title: Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects.
abstract: Using surface plasmon resonance (SPR) and electrospray mass spectrometry (ESI-MS), proinsulin C-peptide was found to influence insulin-insulin interactions. In SPR with chip-bound insulin, C-peptide mixed with analyte insulin increased the binding, while alone C-peptide did not. A control peptide with the same residues in random sequence had little effect. In ESI-MS, C-peptide lowered the presence of insulin hexamer. The data suggest that C-peptide promotes insulin disaggregation. Insulin/insulin oligomer muM dissociation constants were determined. Compatible with these findings, type 1 diabetic patients receiving insulin and C-peptide developed 66% more stimulation of glucose metabolism than when given insulin alone. A role of C-peptide in promoting insulin disaggregation may be important physiologically during exocytosis of pancreatic beta-cell secretory granulae and pharmacologically at insulin injection sites. It is compatible with the normal co-release of C-peptide and insulin and may contribute to the beneficial effect of C-peptide and insulin replacement in type 1 diabetics.
authors.affiliation: Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden.
authors.forename: J
authors.initials: J
authors.lastname: Shafqat
authors.forename: E
authors.initials: E
authors.lastname: Melles
authors.forename: K
authors.initials: K
authors.lastname: Sigmundsson
authors.forename: B-L
authors.initials: BL
authors.lastname: Johansson
authors.forename: K
authors.initials: K
authors.lastname: Ekberg
authors.forename: G
authors.initials: G
authors.lastname: Alvelius
authors.forename: M
authors.initials: M
authors.lastname: Henriksson
authors.forename: J
authors.initials: J
authors.lastname: Johansson
authors.forename: J
authors.initials: J
authors.lastname: Wahren
authors.forename: H
authors.initials: H
authors.lastname: Jörnvall
mesh_terms: D000328:Adult; D002096:C-Peptide / Q000378:metabolism* / Q000627:therapeutic use; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy* / Q000378:metabolism; D005260:Female; D005947:Glucose / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000378:metabolism* / Q000627:therapeutic use; D007328:Insulin / Q000378:metabolism* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D011485:Protein Binding; D021241:Spectrometry, Mass, Electrospray Ionization; D020349:Surface Plasmon Resonance
chemical_list: D002096:C-Peptide; D007004:Hypoglycemic Agents; D007328:Insulin; D005947:Glucose