title: Can C-peptide mediated anti-inflammatory effects retard the development of microvascular complications of type 1 diabetes?
abstract: Hyperglycemia is considered to be the major cause of microvascular complications of diabetes. Growing evidence highlights the importance of hyperglycemia-mediated inflammation in the initiation and progression of microvascular complications in type 1 diabetes. We hypothesize that lack of proinsulin C-peptide and lack of its anti-inflammatory properties contribute to the development of microvascular complications. Evidence gathered over the past 20 years shows that C-peptide is a biologically active peptide in its own right. It has been shown to reduce formation of reactive oxygen species and nuclear factor-κB activation induced by hyperglycemia, resulting in inhibition of cytokine, chemokine and cell adhesion molecule formation as well as reduced apoptotic activity. In addition, C-peptide stimulates and induces the expression of both Na⁺, K⁺-ATPase and endothelial nitric oxide synthase. Animal studies and small-scale clinical trials in type 1 diabetes patients suggest that C-peptide replacement combined with regular insulin therapy exerts beneficial effects on kidney and nerve dysfunction. Further clinical trials in patients with microvascular complications including measurements of inflammatory markers are warranted to explore the clinical significance of the aforementioned, previously unrecognized, C-peptide effects.
authors: Division of Immunogenetics, Department of Pediatrics, Children's Hospital of Pittsburgh of UPMC, Rangos Research Center, Pittsburgh, PA 15201, USA.
authors: Patrizia
authors: P
authors: Luppi
authors: Åsa
authors: Å
authors: Kallas
authors: John
authors: J
authors: Wahren
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000378:metabolism / Q000627:therapeutic use*; D002096:C-Peptide / Q000378:metabolism / Q000627:therapeutic use*; D003922:Diabetes Mellitus, Type 1 / Q000150:complications / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D003925:Diabetic Angiopathies / Q000188:drug therapy / Q000276:immunology / Q000378:metabolism / Q000517:prevention & control*; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D006801:Humans; D055806:Microvessels / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D002096:C-Peptide
keywords: C-peptide; inflammation; type 1 diabetes