RESEARCHERS OF VBU MAKE A BREAKTHROUGH IN STUDY OF DIABETES
BREAKTHROUGH IN STUDY OF DIABETES ACHIEVED IN ZOOLOGY DEPARTMENT, VISVA BHARATI UNIVERSITY BREAKTHROUGH IN STUDY OF DIABETES: A team of researchers from Visva Bharati University’s ‘Cellular & Molecular Endocrinology Laboratory’ of the Zoology Department, under the stellar guidance of Professor Samir Bhattacharya identifies the basic mechanism behind a very common metabolic disorder ‘diabetes’. Basically in diabetic state the inherent metabolic mechanism of the body fails to break down the large sugar (chiefly glucose) molecules to more basic components. The broken and simplified components of sugar molecules are usually combusted with oxygen in millions of body cells to generate the basic energy to run the complex bio-chemical systems of the body. In diabetic state blood contains excess unbroken sugar molecules, and in spite of the presence of sufficient quantity of the basic energy supplier-glucose in blood, the body remains severely energy deficient due to inability to harness energy by breaking down the glucose molecules in the system. In such a scenario the standard remedy is to reduce the intake of foods with high glucose content, and to get doses of insulin, a catalyst to break down sugar.
There are two types of diabetes Type-1 & Type-2. In Type-1 diabetes, insulin, the chief catalyst used for breaking down glucose molecules is not produced in the body in sufficient quantity. Only 3 to 5 percent of diabetic patients fall into this category. Remaining 95% of diabetic patients suffer from Type-2 diabetes, where the body fails to utilize the service of Insulin in spite of sufficient production of Insulin by pancreas! So, in Type-2 diabetes, the more prevalent one, the body suddenly fails to utilize the insulin, so far the medical scientists did not know the reason of which explicitly. Though statistically the cause could be related to presence of excessive free flowing saturated fatty acids (SFA) in blood, the exact mechanism behind the malady was not clear.
The research team of Visva Bharati manages to identify the exact mechanism, which disrupts the sugar molecule breaking down capability of body. Let us try to understand the phenomenon, according to the breakthrough achieved by the research team of ‘Cellular & Molecular Endocrinology Laboratory’ of the Zoology Department, Visva Bharati University.
The chief problem for us here is to simplify a fairly advanced and complicated scientific study to the level of understanding of general people, many of which are without much of a hard core scientific back ground. Personally, I have gone through the paper published in ‘Nature Medicine 18, page-1279-1285’ but could comprehend little, as the paper was too technical for common folks like us. So, I applied my own imagination (a bad tool to decipher science) and intuition to write this article, which has a chance of being over simplified and hence inexact in nature. Please pardon my inability and please contact Professor Samir Bhattacharya at firstname.lastname@example.org for further rectification/clarification.
METABOLISM IN HUMAN BODY: Great chemical reactions and exchanges are always taking place in the human body with active participation of numerous biological agents. Our body in fact is akin to, or to be frank infinitely more complex and elaborate a system than the most sophisticated chemical plants conceived by engineers in any part of the world, where numerous chemical reactions takes place aided by the fluids of the body. Blood is the most efficient fluid, which carries all such chemical compounds to several parts of the body where reactions take place. The whole process taken together is the metabolic state of the body- where balanced and chain chemical reactions are conducted by the biological agents within the body. A smooth function, i.e. a normal metabolic state would effectively mean that all chemical reactions are being conducted properly, and the presence of all chemical and biological agents in the fluid is in right proportion. Any out of proportion presence of any element in body fluid suggests a dis-balanced state of metabolism, and we may assume that some chemical reactions in the body has gone haywire, or new kind of undesirable reactions are taking place in the body. In short the body is in an abnormal state then. Some abnormal metabolic states can be temporary, like when a common virus attacks a body. The composition of the body fluid, blood, then changes by (1) the inherent mechanism in the body to generate fighters to attack the virus and by (2) the medicine applied which normally tries to subdue the activity of the virus or making the affected components immune to the ill effects of the virus and etc. This can be called an exited state of metabolism, or in more scientific term a ‘metabolic inflammation’. In the above mentioned case the body gradually gets back to the normal state. But, if we are more discernible, all such tiny intrusions and subsequent recovery actions changes the metabolic state of the body in miniscule manners! Well, as a human being we learn to live with such miniscule changes in our metabolic state every now and then!
