title: Glucose stimulation of cytochrome C reduction and oxygen consumption as assessment of human islet quality.
abstract: BACKGROUND
  An in vitro method to assess human islets could prevent transplantation of nonviable islets and facilitate the optimization of islet preparation. We hypothesize that glucose-stimulated cytochrome c reduction and oxygen consumption by human islets can be used as predictors of transplant success.
  
  
  METHODS
  Isolated human islets were obtained from research-grade pancreata. Using a previously developed islet flow culture system, the response of cytochrome c reduction and oxygen consumption to glucose was compared to the ability of islets transplanted into nondiabetic NOD-SCID mice to secrete C-peptide in response to a glucose tolerance test conducted 7 days following transplant (n=10).
  
  
  RESULTS
  In vitro responses by human islets were qualitatively similar to those seen in rat islets: glucose increased both oxygen consumption and cytochrome c reduction. However, the responses were smaller in magnitude and quite variable. Scatter plots of C-peptide and quantiles for ln(C-peptide) indicated that 12 ng/ml could be used as threshold of transplant success with which to evaluate the diagnostic potential of cytochrome c and oxygen consumption. Data was analyzed by generating receiver operating curves and the area under the curve was 0.889 (95% CI: 0.645-1.000) and 0.738 (95% CI: 0.413-1.000) for cytochrome c reduction and oxygen consumption respectively (1 indicates absolute predictive capability and 0.5 indicates no predictive capability).
  
  
  CONCLUSIONS
  The detection of glucose-stimulated cytochrome c reduction and oxygen consumption may have utility as criteria for the assessment of human islet quality.
authors.affiliation: Department of Medicine, University of Washington, Seattle, WA 98195-7710, USA. isweet@u.washington.edu
authors.forename: Ian R
authors.initials: IR
authors.lastname: Sweet
authors.forename: Merle
authors.initials: M
authors.lastname: Gilbert
authors.forename: Rich
authors.initials: R
authors.lastname: Jensen
authors.forename: Omaima
authors.initials: O
authors.lastname: Sabek
authors.forename: Daniel W
authors.initials: DW
authors.lastname: Fraga
authors.forename: Ahmed O
authors.initials: AO
authors.lastname: Gaber
authors.forename: JoAnna
authors.initials: J
authors.lastname: Reems
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D045304:Cytochromes c / Q000032:analysis / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology*; D006801:Humans; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D008297:Male; D051379:Mice; D016513:Mice, SCID; D010084:Oxidation-Reduction; D010101:Oxygen Consumption / Q000187:drug effects*; D051381:Rats; D011916:Rats, Inbred F344
chemical_list: D007328:Insulin; D045304:Cytochromes c; D005947:Glucose