Unordered structure of proinsulin C-peptide in aqueous solution and in thepresence of lipid vesicles

Proinsulin C-peptide ameliorates renal and autonomic nerve function and inc reases skeletal muscle blood flow, oxygen uptake and glucose transport in p atients with insulin-dependent diabetes mellitus. These effects have in par t been ascribed to the stimulatory influence of C-peptide on Na+, K+-ATPase and endothelial nitric oxide synthase. To evaluate the capacity of C-pepti de to insert into lipid bilayers and form ion channels, C-peptide secondary structure and membrane interactions were studied with circular dichroism s pectroscopy and size exclusion chromatography. C-peptide is shown to Lack a stable secondary structure, both when part of proinsulin and when free in aqueous solution, although the N-terminal third of the peptide exhibits an alpha-helical conformation in trifluoroethanol. Moreover, C-peptide remains disordered in the aqueous solvent in the presence of lipid vesicles, regar dless of vesicle composition. In conclusion, C-peptide is unlikely to elici t physiological effects through stable conformation-dependent interactions with lipid membranes.