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
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.
PREVention Of Diabetes Through Lifestyle Intervention And Population Studies In Europe And Around The World
Funder
National Health and Medical Research Council
Funding Amount
$345,281.00
Summary
The PREVIEW Study will identify the most efficient lifestyle pattern for the prevention of type-2 diabetes in a population of pre-diabetic overweight or obese individuals. The project comprises two distinct lines of evidence, an intervention study and population studies. The focus will be on diet (specifically protein and glycemic index) and intensity of physical activity, as well as their interaction with the lifestyle factors, habitual stress, sleeping pattern, behavioural, environmental, cult ....The PREVIEW Study will identify the most efficient lifestyle pattern for the prevention of type-2 diabetes in a population of pre-diabetic overweight or obese individuals. The project comprises two distinct lines of evidence, an intervention study and population studies. The focus will be on diet (specifically protein and glycemic index) and intensity of physical activity, as well as their interaction with the lifestyle factors, habitual stress, sleeping pattern, behavioural, environmental, cultural, and socioeconomic variables.Read 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.
Intervention To Reduce The Risk Of Diabetic Retinopathy And Early Adverse Retinal Changes In Type 1 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$1,294,846.00
Summary
The long term effects of young onset T1D may be devastating: diabetes is the leading cause of visual loss in young adults in Australia and other countries. We have the unique opportunity to investigate whether ACEI and statins will modify retinopathy through our collaboration with an already funded international multicentre trial. This study will treat adolescents for 4 years and will follow them for the next 5-10 years. We will use novel measures of retinal blood vessels size and fractals.
Regulation Of Bone Resorption And Formation In Health And Disease
Funder
National Health and Medical Research Council
Funding Amount
$5,596,183.00
Summary
Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. ....Bone is continually being formed and broken down, and these two processes are critical forthe maintenance of a normal skeleton. These processes are dependent upon communication between the bone building and degrading cells, and the hormones growth factors and cytokines that are present in the circulation or produced in bone. The tightly regulated processes of bone formation and degradation need to remain equal, and are essential for the achievement and maintenance of skeletal strength and form. Osteoporosis results from an excess of bone breakdown over formation, and our Program aims to identify the factors that regulate these processes, and develop new therapies that can modify them. We will also determine what it is about bone cell properties that make some cancers, especially those of breast and prostate, particularly prone to spread to bone.Read moreRead less
Impact Of Islet Beta Cell Heparan Sulfate In Type 2 Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$576,777.00
Summary
Type 2 diabetes (T2D) is a chronic metabolic disease which ultimately leads to the death of insulin-producing islet beta cells, elevated blood sugar levels and daily insulin injections. Since beta cells require the complex sugar heparan sulfate (HS) for survival, we will investigate whether beta cell failure in T2D results from defective HS production. HS replacement will be evaluated as a new therapeutic strategy for preserving beta cell function and preventing the need for insulin injections.