Targeting Ceramide Metabolism To Improve Lipid-induced Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$604,327.00
Summary
We have shown that the buildup of ceramide in muscle plays a key role in the inhibition of normal insulin action when the body is exposed to excessive amounts of fat, which leads to poor control of blood sugar levels and Type 2 diabetes. Using mass spectrometry we will now measure different ceramide types, to investigate which contribute to defects in insulin action. We will also examine whether enzymes involved in ceramide formation or degradation can be targeted to improve insulin responses.
Fragility Fractures: The Neglected Role Of Cortical Porosity
Funder
National Health and Medical Research Council
Funding Amount
$865,474.00
Summary
We just discovered that bone lost with age occurs mostly from pores within the cortex (outer shell) of the bone; These pores become larger (porosity) making bones fragile. This process is poorly detected by bone density (currently used tool) so that most people with weak bones are missed. To address this issue, we have for the first time, develop a technology to accurately quantify porosity in living peoples. With teams around the world, we aim here to fill this gap in the diagnosis.
NR4A Orphan Nuclear Receptor Signalling In Skeletal Muscle: Evidence For Crosstalk With The Beta-adrenergic Pathway.
Funder
National Health and Medical Research Council
Funding Amount
$323,749.00
Summary
The NR4A subgroup of are 'orphan' members of the nuclear hormone receptor (NR) superfamily (that are all implicated in human disease). NRs are hormone-dependent DNA binding proteins that translate nutritional and pathophysiological signals into gene regulation. The importance of this 'drugable' gene family in the context of promoting and maintaining human health is underscored by the diversity of medicinals associated with dysfunctional hormone signalling, in the context of inflammation, diabete ....The NR4A subgroup of are 'orphan' members of the nuclear hormone receptor (NR) superfamily (that are all implicated in human disease). NRs are hormone-dependent DNA binding proteins that translate nutritional and pathophysiological signals into gene regulation. The importance of this 'drugable' gene family in the context of promoting and maintaining human health is underscored by the diversity of medicinals associated with dysfunctional hormone signalling, in the context of inflammation, diabetes, dyslipidemia, and endocrine disorders (e.g ~15% of the top selling therapeutic compounds target NRs). The NR4A subgroup are stress response genes which are induced by a wide range of physiological stimuli and have been implicated in the response to energy excess (over-eating) and diet induced obesity. The NR4A subgroup are expressed in skeletal muscle, a major mass peripheral tissue that accounts for ~40% of the body mass and energy expenditure. This lean tissue is a major site of fat oxidation, insulin-stimulated glucose utilization and cholesterol metabolism. Therefore this tissue plays a notable role in insulin sensitivity, the blood lipid profile, and energy balance. Accordingly, muscle has a significant role in the progression of dyslipidemia, diabetes and obesity. Surprisingly, the function of the NR4A subgroup in skeletal muscle metabolism has not been examined. Nevertheless, given the data on NR4A mediated gene regulation, and the potential therapeutic utility for the treatment of metabolic disease, the contribution of skeletal muscle to NR4A action must be defined. Correspondingly, the objective of this proposal is to examine the role of the NR4A subgroup and is relevant to understanding the basis of dyslipidemia and obesity.Read moreRead less
Sex Steroids Modulate The Neuronal Control Of Bone Formation
Funder
National Health and Medical Research Council
Funding Amount
$620,647.00
Summary
It is well recognised that changes in sex hormones are pivotal to the development of osteoporosis in both men and women. Our group has been instrumental in identifying a novel and powerful system regualting bone mass and strength by neural activity. Recent findings indicate critical interactions between these two pathways in the control of bone formation. Greater understanding of these interactions could lead to therapies capable of controlling this extremely common disease.
Novel Metabolic Actions Of HDL With Therapeutic Potential For Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$559,471.00
Summary
Our proposal investigates a novel approach to treat type 2 (late onset) diabetes. We have identified an important link between HDL (good) cholesterol and glucose metabolism. The current proposal is to conduct studies in humans to determine whether therapies which increase HDL result in sustained reduction of blood glucose. Given the escalating global prevalence of obesity and type 2 diabetes, this work is potentially of great significance.