Boosting the immune system to better fight diabetes
Type 1 diabetes is a severe metabolic disease that affects millions of people worldwide. In Switzerland alone, thousands of people live with it. The discovery of insulin a century ago transformed diabetes from a fatal condition into a manageable one and saved countless lives. Yet, insulin therapy is not a cure. Many patients still face an increase in fats and ketones in the blood that can lead to long-term complications such as heart disease and kidney damage.
Exploring new strategies beyond insulin
Immune cells are not only guardians against infections but also help to regulate how our body uses energy. In a new study published in Endocrinology, researchers from the laboratory of Prof. Roberto Coppari found that insulin deficiency alters the “immune landscape” of the liver. The number of T cells, a type of white blood cell, dropped sharply, while other immune cells, the Kupffer cells, increased and shifted their activity in harmful ways. These changes contributed to problems such as high blood fat and ketone levels, opening up a new avenue: could the immune system itself be used to fight diabetes?
S100A9, a molecule able to reprogram immune cells
Building on their previous discovery of the role of the S100A9 protein in type 1 diabetes, the research team explored its impact on the immune system using mouse models. Treatment with S100A9 reset Kupffer cells back to a healthier state, improved fat metabolism in the liver, and reduced the dangerous increase of fats and ketones in the blood. It also boosted sugar uptake in muscles, helping to lower blood glucose levels. All these effects relied on a receptor called TLR4, providing scientists with a new alternative strategy independent of insulin.
Instead of relying solely on insulin, we can now envisage therapies that reprogramme immune cells to improve both liver function and overall metabolism.
A new approach to treating diabetes
These findings highlight the deep connections between immunity and metabolism. They suggest that in the future, type 1 diabetes treatment could benefit from combining insulin with alternative drugs able to harness the body’s own immune system to maintain metabolic balance. Such strategy should help to prevent severe complications and improve patients’ quality of life. The research team launched a spin-off to advance the clinical development of this promising therapy. They have now finalised pre-clinical studies to assess the safety and stability of S100A9 and aim to enter the clinical phase soon.