Collagen might affect your Type 2 diabetes, says a new study

In a recent study by IIT Bombay, collagen may have a role to play in making your Type 2 diabetes worse. Type 2 diabetes, which affects more than 500 million people worldwide, is expected to grow significantly in the coming decades, posing a major public health crisis.

Type 2 diabetes may be a major public health crisis in future

This growing health problem is caused by a mix of lifestyle, genetics, and complex biological mechanisms that drive the disease progression. Diabetes, at the cellular level, is marked by the progressive dysfunction of pancreatic β-cells, which are responsible for producing insulin—a hormone essential for regulating blood sugar levels. In type 2 diabetes, either insulin is not produced enough, or the body’s cells become less responsive to it, resulting to a spike in the blood sugar levels.

Along with insulin, another hormone called amylin helps control blood sugar after meals. The same pancreatic β-cells release both insulin and amylin. In diabetes, when a body tries to release more insulin, it also ends up making more amylin, which unlike insulin, tend to misfold and stick together, forming clumps that are toxic to cells. Previous research has shown that these clumps can damage the outer layer of cells, block the movement of nutrients, and even cause cell death. However, it is unclear what factors in the tissues of people with diabetes promote this clumping.

But, how would collagen affect?

In a recent study published in the Journal of the American Chemical Society, researchers from the Indian Institute of Technology Bombay (IIT Bombay), and collaborators from the Indian Institute of Technology Kanpur (IIT Kanpur), and the Chittaranjan National Cancer Institute (CNCI), Kolkata have identified an important missing link: fibrillar collagen I, a major component of the extracellular matrix. “Every tissue is composed of cells and an acellular component, the extracellular matrix. It is the matrix that holds together all cells and gives shape to organs,” explains Prof. Shamik Sen from the Department of Biosciences and Bioengineering at IIT Bombay, who led and oversaw the project.

In diabetic pancreatic tissue, the protein collagen I, that is found abundantly in connective tissues like skin and bones, becomes more abundant. And now, from the study, it is found to serve as a platform that accelerates amylin aggregation, which damages the insulin-producing β-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,” says Prof. Sen. “Rather than aggregating in isolation, amylin appears to use the collagen fibres like train tracks, accelerating its accumulation and increasing toxicity to nearby cells,” adds Prof. Sen.

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. “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 adds.

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.

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