14 May 2009
Researchers at the Garvan Institute in Sydney have teamed up with Shanghai’s scientific experts in Chinese medicines used for hundreds of years to treat diseases like Type 2 Diabetes.
The goal of the Garvan team, led by Professor David James, is not to work with these medicines in the traditional sense, but to bring them into the modern-day world. And they have succeeded, identifying unique compounds in Chinese plants that overcome insulin-action impairment in both cellular and animal models.
In this podcast, Prof James tells Stuart Cameron about the thinking behind this and other trailblazing research into novel treatments for Type 2 Diabetes.
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Voice-over: Welcome to the National Health and Medical Research Council podcast. Our podcasts aim to keep you in touch with major health and medical research issues and the people who shape them.
Introduction: Hello and welcome to the National Health and Medical Research Council podcast series, Ten of the Best Research Projects 2008. My name is Stuart Cameron.
More that 150 million people around the world suffer from Type 2 Diabetes and the disease has been described as a modern epidemic with serious medical implications for sufferers. Professor David James of the Garvan Institute in Sydney has been trailblazing new research into the causes and treatments of Type 2 Diabetes. David James and his team have discovered a range of new compounds that will reverse insulin resistance in animals and I met with him recently at his Sydney laboratory to find out more about this important area of research.
Interviewer: Professor David James in recent years substantial media attention has been paid to Type 2 Diabetes and its possible correlation with the obesity epidemic. What is Type 2 Diabetes and what are the implications of its widespread occurrence in Australia?
Prof. James: Before answering that question let me just address another question, which is, what is the difference between Type 1 Diabetes and Type 2 Diabetes? So there are two different kinds of diabetes and most people in the population I think are more familiar with the Type 1 form of diabetes – this is the form that affects young children – it’s an auto-immune disease where the immune system of the body turns itself against, in this case the pancreas, and destroys the pancreas and thus eliminating the ability of these individuals to produce insulin. And this results in a disruption in glucose metabolism and thus diabetes and these people can be managed quite effectively by insulin injection.
Type 2 Diabetes, although it also results in a disruption to glucose metabolism, is a very different disease. In the earliest part of the disease, here we see a defect in the ability of insulin to work properly in peripheral tissues such as muscle fat and liver, and if that defect goes on and on long enough, then it can result in the inability of the pancreas to produce insulin and thus diabetes.
Now it turns out, to answer your first question specifically, that obesity is one of the factors that for some reason leads to an impairment in insulin action and so therefore obesity is one of the major risk factors for the development of Type 2 Diabetes. Now the problem with Type 2 Diabetes as far as the Australian population is concerned is that first of all as you said, the figures are escalating through the roof and in fact alarmingly as many of us are aware. I think last week figures were announced to show that we’ve just overtaken the Americans in the obesity stakes, we’re now the fattest nation in the world – God, something to be proud of – and you know what this means is that at some point in the future the incidence of Type 2 Diabetes in Australia is going to go up and up and up. The problem with that is that it’s a very expensive disease to treat. During the course of a lifetime, and these individuals may live quite a long time of life, they acquire a whole host of complications. They have disorders in peripheral blood circulation, they might have problems with their eyes, their kidneys, they might develop heart disease and so on. All of these things are incredibly expensive to treat and so the cost to the Australian health care system will become I think one of the biggest issues that we have to face in the next ten to fifty years.
Interviewer: Research into the causes of, and treatments for, Type 2 Diabetes is very common around the world but your work at the Garvan Institute has taken a different path to most. Can you tell me about your quest to discover new compounds that may help with the treatment of Type 2 Diabetes?
Prof. James: Yes we’ve I think taken several new tacks. I mean let me just describe briefly for you what we have here at the Garvan. It’s a very exciting place and the Garvan doesn’t just do diabetes research but it’s one of the larger programs here at the Institute. We comprise more than 70 scientists all of whom are working on various aspects of Type 2 Diabetes, both the basic end of the disease as well as clinical research, and that’s I think one of the more exciting aspects of our program because we can cover the entire spectrum of the disease. So we can discover something in cells or in the test tube and we can then, in collaboration with our clinical colleagues, begin looking at the validity of that observation actually in the human with the disease.
Now one of the approaches that we’ve taken over the last five years which I think is somewhat novel, is we’ve teamed up with a very spectacular group of scientists in Shanghai who have expertise in working with traditional Chinese medicines. But our goal is not to work with these medicines in the traditional sense, but in fact to bring these medicines into the modern-day world. So our goal quite simply was that we believed that because some of these herbs have been used to treat people for hundreds and hundreds of years in China with diseases like diabetes, let’s assume that maybe there are things in these plants that have efficacy. So our goal was to take some of these herbs and so on and then fractionate them into all of the individual components that make up the plant. And then using some of the proprietary assays and technology that we have here at the Garvan, to ask: can we identify individual purified components from those plants that might have efficacy in the treatment of Type 2 Diabetes?
