title: Essential phospholipids prevent islet damage induced by proinflammatory cytokines and hypoxic conditions.
abstract: BACKGROUND
  The pancreatic islet damage that occurs through an inflammatory response and hypoxia after infusion is a major hurdle in islet transplantation. Because essential phospholipids (EPL) have been shown to exhibit anti-inflammatory properties in liver disease, we analysed their protective effect on islets in inflammatory or hypoxic conditions.
  
  
  METHODS
  We evaluated the viability of mouse and human islets cultured with cytokines or in hypoxic conditions for 48 h and measured cytokine expression in islets by quantitative polymerase chain reaction. We then employed an in vivo mouse assay, transplanting a marginal dose of human islets treated with or without EPL into the subcapsule of the kidney in diabetic nude mice and determining the cure rate.
  
  
  RESULTS
  The viability of mouse and human islets damaged by cytokines was significantly improved by supplementation of EPL in the culture (p = 0.003 and <0.001 for mouse and human islets respectively). EPL significantly inhibited intracellular expression of IL-1β and IL-6 in cytokine-damaged human islets (p < 0.001). The viability of human islets in hypoxic conditions was significantly better when treated with EPL (p < 0.001). In the in vivo mouse assay, the EPL-treated islet group had a higher cure rate than the untreated control, with marginal statistical significance (75 and 17% respectively, p = 0.07).
  
  
  CONCLUSIONS
  EPL could be a potent agent to protect islets from inflammatory and hypoxic conditions after isolation procedures. Further studies to clarify the effect of EPL in islet transplantation are warranted.
authors.affiliation: Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Rauf
authors.initials: R
authors.lastname: Shahbazov
authors.affiliation: The Institute of Biomedical Studies, Baylor University, Waco, TX, USA.
authors.forename: Mazhar A
authors.initials: MA
authors.lastname: Kanak
authors.affiliation: Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Morihito
authors.initials: M
authors.lastname: Takita
authors.affiliation: Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Faisal
authors.initials: F
authors.lastname: Kunnathodi
authors.affiliation: Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Omar
authors.initials: O
authors.lastname: Khan
authors.affiliation: Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Nofit
authors.initials: N
authors.lastname: Borenstein
authors.affiliation: Islet Cell Laboratory, Baylor Research Institute, Dallas, TX, USA.
authors.forename: Michael C
authors.initials: MC
authors.lastname: Lawrence
authors.affiliation: Baylor Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Marlon F
authors.initials: MF
authors.lastname: Levy
authors.affiliation: Baylor Annette C. and Harold C. Simmons Transplant Institute, Baylor University Medical Center, Dallas, TX, USA.
authors.forename: Bashoo
authors.initials: B
authors.lastname: Naziruddin
mesh_terms: D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D016207:Cytokines / Q000633:toxicity*; D003921:Diabetes Mellitus, Experimental / Q000209:etiology / Q000473:pathology / Q000517:prevention & control*; D006801:Humans; D000860:Hypoxia / Q000503:physiopathology*; D007124:Immunoenzyme Techniques; D018836:Inflammation Mediators / Q000633:toxicity*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010713:Phosphatidylcholines / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction
chemical_list: D000924:Anticholesteremic Agents; D016207:Cytokines; D018836:Inflammation Mediators; D010713:Phosphatidylcholines; D012333:RNA, Messenger; C011246:essential 303 forte
keywords: hypoxia; inflammation; pancreatic islet transplantation