Patients with severe diabetes, in which the beta cells in the pancreas do not produce or produce enough insulin, rely on regular injections of synthetic insulin for survival.
And insulin therapy is not as risk-free as it is long-term, it can also lead to serious metabolic and cardiovascular problems.
Scientists at the University of Geneva (UNIGE) have been working on an alternative therapy based on the S100A9 protein for several years. They now provide evidence that this protein can significantly improve metabolism in insulin deficiency.
Additionally, by unraveling the biological mechanisms at work, they discovered a previously unknown anti-inflammatory effect that could be a key to preventing diabetes.
The results of this study were published in the journal Nature Communications.
And while insulin therapy, which celebrates its centennial in 2021, has saved the lives of hundreds of millions of people with type 1 diabetes or severe type 2 diabetes, it carries some risks when taken in doses. or directly responsible for very low and even some fatal cases. Thus, the life expectancy of insulin-dependent diabetics is shortened by 10 to 15 years compared to normal.
Roberto Coppari, Professor of Cell Physiology and Metabolism, Department of Cell Physiology and Metabolism at the University of Geneva, who led this study, indicates that serious effects of insulin, such as life-threatening hypoglycemia, have a negative effects on the body. lipid metabolism and cholesterol increase, “This is why we are trying to develop complementary or alternative therapies that are more effective and less dangerous.”
In 2019, Professor Kupari’s team identified a protein called S100A9, which regulates blood sugar, lipids and ketones (a product of fatty acid oxidation in the liver when there is not enough glucose in the body) without the side effects of insulin.
“To develop a drug, we need to fully understand how this protein works and demonstrate its effectiveness in animal models,” said Giorgio Ramadore, a research fellow in Professor Coppari’s lab and lead author of learning.
The team first set out to determine how S100A9 works in diabetic mice.
“This protein appears to act in the liver. It activates the TLR4 receptor, which is found in the membrane of some cells but not in hepatocytes, the main functional cells of the liver,” said Gloria Ursino. – PhD member of the research team and co-author of the study.
This is very important from a pharmacological point of view, because it means that S100A9 does not need to enter the hepatocytes to work and allows a simple method of injection administration.
In people with diabetes, a lack of insulin can cause a sudden increase in ketones and acidification of the blood, a mechanism called diabetic ketoacidosis. It is a life-threatening emergency that affects 2-4% of patients with type 1 diabetes each year.
“Activation of TLR4 in the liver regulates ketone production. But this activation process does not lead to inflammation, whereas TLR4 is generally a pro-inflammatory. So the S100A9-TLR4 dialogue seems to act as a completely unexpected anti-inflammatory drug, “explains Gloria Orsino.
The scientists completed their results by analyzing the blood of diabetic patients who came to the emergency room with severe insulin deficiency. “A slight but not sufficiently normal increase was seen in S100A9. Therefore, the additional application of S100A9 is expected to enhance this compensatory mechanism,” explained Giorgio Ramadore.
While the idea of a drug combination has been explored, previous research has focused on drugs that increase insulin sensitivity. Roberto Coppari explains: “But it only leads to the same results at lower doses. The side effects of insulin therapy remain the same. Here we propose a radically different approach to a drug that acts independently of insulin and does not cause hypoglycemia or disrupt lipid metabolism.”
The scientists will initially test their drug in combination with low-dose insulin, but they do not rule out the possibility that S100A9 will be given alone in certain situations in the future.
Source: Medical Express
Source: Arabic RT
