{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T01:30:58Z","timestamp":1787535058647,"version":"build-2736575974"},"reference-count":32,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2013,12,5]],"date-time":"2013-12-05T00:00:00Z","timestamp":1386201600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Rapid Comm Mass Spectrometry"],"published-print":{"date-parts":[[2014,1,30]]},"abstract":"<jats:sec>\n                    <jats:title>RATIONALE<\/jats:title>\n                    <jats:p>Insulin, islet amyloid polypeptide (IAPP), and the C\u2010peptide part of proinsulin are co\u2010secreted from the pancreatic beta cell granules. IAPP aggregation can be inhibited by insulin and insulin aggregation by C\u2010peptide, but different binding and disaggregating interactions may apply for the peptide complexes. A more detailed knowledge of these interactions is necessary for the development strategies against diabetic complications that stem from peptide aggregations.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>METHODS<\/jats:title>\n                    <jats:p>Mass spectrometry (MS) is utilized to investigate pH\u2010dependencies, sequence determinants and association strengths of interactions between pairs of all three peptides. Electrospray ionization (ESI)\u2010MS was used to monitor complex formation and interaction stoichiometries at different pH values. Collision\u2010induced dissociation (CID) was employed to probe relative association strengths and complex dissociation pathways.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>RESULTS<\/jats:title>\n                    <jats:p>IAPP, like C\u2010peptide, removes insulin oligomers observable by ESI\u2010MS. Both C\u2010peptide and IAPP form stable\u20091:1 heterodimers with insulin. Complexes of the negatively charged C\u2010peptide with the positively charged IAPP, on the other hand, are easily dissociated. Replacement of the conserved glutamic acid residues in C\u2010peptide with alanine residues increases the stability, indicating that net charge alone does not predict association strength. Binding to insulin has been suggested to stabilize a helical fold in IAPP via charge and hydrophobic interactions, which is in agreement with the now observed high gas\u2010phase stability and sensitivity to low pH.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>CONCLUSIONS<\/jats:title>\n                    <jats:p>Combined, these results suggest that the C\u2010peptide\u2013insulin and IAPP\u2013insulin interactions are mediated by a defined binding site, while such a feature is not apparent in the IAPP\u2013C\u2010peptide association. Hence, IAPP and C\u2010peptide are interacting in similar manners and with similar monomerizing effects on insulin, suggesting that both peptides can prevent insulin aggregation. Simultaneous interactions of all three peptides cannot be excluded but appear unlikely from the uneven pairwise binding strengths. Copyright \u00a9 2013 John Wiley &amp; Sons, Ltd.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/rcm.6772","type":"journal-article","created":{"date-parts":[[2013,12,15]],"date-time":"2013-12-15T20:04:02Z","timestamp":1387137842000},"page":"178-184","source":"Crossref","is-referenced-by-count":7,"title":["Insulin, islet amyloid polypeptide and C\u2010peptide interactions evaluated by mass spectrometric analysis"],"prefix":"10.1002","volume":"28","author":[{"given":"Michael","family":"Landreh","sequence":"first","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics  Karolinska Institutet S\u2010171 77 Stockholm Sweden"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gunvor","family":"Alvelius","sequence":"additional","affiliation":[{"name":"Department of Medical Biochemistry and Biophysics  Karolinska Institutet S\u2010171 77 Stockholm 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