title: Activated protein C and its potential applications in prevention of islet β-cell damage and diabetes.
abstract: Activated protein C (APC) is derived from its precursor, protein C (PC). Originally thought to be synthesized exclusively by the liver, recent reports have shown that PC is also produced by many other cells including pancreatic islet β cells. APC functions as a physiological anticoagulant with anti-inflammatory, anti-apoptotic, and barrier-stabilizing properties. APC exerts its protective effects via an intriguing mechanism requiring combinations of endothelial PC receptor, protease-activated receptors, epidermal growth factor receptor, Tie2 or CD11b, depending on cell types. Diabetes is a chronic condition resulted from the body's inability to produce and/or properly use insulin. The prevalence of diabetes has risen dramatically and has become one of the major causes of premature mortality and morbidity worldwide. Diabetes prevention is an ideal approach to reduce this burden. Type 1 and type 2 diabetes are the major forms of diabetes mellitus, and both are characterized by an autoimmune response, intraislet inflammation, β-cell apoptosis, and progressive β-cell loss. Protecting β-cell from damage is critical in both prevention and treatment of diabetes. Recent in vitro and animal studies show that APC's strong anti-inflammatory and anti-apoptotic properties are beneficial in preventing β-cell destruction and diabetes in the NOD mouse model of type 1 diabetes. Future preventive and therapeutic uses of APC in diabetes look very promising.
authors.affiliation: Sutton Arthritis Research Laboratories, Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia. Electronic address: meilang.xue@sydney.edu.au.
authors.forename: Meilang
authors.initials: M
authors.lastname: Xue
authors.affiliation: Sutton Arthritis Research Laboratories, Kolling Institute of Medical Research, The University of Sydney at Royal North Shore Hospital, St Leonards, New South Wales, Australia.
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Jackson
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D003922:Diabetes Mellitus, Type 1 / Q000276:immunology / Q000473:pathology* / Q000517:prevention & control / Q000628:therapy; D004789:Enzyme Activation; D006801:Humans; D007166:Immunosuppressive Agents / Q000494:pharmacology / Q000627:therapeutic use; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000276:immunology / Q000473:pathology; D016381:Islets of Langerhans Transplantation / Q000009:adverse effects / Q000276:immunology / Q000473:pathology; D008954:Models, Biological; D020011:Protective Agents / Q000494:pharmacology* / Q000627:therapeutic use; D011486:Protein C / Q000235:genetics / Q000494:pharmacology* / Q000627:therapeutic use; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D007166:Immunosuppressive Agents; D020011:Protective Agents; D011486:Protein C; D011994:Recombinant Proteins
keywords: Activated protein C; Apoptosis; Diabetes; Endothelial protein C receptor; Islet β-cells