Scientists stumble upon potential drug target for diabetes

A team of Indian researchers has stumbled upon a potential new drug target for treating diabetes while on the path to unravel the mystery behind the spurt in levels of a protein linked to the disease.

The team from Kolkata's CSIR-Indian Institute of Chemical Biology, Republic of Korea's Institute for Basic Science (IBS), Kolkata's Vidyasagar College and the Institute of Postgraduate Medical Education and Research (IPGMER) here has in a recent study answered a long standing question as to why diabetics have more amount of an enzyme called dipeptidyl peptidase 4 or DPP4 in their blood.

To rein in the levels, diabetics take a group of pills called DPP4 inhibitors: sitagliptin, vildagliptin, saxagliptin etc. But why diabetic patients start accumulating DPP4 in the blood is still an enigma.

The team led by CSIR-IICB's Partha Chakrabarti identified the contribution of a particular class of white blood cells called T lymphocytes (Th17) behind the aberrant abundance of DPP4 in diabetics.

"Diabetics have abundant DPP4 in blood (we first time showed it for Indian patients), but its tissue source was not known. We found that certain immune cells (Th17 cells) shed DPP4 at enhanced rate. This process needs another enzyme KLK5. This is a new finding that answers a long standing question as to why diabetics have more DPP4," Chakrabarti told IANS.

Kallikrein-related peptidase 5 or KLK5 cleaves off the DPP4 present on the surface of Th17 cells and the freely circulating DPP4 starts piling up in blood. DPP4 destroys the hormone incretin that stimulates insulin secretion in response to meals. Incretin assists the body in producing more insulin only when it is needed and reduces the amount of glucose being produced by the liver when it is not needed.

"This new discovery points to KLK5 as another interesting target for antidiabetic therapy," Chakrabarti said. The results were published in the journal Molecular Metabolism in September. The study was carried out by Titli Nargis, a senior research fellow in Chakrabarti's lab.

The interdisciplinary work had contributions from research fellows Krishna Kumar and Amrit Raj Ghosh and scientists Dipyaman Ganguly and Saikat Chakrabarti - all from CSIR-IICB.

Dipayan Rudra and Amit Sharma from IBS, Korea, also joined hands with the Kolkata team for this study. IPGMER's Satinath Mukhopadhyay from the Department of Endocrinology was the clinical collaborator in the work.