In a discovery that could reshape our understanding of diabetes, researchers at the Indian Institute of Technology (IIT) Kanpur have identified a molecular switch through which immune cells in the pancreas can shut down insulin release within minutes.

 

The breakthrough challenges the long-held understanding that obesity-related inflammation damages insulin-producing cells gradually over months and years. Instead, the study reveals that immune cells can directly instruct neighbouring pancreatic cells to stop releasing insulin through a rapid exchange of molecular signals.

 

Published in the prestigious Journal of Clinical Investigation, the study identifies a previously unknown pathway that could offer new targets for drugs aimed at preserving insulin production in people with obesity and type 2 diabetes.

 

The research was jointly led by Simran Singh and Ashish Kumar, the co-first authors, under the supervision of Dr. Sai Prasad Pydi of the Department of Biological Sciences and Bioengineering at IIT Kanpur.

 

"We discovered that immune cells that are present next to beta cells can switch off insulin release within minutes," said Sai Prasad Pydi, Assistant Professor in the Department of Biological Sciences and Bioengineering at IIT Kanpur who led the study. 

 

"And they do it without giving any of the classical inflammation signals we have been studying for decades. The findings change our fundamental understanding of how immune cells influence insulin production. The effect is not slow damage from inflammation but instruction that is delivered in minutes. The fact that this works the same way in human tissue is what makes it exciting, It is not just a finding in tissues of laboratory mice, but a real biological circuit that could be targeted with a drug "

 

The human pancreas contains insulin-producing beta cells and immune cells known as macrophages. While beta cells regulate blood sugar by releasing insulin, macrophages help maintain tissue health and immune balance.

 

The IIT Kanpur study has uncovered how these two cell types communicate directly, with macrophages capable of rapidly suppressing insulin secretion from neighbouring beta cells.

 

Until now, scientists largely believed that obesity triggered low-grade inflammation, which progressively damaged beta cells. The new findings point to a much faster mechanism — one in which immune cells send molecular instructions that interfere directly with the insulin-release machinery.

 

Using a precision genetic technique to switch a specific signalling pathway on and off inside immune cells, the researchers demonstrated that activating the pathway in macrophages sharply reduced insulin release in mouse models.

 

Switching it off produced the opposite effect, improving insulin secretion.

 

The researchers identified the molecular messengers as sphingolipids, a class of fat molecules rather than the inflammatory proteins traditionally associated with immune-related damage.

 

Once activated, macrophages rapidly released these lipids. Neighbouring beta cells absorbed them through a transporter on their surface, triggering interference with the cells' internal insulin-release machinery.

 

The team traced the process to GPR18, a receptor on macrophages that acts as the starting point of this molecular chain reaction.

 

Crucially, blocking GPR18 — or disrupting any of the downstream steps — restored normal insulin release. This gives researchers three potential intervention points for future drug development: the receptor, the lipid signal and the mechanism through which beta cells absorb it.

 

Perhaps the most significant finding is that the pathway is not limited to laboratory mice.

 

In collaboration with the Indiana Biosciences Research Institute in the United States, the IIT Kanpur team established that GPR18 is highly concentrated in immune cells within human pancreatic islets.

 

When researchers activated the pathway in donated human pancreatic tissue, insulin secretion was suppressed there as well.

 

The confirmation that the same biological mechanism operates in human tissue significantly strengthens the case for exploring it as a potential therapeutic target.

 

While the findings do not offer an immediate treatment or cure for diabetes, they open a promising new direction for research into protecting insulin-producing cells, particularly in people with obesity and type 2 diabetes.