Role Of Islet ?-cell Failure In The Pathogenesis Of Non-alcoholic Steatohepatitis
Funder
National Health and Medical Research Council
Funding Amount
$560,111.00
Summary
Some people respond to obesity poorly developing diseases such as non-alcoholic steatohepatitis (NASH) and diabetes. Other people do not, safely storing the excess energy in non-abdominal fat. The applicants will study 2 obese strains of mice; one develops “adipose tissue restriction”, NASH and diabetes, the other does not. The hypothesis that failure of compensatory insulin secretion to over-nutrition is an upstream event causing adipose tissue restriction, followed by NASH, will be tested.
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
How Intra-abdominal Transplantation Of Subcutaneous Adipose Tissue Prevents High-fat Diet-induced Insulin Resistance And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$358,465.00
Summary
In obese humans, storing excess fat within the abdomen is associated with the development of adult-onset diabetes and cardiovascular disease. However, the mechanisms linking intra-abdominal fat accumulation with these diseases are not well understood. We have studied intra-abdominal fat accumulation in mice using a transplant model, and we have found that transplanting subcutaneous fat intra-abdominally prevents diet-induced obesity and glucose intolerance. We aim to investigate the underlying m ....In obese humans, storing excess fat within the abdomen is associated with the development of adult-onset diabetes and cardiovascular disease. However, the mechanisms linking intra-abdominal fat accumulation with these diseases are not well understood. We have studied intra-abdominal fat accumulation in mice using a transplant model, and we have found that transplanting subcutaneous fat intra-abdominally prevents diet-induced obesity and glucose intolerance. We aim to investigate the underlying mechanisms.Read moreRead less
Can Vitamin D Prevent Diabetes By Improving Insulin Sensitivity And Secreation In Overweight Humans?
Funder
National Health and Medical Research Council
Funding Amount
$715,371.00
Summary
Vitamin D is mainly produced by the action of sunlight on skin. Low levels of vitamin D are becoming more common, as we work more indoors and avoid the sun and have been associated with type 2 diabetes. In proposed study, healthy overweight people, with low vitamin D, will be given vitamin D for 16 weeks to optimise blood levels of this vitamin. We will examine the changes in sugar metabolism. This study should provide important evidence on how vitamin D protects against diabetes and will suppor ....Vitamin D is mainly produced by the action of sunlight on skin. Low levels of vitamin D are becoming more common, as we work more indoors and avoid the sun and have been associated with type 2 diabetes. In proposed study, healthy overweight people, with low vitamin D, will be given vitamin D for 16 weeks to optimise blood levels of this vitamin. We will examine the changes in sugar metabolism. This study should provide important evidence on how vitamin D protects against diabetes and will support novel approaches to diabetes prevention.Read moreRead less
Understanding Sphingolipid Mediators Of Insulin Resistance
Funder
National Health and Medical Research Council
Funding Amount
$643,447.00
Summary
Sphingolipids are a class of lipid metabolites that have a variety of functions within cells. It has been known for some time that an accumulation of excess lipid, including certain sphingolipids, can adversely impact insulin action and glucose metabolism in cells. In this project we will a combination of strategies to test the hypothesis that the sphingolipid profile can be manipulated to have favourable effects on metabolism.
Hepatic Oxidative Stress, PTPs & STAT Signalling In Obesity
Funder
National Health and Medical Research Council
Funding Amount
$1,086,547.00
Summary
Obesity is increasing at an alarming rate worldwide and is a leading cause of morbidity and mortality. Obesity is causally linked to the development of insulin resistance, a prelude to type 2 diabetes. In this proposal we will define a novel liver centric mechanism by which insulin resistance and oxidative stress may promote the development of morbid obesity, type 2 diabetes and liver disease.
Polycystic Ovary Syndrome - Targeting The Sympathetic Nervous System To Improve Outcomes
Funder
National Health and Medical Research Council
Funding Amount
$353,140.00
Summary
Polycystic ovary syndrome (PCOS) affects approximately 10% of women of reproductive age, rendering it a major public health issue. Due to the combined development of abdominal obesity, hypertension and insulin resistance patients with PCOS are at increased risk of developing heart disease. The etiology of PCOS remains unknown but work by us implicates involvement of the sympathetic nervous system. We aim to elucidate the role of the sympathetic nervous system in PCOS and to examine the effect of ....Polycystic ovary syndrome (PCOS) affects approximately 10% of women of reproductive age, rendering it a major public health issue. Due to the combined development of abdominal obesity, hypertension and insulin resistance patients with PCOS are at increased risk of developing heart disease. The etiology of PCOS remains unknown but work by us implicates involvement of the sympathetic nervous system. We aim to elucidate the role of the sympathetic nervous system in PCOS and to examine the effect of pharmacological treatment targeting this system.Read moreRead less
ADVANCE-ON: A Post-trial Observational Study Of ADVANCE
Funder
National Health and Medical Research Council
Funding Amount
$775,867.00
Summary
The ADVANCE (Action in Diabetes and Vascular Disease) study demonstrasted that intensive control of blood glucose only reduced kidney disease but that control of blood pressure reduced both cardiovascular and kidney disease. This 10-year post-trial follow up study will determine whether intensive control of blood glucose exerts cardiovascular benefits that emerge in the long term in patients with type 2 diabetes.
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.
Development Of A Multi-faceted Diagnostic And Predictive Tool To Characterise Type Of Diabetes, Therapeutic Progression And Outcome
Funder
National Health and Medical Research Council
Funding Amount
$352,550.00
Summary
Diabetes is diagnosed using clinical assessment complemented by a few selected basic conventional laboratory tests. We plan to determine, in a representative community-based sample of Australian with diabetes, whether additional knowledge of genetic markers, diabetes-related antibody levels and tests of insulin secretory capacity adds to diagnosis of diabetes type, prediction of therapeutic progression over time, complications and death.