But a metabolic change of state can be disastrous if it is permanent in nature. Diabetes, like high blood pressure, is one such change in the metabolic state of the body, which is permanent, i.e. a diabetic patient cannot revert back to his normal state of metabolism- at least by the knowledge of conventional medical science as of today. So a diabetic patient is generally prescribed extra supplement of insulin (can be a highly inappropriate treatment for Type-2 diabetes, as observed by the recent findings, to be discussed later), control of diet and regular exercises to burn down the excess sugar (excess sugar can cause several other ill effects in the body) in his system to protect his well-being.
HOW SUGAR IS KNOCKED DOWN (DISMANTLED) TO MORE BASIC COMPONENTS: Glucose is the great energy supplier, only if it can be broken down to more simple chemical forms to which Oxygen can easily combine to generate heat to run the several organic machines of our body. The liver cells chiefly along with a few others, aided by the catalyst ‘Insulin’ secreted by the pancreas, basically break down the glucose in Liver, and other tissues, and supply the simpler components back to the blood stream. Sugar, absorbed in blood through small intestine reaches blood after a meal, sensing this the pancreas pumps in adequate quantity of Insulin and the recipient cells start their sugar breaking activity action in liver and elsewhere.
I would rather like to use an analogy first to understand this phenomenon. Take our mobile phone; a particular signal (small electro-magnetic wave) reaches the mobile. If the signal matches, a gate in the mobile is opened to receive it, or in more mathematical terms a logic gate opens in the mobile chip to let in the call; we talk and by another appropriate logic gate our voice is transmitted back to the caller. If the initial signal do not match, or do not reach the mobile, no gates are opened to receive the call. A faulty signal receptor similarly may activate a call from a wrong number, once a big headache for land-line users- in those times we often got trapped into cross connections as well and were horrified listening to two other people having a chat over telephone. In short the signaling system is a key part for correct functioning of a mobile or land phone, a wrong yet manipulative signal or a defective signal processing system, both can produce undesirable results.
Similarly, the immune systems of the body works on the imminent danger signals generated from within the body when attacked by say a virus. Some warning cells feeling the pinch of the virus, sends out SOS/warning signals and the signal is then processed through the biological logic gates (specific proteins entrusted with such jobs). The biological processor here creates the anti-bodies or the fighters who start working against the ill effects of the virus. The above-mentioned case is a correct processing of a signal, which results in a correct retaliatory action by the body.
What if the signal is not deciphered correctly by the biological information processing protein, or the retaliatory action created by processing of such danger signals fails to give the desired result and instead harms something else than the original mischief monger? The result will obviously be harmful to the body. Type-2 diabetes is actually a sort of a failure in the processing of a signal by the immunology department of the body, releasing retaliatory agents, which harms the insulin utilization capacity of cells. It appears that Diabetes Type-2 is very much a self-inflicted disease, a side effect of failure of signal processing units of immune system of the body. In comparison to telephones, this can be similar to the case of cross-connections or wrong numbers, where one signal produces an undesirable result connecting unwanted people with each other!
THE FINDING OF VISVA BHARATI RESEARCH TEAM: The research team of ‘Cellular & Molecular Endocrinology Laboratory’ of the Zoology Department, Visva Bharati University identifies the whole process and locates a particular protein in blood Fetuin-A, which in excessive quantity than normal in circulation, triggers inappropriate activation of immune system in the body by facilitating saturated fatty acids (the signals) to combine with TLR4 (the signal processing unit). This is a case of an unwanted or unnecessary signal combining with the signal processor, aided by a mutual friend (or foe?) Fetuin-A. And this unwarranted combination of Saturated Fatty Acids with processor/receptor TLR4 releases lot of cytokines, which, of all things prevents the capacity of individual cells to utilize Insulin. In technical term cytokines make the cells insulin-resistant; by destroying that particular signal processing mechanism. Now we would have liked our cells to become virus-resistant, or small pox resistant, but here something secreted in our own body by our own immune system is making our cells ‘Insulin resistant’- a horrific result of some break down in our own signal processing system of the immunology department of our own body! The signal itself might be a manipulative wrong signal, which manages to fool the biological processors of the body. Or, the signal might be right, but wrongly interpreted by the processor. For example, the Fetuin-A is actually a result of excessive saturated fatty acids in the body, it can be a signal to TLR4 to do something about so much excessive fatty acids in blood, but instead thereceptor/processor TLR4 in this case might read the signal wrong and start producing cytokine agents which makes the cells insulin resistant, instead of tackling the excessive fatty acid problem! It is really a very interesting (but understandably complicated) topic to deal with!
