Short Term Effects Of Overfeeding On Metabolic Risk In Humans
Funder
National Health and Medical Research Council
Funding Amount
$380,558.00
Summary
Obesity is associated with increased risk of diabetes, heart disease and cancer. Obesity prevalence is rapidly increasing and consitutes one of the greatest threats to human health. The aim of this study is to determine mechanism-s underlying the close relationship between obesity and insulin resistance by inducing experimental weight gain in humans with and without a genetic predisposition to diabetes. This project will help identify new candidates for anti-diabetes drugs.
Gene Variants In Adiponectin And Its Receptors As Risk Factors For Metabolic And Cardiovascular Disease
Funder
National Health and Medical Research Council
Funding Amount
$534,107.00
Summary
Obesity has a major impact on the development of metabolic syndrome (MetS), type 2 diabetes (T2D), and cardiovascular disease (CVD). It is important to identify the molecular links between obesity and these conditions. Adiponectin, an adipocyte-specific hormone, is a likely molecular candidate because of its pleiotropic metabolic actions. We will investigate the role of adiponectin, the variants within its gene ADIPOQ, and that of its two receptors, in the development of MetS, T2D, and CVD.
IGF BINDING PROTEIN-2 A MODULATOR OF IGF ACTION IN DEVELOPING AND NEOPLASTIC NEURONAL CELLS.
Funder
National Health and Medical Research Council
Funding Amount
$436,980.00
Summary
In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged ....In early life the brain undergoes rapid growth and remodelling, a process regulated by many factors including the insulin-like growth factor (IGF) system, which potently enhances nerve cell (neuron) survival. Similarly, this system is active in response to brain injury such a stroke, but it may also enhance tumor survival. The regulation of availability of IGFs to the neuron is critical in all these processes. IGF binding protein-2 (IGFBP-2), which is highly abundant in the developing or damaged brain, and in tumours, plays a key role on the surface of neurons in regulating IGF availability. We have shown that IGFBP-2 associates with a specialised protein on the nerve cells, where it is further processed to smaller fragments. We believe that these processes are reactivated following brain injury or in cancer states where IGFBP-2 is highly abundant. We propose to determine how IGFBP-2 influences IGF action on the nerve cell surface, and to further ascertain the function of each step in this process. We will achieve this by examining the effects of the mutated version of IGFBP-2, designed to either prevent its binding to the cell surface or its processing to smaller fragments. We will use various human and mouse nerve cell for these studies, which will not only provide greater understanding of the regulation of IGF availability to developing brain cell, but also point to how these processes may be involved in enhancement of recovery from injury or stroke, or possibly in acceleration of tumour growth. The finding of this study will offer the potential for new and exciting treatment designed to alter the function of the IGF system, to either make it more active in response to brain injury or stroke, or less active in brain tumours.Read moreRead less
The Regulation Of Insulin Action In Liver And Skeletal Muscle By Protein Kinase C Epsilon
Funder
National Health and Medical Research Council
Funding Amount
$647,604.00
Summary
We have identified an enzyme, protein kinase C epsilon, which has a major negative impact on the control of blood glucose levels. We will now examine the mechansisms by which it affects insulin action in liver and muscle, two major target tissues of the hormone responsible for glucose disposal. This work is expected to validate PKCepsilon or its downstream effectors as therapeutic targets in the treatment of the insulin resistance which accompanies obesity and Type 2 diabetes.
Understanding The Cause And Consequence Of Impaired Insulin Secretion In The NZO Mouse A Model Of Diabetes.
Funder
National Health and Medical Research Council
Funding Amount
$711,224.00
Summary
Type 2 diabetes is a major health problem affeting over 1 million Australians. A key feature of this disease is reduced secretion of the pancreratic hormone insulin which results in high blood sugar levels. We are using a naturally occurring animal model of diates called the NZO mouse to understand why the pancreas secretes less insulin and the consequences of this defect. This project has the potential of providing better therapeutic strategies for patients with Type 2 diabetes.
A Longitudinal Study Of Nerve Morphology In Diabetic Neuropathy Using Novel Non-invasive Ophthalmic Surrogate Markers
Funder
National Health and Medical Research Council
Funding Amount
$540,372.00
Summary
This research project will use two new ophthalmic instruments - the corneal confocal microscope and non-contact corneal aesthesiometer - to directly monitor changes in corneal nerves and corneal sensitivity, over a 5 year period, in diabetic patients suffering from a painful condition of the arms and legs known as diabetic neuropathy. This study will generate important new information that could allow diabetic doctors to more accurately monitor the progression of the disease.