Definition
Proinsulin is a prohormone produced by B-cells of pancreatic islets from the cleavage of pre-proinsulin. It is the precursor of insulin and contains the connecting C peptide. Proinsulin is secreted along with insulin and ligates to insulin receptors but with lower biological activity. Altered proinsulin levels can be detected in patients affected by diabetes mellitus, insulinomas, and in some rare genetic conditions.
Features
Proinsulin is the prohormone of insulin and is coded by the INS gene (11p15.5) in B-cells of the pancreatic islets of Langerhans (Bell et al. 1980; Kitabchi 1977). It is synthetized within its precursor protein pre-proinsulin and obtained after the cleavage of the signal peptide attached to the N-terminus site. Proinsulin is an 86 amino acids single chain peptide with a molecular weight of 9.4 kDa, which includes the A and the B chains of insulin and the C peptide. In the Golgi apparatus, proinsulin is cleaved by prohormone convertases (PC1/3 and PC2)...
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References and Further Reading
Bell, G. I., Pictet, R. L., Rutter, W. J., Cordell, B., Tischer, E., & Goodman, H. M. (1980). Sequence of the human insulin gene. Nature, 284(5751), 26–32.
Hernández-Sánchez, C., Mansilla, A., de la Rosa, E. J., & de Pablo, F. (2006). Proinsulin in development: New roles for an ancient prohormone. Diabetologia, 49(6), 1142–1150.
Horwitz, D. L., Starr, J. I., Mako, M. E., Blackard, W. G., & Rubenstein, A. H. (1975). Proinsulin, insulin, and C-peptide concentrations in human portal and peripheral blood. The Journal of Clinical Investigation, 55(6), 1278–1283.
Kitabchi, A. E. (1977). Proinsulin and C-peptide: A review. Metabolism, 26(5), 547–587.
MartÃn, M. G., Lindberg, I., Solorzano-Vargas, R. S., Wang, J., Avitzur, Y., Bandsma, R., et al. (2013). Congenital proprotein convertase 1/3 deficiency causes malabsorptive diarrhea and other endocrinopathies in a pediatric cohort. Gastroenterology, 145(1), 138–148.
Melani, F., Ryan, W. G., Rubenstein, A. H., & Steiner, D. F. (1970). Proinsulin secretion by a pancreatic beta-cell adenoma. Proinsulin and C-peptide secretion. The New England Journal of Medicine, 283(14), 713–719.
Mezza, T., Ferraro, P. M., Sun, V. A., Moffa, S., Cefalo, C. M. A., Quero, G., Cinti, F., Sorice, G. P., Pontecorvi, A., Folli, F., Mari, A., Alfieri, S., & Giaccari, A. (2018). Increased β-cell workload modulates proinsulin-to-insulin ratio in humans. Diabetes, 67(11), 2389–2396.
Murtha, T. D., Lupsa, B. C., Majumdar, S., Jain, D., & Salem, R. R. (2017). A systematic review of proinsulin-secreting pancreatic neuroendocrine tumors. Journal of Gastrointestinal Surgery, 21(8), 1335–1341.
Sims, E. K., Bahnson, H. T., Nyalwidhe, J., Haataja, L., Davis, A. K., Speake, C., et al. (2019). Proinsulin secretion is a persistent feature of type 1 diabetes. Diabetes Care, 42(2), 258–264.
Steiner, D. F., & James, D. E. (1992). Cellular and molecular biology of the beta cell. Diabetologia, 35(Suppl 2), S41–S48.
Wahren, J., Shafqat, J., Johansson, J., Chibalin, A., Ekberg, K., & Jörnvall, H. (2004). Molecular and cellular effects of C-peptide – new perspectives on an old peptide. Experimental Diabesity Research, 5(1), 15–23.
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Sciarra, A. (2022). Proinsulin. In: van Krieken, J. (eds) Encyclopedia of Pathology. Encyclopedia of Pathology. Springer, Cham. https://doi.org/10.1007/978-3-319-28845-1_5144-1
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DOI: https://doi.org/10.1007/978-3-319-28845-1_5144-1
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