Kanpur, Nov. 13 -- Researchers at the Indian Institute of Technology-Kanpur (IIT-K) claim to have discovered how immune cells in the pancreas can switch off insulin secretion within minutes, uncovering a previously unknown mechanism that could open new avenues for treating type 2 diabetes. The study, published in the 'Journal of Clinical Investigation', identifies a molecular pathway through which macrophages-immune cells present alongside insulin-producing beta cells-interfere directly with insulin release. The researchers have also confirmed that the same mechanism operates in human pancreatic tissue, strengthening its potential as a target for future diabetes drugs. The research was jointly led by Simran Singh and Ashish Kumar under the supervision of Dr Sai Prasad Pydi, assistant professor in the department of biological sciences and bioengineering at IIT-Kanpur. Until now, the understanding was that obesity-related inflammation gradually damaged pancreatic beta cells over months and years, eventually impairing their ability to produce insulin. The IIT-Kanpur study has uncovered a more immediate process in which immune cells actively suppress insulin secretion without relying on conventional inflammatory signals. "We discovered that immune cells that are present next to beta cells can switch off insulin release within minutes," Dr Pydi said. The researchers found that macrophages release sphingolipids, a class of fats, which are taken up by neighbouring beta cells through a transporter on their surface. These lipids interfere with the cells' internal machinery responsible for insulin secretion. The team traced the mechanism to GPR18, a receptor on macrophages that triggers the signalling pathway. Activating it sharply reduced insulin secretion in mouse models, while switching it off improved insulin release. Blocking GPR18 or other steps in the pathway restored normal insulin secretion, according to the study. The findings point to three potential targets for drug development: the GPR18 receptor, the lipid signals released by macrophages and the transporter through which beta cells absorb them. The researchers also tested the mechanism in human pancreatic tissue in collaboration with the Indiana Biosciences Research Institute in the United States. They found that GPR18 was concentrated in immune cells within human pancreatic islets. Activating the pathway in donated human tissue blocked insulin secretion, confirming that the mechanism was not confined to laboratory mice. The study does not offer an immediate treatment for diabetes. However, the confirmation of the pathway in human tissue provides a foundation for investigating whether blocking it could help preserve insulin secretion in people with obesity and type 2 diabetes....