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Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection

A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that oc...

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Autores principales: Souto, Selma B., Campos, Joana R., Fangueiro, Joana F., Silva, Amélia M., Cicero, Nicola, Lucarini, Massimo, Durazzo, Alessandra, Santini, Antonello, Souto, Eliana B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013900/
https://www.ncbi.nlm.nih.gov/pubmed/31963760
http://dx.doi.org/10.3390/ijms21020645
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author Souto, Selma B.
Campos, Joana R.
Fangueiro, Joana F.
Silva, Amélia M.
Cicero, Nicola
Lucarini, Massimo
Durazzo, Alessandra
Santini, Antonello
Souto, Eliana B.
author_facet Souto, Selma B.
Campos, Joana R.
Fangueiro, Joana F.
Silva, Amélia M.
Cicero, Nicola
Lucarini, Massimo
Durazzo, Alessandra
Santini, Antonello
Souto, Eliana B.
author_sort Souto, Selma B.
collection PubMed
description A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic β-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive β-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal–regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed.
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spelling pubmed-70139002020-03-09 Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection Souto, Selma B. Campos, Joana R. Fangueiro, Joana F. Silva, Amélia M. Cicero, Nicola Lucarini, Massimo Durazzo, Alessandra Santini, Antonello Souto, Eliana B. Int J Mol Sci Review A major hallmark of diabetes is a constant high blood glucose level (hyperglycaemia), resulting in endothelial dysfunction. Transient or prolonged hyperglycemia can cause diabetic vasculopathy, a secondary systemic damage. C-Peptide is a product of cleavage of proinsulin by a serine protease that occurs within the pancreatic β-cells, being secreted in similar amounts as insulin. The biological activity of human C-peptide is instrumental in the prevention of diabetic neuropathy, nephropathy and other vascular complications. The main feature of type 1 diabetes mellitus is the lack of insulin and of C-peptide, but the progressive β-cell loss is also observed in later stage of type 2 diabetes mellitus. C-peptide has multifaceted effects in animals and diabetic patients due to the activation of multiple cell signalling pathways, highlighting p38 mitogen-activated protein kinase and extracellular signal–regulated kinase ½, Akt, as well as endothelial nitric oxide production. Recent works highlight the role of C-peptide in the prevention and amelioration of diabetes and also in organ-specific complications. Benefits of C-peptide in microangiopathy and vasculopathy have been shown through conservation of vascular function, and also in the prevention of endothelial cell death, microvascular permeability, neointima formation, and in vascular inflammation. Improvement of microvascular blood flow by replacing a physiological amount of C-peptide, in several tissues of diabetic animals and humans, mainly in nerve tissue, myocardium, skeletal muscle, and kidney has been described. A review of the multiple cell signalling pathways of human proinsulin C-peptide in vasculopathy protection is proposed, where the approaches to move beyond the state of the art in the development of innovative and effective therapeutic options of diabetic neuropathy and nephropathy are discussed. MDPI 2020-01-18 /pmc/articles/PMC7013900/ /pubmed/31963760 http://dx.doi.org/10.3390/ijms21020645 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Souto, Selma B.
Campos, Joana R.
Fangueiro, Joana F.
Silva, Amélia M.
Cicero, Nicola
Lucarini, Massimo
Durazzo, Alessandra
Santini, Antonello
Souto, Eliana B.
Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection
title Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection
title_full Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection
title_fullStr Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection
title_full_unstemmed Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection
title_short Multiple Cell Signalling Pathways of Human Proinsulin C-Peptide in Vasculopathy Protection
title_sort multiple cell signalling pathways of human proinsulin c-peptide in vasculopathy protection
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7013900/
https://www.ncbi.nlm.nih.gov/pubmed/31963760
http://dx.doi.org/10.3390/ijms21020645
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