New Delhi, Sept. 7: Scientists in Calcutta have deciphered a key mechanism to explain why obese people develop diabetes through a study that they say could also help drug-designers explore new anti-diabetic therapies.
The researchers at the Indian Institute of Chemical Biology, a laboratory under the Council of Scientific and Industrial Research, have shown that a protein secreted by fat cells activates the immune system to trigger inflammation and a poor response to insulin.
Doctors have known for decades that obesity is a risk factor for diabetes and that obesity is associated with a chronic, low-grade inflammation in fat tissues that alter the way the cells use up energy or respond to insulin. However, the molecular pathways to link this inflammation and insulin resistance - a precursor to diabetes - had remained unclear.
The study by the IICB scientists is a fresh advance towards unravelling these pathways. Pioneering research by two independent groups at Columbia University and the Novartis Institutes of Biomedical Research in the US had in December 2003 shown that obese fatty tissue is infiltrated by macrophages, a class of immune system cells.
The US groups had also demonstrated that macrophages are an important source of inflammation in these tissues.
"Why do macrophages infiltrate obese fatty issue has been a mystery," said Dipyaman Ganguly, a scientist at the IICB who led the new study. "Macrophages are usually activated by infections, their activation in the obese fatty tissue leading to chronic inflammation in the absence of any infection remain unexplained."
To look for answers, Ganguly worked with research scholar Amrit Raj Ghosh and other colleagues at IICB and doctors at Calcutta's Institute of Postgraduate Medical Education and Research and the ILS Hospitals. The team ran biochemical tests on 83 obese and 28 lean people who volunteered for the study.
They found that fat cells in the obese people produce unusually high levels of a protein called chemerin. They also found that chemerin draws a specific type of immune cells into fatty tissue, triggering a cascade of immunological events, leading to the production of a substance called interferon-alpha and the activation of macrophages.
"This in turn leads to insulin-resistance," said Satinath Mukhopadhyay, a collaborating endocrinologist at SSKM Hospital. "This is a condition where the body cannot use insulin efficiency and is a precursor for diabetes - people may be in an insulin-resistant state years before they develop diabetes," he said.
The scientists have described their chemerin-triggered mechanism in the journal Diabetes and proposed that it may help in the identification of new molecular targets for drug design.
For example, pharmacological researchers could think about targeting either the chemerin protein or interferon-alpha as a way to treat diabetes or prevent insulin-resistance.
The scientists say the unusually high levels of chemerin in obese people may also make it an early biomarker for insulin resistance.
"We think a blood test that looks for chemerin could help predict insulin resistance and diabetes years in advance," Mukhopadhyay said.
