Does Exercise Increase Skeletal Muscle Insulin Sensitivity Via Nitric Oxide?
Funder
National Health and Medical Research Council
Funding Amount
$562,815.00
Summary
Almost one in four Australian adults have either diabetes or impaired glucose metabolism. A major benefit of exercise is that it increases the sensitivity of muscle to insulin for many hours after the exercise is completed. We don't fully understand the mechanisms that exercise increases muscle insulin sensitivity. If we discover how nitric oxide production during exercise is involved, drugs that mimic these exercise effects may be designed to benefit those with diabetes.
Regulation Of Skeletal Muscle AMP-activated Protein Kinase By Glycogen
Funder
National Health and Medical Research Council
Funding Amount
$561,558.00
Summary
The enzyme AMP protein kinase has three parts (subunits) and is central to controlling the body's metabolism. We have discovered that one subunit is essential for tightly associating the enzyme with muscle glycogen which is a source of high energy and efficient metabolism. We will identify where the enzyme attaches to glycogen, and how diet and exercise alter this association. Understanding this could lead to new approaches for treating Type 2 diabetes where energy metabolism is disrupted.
Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as h ....Visualising vascular adaptation at the micro-scale in humans. The project aims to investigate fundamental issues in the mechanisms underlying vascular remodelling. It plans to develop novel optical scanning techniques to acquire high-resolution images of the cutaneous microvasculature, alongside absolute blood flow quantification. These novel tools would allow us to visualise and quantify functional and structural adaptations in the microvasculature in response to physiological stimuli such as heat exposure and exercise. The non-invasive tool aims to enable us to assess adaptations in microvasculature health, improving our understanding of cardiovascular diseases and type 2 diabetes and potentially reducing the impact of costly and debilitating morbidities such as nephropathy, neuropathy, retinopathy, impotence and skin ulceration.Read moreRead less
IS NITRIC OXIDE A CENTRAL REGULATOR OF EXERCISE-INDUCED SKELETAL MUSCLE MITOCHONDRIAL BIOGENESIS?
Funder
National Health and Medical Research Council
Funding Amount
$340,750.00
Summary
Mitochondria are the energy producing parts of the cell and are the major controllers of metabolism. There is now good evidence that reduced muscle mitochondrial size contributes to diabetes. Exercise is good for diabetics due partly to increasing muscle mitochondrial production (mitochondrial biogenesis). Unfortunately, little is known about the mechanisms involved in increased muscle mitochondrial biogenesis following exercise. It has been shown recently that nitric oxide (NO), a gas made by m ....Mitochondria are the energy producing parts of the cell and are the major controllers of metabolism. There is now good evidence that reduced muscle mitochondrial size contributes to diabetes. Exercise is good for diabetics due partly to increasing muscle mitochondrial production (mitochondrial biogenesis). Unfortunately, little is known about the mechanisms involved in increased muscle mitochondrial biogenesis following exercise. It has been shown recently that nitric oxide (NO), a gas made by muscle during exercise, plays a role in mitochondrial biogenesis in fat cells. This project will determine whether NO is a central regulator of exercise-induced mitochondrial biogenesis in skeletal muscle. If we find that NO increases mitochondrial biogenesis in muscle, drugs designed to mimic these exercise effects may prevent or improve diabetes. We will firstly establish if specific drug treatments that alter NO levels in muscle cells grown in culture alter mitochondrial biogenesis. These results will help us to clarify the role of NO in mitochondrial biogenesis. However, it is difficult to directly examine the effects of exercise in cultured cells. Therefore, further studies will then use real life models such as rodents that have been exercised to examine the role of NO and exercise on mitochondrial biogenesis. We will feed a drug to decrease NO levels in normal rats; and use mice, genetically altered to be lacking in NO to determine if these treatments decrease mitochondrial biogenesis that is normally seen following endurance exercise. Furthermore, since defects in mitochondrial biogenesis have such an important impact on diabetic humans, we will use humans to examine if differences in NO levels in skeletal muscle among type 2 diabetics or endurance-trained athletes correlate with mitochondrial biogenesis. Finally, we will infuse a drug into type 2 diabetics that increases NO in muscle to determine if it also increases mitochondrial biogenesis.Read moreRead less
Does Manipulation Of Arterial Shear Stress Enhance Cerebrovascular Function And Cognition In The Aging Brain?
Funder
National Health and Medical Research Council
Funding Amount
$707,914.00
Summary
Globally, 9.2 million less cases of dementia could result from delaying it by as little as 12 months. We will assess the impact, on artery health and cognition, of a novel exercise intervention involving enhanced patterns of brain blood flow and arterial shear stress during exercise, stimuli which should optimise cerebrovascular health. Given that pharmacological approaches to prevention are ineffective, this project has the potential to address the future impact of this common and debilitating ....Globally, 9.2 million less cases of dementia could result from delaying it by as little as 12 months. We will assess the impact, on artery health and cognition, of a novel exercise intervention involving enhanced patterns of brain blood flow and arterial shear stress during exercise, stimuli which should optimise cerebrovascular health. Given that pharmacological approaches to prevention are ineffective, this project has the potential to address the future impact of this common and debilitating disease in Australians.Read moreRead less
Discovering And Targeting Genes Regulating Skeletal Muscle Function, Metabolism, And Adaptations To Exercise Interventions
Funder
National Health and Medical Research Council
Funding Amount
$431,000.00
Summary
Muscle wasting and decreased in mitochondrial function due to ageing or lack of physical activity are associated with reduced quality of life. The overarching aim is to develop a unique research program focusing on targeting specific genes, and to discover novel genes regulating muscle wasting and mitochondrial (dis)function. I anticipate this approach to assist in the development of targeted and personalised prevention and therapy for diseases associated with muscle (dis)function.
One Size Does Not Fit All: Personalised Exercise Strategies To Improve Cardiovascular And Metabolic Health In Patients With Non-alcoholic Fatty Liver Disease.
Funder
National Health and Medical Research Council
Funding Amount
$318,768.00
Summary
Non-alcoholic fatty liver disease (NAFLD) affects one third of Australian adults and is linked with numerous chronic health conditions. Regular exercise reduces NAFLD, even without weight loss. However, response to exercise therapy is highly variable and there is a need for more personalised approaches. This research will identify which personalised exercise strategies effectively treat NAFLD, and, which measures can accurately monitor the progression of the disease in clinical practice.
Impact Of Exercise Intervention On The Phenome (Metabolism And Predictive Complications) In Well Characterised Prediabetes And New Onset Type 2 Diabetes Cohorts In China And Australia (TheDiabeEx.JointStudy).
Funder
National Health and Medical Research Council
Funding Amount
$567,323.00
Summary
This proposal will study people with prediabetes or a new diagnosis of type 2 diabetes, compared with a group with normal blood glucose, in China and in Australia. It will examine, in well defined cohorts: 1. the extent of traditional and more novel organ complications and metabolic markers early in the disease course; 2. in people with abnormal blood glucose, the potential benefits of an exercise regimen to their metabolic health, biomarkers and complications.