The C-peptide is a fragment of proinsulin, the cleavage of which forms active insulin. In recent years, new information has appeared on the physiological effects of the C-peptide, indicating its positive effect on many organs and tissues, including the kidneys, nervous system, heart, vascular endothelium and blood microcirculation. Studies on experimental models of diabetes mellitus in animals, as well as clinical trials in patients with diabetes, have shown that the C-peptide has an important regulatory effect on the early stages of functional and structural disorders caused by this disease. The C-peptide exhibits its effects through binding to a specific receptor on the cell membrane and activation of downstream signaling pathways. Intracellular signaling involves G-proteins and Ca2+-dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+/K+-ATPase and important transcription factors involved in apoptosis, anti-inflammatory and other intracellular defense mechanisms. This review gives an idea of the C-peptide as a bioactive endogenous peptide that has its own biological activity and therapeutic potential.
Download PDF:
Keywords: C-peptide, mechanism of action, diabetic nephropathy, neuropathy, apoptosis, review
Citation:
Poteryaeva O.N., Usynin I.F. (2020) Molecular mechanisms of action and physiological effects of the proinsulin C-peptide (a systematic review). Biomeditsinskaya Khimiya, 66(3), 196-207.
Poteryaeva O.N. et al. Molecular mechanisms of action and physiological effects of the proinsulin C-peptide (a systematic review) // Biomeditsinskaya Khimiya. - 2020. - V. 66. -N 3. - P. 196-207.
Poteryaeva O.N. et al., "Molecular mechanisms of action and physiological effects of the proinsulin C-peptide (a systematic review)." Biomeditsinskaya Khimiya 66.3 (2020): 196-207.
Poteryaeva, O. N., Usynin, I. F. (2020). Molecular mechanisms of action and physiological effects of the proinsulin C-peptide (a systematic review). Biomeditsinskaya Khimiya, 66(3), 196-207.
Newsome C.L. (2015) Investigation into the biological importance and function of proinsulin C-peptide. Theses, Dissertations and Capstones, 958. Scholar google search
Bathgate R.A., Halls M.L., van der Westhuizen E.T., Callander G.E., Kocan M., Summers R.J. (2013) Physiol. Rev., 93, 405-480. CrossRef Scholar google search
Lindahl E., Nyman U., Melles E., Sigmundsson K., Ståhlberg M., Wahren J., Öbrink B., Shafqat J., Joseph B., Jörnvall H. (2007) Cell. Mol. Life Sci., 64(4), 479-486. CrossRef Scholar google search
Vague P., Coste T.C., Jannot M.F., Raccah D., Tsimaratos M. (2004) Exp. Diabesity Res., 5(1), 37-50. CrossRef Scholar google search
Ohtomo Y., Aperia A., Sahlgren B., Johansson B.L., Wahren J. (1996) Diabetologia, 39(2), 199-205. CrossRef Scholar google search
Kunt T., Schneider S., Pfutzner A., Goitum K., Engelbach M., Schauf B., Beyer J., Forst T. (1999) Diabetologia, 42(4), 465-471. CrossRef Scholar google search
Hach T., Forst T., Kunt T., Ekberg K., Pfützner A., Wahren J. (2008) Exp. Diabetes Res., 2008, Article ID: 730594, DOI: 10.1155/2008/730594. CrossRef Scholar google search
Forst T., de la Tour D.D., Kunt T., Pfützner A., Goitom K., Pohlmann T., Schneider S., Johansson B.L., Wahren J., Löbig M., Engelbach M., Beyer J., Vague P. (2000) Clin. Sci. (Lond.), 98(3), 283-290. CrossRef Scholar google search
Sima A.A., Zhang W., Sugimoto K., Henry D., Li Z., Wahren J., Grunberger G. (2001) Diabetologia, 44(7), 889-897. CrossRef Scholar google search
Fiorina P., Folli F., Zerbini G., Maffi P., Gremizzi C., Di Carlo V., Bertuzzi F., Kashgarian M., Secchi A. (2003) J. Am. Soc. Nephrol., 14(8), 2150-2158. CrossRef Scholar google search
Wallerath T., Kunt T., Forst T., Closs E.L., Lehmann R., Flohr T., Gabriel M., Schäfer D., Göpfert A., Pfützner A., Beyer J., Förstermann U. (2003) Nitric Oxide, 9(2), 95-102. CrossRef Scholar google search
Zhong Z., Davidescu A., Ehren I., Ekberg K., Jörnvall H., Wahren J., Chibalin A.V. (2005) Diabetologia, 48(1), 187-197. CrossRef Scholar google search
Kitamura T., Kimura K., Jung B.D., Makondo K., Okamoto S., Canas X., Sakane N., Yoshida T., Saito M. (2001) Biochem. J., 355(Pt1), 123-129. CrossRef Scholar google search
Kitamura T., Kimura K., Jung B.D., Makondo K., Sakane N., Yoshida T., Saito M. (2002) Biochem. J., 366(Pt3), 737-744. CrossRef Scholar google search
Grunberger G., Qiang X., Li Z., Mathews S.T., Sbrissa D., Shisheva A., Sima A.A. (2001) Diabetologia, 44 (10), 1247-1257. CrossRef Scholar google search
Al-Rasheed N.M., Chana R.S., Baines R.J., Willars G.B., Brunskill N.J. (2004) J. Biol. Chem., 279(48), 49747-49754. CrossRef Scholar google search
Kitamura T., Kimura K., Makondo K., Furuya D.T., Suzuki M., Yoshida T., Saito M. (2003) Diabetologia, 46(12), 1698-1705. CrossRef Scholar google search
Li L., Oshida Y., Kusunoki M., Yamanouchi K., Johansson B.L., Wahren J., Sato Y. (1999) Diabetologia, 42(8), 958-964. CrossRef Scholar google search
Kamikawa A., Ishii T., Shimada K., Makondo K., Inanami O., Sakane N., Yoshida T., Saito M., Kimura K. (2008) Diabetes Metab. Res. Rev., 24(4), 331-338. CrossRef Scholar google search
Maezawa Y., Yokote K., Sonezaki K., Fujimoto M., Kobayashi K., Kawamura H., Tokuyama T., Takemoto M., Ueda S., Kuwaki T., Mori S., Wahren J., Saito Y. (2006) Diabetes Metab. Res. Rev., 22(4), 313-322. CrossRef Scholar google search
Panero F., Novelli G., Zucco C., Fornengo P., Perotto M., Serge O., Grassi G., Cavallo-Perin P., Bruno G. (2009) v Diabetes Care, 32(2), 301-305. CrossRef Scholar google search
Johansson B.L., Borg K., Fernqvist-Forbes E., Kernell A., Odergren T., Wahren J. (2000) Diabet. Med., 17(3), 181-189. CrossRef Scholar google search
Sawyer R., Flynn E., Hutchens Z., Williams J., Garrett M., Maric-Bilkan C. (2012) Am. J. Physiol. Renal. Physiol., 303(6), F893-F899. CrossRef Scholar google search
