You've heard a lot about what a difficult disease diabetes is to both treat and also to diagnose. However, if we were to have physical activity and we were to prevent obesity, at least for type 2 diabetes, we would eradicate the disease. In the regions of the world like the Western Pacific region and Southeast Asia diabetes is very common.
There is a reason for this is linked to the genetics of people in these areas. It's such a prevalent disease in the western Pacific area due to Darwinian survival. People were selected to store energy because when they moved from island to island, they had to endure weeks of famine. The only ones that survived were the ones that were genetically predisposed to store energy. Now that in these regions food is plentiful, it's become a big problem and it's a problem all over the world. However, it's starting to emerge in cultures where people aren't used to having plenty.
There's a reason why diabetes is getting worse:
In 2013 there are 380 million people with type 2 diabetes. It's projected to be 600 million by 2035 which is a staggering increase in percentage. The good news is if people are active, we can prevent it. If you do some exercise per week, your relative risk is half. Metformin is the front-line drug to treat diabetes. However, if you implement a healthy lifestyle it reduces the cognitive incidence of diabetes better than Metformin.
We strive to give definitive proof as to why exercise is important. We look at this at a molecular level to come up with drugs that can mimic exercise. Nothing is going to be able to meet exercise perfectly. Exercising has social benefits, cognitive benefits, and benefits against non-communicable diseases.
But there are some people who simply can't exercise. And for those people, we try and design what we call exercise mimetics. Here are some of the benefits of exercise in people with type 2 diabetes. Some of the things that are important is that you decrease reliance on medications. Also, it’s important to note that there is no absolutely safe medication. There is always going to be some side effect but the medications are prescribed when the side effect is way less than the desired benefit. But if you can decrease your meds by exercising this is a really good thing.
Lipoprotein or fat profile in the blood is related to cardiovascular disease. Many people don't die from diabetes. They die of complications and one of the complications is a cardiovascular event. So, exercise is very good for this.
There was research done to find out the interconnection between exercising and diabetes. Among Americans with diabetes, 15% of those exercised less than 30 minutes in a week. But those who did exercise at least 30 minutes, 4-6 time a week, were only 8%. It's almost halved. And if we look at non-obese adults, the trend is the same. Simply by exercising you decrease the incidence of diabetes. This paper came out last year and it's actually quite scary because low physical capacity is second only to smoking as the highest death risk now. This paper actually was published in Nature. One of the most reputable journal journals. This paper showed that they did a global analysis of physical activity in the whole world and their conclusion was the whole of humanity is not exercising enough.
It's not just diabetes we worried about. If you think about the economic impact, we all are touched by this because the governments are spending enormous amounts of money. But if they put more money into research and into prevention, it would benefit in the long run these up. The economic impact of sedentary behavior is increasing. The lack of physical activity is a global health crisis. We all know that exercise is good for us. But how do we really know? How does exercise help? and why should we care?
Females are a little bit more perceptive to hard evidence than males. The smoking rates among males and females started plummeting after the surgeon general of the US released the first report that suggested smoking caused cancer. It was suspected through these years that smoking cause cancer and people said smoking is bad for you. But people continued to smoke until there was clear evidence that smoking caused cancer.
“Now we're striving in our lab to provide evidence that exercise is good. People need hard evidence to invoke behavior change. Martin Windham is one of the talented people in my laboratory. We look at a cluster of diseases and we look at inactivity and its effect on these diseases. Our goal in our lab to prove that exercise is a preventative treatment for non-contagious diseases. And we aim to characterize the therapeutic potential of muscles secreted protein. We believe that the muscle releases factors during exercise that they have positive benefits on other parts of the body. We coined the term “myokines”. My lab is fairly well renowned for this discovery. We actually do very distinct track, what's called transcript dynamics. We look at the RNA level of genes encoding proteins and the proteins themselves to identify things that come out of the muscle that could be of benefit. This is the concept that myokines will release proteins. The muscle will release microns and these will block an increase in adiposity and prevent diabetes cardiovascular disease cancer and osteoporosis.
