For more than 100 years, scientists have pursued the idea of insulin in pill form, often described as a “dream” cure for diabetes. The challenge was the body itself. Enzymes in the digestive system break down insulin before it can do its job, and the intestines have no natural way to absorb insulin into the bloodstream. As a result, many patients remain dependent on daily injections, which can negatively impact their quality of life.
A team at Kumamoto University led by Associate Professor Shingo Ito has developed a promising solution. Their approach uses a cyclic peptide known as a DNP peptide that can pass through the small intestine. This platform allows insulin to be administered orally in a way that was not possible before.
Two effective strategies for intestinal absorption
To make this work, researchers designed two different ways to allow insulin to cross the intestinal barrier.
- Mixed method (interaction-based): The research team combined a modified D-DNP-V peptide with zinc-stabilized insulin hexamers. When this mixture was orally administered to several diabetes models, including chemically induced (STZ mice) and genetic models (bear mice), blood sugar levels quickly dropped to normal levels. Stable glucose control was maintained for 3 consecutive days with once-daily dosing.
- Binding method (covalent bond-based): The researchers used click chemistry to directly attach the DNP peptide to insulin, creating a “DNP-insulin conjugate.” This version lowered blood sugar levels as effectively as the mixed method, confirming that the peptide actively aided the transport of insulin through the intestines.
Lower doses make oral insulin more practical
One of the biggest drawbacks to oral insulin is that it requires very high doses (sometimes 10 times more than injections). This new platform significantly reduces that requirement. Approximately 33–41% pharmacological bioavailability was achieved compared to subcutaneous injection. This level of efficiency suggests that oral insulin could become much more practical in real-world use.
Future possibilities for diabetes treatment
Associate Professor Shingo Ito says, “Insulin injections remain a daily burden for many patients.” “Our peptide-based platform provides a new route for oral administration of insulin and has potential applications in long-acting insulin formulations and other biological injectables.”
The research results were published in a magazine Molecular medicine. The researchers are currently conducting additional studies, including testing in larger animal models and systems that mimic the human intestine, with a view to eventual clinical application.