In more scientific term (as far as possible by me!) protein Fetuin-A, links Saturated Fatty Acids with receptor TLR4, the two proteins then combines to form cells with new kind of structures, which in turn releases hosts of cytokine fighters which manages to block another ‘logic gate’ for the normal cells to access Insulin, and hence glucose can no more be broken down to simplistic forms for ready consumption of energy.
So far, in spite of intensive search world over, the exact mechanism leading to growing insulin resistance by normal healthy cells were not known, though a statistical correlation of Unsaturated Fatty Acids and Type-2 Diabetes were established almost about 25 years back. Visva Bharati research team manages to identify the exact mechanism with triggers insulin resistance in body cells.
In practical terms, the presence of the protein Fetuin-A in excessive quantity than normal is the chief mischief monger disrupting the sugar molecules breaking down capability of the body leading to the dreaded metabolic condition ‘diabetes’. The implication of the finding is certainly going to change the diagnosis and treatment of diabetes dramatically. The finding is powerful enough to deserve publication of the paper in topmost international scientific journal ‘Nature-Medicine’, where the previous Indian paper was published a whole decade back, and in totality only 5 papers from India have so far found a place in that journal since its time of inception. So, the Zoology Department, the only department of Visva Bharati University recognized by UGC as an ‘Advanced Study Centre’, has come into the league of top research institute in Zoology in world-level.
THE IMPLICATIONS OF THE FINDING: The implication of the finding for medical science is immense and intriguing at the same time. The chief mischief monger ‘Fetuin-A’ itself can be a very interesting element to focus on. From the diagnostic point of view excessive presence of Fetuin-A can be a sure pointer for the metabolic state of the body heading for a permanent change and turning diabetic. Interestingly Diabetes now is detected by excessive presence of sugar molecules in blood, i.e. when the patient has already turned diabetic. But ‘Fetuin-A’ starts its mischief much before a person actually turns diabetic. Continuous tampering by this protein to the functioning of TLR4, the biological signal receptor & processor, for years ultimately leads to the complete collapse of the sugar dismantling system of the body. So, identifying the presence of Fetuin-A in blood in more than desirable limit, a relatively easy pathological process, can actually predict future diabetes, which ultimately may set in years later. So, there is definitely a huge scope for early detection and prevention of diabetes, where still the metabolic state of the body had not gone for that disastrous permanent change, which makes a patient chronically diabetic.
Secondly, it also points out that the actual malady is not really in unavailability of sufficient insulin, but a fault in the signal processing system of the immunology department of body. In such cases extra supplement of insulin, doled out by physicians, is actually of no help, but on the contrary the extra supply of insulin gradually makes the normal and healthy insulin-producing units in pancreas feel redundant, and these cells gradually stop producing insulin. A patient then becomes more dependants on outside supply of insulin for no apparent fault in the insulin producing system of his! So, there is enough scope of re-thinking on the existing modes of treatment for patients who have already turned confirmed diabetics.
The medical science will obviously need to probe much deeper to be able to actually prevent the malady by proper intervention at suitable time. The research team has already suggested that a medicine, which can block the ‘Fetuin-A’ aided, Saturated Fatty Acid and TLR4 combination, can be an ideal one. But this is a tricky area, as in this particular case, we shall have to tinker with our own immune system and naturally will have to consider many other pros and cons not to allow our immune system to go haywire by one particular medical intervention. This will actually be a long study for the medical science teams and pharmaceutical industries to discover some kind of proper medical treatment for Type-2 Diabetes, a guideline for which however is firmly established now by the research team of Visva Bharati, Santiniketan. It seems the treatment of diabetes was so far not based on solid foundation of bodily functions at molecular scale, and was rather vague in nature. The findings will be able to put the diagnosis and treatment of diabetes on a much rational & focused path. The research team of Visva Bharati in the meanwhile will remain focused on the basic science to understand diabetes.
