The Role Of Nitric Oxide In The Regulation Of Skeletal Muscle Glucose Uptake During Exercise
Funder
National Health and Medical Research Council
Funding Amount
$249,250.00
Summary
When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participa ....When a muscle is at rest it takes up and uses glucose from the blood. When that muscle is stimulated to contract it increases its glucose use to provide, in part, the energy for that contraction. These facts have been known for decades but the muscle signals involved with the movement of glucose from the blood into skeletal muscle remain poorly understood. Very recently, a new potential regulator of skeletal muscle glucose uptake has surfaced. Nitric oxide (NO), which has been shown to participate in blood flow, nerve transmission and immune function, appears to be a necessary component for muscle glucose uptake at rest and during exercise. We have shown that blocking muscle NO production substantially reduces leg glucose uptake during exercise. The aim of this project is to verify this finding and to determine the mechanisms underlying this result. One way we intend to do this is to see whether a drug (Viagra) which increases the effects of NO, raises muscle glucose uptake at rest and during exercise. In rats, a drug almost identical to Viagra stimulates muscle glucose uptake. If Viagra is shown to increase glucose uptake this information may provide the initial human data necessary to develop new drugs to lower blood glucose levels in people with diabetes.Read moreRead less
Acute Exercise And Digoxin Effects On Skeletal Muscle Na+,K+ATPase Regulation, K+ Homeostasis And Fatigue In Humans:
Funder
National Health and Medical Research Council
Funding Amount
$177,000.00
Summary
This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined ....This grant investigates the regulation of an enzyme in skeletal muscle referred to as the sodium-potassium pump, since its function is to pump potassium into the cell and sodium out of the cell. This enzyme is vital in enabling the muscles to contract and plays a key role in supporting our capacity to exercise. Our studies have suggested that acute exercise depresses the maximal capacity (activity) of this enzyme, thereby rendering the muscle liable to fatigue. We examine whether a well-defined exercise leading to fatigue, does inhibit the sodium-potassium pump and whether recovery occurs within 3 hours after exercise. The sodium-potassium pump is comprised of several variations of very similar enzymes, known as isoforms, each under the control of a separate gene and having slightly different functions and regulation. We explore whether exercise causes the genes regulating these isoforms to be activated and whether this results in an increased isoform formation in the muscle cell. We use a drug commonly used in patients with heart failure, called digoxin, which blocks the action of the sodium-potassium pump. In rat muscles this reduces muscular performance, with earlier and more pronounced fatigue. We examine whether a similar detrimental effect occurs in muscles of exercising humans and measure the resultant effects on muscle sodium and potassium levels. Increased knowledge about the effects of a single exercise bout on muscle is important fundamental knowledge. The study will lead to new knowledge about sodium-potassium pump regulation in exercising humans and thus enhance our understanding of muscle fatigue and gene responses to exercise. Understanding exercise effects will assist in development of strategies to counter physical inactivity, which is a major burden on health in Australia. Improved understanding of the actions of digoxin will also benefit patients with heart failure, through modified drug use and development of more specific treatment.Read moreRead less
The Role Of The AMPK-ACC2 Signaling Axis In Metabolic Control During Exercise And Obesity
Funder
National Health and Medical Research Council
Funding Amount
$540,973.00
Summary
Australian society is experiencing an epidemic of obesity that is contributing to diabetes, cardiovascular disease and premature death. This project is investigating how exercise might prevent obesity and type 2 diabetes by examining the major pathways that regulate fat metabolism.
Glucose Uptake During Exercise: Important Role Of AMP-activated Protein Kinase And Nitric Oxide?
Funder
National Health and Medical Research Council
Funding Amount
$379,875.00
Summary
Almost one in four Australians aged 25 and over has either diabetes or impaired glucose metabolism. In people with type 2 diabetes the rate of glucose uptake into muscles in response to insulin is reduced. However, glucose uptake during exercise is normal. Therefore, the hyperglycaemia of diabetes tends to normalise during exercise. The signals within the muscle which result in glucose uptake during exercise are largely undefined, but are known to differ to to that of insulin. This project will ....Almost one in four Australians aged 25 and over has either diabetes or impaired glucose metabolism. In people with type 2 diabetes the rate of glucose uptake into muscles in response to insulin is reduced. However, glucose uptake during exercise is normal. Therefore, the hyperglycaemia of diabetes tends to normalise during exercise. The signals within the muscle which result in glucose uptake during exercise are largely undefined, but are known to differ to to that of insulin. This project will determine whether the skeletal muscle enzymes AMP-activated protein kinase (AMPK) and nitric oxide synthase (NOS) play a critical role in the activation of glucose uptake during exercise. Exercise is considered the best prevention and treatment option for diabetes. Unfortunately, approximately 50% of people with diabetes do not exercise regularly with adherence to exercise programs being poor. Therefore, other alternatives must be sought to effectively manage diabetes. If it is found that skeletal muscle AMPK and-or NOS regulate glucose uptake during exercise, efforts can then be made to design drugs for diabetics that mimic these exercise effects on skeletal muscle glucose uptake resulting in improved glycemic control and consequently reduced diabetic complications.Read moreRead less