Type 2 Diabetic Renal Complications And Microvascular Injury: Novel Predictors Of Onset And Progression, Mechanisms Of Association With Cardiovascular Disease And The Benefits Of Fenofibrate.
Funder
National Health and Medical Research Council
Funding Amount
$84,448.00
Summary
We will investigate the mechanisms of diabetic complications related to kidney and blood vessel disease, focusing on identifying people at greater risk and ways to improve or prevent these complications. In addition, we will look at how diabetic kidney disease affects non-kidney related problems like heart disease and examine the benefit of fenofibrate on both. This greater understanding will aid further drug development in kidney and cardiovascular diseases.
Central And Peripheral Actions Of Insulin For The Control Of Muscle Capillary Recruitment
Funder
National Health and Medical Research Council
Funding Amount
$433,973.00
Summary
Type 2 diabetes is on the increase world wide and reflects the ever-increasing incidence of obesity. Whereas the likely cause of type 2 diabetes includes low physical activity and high fat diet, the primary metabolic abnormality is likely to be muscle insulin resistance. The cause of this resistance is controversial, but may stem from microvascular dysfunction where muscle becomes poorly perfused and unresponsive to the action of insulin to recruit capillary flow. In this project we will further ....Type 2 diabetes is on the increase world wide and reflects the ever-increasing incidence of obesity. Whereas the likely cause of type 2 diabetes includes low physical activity and high fat diet, the primary metabolic abnormality is likely to be muscle insulin resistance. The cause of this resistance is controversial, but may stem from microvascular dysfunction where muscle becomes poorly perfused and unresponsive to the action of insulin to recruit capillary flow. In this project we will further extend our seminal discoveries that insulin mediates capillary recruitment under normal circumstances and that in various models of insulin resistance insulin's ability to increase the perfusion of muscle is markedly impaired. We will explore the hypothesis, that insulin controls microvascular perfusion of muscle by a central neural mechanism ending at terminal arterioles on the vasculature and endeavour to identify the details of this control. We will use in-house novel techniques for examining both the role of central control mechanisms involving the brain as well as peripheral mechanisms by local infusion of various agents likely to either enhance or block insulin's microvascular action. A positive outcome will enhance our understanding of insulin action and the insulin resistance that precedes type 2 diabetes. There is also the possible outcome that important clues will be obtained leading to new therapeutic agents that could be used to treat type 2 diabetes.Read moreRead less
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
Diabetes affects over one million Australians and is an increasing health problem in Australia and worldwide. Diabetes can damage small blood vessels, harming the kidneys and eyes and large blood vessels leading to heart attack, stroke and leg amputation. The research team leading this Centre for Clinical Research Excellence (CCRE) has wide experience in diabetes research and includes experts in diabetes management in hospitals and in the community setting of general practice. There is special e ....Diabetes affects over one million Australians and is an increasing health problem in Australia and worldwide. Diabetes can damage small blood vessels, harming the kidneys and eyes and large blood vessels leading to heart attack, stroke and leg amputation. The research team leading this Centre for Clinical Research Excellence (CCRE) has wide experience in diabetes research and includes experts in diabetes management in hospitals and in the community setting of general practice. There is special expertise in eye disease and in dietary management of diabetes. The research team will conduct research into diabetes, both type 1 diabetes, which usual starts in childhood, and type 2 diabetes that generally affects middle aged or older people, although increasingly is occurring in younger adults as the population becomes more obese. We will focus on the complications, which are common to both types of diabetes, looking for ways to detect them early and prevent them. Our studies will involve groups of up to 10,000 people with diabetes, sometimes followed over 5 or more years. Indigenous Australian groups will be included in the studies as they have a high rates of diabetes and its complications. We will also study ways in which people with type 2 diabetes can be more involved in improving the management of their illness. An exciting part of the study program will involve patients having transplants of insulin producing human islet cells. Although this treatment will be available for only a few patients, it is an important advance towards future treatments using human cells. The CCRE will have a very strong focus on recruiting and training the next generation of doctors and other clinicians involved in diabetes research, including nurses, dietitians and optometrists.Read moreRead less