Investigations of Strategies to Counteract Proinflammatory Cytokines in Experimental Type 1 Diabetes

" The reasonable man adapts himself to the world; the unreasonable one persists in trying to adapt the world to himself. Therefore, all progress depends on the unreasonable man. " III Börjesson A and Carlsson C. Altered proinsulin conversion in rat pancreatic islets exposed long-term to various glucose concentrations or interleukin-1ȕ. regulation of the expression of TNF-Į, IFN-Ȗ and IL-10 by splenocytes in murine multiple low dose streptozotocin diabetes. Suppressor of cytokine signalling-3 expression inhibits cytokine-mediated destruction of primary mouse and rat pancreatic islets and delays allograft rejection. Abbreviations APC Antigen presenting cell DAG Diacylglycerol ELISA Enzyme-linked immunosorbent assay eNOS Endothelial nitric oxide synthase FasL Fas ligand FCS Fetal calf serum G6PDH Glucose-6-phosphate dehydrogenase IFN-Ȗ Interferon gamma IL-1ȕ Interleukin-1 beta iNOS Inducible nitric oxide synthase IRF Interferon regulatory factor JAK Janus activated kinase KRBH Krebs-Ringer bicarbonate HEPES MHC Major histocompatibility complex MAPK Mitogen-activated protein kinase MLDSTZ Multiple low dose streptozotocin NF-țB Nuclear factor kappa B nNOS Neuronal nitric oxide synthase NO Nitric oxide NOD Non-obese diabetic PC Proinsulin convertase PDX-1 Pancreatic and duodenal homeobox gene 1 PKC Protein kinase C PLD Phospholipase D PRL Prolactin RT-PCR Real time polymerase chain reaction SEM Standard error of the mean SOCS Suppressors of cytokine signalling STAT Signal transducers and activators of transcription STZ Streptozotocin TNF-Į Tumour necrosis factor alpha Wt Wild type 11 Introduction