Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects |
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Authors: | J Shafqat E Melles K Sigmundsson B -L Johansson K Ekberg G Alvelius M Henriksson J Johansson J Wahren H Jörnvall |
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Affiliation: | Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden. |
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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 μM 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 β-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.
Received 3 May 2006; received after revision 9 June 2006; accepted 12 June 2006 Free Online Access |
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Keywords: | Surface plasmon resonance electrospray ionization mass spectrometry insulin effect diabetes type 1 proinsulin C-peptide insulin disaggregation insulin hexamer decrease |
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