Diabetes is a metabolic disease caused by a low production of the insulin hormone in your pancreas or your body’s ineffective use of this hormone, and this affects the wellbeing of over 300 million people worldwide. Diabetes comes with many wellness-harming symptoms such as tiredness, weight loss, neuropathies, problems of vision and, in extreme cases, death, due to a high concentration of blood glucose, and diabetics therefore need to monitor their levels closely. However thanks to CIC bioGUNE researchers there is a new, more reliable way to do this.
The team of scientists, led by Dr. Oscar Millet, from the Structural Biology Unit at CIC bioGUNE, have found a way to measure the glucose in your blood, as well as in other fluids, such as urine. However, this discovery has led researchers to call into question a dominant paradigm amongst the scientific community, about how proteins bind and communicate.
Whether between themselves or with metabolites and other ligands, proteins have been known, up until now, to either take the shape of the ligand during the association process, or only bind with a shape that is appropriate for the protein, much like the way that a specific key fits with a specific lock. Yet this study, which was published in the Journal of the American Chemical Society, proposes that if you use genetic engineering to slightly modify hinge regions between two proteins, this is all you need to alter the binding mechanism itself. Millet explained ‘The main result of our work has shown that both mechanisms are intimately connected and that we can go from one to another just by introducing small modifications in the protein’.
He continued ‘Not only have we understood this mechanism, but we have seen that the difference between this induced fit and the conformational selection is very subtle; they are actually not two independent processes – but everything is, in fact, connected. Nature is always subtle, and small variations to the chemical composition of the hinge lead us from one mechanism to the other’.
But what does this mean for people with diabetes? ‘Understanding the mechanism by which periplasmic proteins trap glucose to insert it into the cells opens the possibility of using these molecules as biosensors’, Millet explained. This means that you can measure your glucose levels in your other fluids, like your urine, rather than in your blood. Therefore, the process would be easier and more reliable than it has ever been. The current techniques used for monitoring glucose only give an estimate, as there are other substances that hide glucose in the blood, and so this advance in knowledge could eventually improve your control of the disease.
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