Biomarkers For Risk And Outcomes Of Type 2 Diabetes: A Discovery And Validation Approach In Australian And Chinese Subjects
Funder
National Health and Medical Research Council
Funding Amount
$599,489.00
Summary
The aim is to make better outcomes for people with Type 2 diabetes in Australia and China, by exploring various tests to improve prediction of diabetes progression, complication risk and treatment response. The team has data and samples from the Fenofibrate Intervention and Event Lowering in Diabetes Trial and from the Shanghai Diabetes Study. This approach is very time and cost-effective. We will also study animal models to understand mechanisms of diabetes damage, and test new treatments.
Role Of UBL-5 In Mitochondrial Function And Glucose Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$647,539.00
Summary
Type 2 diabetes is caused by insulin resistance, a condition that is characterised by the inability of insulin to elicit its normal function to lower blood sugar levels. The cause of insulin resistance is not known. In this study we will determine the role of a novel gene called UBL-5 to elicit insulin resistance in muscle and fat by generating genetically-induced models in which this gene has been deleted. By understanding the role of UBL-5 in insulin resistance, better therapeutic strategies c ....Type 2 diabetes is caused by insulin resistance, a condition that is characterised by the inability of insulin to elicit its normal function to lower blood sugar levels. The cause of insulin resistance is not known. In this study we will determine the role of a novel gene called UBL-5 to elicit insulin resistance in muscle and fat by generating genetically-induced models in which this gene has been deleted. By understanding the role of UBL-5 in insulin resistance, better therapeutic strategies can be developed to treat Type 2 diabetes.Read moreRead less
Targeting Nicotinamide Adenine Dinucleotide Biosynthesis To Improve Metabolism
Funder
National Health and Medical Research Council
Funding Amount
$844,596.00
Summary
Nicotinamide adenine dinucleotide (NAD) is a cellular metabolite that regulates many biological processes. NAD levels decline with age and also in obesity and interventions that increase NAD levels produce favourable metabolic effects. In this proposal we will utilise a range of novel experimental models to define the molecular pathways that mediate the beneficial effects of NAD.
Mitochondrial Sirtuins, Energy Metabolism And Insulin Action
Funder
National Health and Medical Research Council
Funding Amount
$582,925.00
Summary
Post-translational modification of lysine residues has a major influence on protein function. Many mitochondrial proteins are affected by lysine modifications and recent work has described a role for sirtuin enzymes in regulating these processes. This proposal will investigate whether targeted increases in sirtuin activity can improve mitochondrial function and insulin action in mouse models of obesity and insulin resistance.
NAD+ And SIRT2 Regulation Of Mitotic Lifespan, Senescence And Healthy Ageing
Funder
National Health and Medical Research Council
Funding Amount
$617,274.00
Summary
During youth, cells in our body undergo a continual process of self-renewal, known as mitosis, where cells divide and accurately provide equal number of chromosomes into each daughter cell. During old age, dysfunctional mitosis leads to senescence, where cells no longer divide, and are unable to renew old tissue. We have uncovered a new molecular pathway involving the enzyme SIRT2 that maintains healthy mitosis, and will determine if targeting this pathway preserves health into old age, and ulti ....During youth, cells in our body undergo a continual process of self-renewal, known as mitosis, where cells divide and accurately provide equal number of chromosomes into each daughter cell. During old age, dysfunctional mitosis leads to senescence, where cells no longer divide, and are unable to renew old tissue. We have uncovered a new molecular pathway involving the enzyme SIRT2 that maintains healthy mitosis, and will determine if targeting this pathway preserves health into old age, and ultimately extends lifespanRead moreRead less
Investigation Of The Mechanism By Which Medium Chain Fatty Acids Prevent The Development Of Obesity And Insulin Resistance - What Role For GPR84?
Funder
National Health and Medical Research Council
Funding Amount
$512,541.00
Summary
Medium chain fatty acids do not induce the same degree of obesity and insulin resistance as long chain fatty acids and this is due to changes in metabolism in skeletal muscle and adipose tissue. In this proposal we will investigate whether medium chain fatty acids induce their beneficial effects by interacting with a specific G protein-coupled receptor named GPR84. This receptor may be a new therapeutic target for the treatment of metabolic diseases.
Short-term Effects Of Overfeeding On Metabolic Risk In Humans
Funder
National Health and Medical Research Council
Funding Amount
$417,196.00
Summary
The prevalence of obesity is rapidly increasing in Australia and other parts of the world. Obesity is closely associated with insulin resistance and plays a role in the development of type 2 diabetes. However, the effects of short-term periods of over nutrition in humans remain unclear. In the proposed study, we will investigate the effects of short-term weight gain by high fat feeding in lean subjects, in subjects who are overweight and in subjects who are genetically more likely to develop dia ....The prevalence of obesity is rapidly increasing in Australia and other parts of the world. Obesity is closely associated with insulin resistance and plays a role in the development of type 2 diabetes. However, the effects of short-term periods of over nutrition in humans remain unclear. In the proposed study, we will investigate the effects of short-term weight gain by high fat feeding in lean subjects, in subjects who are overweight and in subjects who are genetically more likely to develop diabetes (due to strong family history). The aims are to distinguish physiological and endocrine characteristics of individuals who store more fat in response to overfeeding. We will identify differences between these individuals and whether they have defects in upregulating machinery involved in fat oxidation and energy production in skeletal muscle that may help them adapt during to energy excess. We will look for changes in type 2 diabetes risk and we will have the potential to identify defects in factors that are involved in this response. We will also re-examine indivudals again after calorie restriction and weight loss. We also plan to confirm the role of the candidate genes involved in fat oxidation that have been identifieid in human studies by in vivo gene transfer technology in rodents. This study will determine whether overweight and lean subjects behave similarly when faced with an overfeeding challenge. We expect that individuals with a genetic predisposition for T2DM will become more IR, due to metabolic inflexibility and a decreased ability to upregulate machinery involved in fatty acid oxidation and mitochondrial function. By characterising the physiological and endocrine responses to overfeeding, we will establish quantifiable markers allowing us to distinguish those at risk and identify new targets for pharmacological or lifestyle intervention.Read moreRead less