Now excitingly at the beginning of this year we reported a very exciting observation where we took one such plant – in this case the vegetable, Bitter Melon. Bitter Melon has been prescribed for the treatment of a variety of diseases in China, including Type 2 Diabetes, for the last three to four hundred years. We took about one ton of this vegetable, we ground the ton of vegetable up and ran it through a variety of purification techniques and isolated hundreds of individual components, and we then have now identified two or three components that appear to overcome this impairment in insulin action in our cellular models and in some of our animal models. So this is very exciting because these compounds that we’ve identified are completely unique, so we’ve solved their structure – they’ve never been described before – and that means we’ve been able to take out a patent and protect our intellectual property and it also I think provides us an edge in being able to develop these further. And so that’s where we’re currently at. We’re very excited about it and we’d like to take this observation forward into human clinical trials as soon as is feasible.
Interviewer: Chinese medicine has been treated with suspicion at least, by many Australians medical professionals and scientists but you’ve found a number of compounds sourced from these Chinese traditions that your research indicates, as you say, that there’ll be some benefit provided. What sort of response have you had to your research from the international research community given the controversy around Chinese medicine and traditional medicines generally?
Prof. James: Yeah look this is a very good question. I think that really some people are sceptical of things like Chinese medicines or traditional medicines in general because it, you know, has that flavor of old wives tales about it. But you know the reason that there’s scepticism is that much of the evidence to support the use of these things in the treatment of disease is based upon anecdotal evidence. And as scientists you know we can only believe something if we can see a graph with error bars and statistics and so on and so forth and really that’s been our goal – it’s been to take what would have been an anecdotal reporting and turn that into something with some more scientific validity. Now in terms of what our scientific colleagues have said about our observations, in fact you know I think everybody’s quite excited and they say not surprisingly so. And the reason is that of course for those of us who have been dealing with therapeutic development for a number of years of course we know that many, many medicines that are out there that are used to treat a whole host of human diseases actually come from plants. Plants are one of the richest sources of useful compounds for the treatment of a variety of diseases. And so we’ve just viewed traditional medicines as another source of these compounds and so that I think is proving to be the case.
Interviewer: Oxygen is thought of as one of the immutable essentials of life, but you’ve discovered that oxygen can also have a nasty effect on the human body under certain circumstances and that it might actually contribute to the onset of Type 2 Diabetes. Can you describe for me how this can happen?
Prof. James: Yes, so as I said earlier one of the earliest defects that you can see prior to the development of Type 2 Diabetes is what’s called insulin resistance. This is where insulin is unable to work properly and facilitate glucose metabolism. Now what we believe is that one of the major stresses or risk factors for the development of insulin resistance is in fact over-eating – of course this is something that we’re all prone to do these days in modern life – and one of the consequences of eating too much food is that we are bombarding our cells, as well as the organelles within our cells, with too many nutrients constantly. And, you know, really our bodies are designed only to be fed at sort of sparse intervals so that we can replenish the stores that we have within our cells to be used later on for exercise or work and so on and so forth. We are not designed for this sort of bombardment of the modern day life, that’s the problem.
Now, one of the organelles within our cells that is very important for using energy is an organelle called mitochondria. Mitochondria is sort of like the nuclear warehouse of the cell. Energy comes in, such as glucose or fat from our food, and it’s turned into the basic unit of life, this molecule called ATP. Now in order to convert fat and glucose into ATP we rely on oxygen and that’s why oxygen is such an important fundament of all life forms. However, if we bombard the mitochondria with too many nutrients what happens is the mitochondria decide it’s not a good idea to make ATP any more because we don’t really need it. And so instead of converting the glucose and the fat into ATP, we actually divert some of the electrons from these intermediates to oxygen forming what’s called ‘free radicals’. This is sort of a by product, a waste product if you will, of mitochondrial metabolism and so if you eat too much, if you bombard the mitochondria with nutrients, you now will increase your production of free radicals and we believe this may be one of the major threats, one of the major stresses that leads ultimately to the demise of the cell and in this case Type 2 Diabetes.
Interviewer: What are some of the potential diagnostic and clinical outcomes for treatment from your research?
Prof. James: Well for instance, in the case of this oxygen free radical theory, what we are trying to do now is to develop anti-oxidants, not anti-oxidants that have been used in the past – I think you can go down to your local natural herb marketplace and you can probably buy yourself a bottle of anti-oxidants for $74.50 – the problem with many of those medicines is that they don’t have any selectivity for the way in which they work. The key in what I just said is that we believe that the free radicals are produced within the mitochondria – this unique place within the cell – and so one of the areas that we’re currently investigating is to try to develop anti-oxidants that will uniquely work within this compartment of the cell and we believe that may be a much better form of targeted therapy that can be used to treat people who are at risk of developing Type 2 Diabetes.
Interviewer: Professor David James thank you for your time today.
Prof. James: My pleasure.
Voice-over: This podcast was brought to you by the National Health and Medical Research Council, working to build a healthy Australia. You’ll find more information about this and other health and medical research issues on our website at www.nhmrc.gov.au.