The work done in a biology lab tucked away in the verdant settings of Santiniketan may be central to humankind’s fight against diabetes. A team of researchers from Visva-Bharati’s Cellular and Molecular Endocrinology Laboratory (CMEL) has unravelled a key element in the cascade of metabolic events that eventually lead to diabetes.

The work, published online in the journal Nature Medicine yesterday, is significant because the molecular mechanism that the Visva-Bharati scientists unveiled is a step that happens very early on in one’s progress into diabetes. If this basic understanding can be translated into clinical practice, it will brighten the chances of preventing this disease that plagues a significant portion of the Indian population.

The recent research throws light on the exact mechanisms involved in triggering a process called metabolic inflammation, which sets in many years before diabetes rears its ugly head and leads to insulin resistance. Inflammation is basically an immune system response to protect the body from infection.

Scientists studying diabetes have known for a while that lipids (fatty acids) freely circulating in the blood trigger inflammation. This metabolic inflammation slowly induces insulin insensitivity or insulin resistance in the body. It is a physiological condition in which the insulin hormone becomes less effective in lowering blood sugar levels. What actually happens is that the body is unable to break down and absorb all the sugars in the diet, leading to higher levels of sugar in the blood. Insulin is a hormone produced by the pancreas to aid the liver to absorb the glucose that is derived from the food we eat. Over the years, insulin resistance leads to diabetes.

“But our knowledge of how lipids trigger metabolic inflammation is quite patchy. It was thought that lipids are directly responsible for this inflammation,” says Samir Bhattacharya, an INSA (Indian National Science Academy) professor at CMEL at the School of Life Science in Visva-Bharati, and the main author of the paper.

The latest work by the Visva-Bharati team has, however, shown that lipids don’t turn nasty without the presence of a protein. They found that the protein Fetuin-A is a vital cog in the whole process and its presence is critically important in the inappropriate activation of the immune system. This leads to the immune system dispatching molecules called cytokines, which are the body’s aggressive immune soldiers, into the bloodstream.

“If Fetuin-A is not present in elevated levels, cytokines such as toll-like receptor 4 or TLR4 (the molecules responsible for inflammation) are not released,” says Suman Dasgupta, who carried out the research together with Durba Pal, another of Bhattacharya’s research students. So the presence of a higher level of Fetuin-A in blood is a signal that you may be developing insulin resistance.

“The body tries to compensate for insulin resistance by producing more and more insulin. This puts a lot of pressure on the beta cells (in the pancreas) that produce the hormone. By the time diabetes actually manifests, nearly half the beta cells are gone,” says Satinath Mukhopadhyay, a co-author and a practising endocrinologist at the SSKM Hospital in Calcutta.

“In our studies with mice, we have shown that when the gene responsible for Fetuin-A is knocked off, the animals did not develop insulin resistance despite being fed a high fat diet continuously,” says Dasgupta, who currently works at the North-East Institute of Science and Technology, a Council of Scientific and Industrial Research laboratory based in Jorhat, Assam.

“This is certainly an interesting study. But it is still at a basic level,” says Nihal Thomas, a doctor at the Christian Medical College in Vellore. “As a treatment, it may be a good 15 to 20 years away,” he points out.

Mukhopadhyay says that it is critically important to understand how insulin resistance works as it will make an early intervention in diabetes care and management possible. Therein lies the significance of this study.

Explaining the mechanism, scientists say the main function of adipose tissues — the tissues beneath the skin or around internal organs — is to absorb fatty acids available from the diet and store them as fat. But in an insulin resistant person, these adipose tissues are damaged and hence can’t absorb fatty acids. These fatty acids travel to the liver through the bloodstream and are deposited there. This leads to a fatty liver, which cannot utilise the available glucose to the fullest possible extent. That means an increased glucose output from the liver into the bloodstream, leading to high blood sugar or diabetes. By the time diabetes is diagnosed, more than half of the beta cells in the pancreas have already been destroyed by overwork. So the only option left is to introduce insulin into the body.

“Currently, we are able to diagnose diabetes at a very late stage,” says Mukhopadhyay, who hopes that the understanding derived from the current work will pave the way for an early intervention.

And if that happens, it will certainly be a defining moment in humankind’s fight against the lifestyle disease.