Insulinotropic activity of the host-defense peptide frenatin 2D: Conformational, structure-function and mechanistic studies.

Biochimie
Vishal MusaleJ Michael Conlon

Abstract

Of four naturally occurring frenatin peptides tested, frenatin 2D (DLLGTLGNLPLPFI.NH2) from Discoglossus sardus was the most potent and effective in producing concentration-dependent stimulation of insulin release from BRIN-BD11 rat clonal β-cells without displaying cytotoxicity. The peptide also stimulated insulin release from 1.1B4 human-derived clonal β-cells and isolated mouse islets and improved glucose tolerance concomitant with increased circulating insulin concentrations in mice following intraperitoneal administration. The insulinotropic activity of frenatin 2D was not associated with membrane depolarization or an increase in intracellular [Ca2+] but incubation of the peptide (1 μM) with BRIN-BD11 cells produced a modest, but significant (P < 0.05), increase in cAMP production. Stimulation of insulin release was abolished in protein kinase A-downregulated cells but maintained in protein kinase C-downregulated cells. Circular dichroism studies showed that, in the presence of dodecylphosphocholine micelles, frenatin 2D exhibited a helical content of 35% and a turn content of 28%. Substitution of the Thr5, Asn8, Pro10, and Ile14 residues in frenatin-2D by Trp and interchange of Pro12 and Phe13 led to loss of insulinotropi...Continue Reading

Citations

Feb 9, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Jelena PanticJ Michael Conlon

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