies And Screening Methods For PKC Epsilon Antagonists In The Treatment Of Type 2 Diabetes

    Funder
    National Health and Medical Research Council
    Funding Amount
    $157,375.00
    Summary
    Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown .... Type 2 diabetes is a chronic disease affecting over a million Australians and hundreds of millions of people worldwide. Its prevalence is rising due to several factors such as an increase in caloric intake, the aging of the population, and the common sedentary lifestyle of Western civilization. Type 2 diabetes occurs when the pancreas is unable to produce enough insulin for the body to cope with rising blood glucose levels after a meal, and has been strongly linked to obesity. We have now shown that an enzyme found in the pancreas becomes inappropriately activated under conditions of fat oversupply, and plays an important role in the development of defects in insulin release from the pancreas in response to glucose. Excitingly, we have also shown that inhibition of this enzyme can partly reverse these defects once they have been established. We now intend to further validate this enzyme as a drug target by determining the optimum dosing regimen for the treatment of type 2 diabetes in a mouse model, and testing whether this approach can be used in conjunction with previously-developed drugs which promote insulin action, to improve bood glucose handling better than either treatment alone. This would promote the enzyme as a therapeutic strategy in the treatment of Type 2 diabetes. We also plan to develop a high throuhput screen to identify novel inhibitors of the enzyme, which will further increase the attractiveness of the project to pharmaceutical companies, who are better able to implent full commercialization of our findings.
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