Assessment of the potential of temporin peptides from the frog Rana temporaria Rana temporariaRana temporaria (Ranidae) as anti‐diabetic agents

摘要

> Temporin A (FLPLIGRVLSGIL‐NH ₂ ), temporin F (FLPLIGKVLSGIL‐NH ₂ ), and temporin G (FFPVIGRILNGIL‐NH ₂ ), first identified in skin secretions of the frog Rana temporaria , produced concentration‐dependent stimulation of insulin release from BRIN‐BD11 rat clonal β‐cells at concentrations ≥1?nM, without cytotoxicity at concentrations up to 3?μM. Temporin A was the most effective. The mechanism of insulinotropic action did not involve an increase in intracellular Ca 2+ concentrations. Temporins B, C, E, H, and K were either inactive or only weakly active. Temporins A, F, and G also produced a concentration‐dependent stimulation of insulin release from 1.1B4 human‐derived pancreatic β‐cells, with temporin G being the most potent and effective, and from isolated mouse islets. The data indicate that cationicity, hydrophobicity, and the angle subtended by the charged residues in the temporin molecule are important determinants for in vitro insulinotropic activity. Temporin A and F (1?μM), but not temporin G, protected BRIN‐BD11 cells against cytokine‐induced apoptosis ( P ?P ?