IIT Kanpur Identifies GPR18 Pathway Suppressing Insulin Release in Type-2 Diabetes Research

The news

Researchers at the Indian Institute of Technology-Kanpur have identified a molecular pathway through which immune cells in the pancreas can rapidly suppress insulin release, opening up a potential new avenue for developing therapies to protect insulin production in people with obesity and Type-2 diabetes. The findings, published in the Journal of Clinical Investigation, show that immune cells called macrophages can switch off insulin secretion by neighbouring beta cells within minutes, rather than gradually damaging them through inflammation over months or years, according to a note issued by IIT-Kanpur on Thursday.

The researchers found that the process involves sphingolipids, a class of fats released by macrophages, rather than the inflammatory proteins traditionally associated with obesity-related pancreatic damage. The team traced the trigger to GPR18, a receptor on macrophages. Once activated, it prompts the immune cells to release sphingolipids, which are taken up by neighbouring beta cells through a surface transporter and interfere with their insulin-producing machinery. Using a precision genetic technique, the researchers found that activating this pathway reduced insulin secretion in mouse models, while switching it off improved insulin release. Blocking GPR18 or other steps in the pathway also restored insulin secretion. The team, working with the Indiana Biosciences Research Institute in the US, confirmed that the same pathway was present and active in human pancreatic tissue. Activating it in donated human tissue also suppressed insulin secretion, the communique said. While the study does not offer an immediate treatment for diabetes, the findings establish a potential target for developing drugs to preserve insulin production in people with obesity and Type-2 diabetes, it said.

How does the newly identified pathway work?

The pathway begins with the activation of the GPR18 receptor on macrophages, immune cells present near pancreatic beta cells. Once activated, macrophages release sphingolipids, a class of fats. These sphingolipids enter neighbouring beta cells through a surface transporter and interfere with the cells' insulin-producing machinery. In mouse models, activating the pathway reduced insulin secretion, while blocking GPR18 or other steps in the pathway restored secretion. The same pathway was confirmed to be active in donated human pancreatic tissue, where its activation also suppressed insulin secretion.

What has the research achieved and what remains to be done?

The study has identified a potential drug target—GPR18 and other steps in the pathway—for preserving insulin production in people with obesity and Type-2 diabetes. However, the finding is not an immediate treatment. Further research is needed to determine whether blocking the pathway can be developed into a safe and effective therapy. The experimental findings should not be confused with an available diabetes treatment, the institute said.