Targeting a Protein Linked to Insulin Cell Death May Delay Type 1 Diabetes Onset

Type 1 diabetes develops when the immune system attacks the insulin-producing beta cells in the pancreas. Over time, more beta cells are lost, and blood sugar control declines. Researchers have noticed that apolipoprotein CIII (apoCIII)—a protein that regulates fat metabolism—is elevated in people with Type 1 diabetes and is thought to contribute to beta cell death.

This observation has made apoCIII a target for researchers exploring whether lowering it could slow or delay the loss of beta cells before diabetes symptoms appear. The idea is to intervene during the prediabetic phase, when the immune attack is underway but most beta cell function remains intact.

In this study, researchers used small interfering RNA (siRNA)—a molecular tool that silences specific genes—to reduce apoCIII in diabetes-prone BioBreeding (DPBB) rats, a standard animal model of Type 1 diabetes. They designed two different siRNAs targeting rat apoCIII and tested them in young rats to identify which was most effective and which produced the fewest unintended effects on other genes.

One siRNA showed off-target effects and was excluded from further testing. The other, called apoCIII-siRNA2, effectively reduced apoCIII in the liver and bloodstream without affecting neighboring genes. A single injection lowered plasma apoCIII levels for about one week, and weekly injections maintained consistently low levels.

To understand how apoCIII reduction affects beta cell health, the team transplanted young islets into the eyes of diabetes-prone rats—a method that allows direct observation of islet structure and immune activity under a microscope. Starting at day 30 (during the final prediabetic month), rats received weekly intravenous injections of apoCIII-siRNA2 until they developed diabetes.

Detailed imaging at three and five weeks after transplantation showed that lowering apoCIII preserved islet morphology, maintained blood vessel formation around the islets, and reduced immune cell infiltration. These findings suggest that reducing apoCIII helps protect the structural and functional integrity of insulin-producing tissue during the prediabetic phase.

This work extends previous findings that antisense oligonucleotides—a different molecular tool—could delay diabetes onset by reducing apoCIII. By demonstrating that siRNA can achieve similar results, researchers now have multiple molecular approaches to pursue apoCIII reduction in further studies.

The timing of treatment is particularly significant: the intervention occurred during the final prediabetic month in rats, suggesting that the window for delaying disease onset may be narrower than previously thought. Future work will need to determine whether these benefits hold in people with Type 1 diabetes at risk, what the optimal dose and treatment schedule should be, and how long benefits might persist.

Source: Biomedicines. 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.