Abstract
One of the most important outgrowths of the discovery of proinsulin was the finding that the 31-residue connecting segment, or C-peptide, that joins the insulin chains in the prohormone is excised intact and secreted in equal amounts along with insulin. This finding allowed the development of the human C-peptide radioimmunoassay which has become indispensable as an accurate measure of insulin production in vivo in various forms of diabetes [1].
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References
Steiner DF, Park SY, Støy J, et al. A brief perspective on insulin production. Diabetes Obes Metab. 2009;11 Suppl 4:189–96.
Keenan HA, Sun JK, Levine J, et al. Residual insulin production and pancreatic β-cell turnover after 50 years of diabetes: Joslin Medalist Study. Diabetes. 2010;59:2846–53.
Rouillé Y, Duguay SJ, Lund K, et al. Proteolytic processing mechanisms in the biosynthesis of neuroendocrine peptides: the subtilisin-like proprotein convertases. Front Neuroendocrinol. 1995;16:322–61.
Zhou A, Webb G, Zhu X, et al. Proteolytic processing in the secretory pathway. J Biol Chem. 1999;274:20745–8.
Remacle AG, Shiryaev SA, Oh ES, et al. Substrate cleavage analysis of furin and related proprotein convertases. A comparative study. J Biol Chem. 2008;283:20897–906.
Yang Y, Hua QX, Liu J, et al. Solution structure of proinsulin: connecting domain flexibility and prohormone processing. J Biol Chem. 2010;285:7847–51.
Gliemann J, Sorensen HH. Assay of insulin-like activity by the isolated fat cell method. IV. The biological activity of proinsulin. Diabetologia. 1970;6:499–504.
Støy J, Edghill EL, Flanagan SE, et al. Insulin gene mutations as a cause of permanent neonatal diabetes. Proc Natl Acad Sci U S A. 2007;104:15040–4.
Hodish I, Liu M, Rajpal G, et al. Misfolded proinsulin affects bystander proinsulin in neonatal diabetes. J Biol Chem. 2010;285:685–94.
Rajpal G, Liu M, Zhang Y, et al. Single-chain insulins as receptor agonists. Mol Endocrinol. 2009;23:679–88.
Steiner DF. The proinsulin C-peptide A multirole model. Exp Diabesity Res. 2004;5:7–14.
Zhu X, Orci L, Carroll R, et al. Severe block in processing of proinsulin to insulin accompanied by elevation of des-64,65 proinsulin intermediates in islets of mice lacking prohormone convertase 1/3. Proc Natl Acad Sci U S A. 2002;99:10299–304.
Grant PT, Coombs TL, Frank BH. Differences in the nature of the interaction of insulin and proinsulin with zinc. Biochem J. 1972;126:433–40.
Rajpal G, Liu M, Zhang Y, et al. Insulin crystallization depends on zinc transporter ZnT8 expression, but is not required for normal glucose homeostasis in mice. Proc Natl Acad Sci U S A. 2009;106:14872–7.
Nicolson TJ, Bellomo EA, Wijesekara N, et al. Insulin storage and glucose homeostasis in mice null for the granule zinc transporter ZnT8 and studies of the type 2 diabetes-associated variants. Diabetes. 2009;58:2070–83.
Robertson RP. The welcome resurgence of the α-cell: a pro glucagon commentary. Diabetes. 2010;59:2735–6.
Shafqat J, Melles E, Sigmundsson K, et al. Proinsulin C-peptide elicits disaggregation of insulin resulting in enhanced physiological insulin effects. Cell Mol Life Sci. 2006;63:1805–11.
Hills CE, Brunskill NJ. C-peptide and its intracellular signaling. Rev Diabet Stud. 2009;6:138–47.
Lindahl E, Nyman U, Zaman F, et al. Proinsulin C-peptide regulates ribosomal RNA expression. J Biol Chem. 2010;285:3462–9.
Lind J, Lindahl E, Perálvarez-Marín A, et al. Structural features of proinsulin C-peptide oligomeric and amyloid states. FEBS J. 2010;277:3759–68.
Brailoiu E, Dun SL, Gao X, et al. C-peptide of preproinsulin-like peptide 7: localization in the rat brain and activity in vitro. Neuroscience. 2009;159:492–500.
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Steiner, D.F. (2012). C-Peptide and Insulin: A Happy Marriage. In: Sima, A. (eds) Diabetes & C-Peptide. Contemporary Diabetes. Humana Press. https://doi.org/10.1007/978-1-61779-391-2_1
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DOI: https://doi.org/10.1007/978-1-61779-391-2_1
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