IS NITRIC OXIDE A CENTRAL REGULATOR OF EXERCISE-INDUCED SKELETAL MUSCLE MITOCHONDRIAL BIOGENESIS? [ 2005 - 2007 ]

Research Grant

Researchers: Prof Glenn Mcconell (Principal investigator)

Brief description 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.

Funding Amount $AUD 340,750.00

Funding Scheme NHMRC Project Grants

Notes Standard Project Grant