中国生物工程杂志

A new type of neuroendocrine peptide, pituitary adenylate cyclase activating peptide (PACAP), has been found to play an important role in carbohydrate or lipid metabolism but is susceptible to dipeptidyl peptidase IV degradation. Chitosan-modified nano-selenium (SeNPs-CTS, SC) was used as a carrier and the PACAP-derived peptide MPL-2 was loaded by amide bond to prepare a stable and stable nanoparticle peptide SeNPs- CTS-MPL-2 (SCM). The experimental results show that the high stability nano-composite peptide SCM was successfully constructed. The average particle diameter of SCM was 158nm, the particle size was relatively concentrated, and the surface Zeta potential was 35.6mV, which was significantly different from the SC particle size and Zeta potential. These proved that MPL-2 successfully connected to the SC surface. SCM was stable in aqueous solution for 40 days and has strong stability in aqueous solution. In vitro sustained release experiments showed that SCM released MPL-2 continuously within 48 hours, effectively prolonging the action time of MPL-2. Type 2 diabetes model mice (db/db mice) were injected intraperitoneally with SCM. Glucose tolerance test results showed that SCM sustained release of MPL-2 in vivo after MPL-2 was loaded onto carrier SC, prolonged the effect time of MPL-2 and enhanced the efficacy of MPL-2. During 8 weeks of continuous medication, SCM significantly increased insulin sensitivity in mice with type 2 diabetes mellitus, significantly more potent than MPL-2 and SC alone. The nanocomposite peptide SCM was constructed to effectively prolong the action time of MPL-2 and to exert the biological effect of treating type II diabetes.