Application of novel peptide (Pp1) improving the half-life of exendin-4 in vivo

AimsThe multiple physiological characterizations of exendin-4 make it as a promising drug candidate for the therapy of type 2 diabetes. Although the longer biological half-life offered the exendin-4 with excellent therapeutic potentials for the clinical utility of type 2 diabetes than glucagon-like peptide-1, the exendin-4 still did not free from the inconveniently frequent injections. Therefore, there are increasing requirements for the long-acting exendin-4.MethodsPp1 regard as a novel exendin-4 protecting peptide, which are predicted to have the ability of increasing the stabilization of exendin-4 in vivo. Protecting peptide is able to form stable complex by non-covalent interaction with human exendin-4.ResultsIn this study, the stability of the exendin-4/Pp1 complex was investigated, and the physiological functions of it were analyzed. Results indicated that exendin-4/Pp1 complex remarkably raised the stabilization of exendin-4 in vivo; it also showed better glucose tolerance and higher HbA1c reduction than exendin-4 which was utilized chronically in rodents.ConclusionBased upon these results, it is suggested that an exendin-4/Pp1 complex might be utilized as a potent anti-diabetic drug in the treatment of type 2 diabetes mellitus.

Research highlights
► Exendin-4/Pp1 complex extended the half-life of exendin-4 in vitro and in vivo.
► Formation of complex remained the biological activity of exendin-4.
► Complex showed better glucose tolerance and higher HbA1c reduction than exendin-4.
► Complex might be utilized as a long-lasting drug for type 2 diabetes.