New Delhi, July 1 Researchers at the Indian Institute of Technology (IIT) Bombay have identified a previously unknown trigger of diabetes in collagen -- the most abundant protein in the human body -- that is also worsening the blood sugar condition.
The study, published in the Journal of the American Chemical Society, showed how collagen accelerates the clumping of hormones in the pancreas, finding a potential new drug target.
In Type 2 diabetes which affects more than 500 million people worldwide, either not enough insulin -- a hormone essential for regulating blood sugar levels -- is produced, or the body’s cells become less responsive to it, resulting in high blood sugar levels.
And when the body tries to release more insulin, it also ends up making more amylin -- another hormone that helps control blood sugar after meals.
But the team found that fibrillar collagen I -- a major component of the extracellular matrix -- acts as a key platform that accelerates amylin aggregation.
Misfolded amylin tends to stick together, forming clumps that are toxic to cells, explained the researchers, led by Prof. Shamik Sen from the Department of Biosciences and Bioengineering at IIT Bombay.
In diabetic pancreatic tissue, the protein collagen I, which is found abundantly in connective tissues like skin and bones, becomes more abundant.
The amylin aggregation 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.
“It almost seems that the amylin completely physically coats the collagen surface forming stable aggregates that are more difficult for cells to clear. That was a very striking finding for us,” said Sen.
In diabetic mice and human pancreatic tissue, both collagen and amylin levels increased simultaneously as diabetes progressed.
This study also helps explain why some diabetes treatments, that mainly focus on processes inside the cells may not be very effective in halting disease progression, the researchers said.
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