New Protein Discovery Offers Potential to Replace Insulin for Diabetics

Researchers at the University of Geneva have made a groundbreaking discovery in the search for more effective treatments for diabetes, AOL reports.

A new protein, known as S100A9, has shown the potential to manage blood sugar and ketone levels in diabetics, offering a promising alternative to insulin therapy.

For individuals with type 1 diabetes or those with severe insulin deficiency, daily insulin injections are essential for survival. While insulin has been a life-saving treatment, it comes with challenges, such as difficulty in dosing, side effects, and risks like hypoglycemia or diabetic ketoacidosis (DKA), a dangerous condition caused by high ketone levels. The discovery of S100A9 may provide an innovative approach that could help manage diabetes with fewer risks.

Under normal circumstances, the body produces ketones as an alternative energy source during periods of fasting. This process, known as ketogenesis, occurs in liver cells and helps fuel tissues like the brain and muscles. However, in people with diabetes, particularly those with insufficient insulin, ketogenesis can become uncontrolled, leading to dangerous ketone accumulation and potentially life-threatening DKA.

For decades, insulin has been the primary method to control ketone production and maintain balance. However, insulin use is not without its own set of risks, including the potential for low blood sugar and long-term metabolic complications. As a result, researchers have been searching for alternative therapies that might reduce reliance on insulin.

In 2019, Professor Roberto Coppari and his team at the University of Geneva identified the protein S100A9, which appeared to regulate blood sugar and ketone levels without the need for insulin. Unlike insulin, S100A9 did not cause dangerous side effects and showed promise in improving lipid profiles in diabetic mice.

The key to this protein’s function lies in its activation of the Toll-like receptor 4 (TLR4) on liver cells. This activation triggers a protein complex known as mTORC1, which subsequently reduces ketone production in the liver. Interestingly, the S100A9 pathway does not cause inflammation, despite TLR4’s usual role in immune responses, and may even provide anti-inflammatory benefits.

According to Gloria Ursino, a postdoctoral fellow and first author of the study, “The S100A9-TLR4 interaction seems to act as a totally unexpected anti-inflammatory drug.”

This discovery could help mitigate the dangers of high ketone levels without the inflammatory side effects that usually accompany immune system activation.

The researchers tested S100A9 on diabetic mice and found that it reduced ketone levels and improved blood sugar management without inducing hypoglycemia, a common side effect of insulin. In fact, even mice with no insulin-producing cells lived longer when treated with S100A9, suggesting its potential to replace insulin in certain scenarios.

Building on these results, the researchers are now preparing for clinical trials, thanks to a CHF 2.5 million grant from the Helmsley Charitable Trust. This funding will support preclinical studies and the application process for human testing, which is expected to begin in 2025.

S100A9’s potential lies not only in its ability to control ketone production but also in its ability to function without the need for insulin. Current diabetes treatments generally focus on improving insulin sensitivity, but S100A9 offers a completely different approach. By bypassing insulin altogether, it could reduce the risks associated with insulin therapy, including long-term complications related to fat metabolism and cholesterol levels.

While the initial goal is to combine S100A9 with low doses of insulin, researchers are optimistic that it could one day be used independently. This could be particularly beneficial for individuals who are unable to produce insulin, such as those who have undergone a pancreas transplant or suffer from severe forms of type 2 diabetes.