Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects
| العنوان: | Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects |
|---|---|
| المؤلفون: | Jan Johansson, Gunvor Alvelius, Jawed Shafqat, Kristmundur Sigmundsson, Hans Jörnvall, Mikael Henriksson, John Wahren, Bo-Lennart Johansson, Karin Ekberg, Ermias Melles |
| المصدر: | Cellular and Molecular Life Sciences |
| بيانات النشر: | Springer Nature |
| مصطلحات موضوعية: | Adult, Male, Spectrometry, Mass, Electrospray Ionization, medicine.medical_specialty, medicine.medical_treatment, electrospray ionization mass spectrometry, Peptide, Carbohydrate metabolism, insulin hexamer decrease, Exocytosis, chemistry.chemical_compound, Cellular and Molecular Neuroscience, Insulin receptor substrate, Internal medicine, proinsulin C-peptide, medicine, Humans, Hypoglycemic Agents, Insulin, diabetes type 1, Molecular Biology, Proinsulin, chemistry.chemical_classification, Pharmacology, C-Peptide, Chemistry, C-peptide, Cell Biology, Middle Aged, Surface Plasmon Resonance, Insulin oscillation, insulin disaggregation, Diabetes Mellitus, Type 1, Glucose, Endocrinology, insulin effect, Molecular Medicine, Female, Protein Binding, Research Article |
| الوصف: | 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. |
| اللغة: | English |
| تدمد: | 1420-682X |
| DOI: | 10.1007/s00018-006-6204-6 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::3d92ad7de07de305d3691efb11c2094eTest |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....3d92ad7de07de305d3691efb11c2094e |
| قاعدة البيانات: | OpenAIRE |
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