Scientists Identify a New Target in the Immune Process Behind Type 1 Diabetes

Type 1 diabetes occurs when the immune system mistakenly attacks the insulin-producing beta cells in the pancreas. This attack involves multiple types of immune cells, including T-cells and macrophages, which flood the islets and release inflammatory molecules like TNF-alpha and interferon-gamma. While scientists have long understood that this immune attack destroys beta cells, many details about how and why it happens remain unclear.

A team of researchers recently identified a protein called NAMPT as a potential key player in this process. NAMPT controls the production of a molecule called NAD, which cells use as fuel and as a signaling molecule. The team hypothesized that abnormally high levels of NAD in the islets might be driving the immune attack, and decided to test whether blocking NAMPT could slow or stop it.

The researchers first tested their idea in isolated islets—both from mice and from human tissue donated for research. When they treated these islets with pro-inflammatory cytokines (immune signaling molecules) and simultaneously blocked NAMPT using a compound called FK866, the beta cells were protected. They showed less dysfunction and cell death compared to islets exposed to inflammatory signals alone.

Gene sequencing revealed that NAMPT inhibition stopped the expression of genes linked to inflammation and the migration of immune cells. In other words, blocking NAMPT not only protected the beta cells directly, but also appeared to dampen the inflammatory signals that recruit and activate immune cells in the first place.

To test whether these findings held true in a living organism, the researchers used a mouse model of Type 1 diabetes. They gave mice a series of low-dose injections of streptozotocin, a chemical that triggers diabetes by damaging beta cells and activating the immune system in a way that mimics human Type 1 diabetes.

Half of the mice received FK866, the NAMPT inhibitor, while the other half received a placebo. The mice treated with FK866 showed better blood sugar control and had healthier, more functional beta cells than the placebo group. When researchers examined the pancreases, they found that FK866 treatment reduced the number of immune cells infiltrating the islets—including TNF-alpha-producing T-cells and macrophages. The compound also slowed the growth of immune cells both in the islets and in the spleen.

In additional experiments, FK866 also blocked the ability of inflammatory cytokines to drive immune cells, particularly cytotoxic CD8 T-cells, toward and into islets.

These findings suggest that NAMPT could be an important target for new Type 1 diabetes therapies. Unlike treatments that broadly suppress the immune system, blocking NAMPT might specifically reduce the immune attack on beta cells while potentially preserving other immune functions. This could offer an advantage in terms of safety and tolerability.

However, it is crucial to note that this research is early-stage. The experiments were conducted in mice and in human islet tissue in the laboratory—not in people with Type 1 diabetes. Before FK866 or similar NAMPT inhibitors can be tested in patients, further research is needed to confirm safety, understand potential side effects, and determine the optimal way to use such compounds. The path from laboratory discovery to an approved therapy typically takes many years.

Source: Cell death & disease. Evidence type: PubMed indexed literature. Type1Cure is an information and intelligence hub, not a medical advice service. This article summarizes published research and does not provide diagnosis, treatment, or personal medical guidance. Always talk to your own care team before changing anything about your Type 1 diabetes management.