Why the obese are prone to diabetes: a protein gives a clue

IT IS commonly known that obese, or overweight, people face a much greater risk of acquiring diabetes. It is not just a statistical link. Following several years of research, scientists have been able to show that the extra fat accumulated around the organs in an obese person is somehow associated with improper functioning of the naturally produced insulin hormone, leading to faulty sugar uptake by cells and high sugar amounts in blood, eventually leading to diabetes.

Insulin, which is produced by the pancreas, performs the important function of promoting glucose, or other forms of sugar in our food, to enter our body cells where the sugar is converted into energy. But why the function of insulin becomes faulty in an obese person is not known properly.

In 2003, two independent scientific groups, one at Columbia University and the other from Novartis Institute of Biomedical Research, showed that in obese people a set of “immune cells”, called macrophages, infiltrates the adipose tissues, and chemical mediators released by these immune cells prevent proper functioning of insulin.

This was a big step forward in our understanding of the link between obesity and diabetes. But we still did not know the reason or the mechanism for this infiltration and stimulation of macrophages and release of these chemicals inside the adipose tissues. Macrophages usually release these chemicals in response to infections. In the absence of any infection why these macrophages get stimulated inside the fat tissue was thus an enigma.

It is here that our team at IICB, in collaboration with clinicians from ILS Hospital, Kolkata, and the Institute of Post-graduate Medical Education and Research, Kolkata, has been able to make a breakthrough with new information. We have discovered that the extra fat in obese people leads to the unusually high production of a protein called chemerin. This chemerin was seen to attract a specific set of immune cells, called plasmacytoid dendritic cells (or pdcs), inside the tissue. A series of other biochemical processes follow, leading to the production of a chemical called “type one interferons”.

These interferons were seen to be stimulating the macrophages to release the harmful chemicals in the adipose tissue. It was also observed that the levels of interferons were directly proportional to the resistance to insulin.

Our work has very important implications, not just in understanding the link between obesity and diabetes, but also in the development of new-generation drugs for the disease. For example, we now know that it is the excess of chemerin protein in an obese person that triggers all the processes leading up to the resistance to insulin absorption. Therefore, if high levels of chemerin is noticed in an obese person, it can be an indicator of a greater probability of the person acquiring diabetes.

On the other hand, the discovery of the role of type one interferons in driving the disease process leads to the possibility of using it as a marker for predicting impending diabetes, perhaps in non-obese persons as well. Moreover, new types of drugs can be developed to reduce the effect of chemerin or type one interferons in obese people to prevent them from getting diabetes.

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