C-peptide: New findings and therapeutic possibilities

• Published in: Diabetes research and clinical practice Vol. 107; no. 3; pp. 309 - 319
• Main Authors: Wahren, John, Larsson, Charlotte
• Format: Journal Article
• Language: English
• Published: Ireland Elsevier Ireland Ltd 01.03.2015
• Subjects: Animals; Anti-Inflammatory Agents - therapeutic use; C-Peptide - metabolism; C-Peptide - physiology; C-Peptide - therapeutic use; Cell Membrane - metabolism; Diabetes Mellitus, Type 1 - therapy; Diabetic Neuropathies - drug therapy; Endocrinology & Metabolism; eNOS; Humans; Male; Na+, K+-ATPase; Nephropathy; Neuropathy; Nitric Oxide Synthase Type III - metabolism; Reactive oxygen species; Retinopathy; Signal Transduction - drug effects; eNOS; Reactive oxygen species; Nephropathy; Retinopathy; Na+, K+-ATPase; Neuropathy; Na +, K +-ATPase; Na(+), K(+)-ATPase
• ISSN: 0168-8227; 1872-8227; 1872-8227
• DOI: 10.1016/j.diabres.2015.01.016

Much new information on C-peptide physiology has appeared during the past 20 years. It has been shown that C-peptide binds specifically to cell membranes, elicits intracellular signaling via G-protein and Ca2+-dependent pathways, resulting in activation and increased expression of endothelial nitric oxide synthase, Na+, K+-ATPase and several transcription factors of importance for anti-inflammatory, anti-oxidant and cell protective mechanisms. Studies in animal models of diabetes and early clinical trials in patients with type 1 diabetes demonstrate that C-peptide in replacement doses elicits beneficial effects on early stages of diabetes-induced functional and structural abnormalities of the peripheral nerves, the kidneys and the retina. Much remains to be learned about C-peptide's mechanism of action and long-term clinical trials in type 1 diabetes subjects will be required to determine C-peptide's clinical utility. Nevertheless, even a cautious evaluation of the available evidence presents the picture of a bioactive endogenous peptide with therapeutic potential