Is Collagen Worsening Type 2 Diabetes?

A new study published in the Journal of the American Chemical Society offers critical insight into the biological mechanisms underlying type 2 diabetes. Researchers from the Indian Institute of Technology Bombay (IIT Bombay), in collaboration with IIT Kanpur and the Chittaranjan National Cancer Institute (CNCI), Kolkata, have identified a key trigger that accelerates the progression of this widespread disease: the structural protein collagen I.A Rising Global Health CrisisType 2 diabetes currently affects over 500 million people worldwide, and numbers are expected to rise sharply in the coming decades. The disease is primarily driven by a combination of genetics, lifestyle factors, and complex cellular mechanisms. At its core lies the dysfunction of pancreatic β-cells, the insulin-producing cells responsible for regulating blood sugar levels.As diabetes develops, β-cells either fail to produce enough insulin or the body’s cells become resistant to it. A lesser-known yet crucial hormone, amylin, is also secreted by these β-cells and plays a vital role in managing blood sugar after meals. However, in diabetic conditions, excessive amylin production leads to misfolding and toxic clumping, which damages β-cells and accelerates disease progression.Collagen I Accelerates Amylin ClumpingIn the latest study, the research team pinpointed fibrillar collagen I, a common component of the extracellular matrix, as a key factor driving the toxic aggregation of amylin. Found abundantly in connective tissues like skin and bones, collagen I is also present in the pancreatic environment—particularly in diabetic tissues where it is elevated.“Every tissue is composed of cells and an extracellular matrix that provides structural support. In diabetic pancreatic tissue, this matrix, especially collagen I, becomes more prominent,” explained Prof. Shamik Sen, the study’s lead investigator from the Department of Biosciences and Bioengineering at IIT Bombay.The researchers discovered that collagen I acts like a scaffold or platform, accelerating the misfolding and aggregation of amylin, which in turn damages β-cells. This discovery adds a new layer to understanding why the disease worsens over time, even with treatments targeting cellular pathways.Biophysical Evidence Supports FindingsTo investigate how collagen I interacts with amylin, the team used a suite of advanced biophysical tools. These included surface plasmon resonance to measure binding strength, atomic force microscopy to study molecular adhesion, thioflavin T fluorescence to track aggregation speed, and NMR spectroscopy to identify interacting regions of the molecules.“Amylin almost coats the collagen fibres, forming stable, toxic aggregates that cells struggle to clear,” said Prof. Sen. The behavior of amylin on collagen fibres resembled trains moving on tracks—quickly and with destructive momentum.Computer simulations by Prof. Prasenjit Bhaumik’s group at IIT Bombay confirmed that fibrillar collagen I accelerates the toxic aggregation process, offering further validation of the molecular interaction.Biological Evidence from Mouse and Human TissuesThe team extended their study to biological samples from diabetic mice and humans. With the help of Prof. Hamim Zafar and Prof. Sai Prasad Pydi from IIT Kanpur, and Dr. Sankhadeep Dutta from CNCI, they analyzed single-cell data and tissue architecture.The findings were striking: as diabetes progressed, both collagen and amylin levels rose, accompanied by damage to pancreatic islets—clusters of cells that house insulin-producing β-cells.Testing the Combined Effect on CellsTo test the functional impact, the researchers grew lab-engineered β-cells on collagen gels containing amylin. These cells showed increased oxidative stress, reduced insulin production, and higher rates of cell death, compared to controls grown without collagen or amylin.This suggests that the extracellular environment, particularly collagen I, plays a central role in worsening β-cell dysfunction in diabetes.The findings could explain why many diabetes treatments fall short—they overlook the external microenvironment contributing to disease progression. “Unless we disrupt the interaction between amylin and collagen, we may not be able to eliminate the toxic pancreatic environment,” said Prof. Sen.Looking ahead, the team is working on cryo-electron microscopy (cryo-EM) models to visualize how amylin and collagen interact at the molecular level. They are also exploring 3D tissue engineering strategies to restore pancreatic function by replicating healthy extracellular conditions.

Is Collagen Worsening Type 2 Diabetes?

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