Comparison Between AICAR And Exercise-induced Stimulation Of Skeletal Muscle AMP-K On Fat/glucose Metabolism In Diabetes
Funder
National Health and Medical Research Council
Funding Amount
$347,036.00
Summary
Background and Rationale: Exercise is important in the life of the diabetic. In well controlled diabetes, the rates of whole body sugar usage and energy production in skeletal muscle (SkM) in response to acute exercise are similar to non-diabetics. However in diabetics, little information is available as to how SkM processes sugar and produces energy during exercise. Insulin controls SkM sugar and energy processing in sedentary subjects. During exercise, these processes are controlled by non-ins ....Background and Rationale: Exercise is important in the life of the diabetic. In well controlled diabetes, the rates of whole body sugar usage and energy production in skeletal muscle (SkM) in response to acute exercise are similar to non-diabetics. However in diabetics, little information is available as to how SkM processes sugar and produces energy during exercise. Insulin controls SkM sugar and energy processing in sedentary subjects. During exercise, these processes are controlled by non-insulin factors. The chemical catalyst AMP activated protein kinase (AMP-K), which has been investigated only in normal exercising rats, is an important alternative regulator of acute sugar processing and energy supply for exercising SkM. No studies of AMP-K activity are available in diabetes. Our studies will focus on i) how important is the stimulation of SkM AMP-K in diabetes to efficient SkM sugar processing and energy production; ii) if the benefits of exercise can be simulated by pharmacological stimulation of AMP-K in sedentary diabetic subjects. We aim to i) compare the metabolic effects of exercise vs pharmacological stimulation of AMP-K in normal and diabetic subjects; ii) define the molecular mechanisms which trigger the AMP-K metabolic responses; iii) determine if the circulating levels of insulin, blood sugar and-or blood fat influence the AMP-K metabolic responses. Likely Outcomes: pharmacological stimulation of AMP-K will improve SkM sugar metabolism, but less so in diabetes. The associated AMP-K stimulation of SkM fat metabolism may blunt the beneficial SkM sugar responses, particularly in diabetes. This information will be used in future drug developments for diabetics which aim to simulate the beneficial AMP-K metabolic effects of exercise.Read moreRead less
Does Teriparatide Reverse Osteonecrosis Of The Jaw In Patients With Cancer? A Randomised, Controlled Trial
Funder
National Health and Medical Research Council
Funding Amount
$357,412.00
Summary
Osteonecrosis of the jaw (ONJ) is debilitating and associated with drugs that increase bone strength and reduce the bone remodeling rate (bisphosphonates or denosumab). Up to 15% of patients with bone marrow cancer and 1 out of 952 patients with osteoporosis treated with bisphosphonates may get ONJ. This 8-week trial of subcutaneous teriparatide (a hormone that forms new bone) or placebo injections aims to promote resolution of ONJ, measured clinically and by x-ray, and improve quality of life.
Sclerostin: A Key Regulator Of Bone Mineralisation And Bone Catabolism
Funder
National Health and Medical Research Council
Funding Amount
$536,653.00
Summary
The regulation of bone mass is critical for many areas of human disease including osteoporosis, osteoarthritis, inflammatory bone loss conditions, e.g. rheumatoid arthritis, cancers of bone and problems relating to orthopaedic prosthesis failure. The osteocyte, the most abundant bone cell, plays a central role in normal bone biology and is likely key to these diseases. Sclerostin is one osteocyte product that may be a key to understanding how boneÍs mass and composition is controlled locally.