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.
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
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
Investigation Of Novel Triterpenoids As New Potent AMPK Activators For The Treatment Of Insulin Resistant States
Funder
National Health and Medical Research Council
Funding Amount
$574,075.00
Summary
Type 2 Diabetes has major economic and health implications. Current medications are inadequate or have serious adverse effects. Triterpenoids have been used in traditional medicines for various diseases. This project builds on our recent discovery of novel triterpenoids with antidiabetic properties to investigate their efficacy and mechanisms of action. The results will provide valuable information about this class of molecules as potential new therapeutics for Type 2 diabetes.