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C-peptide and Neuropathy in Type 1 Diabetes

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New data indicate that proinsulin C-peptide, contrary to previous views, exerts important physiological effects and shows the characteristics of a bioactive peptide. Studies in animal models and in type 1 diabetes patients have demonstrated multifaceted effects. Peripheral nerve function, as evaluated by determination of sensory nerve conduction velocity and quantitative sensory testing, is improved by C-peptide replacement in diabetes type 1 patients with early stage neuropathy. Similarly, autonomic nerve dysfunction is ameliorated following administration of C-peptide for up to 3 months. C-peptide given to type 1 diabetic animals results in improved nerve conduction velocity and reversal or prevention of nerve structural changes. C-peptide corrects diabetes-induced reductions in endoneurial blood flow and in Na+,K+-ATPase activity. In vitro studies demonstrate that C-peptide binds specifically to cell membranes, activating a G-protein coupled receptor as well as Ca2+-, PKC- and MAPK-dependent signaling pathways, resulting in stimulation of Na+,K+-ATPase and endothelial nitric oxide synthase (eNOS). In addition, C-peptide activates transcription factors resulting in augmented eNOS mRNA and protein content of endothelial cells and modulation of neurotrophic factors as well as apoptotic phenomena in neuroblastoma cells. Combined, the results demonstrate that C-peptide is a bioactive peptide, possibly of importance in the treatment of neuropathy in type 1 diabetes.

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Keywords: G-protein; K+-ATPase; Na+; Neuropathy; endoneurial blood flow; endothelial nitric oxide synthase; intracellular Ca2+; mitogen-activated protein kinase; nerve conduction velocity

Document Type: Research Article

Affiliations: Creative Peptides Sweden,Fogdevreten 2, SE 171 77 Stockholm, Sweden.

Publication date: February 1, 2007

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  • Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry aims to cover all the latest and outstanding developments in the medicinal chemistry and rational drug design for the discovery of new Immunology, Endocrine & Metabolic Agents. Each issue contains a series of timely in-depth reviews written by leaders in the field covering a range of current topics in Immunology, Endocrine & Metabolic medicinal chemistry.

    Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry is an essential journal for every medicinal chemist who wishes to be kept informed and up-to-date with the latest and most important developments in Immunology, Endocrine & Metabolic drug discovery.
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