What if the key to improving diabetes treatments lies not in making more insulin, but in understanding how it behaves before it even enters the bloodstream?
Researchers at the University of St Andrews and University of Dundee have been awarded just over £1 million to explore crucial unanswered questions in hormone biology: how insulin molecules assemble, separate and function inside the body’s insulin-producing cells.
The three-year project, funded by the Biotechnology and Biological Sciences Research Council (BBSRC), is led by Dr Alan Stewart from the School of Medicine at the University of St Andrews, working with Professor Carlos Penedo from the Schools of Biology and Physics & Astronomy at St Andrews and Professor James Cantley from the Faculty of Health at the University of Dundee.
Although insulin has been studied for more than a century, scientists still do not fully understand how the hormone is packaged and stored before it is released to regulate blood sugar.
Inside the beta cells of the pancreas, insulin molecules naturally group together into tiny clusters, held together by zinc. These microscopic structures help store insulin efficiently, but researchers do not yet know exactly how they form, how they break apart, or how this influences the body’s ability to control glucose.
“This is one of the hidden steps in insulin biology,” said Dr Stewart. “We know these clusters exist, but we still don’t understand the rules that govern how they assemble and disassemble, or how that affects insulin once it is released into the bloodstream.”
Professor Cantley added: “Despite decades of research, critical gaps in our understanding of insulin secretion and action remain: this collaborative project aims to generate deeper insights into the regulation of insulin clusters and their role in health and diabetes.”
The team will use state-of-the-art single-molecule imaging techniques that allow scientists to watch individual insulin molecules moving inside living cells in real time. By combining advanced microscopy, fluorescent labelling and genetically engineered mice, the researchers hope to capture an unprecedented view of insulin’s molecular life cycle.
“The ability to count individual insulin molecules one by one to quantitatively dissect the different aggregates present in a mixture is unique to the advanced microscopy methods to be used in this project,” said Professor Penedo. “They will provide us with a level of detail about insulin organization that cannot be achieved by any other technology.”
Early findings have already revealed that insulin forms zinc-dependent clusters of up to six molecules and that albumin – a protein abundant in the bloodstream – can help break these clusters apart, potentially making insulin available to act more quickly.
The researchers will also investigate how the acidity inside insulin storage compartments influences the hormone’s organisation and release, providing another missing piece of the puzzle.
While the research is fundamental, its implications could be far-reaching. A better understanding of insulin’s molecular behaviour may eventually help scientists develop improved insulin therapies, design smarter drugs and identify new approaches to treating diabetes and other metabolic diseases.
The project also showcases interdisciplinary collaboration, bringing together expertise in cell biology, physics, chemistry and metabolism to tackle one of the most fundamental questions in biomedical science.
With diabetes affecting hundreds of millions of people worldwide, the researchers hope their work will provide the foundations for the next generation of discoveries in hormone biology.
