Gene therapy for islet transplantation. Improved understanding of aetiology of type I diabetes. Development of islet transplantation as a clinical therapeutic for type I diabetes. Improved efficacy of islet transplantation. Improved health for subjects with type I diabetes. Decreased diabetic complications. Improved quality of life for subjects with type I diabetes. Reduced burden on health system for management of diabetic complications for subjects with type I diabetes
Regulation Of Insulin Sensitivity By Reactive Oxygen Species
Funder
National Health and Medical Research Council
Funding Amount
$564,644.00
Summary
In morbid obesity and type 2 diabetes chronic levels of reactive oxygen species (ROS) are detrimental and diminish insulin's ability to maintain normal blood glucose levels. Paradoxically, ROS also promote insulin action by inhibiting enzymes known as protein tyrosine phosphatases (PTPs). This proposal will determine whether the promotion of ROS for the inhibition of PTPs early in the progression of type 2 diabetes may be of therapeutic benefit.
The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will ....The impact of female sex hormones on neurodevelopment. This project aims to characterise the contribution of sex hormones to the development of emotional brain circuits in female adolescents. Puberty is associated with profound changes in emotional behaviours in females, but we know little about the underlying brain mechanisms. In particular, research has neglected to consider the role of the sex hormones for which changes are a defining feature of female puberty (eg, oestradiol). This work will be the first to comprehensively advance our understanding of the unique role of sex hormones in shaping the adolescent female brain. It will provide critical understanding of how individual differences in hormonal factors increase risk for emotional problems in females, and inform treatment strategies.Read moreRead less
Targeting Insulin Hypersecretion To Prevent Type 1 And Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$834,596.00
Summary
Diabetes develops when islet beta-cells fail to secrete insulin. While major differences exist in the mechanisms by which type 1 and type 2 diabetes develop, there is overlap in beta-cell susceptibility factors. We will investigate whether an islet 'overwork' response to excess nutrient loads underlies beta-cell susceptibility to failure in both types of diabetes. We will also develop novel pharmacological approaches to reduce islet 'overwork' to prevent and treat type 1 and 2 diabetes.
Nutrient And Hormone Delivery To Muscle: Interactions Between Insulin And Exercise
Funder
National Health and Medical Research Council
Funding Amount
$304,375.00
Summary
Exercise is known to be beneficial in the treatment and prevention of Type 2 diabetes and in particular muscle insulin resistance. Also, exercise and insulin share similar acute actions on muscle. Firstly, muscle contraction has a well established action to increase glucose uptake, and secondly, both muscle contraction and insulin act to increase capillary recruitment. This latter phenomenon is thought to enhance nutrient delivery and waste product removal. There is evidence that the increase in ....Exercise is known to be beneficial in the treatment and prevention of Type 2 diabetes and in particular muscle insulin resistance. Also, exercise and insulin share similar acute actions on muscle. Firstly, muscle contraction has a well established action to increase glucose uptake, and secondly, both muscle contraction and insulin act to increase capillary recruitment. This latter phenomenon is thought to enhance nutrient delivery and waste product removal. There is evidence that the increase in capillary flow due to muscle contraction is accompanied by increases in total blood flow. For insulin action we now have preliminary data to indicate that capillary recruitment occurs within a 5-10 min application of a physiologic dose of insulin independent of a change in total blood flow suggesting a redistribution of flow. Muscle contraction also increases capillary recruitment and it raises the question of whether similar mechanisms underlie insulin- and muscle contraction-induced capillary recruitment or whether there are distinct and complementary pathways. In this project we plan to define the mechanisms responsible for contraction- and insulin-induced capillary recruitment in muscle. We hypothesize that similar mechanisms are operative, with both insulin and muscle contractions acting via NO-dependent mechanisms. Because of capillary reserve, and different initial steps of the signalling systems stimulated by insulin and exercise, capillary recruitment by combined contraction and insulin stimuli will be additive at both sub maximal and perhaps at maximal insulin pathway stimulation. Signalling mechanisms will be compared and the role of non-nutritive route as a flow reserve assessed.Read moreRead less