If you are one of the many millions of type 1 diabetics worldwide, you know that there is a difference in how rapidly and for how long insulin preparations work in the body. For diabetics, these differences are crucial for effective treatment. Getting too little or too much insulin can lead to blood sugar that is either too low or high. Both conditions can be dangerous.
The absorption of insulin in the body is controlled by how insulin molecules assemble themselves in clusters. Whereas a single molecule provides rapid action in the body, clusters of six molecules – known as hexamers – are long-acting. For decades, it has been assumed that insulin assembles with a certain distribution of molecular clusters of either one, two or six molecules. Pharmaceuticals have been designed based upon this assumption.
But with the help of highly advanced single molecule microscopy, researchers at the University of Copenhagen, in collaboration with Aarhus University, have become the first to demonstrate that this important point has been wrong for years. "It is now apparent to us that we’ve gotten things wrong by 200 percent. There are only half as many single molecules in insulin compared to what we thought. Conversely, there are far more six-molecule clusters than we assumed. These experiments were not on animals but were performed on a microscope slide and one should be careful how to interpret their direct application to humans," says Professor Nikos Hatzakis of the Department of Chemistry, the study’s lead author.
He adds: "However, our results may mean that when we believe to be administering a certain dose, it may mean that insulin behaves in a different way than expected and that even better insulin therapeutics can be developed.”
In other words, much of the insulin that diabetics currently put into their bodies may not actually be getting absorbed as expected. While the researchers emphasize that this is not outright dangerous for patients, it does show that there is great potential for the development of more precise medications.
The study, Enhanced Hexamerization of Insulin via Assembly Pathway Rerouting Revealed by Single Particle Studies, has just been published in the scientific journal Communications Biology.
