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C-peptide and diabetic neuropathy.
Expert Opin Investig Drugs 2003; 12(9):1471-88EO

Abstract

Diabetic polyneuropathy (DPN) is the most common chronic complication of diabetes and affects Type 1 diabetic patients disproportionately. In the last two decades it has become increasingly evident that underlying metabolic, molecular and functional mechanisms and, ultimately, structural changes differ in DPN between the two major types of diabetes. In Type 1 diabetes, impaired insulin/C-peptide action has emerged as a prominent pathogenetic factor. C-peptide was long considered to be biologically inactive. During the last number of years it has been shown to have a number of insulin-like effects but without affecting blood glucose levels. Preclinical studies have demonstrated effects on Na(+)/K(+)-ATPase activity, endothelial nitric oxide synthase, expression of neurotrophic factors and regulation of molecular species underlying the degeneration of the nodal apparatus in Type 1 diabetic nerves, as well as DNA binding of transcription factors and modulation of apoptotic phenomena. In animal studies, these effects have translated into protection and improvement of functional abnormalities, promotion of nerve fibre regeneration, protection of structural changes and amelioration of apoptotic phenomena targeting central and peripheral nerve cell constituents. Several small-scale clinical trials confirm these beneficial effects on autonomic and somatic nerve function and blood flow in a variety of tissues. Therefore, evidence to date indicating that replacement of C-peptide in patients with Type 1 diabetes will retard and prevent chronic complication is real and encouraging. Large-scale clinical trials necessary to bring this natural substance into the clinical arena should, therefore, be encouraged and accelerated.

Authors+Show Affiliations

Department of Pathology, Wayne State University, Scott Hall Rm 9275, 540 E. Canfield Ave., Detroit, MI 48201, USA. asima@med.wayne.edu

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S.
Review

Language

eng

PubMed ID

12943492

Citation

Sima, Anders A F.. "C-peptide and Diabetic Neuropathy." Expert Opinion On Investigational Drugs, vol. 12, no. 9, 2003, pp. 1471-88.
Sima AA. C-peptide and diabetic neuropathy. Expert Opin Investig Drugs. 2003;12(9):1471-88.
Sima, A. A. (2003). C-peptide and diabetic neuropathy. Expert Opinion On Investigational Drugs, 12(9), pp. 1471-88.
Sima AA. C-peptide and Diabetic Neuropathy. Expert Opin Investig Drugs. 2003;12(9):1471-88. PubMed PMID: 12943492.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - C-peptide and diabetic neuropathy. A1 - Sima,Anders A F, PY - 2003/8/29/pubmed PY - 2004/1/7/medline PY - 2003/8/29/entrez SP - 1471 EP - 88 JF - Expert opinion on investigational drugs JO - Expert Opin Investig Drugs VL - 12 IS - 9 N2 - Diabetic polyneuropathy (DPN) is the most common chronic complication of diabetes and affects Type 1 diabetic patients disproportionately. In the last two decades it has become increasingly evident that underlying metabolic, molecular and functional mechanisms and, ultimately, structural changes differ in DPN between the two major types of diabetes. In Type 1 diabetes, impaired insulin/C-peptide action has emerged as a prominent pathogenetic factor. C-peptide was long considered to be biologically inactive. During the last number of years it has been shown to have a number of insulin-like effects but without affecting blood glucose levels. Preclinical studies have demonstrated effects on Na(+)/K(+)-ATPase activity, endothelial nitric oxide synthase, expression of neurotrophic factors and regulation of molecular species underlying the degeneration of the nodal apparatus in Type 1 diabetic nerves, as well as DNA binding of transcription factors and modulation of apoptotic phenomena. In animal studies, these effects have translated into protection and improvement of functional abnormalities, promotion of nerve fibre regeneration, protection of structural changes and amelioration of apoptotic phenomena targeting central and peripheral nerve cell constituents. Several small-scale clinical trials confirm these beneficial effects on autonomic and somatic nerve function and blood flow in a variety of tissues. Therefore, evidence to date indicating that replacement of C-peptide in patients with Type 1 diabetes will retard and prevent chronic complication is real and encouraging. Large-scale clinical trials necessary to bring this natural substance into the clinical arena should, therefore, be encouraged and accelerated. SN - 1354-3784 UR - https://www.unboundmedicine.com/medline/citation/12943492/C_peptide_and_diabetic_neuropathy_ L2 - http://www.tandfonline.com/doi/full/10.1517/13543784.12.9.1471 DB - PRIME DP - Unbound Medicine ER -