Cellular and physiological effects of C-peptide

• Published in: Clinical science (1979) Vol. 116; no. 7-8; pp. 565 - 574
• Main Authors: HILLS, Claire E, BRUNSKILL, Nigel J
• Format: Journal Article
• Language: English
• Published: London Portland Press 01.04.2009
• Subjects: Animals; Biological and medical sciences; Blood Glucose - metabolism; C-Peptide - physiology; C-Peptide - therapeutic use; Cell Membrane - metabolism; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - physiopathology; Diabetes Mellitus, Type 1 - drug therapy; Diabetes Mellitus, Type 1 - physiopathology; Diabetes Mellitus, Type 2 - physiopathology; Diabetes. Impaired glucose tolerance; Diabetic Nephropathies - drug therapy; Diabetic Nephropathies - physiopathology; Diabetic Neuropathies - drug therapy; Diabetic Neuropathies - physiopathology; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Etiopathogenesis. Screening. Investigations. Target tissue resistance; General aspects; Humans; Medical sciences; Mice; Endocrinopathy; Type 2 diabetes; Proinsulin; Immunopathology; Peptide hormone; G-protein-coupled receptor; Metabolic diseases; Autoimmune disease; C-Peptide; Medicine; Type 1 diabetes; G protein coupled receptor; Cell
• ISSN: 0143-5221; 1470-8736
• DOI: 10.1042/cs20080441

In recent years, accumulating evidence indicates a biological function for proinsulin C-peptide. These results challenge the traditional view that C-peptide is essentially inert and only useful as a surrogate marker of insulin release. Accordingly, it is now clear that C-peptide binds with high affinity to cell membranes, probably to a pertussis-toxin-sensitive G-protein-coupled receptor. Subsequently, multiple signalling pathways are potently and dose-dependently activated in multiple cell types by C-peptide with the resulting activation of gene transcription and altered cell phenotype. In diabetic animals and Type 1 diabetic patients, short-term studies indicate that C-peptide also enhances glucose disposal and metabolic control. Furthermore, results derived from animal models and clinical studies in Type 1 diabetic patients suggest a salutary effect of C-peptide in the prevention and amelioration of diabetic nephropathy and neuropathy. Therefore a picture of Type 1 diabetes as a dual-hormone-deficiency disease is developing, suggesting that the replacement of C-peptide alongside insulin should be considered in its management.