IIT-Kanpur Finds Pancreatic Immune Switch That Halts Insulin
Scientists at IIT-Kanpur have uncovered a molecular pathway through which pancreatic immune cells called macrophages can shut off insulin release from neighbouring beta cells within minutes, according to The Hindu. Published in the Journal of Clinical Investigation and detailed in an IIT-Kanpur note on Thursday, the study was co-first-authored by Simran Singh and Ashish Kumar under Assistant Professor Sai Prasad Pydi in the department of biological sciences and bioengineering, The Hindu reported.
How the GPR18 and Sphingolipid Pathway Works
Pydi said immune cells located beside beta cells can halt insulin secretion in minutes without sending classical inflammatory signals, challenging the view that obesity-related inflammation only damages beta cells gradually over months or years, Indian Pharma Post reported. Instead of inflammatory proteins, activated macrophages release fat molecules called sphingolipids that neighbouring beta cells absorb via a surface transporter, interfering with their internal insulin-release machinery, The Hindu and Indian Pharma Post reported. The researchers traced the trigger to a macrophage receptor named GPR18, finding in mouse models that activating the pathway lowered insulin secretion while switching it off or blocking GPR18 restored insulin release, The Hindu reported. Macrophage-derived sphingolipids impaired beta-cell insulin signaling and glucose-stimulated insulin secretion through CD36-PKCζ, and inhibiting CD36 restored beta-cell function, according to Journal of Clinical Investigation.
Confirmation in Human Pancreatic Tissue
Working alongside the Indiana Biosciences Research Institute in the United States, the team established that GPR18 is concentrated in immune cells inside human pancreatic islets and confirmed that activating the pathway in donated human tissue also suppressed insulin secretion, Indian Pharma Post and The Hindu reported. While the study does not offer an immediate diabetes treatment, IIT-Kanpur said the findings point to three potential drug-development targets, namely the GPR18 receptor, the sphingolipid signal and the beta-cell uptake mechanism, to help preserve insulin production in people with obesity and type 2 diabetes, Indian Pharma Post reported. The researchers integrated publicly available single-cell RNA sequencing datasets generated from mouse pancreatic islets totaling 1,96,808 cells, according to PubMed Central (PMC12636625).