Mumbai | Researchers at the Indian Institute of Technology Bombay (IIT Bombay) have discovered that the most abundant protein in the human body, collagen I, acts as a key platform in accelerating amylin aggregation that worsens the type 2 diabetes.
Type 2 diabetes affects more than 500 million people worldwide, a number expected to grow significantly in the coming decades, posing a major public health crisis, they cautioned in a study.
In type 2 diabetes, either not enough insulin is produced, or the body's cells become less responsive to it, resulting in high blood sugar levels.
The chronic condition is caused by a mix of lifestyle, genetics and complex biological mechanisms that drive the disease progression, according to the study.
When the body releases insulin, it also ends up making more amylin, a hormone produced in the pancreas that helps control blood sugar after meals.
The pancreas, an organ located in the abdomen, plays an essential role in converting food into fuel for the body's cells.
Researchers from IIT Bombay, who collaborated with IIT Kanpur and the Chittaranjan National Cancer Institute (CNCI), Kolkata, found that collagen I act as a key platform that accelerates amylin aggregation, which damages the insulin-producing beta cells and makes amylin more toxic.
This damage reduces the body's ability to control blood sugar, pushing individuals closer to full-blown diabetes, the study added.
"It almost seems that the amylin completely physically coats the collagen surface forming stable aggregates that are more difficult for cells to clear. Rather than aggregating in isolation, amylin appears to use the collagen fibres like train tracks, accelerating its accumulation and increasing toxicity to nearby cells," stated Professor Shamik Sen from Department of Biosciences and Bioengineering at IIT Bombay, who led and oversaw the project,.
In an experiment, the researchers examined the pancreatic tissue from diabetic mice and also analysed single-cell data from human pancreatic tissue. They found that as diabetes progressed, both collagen and amylin levels rose simultaneously, indicating they were closely linked, said the study.
At the same time, there is disruption in the structure of the pancreatic islets, which are groups of cells where the insulin-making beta cells live.
The study also explained why some diabetes treatments, that mainly focus on processes inside the cells, may not be very effective in halting disease progression.
"Unless we disrupt this interaction between amylin and collagen, we may not be able to fully eliminate the toxic microenvironment in the pancreas," Prof Sen added.
The research team is now working to develop cryo-electron microscopy (cryo-EM) models of how amylin and collagen interact, aiming to guide the development of new drugs.
Researchers are also exploring ways to repair the pancreas, such as transplanting islets with support from 3D structures that mimic the natural environment, to restore beta cell function before significant damage occurs.
