A research group at Kumamoto University succeeded in lowering the blood glucose level of mice by oral administration by mixing a uniquely discovered small intestine permeabilizing cyclic peptide (DNP peptide) with insulin.
Insulin therapy, which is a typical diabetes treatment method for controlling blood glucose, requires self-injection of an insulin preparation, which is a burden for many diabetic patients.Therefore, although the development of oral insulin is strongly desired, there is a problem that orally administered insulin is easily decomposed in the gastrointestinal tract and is not absorbed from the small intestine.
Therefore, in this study, we independently synthesize the small intestinal permeabilizing cyclic peptide DNP (D-form DNP peptide) with D-form amino acids that are not easily degraded by digestive enzymes, and add zinc to suppress the gastrointestinal degradation of insulin. An insulin hexamer (zinc insulin hexamer) was created.When a mixture of these was orally administered to mice, insulin absorption in the small intestine was promoted, and both wild-type mice and diabetic model mice succeeded in lowering blood glucose levels.
In addition, since many insulin injections also contain a hexamer of insulin produced by zinc addition, D-form DNP peptide is added to the insulin injection used clinically and orally administered to mice. As a result, it was found that a hypoglycemic effect can be obtained as well.From this, it was found that it is possible to improve the small intestinal absorption of insulin simply by adding the D-form DNP peptide to the existing insulin injection preparation.
This result has succeeded in building a foundation for the development of oral insulin using DNP peptides, and can be said to have paved the way for future oral insulin drug discovery.
