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Insulin solubility transitions by pH ‐dependent interactions with proinsulin C‐peptide
Author(s) -
Landreh Michael,
Alvelius Gunvor,
Willander Hanna,
Stukenborg JanBernd,
Söder Olle,
Johansson Jan,
Jörnvall Hans
Publication year - 2012
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/febs.12045
Subject(s) - proinsulin , insulin , peptide , c peptide , chemistry , solubility , biochemistry , biophysics , amylin , biology , endocrinology , islet , organic chemistry
Proinsulin processing into insulin and C‐peptide in the secretory granules of the pancreatic β‐cells occurs under mildly acidic conditions and at high peptide concentrations (> 10 m m ). Mature insulin has reduced solubility and a propensity to adopt an amyloid‐like structure, but is physiologically released as a mixture of a zinc‐containing core and a zinc‐free, C‐peptide‐rich fluid phase. C‐peptide is known to function in the insulin secretion, but its exact mode of interaction is not established. We now demonstrate that C‐peptide in sub‐stoichiometric amount versus insulin coprecipitates with insulin at the pH found in secretory vesicles. Precipitation is reversible and the precipitate is dissolved by elevation of the pH . This effect was found to be dependent on relatively conserved glutamate residues in the otherwise poorly conserved C‐peptide. Together, the data show that C‐peptide has the ability to influence insulin solubility. The physiological pH changes between insulin processing and release sites may therefore affect the quaternary structure of insulin, as well as the phase transitions during insulin sorting and secretion. Structured digital abstractInsulin and C-peptide bind by molecular sieving (View Interaction: 1 , 2 ) C-peptide and Insulin bind by dynamic light scattering (View Interaction: 1 , 2 ) C-peptide and Insulin bind by fluorescence technology (View Interaction: 1 , 2 , 3 , 4 )