This is not a new concept. In the last century, Goldstein's suggested that there is a humoral component of muscular exercise. So, this is not a new concept but after he made this hypothesis nobody looked at it. Nobody looked at it until we did.
And this was in the late 90s, somewhat nearly 40 years later. We thought that muscle might secrete proteins because there's what's called cytokine and it's called interleukin 6. And it goes up when you have an infection when you have sepsis. But it seems to go up in response to another cytokine called TANF. These cytokines come from immune cells. But during exercise TANF does not go up at all and aisle six does. So, it's a very different pattern. And while six can't be that bad if it goes up during exercise and everyone thought it was bad because it went up during sepsis.
We spent about 10 years trying to work out where this was coming from. We found out it came from contracting a muscle. What we did is we put a catheter into a vein in a leg and into an artery in a leg. the person did exercise and by sampling blood from the vein and from the artery we looked at the differences in the concentration of proteins. If the protein is higher in the vein than the artery, it means that the contracting leg is releasing that protein. That's exactly what we saw with aisle six. It was coming from contracting leg. This was a very big discovery from our lab.
Now I'm going to fast forward fifteen years and this is where we're at the moment. This is aisle six. This is the structure of the protein that I just showed you and this is another protein and this could never be used as a therapy for reasons I won't get into. But this is another protein called CTF. And what we did was we took this bit off. We pasted this bit onto the rest of that protein and we made a new cytokine called aisle 7. It's a drug that mimics the effect of exercise and it's about to go into a phase one clinical trial if we can raise five million venture capital. We are in the process of doing this. We've just incorporated a new company. This could be a blockbuster new drug. And the reason why we think it works is because it does the same thing which comes from your leg during exercise. So that's just one example where we can interrogate the biology of exercise and come up with exercise and medics. We're very excited about this work and it's just about to be submitted to a very prestigious journal at the end of this week. “– Prof. Mark Febbraio.
The last thing is it's not just diabetes that exercise is really good for. It's very good at preventing cancer. If you increase exercise, you decrease your relative risk of developing breast cancer.
We're very excited about this work because we think we've got the molecular link. There's convincing and probable evidence that exercise decreases the risk of colon breast and endometrial cancer. We did an experiment in which we could identify thousands of proteins released from the muscles in what are called exit zones. We can now look at the whole exercise-induced proteomics in these small microvesicles that are in the blood. When we did a screen, we identified a protein called Declorin. Why was this important to us?
Earlier this millennium a group published that there is an anti-metastatic role of Declorin in breast cancer. We had evidence that a protein that is produced by your muscles when you exercise can be anti-metastatic. They did this in animal studies and they overexpressed this in the tumor. And when they did this it metastasized less, so, physical activity is known to be positive for breast cancer.
What if what's mitigating this effect is different? The first thing we did is we did our AV balance studies in humans and we were able to show very clearly that Declorin is, in fact, goes up with exercise and then goes down with rest. You can see that very clearly in these studies. The part of the tumor that's very important for preventing metastases is called the extracellular matrix. Scientists were able to show that this protein is much lower expressed in the extracellular matrix of tumors than normal tissue. Then, we collaborated with a colleague in the breast cancer network consortium in Queensland and we analysed thousands of samples from women with breast cancer. If the tumours expressed in women’s relapse-free survival time was increased, and they're distant metastases, free survival time was also increased.
Declorin is being released from your muscles when you exercise. So, if you're a female who has breast cancer, if you can get Declorin into the tumor, you will be prevented from metastasizing and it may save your life. We're proving this by doing a lot of animal experiments and some human experiments. These experiments are done to see if women who have breast cancer and who are exercising, have a decline in their tumors when they have surgery. This is something that shows you all of the proteins that have been identified coming from your muscles when you exercise. You can see that they all have positive effects and it's led to a very fertile area of research.
For more details watch the video below.
