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Horm Metab Res 2013; 45(11): 769-773
DOI: 10.1055/s-0033-1347208
Hypothesis
© Georg Thieme Verlag KG Stuttgart · New York

C-Peptide: A Molecule Balancing Insulin States in Secretion and Diabetes-associated Depository Conditions

M. Landreh
1   Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
,
J. Johansson
2   KI-Alzheimer’s Disease Research Center, NVS Department, Karolinska Institutet, Stockholm, Sweden
3   Department of Anatomy, Physiology and Biochemistry, Swedish University of Agricultural Sciences, Uppsala, Sweden
,
H. Jörnvall
1   Department of Medical Biochemistry and Biophysics, Karolinska Institutet, Stockholm, Sweden
› Author Affiliations
Further Information

Publication History

received 21 December 2012

accepted 06 May 2013

Publication Date:
18 June 2013 (online)

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Abstract

Gradually, the C-peptide part of proinsulin has evolved from being viewed upon as a side product of insulin synthesis and secretion to being considered as a bioactive peptide with endocrine functions. Independent of these, its biophysical properties and peptide interactions point to still further roles of C-peptide, in particular regarding possible links to diabetes-related protein aggregations. Insulin, which can deposit at the injection sites in the treatment of diabetes, and islet amyloid polypeptide (IAPP), which can form amyloid fibrils in the islets of Langerhans in diabetes type 2, are kept nonaggregated by charge-based interactions with C-peptide at defined stoichiometries. It is possible that the conformational stabilization of insulin and IAPP by C-peptide may also counterbalance their aggregational tendencies at the high peptide concentrations in the pancreatic β-cell secretory granules. The concentration imbalances of C-peptide, insulin, and IAPP from the hyperpeptidism early in T2DM patients and the insulin-only injections in T1DM patients may distort equilibria of these peptide interactions and promote protein aggregation. Additionally, the chaperone-like actions of C-peptide may increase bioavailability of insulin supplements given to T1DM patients and prevent the formation of insulin deposits. Similarly, peptide interactions may influence depository tendencies in additional peptide systems. In short, biophysical studies are relevant to establish all roles of peptide imbalances in T1DM and T2DM and associated depository diseases.

Key words

proinsulin C-peptide - diabetes types 1 and 2 - IAPP - insulin - amyloid - secretory granules

Supporting Information

 

  • References

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