THE FUTURE PROSPECTS FOR THE RESEARCH TEAM: The research team in Zoology Department Visva Bharati is in fact engaged in multifarious activities, ‘Diabetes’ being one of them with a continuous probe for years now. Many earlier works on diabetes remained a prelude to this particular finding. Naturally the probe will move on. As per as protein Fetuin-A is concerned, it is statistically known that it is correlated to large amount of saturated fatty acids in blood. The research team will naturally focus on the exact mechanism of excessive secretion of Fetuin-A protein in presence of excessive saturated fatty acids, the exact mechanism of which is also not known to medical scientists till date. The exact signal receiving and processing modes of TLR4 might also be studied in much more details for any further development, as in this case it can be an interesting question whether Fetuin-A and saturated fatty acid is a wrong signal for receptor/processor TLR4 or if the resultant cytokines are a result of a wrong processing byTLR4. In fact the unknown always out weighs the known in science and hence there is plenty of arenas to tread on to. The particular finding naturally should lead us to more accurate understanding of our own immune system in particular.
Personally, I felt extremely honoured when Professor Samir Bhattachraya, Professor Shelley Bhattacharya, Dr Sudipta Moitra, Scholar Durba Pal, Dr Rakesh Kundu and several other research scholars tried their level best to make the subject easy for my thick head, and were kind enough to allow me to have a cursory look through their labs, which were brimming with activity even on Sundays (now, an official holiday for VBU). At the same time I am extremely apologetic to them for my sheer inability to grasp the spectacular subject under study in correct perspectives, and I am sorry for some technical errors, which have crept in an attempt to oversimplify science. The quiet yet lively atmosphere of the labs were great energizers, and I realized that Zoology Department is actually covering a fairly wide area of frontline research within the constraint of fairly modest means. It was amazing to find machines belonging to the 90s in perfectly working conditions, where as elsewhere we are so used to find costly instruments bought 2 years back gathering dust in Government run institutions. Professor Samir Bhattacharya firmly confirmed to this by proclaiming ‘We have shown that where there is a will, there is always a way!’- a most poignant assessment of achievements of Zoology Department, Visva Bharati, Santiniketan.
I have a plan to cover the whole of Zoology Department, but that would take a lot of time, as it is always pretty hard to get a proper hold on science, both for the expert and the layman like me! In the end, the achievements of Zoology Department, Visva Bharati University is a matter of great pride for everyone in Santiniketan, in fact the department is a matter of national pride- to put things in correct perspectives. INSA Professor Samir Bhattacharya recalled getting telephone calls from Sweeden, after publication of the paper in ‘Nature-Medicine’, a bewildered scientist enquiring ‘Where is Visva Bharati?’ A similar one from India exclaimed “I only heard Visva Bharati is famous for its music and dance!” Perhaps it is time such perceptions are changed for good! All our regards and best wishes to Samirda, Shelleydi all other faculty members, research scholars, students and ex-students of Zoology Department, Visva Bharati for making us really proud about Science in Santinikertan, and about our own country ‘India’s achievements in the field in particular.
1.INSA Professor Samir Bhattacharya.
2. School children of Visva Bharati University on playful moods.
3. The original campus of the University.
4.The Title of the paper published in Nature Medicine.
5.Dr Sudipta Maitra, on more friendly terms with the writer, probably due to reduced age barrier!
6. Miss Durba Pal, the young research scholar and the chief author of the scientific paper.
7.An illustration by Jan Heinrichsdorff & Jerrod M Olefsky of University of California to make matters more graphic as a review of the main article, also published as review to the main article in ‘Nature-Medicine’ magazine.
8. Inside the prayer hall, Santiniketan, Visva Bharati
9. The classical Visva Bharati.
10. Professor Shelley Bhattacharya.
11. The Flag of Visva Bharati University (on cricket ground!)