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Researchers at the University of Geneva (UNIGE) hope that the S100A9 protein, or Calgranulin B, may contribute to the development of a new-generation anti-diabetic drug.

1| A protein to be exploited in the search for new-generation treatments

Researchers at UNIGE believe that the S100A9 protein, also known as Calgranulin B, may improve the quality of life of patients treated with insulin. They found that it could regulate glucose and lipids.(1)

Insulin, which is essential for the survival of millions of patients with type 1 diabetes and type 2 diabetics with insulin deficiency, is sometimes dangerous when the dose is very high (risk of hypoglycemia) or very low (risk of hyperglycemia).(2)

Yet poor diabetes control causes long-term complications, which is why it is so important to make sure treatment is as effective as possible. Professor Coppari and his team have already carried out research on leptin, a hormone that is believed to regulate blood sugar levels but that is difficult to use due to hypothalamic neuron-induced resistance to the hormone.(4)

2| The S100A9 protein plays a key role in the improvement of blood glucose

Previous studies have observed that over-expression of the S100A9 protein was necessary to prevent interference with the S100A8 protein and the triggering of inflammatory or autoimmune diseases.(1)

Tests on mice have demonstrated improvements in glucose and lipid levels.

According to the UNIGE researchers, the S100A9 protein "improves metabolic imbalance in insulin deficiency". The protein is only expressed in the presence of the TLR4 receptor. Although it is still difficult to explain the mechanism involved, the presence of this receptor is essential for the action of the Calgranulin B protein.(1)

Hence, Professor Coppari is currently conducting an observational clinical study on a population of type 1 and 2 diabetics with very high glucose levels to identify whether there is any correlation between the symptoms observed and S100A9 protein levels.(3)

This research could result in new-generation treatments combining the protein with low insulin doses.

3| Sources

  1. Giorgio Ramadori, Sanda Ljubicic, Serena Ricci, Despoina Mikropoulou, Xavier Brenachot, Christelle Veyrat-Durebex, Ebru Aras, Rafael M. Ioris, Jordi Altirriba, Elisabeth Malle, Dirk Foell, Thomas Vogl & Roberto Coppari, S100A9 extends lifespan in insulin deficiency, volume 10, Article number: 3545 (2019). Doi : 10.1038/s41467-019-11498-x.
  2. Coppari, R. & Bjorbaek, C. Leptin revisited: its mechanism of action and potential for treating diabetes. Nat. Rev. Drug Discov. 11, 692–708, doi.org/10.1038/nrd3757 (2012). Doi : 10.1038/nrd3757.
  3. Vianna, C. R. & Coppari, R. A treasure trove of hypothalamic neurocircuitries governing body weight homeostasis. Endocrinology. 2011 Jan;152(1):11-8. Doi : 10.1210/en.2010-0778.
  4. Des traitements de nouvelle génération pour le diabète ? Communiqué de presse de l’Université de Genève.