title: Pretreatment of donor pigs with a diet rich in soybean oil increases the yield of isolated islets.
abstract: BACKGROUND
  The pig is considered the donor species of choice for islet xenotransplantation. However, isolation of porcine islets is difficult, particularly from young pigs. Early life exposure to a high-fat diet (HFD) reportedly encourages islet β-cell expansion in neonatal rodents and improves islet viability in culture from pretreated weanling pigs. In this study, we examined the influence of young donor pretreatment with a soybean oil-enriched HFD on porcine islet mass and yield after islet isolation.
  
  
  METHODS
  Postweaning and between days 70 and 250, pigs were fed either a standard diet (control group; n = 5) or an HFD (experimental group; n = 6). Biochemical blood parameters and acute C-peptide response to intravenous glucose were monitored before pancreas procurement. The study was blinded to objectively evaluate the influence of treated diet. After procurement, pancreas biopsy samples were taken from control and pretreated donor pigs to assess islet number by using a dithizone scoring method and histologic islet area fraction determination. Control and HFD donor pig islets were isolated by using our standard isolation protocol to determine islet yield. Islet isolation characteristics and islet quality were assessed in both groups, and the results were compared.
  
  
  RESULTS
  There were no significant differences in the donor characteristics (age, body weight, glucose disposal rate, acute C-peptide response to intravenous glucose, cholesterol, and aspartate aminotransferase) except fasting blood glucose level between the control and treatment groups (84 ± 6 vs 99 ± 12 mg/dL; P = .0317). The stimulated insulin and C-peptide levels between groups were similar. However, the dithizone score was slightly higher in the treatment group compared with the control group (95.4 ± 38.5 vs 62.6 ± 23.9; P = .1208). Digestion time, digested pancreas weight, pellet volume, and the fragility index were similar in both groups. However, the average islet count (islet equivalent number/g pancreas) at the digest level was significantly higher in the HFD group than in the control group (1578 ± 994 vs 738 ± 202; P = .0344). The functional viability of 2- and 7 day-cultured islets, as assessed by using oxygen consumption rate corrected for DNA, was similar in both groups.
  
  
  CONCLUSIONS
  Pretreatment of pigs with HFD enriched with soybean oil could potentially be used to improve the islet mass in donor pigs. Further studies are needed to confirm and optimize the use of HFD for the purpose of increasing islet yield from young donor pigs.
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors.forename: G
authors.initials: G
authors.lastname: Loganathan
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors.forename: M L
authors.initials: ML
authors.lastname: Graham
authors.affiliation: Spring Point Project, Minneapolis, Minnesota.
authors.forename: T
authors.initials: T
authors.lastname: Spizzo
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors.forename: M
authors.initials: M
authors.lastname: Tiwari
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors.forename: A D
authors.initials: AD
authors.lastname: Lockridge
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors.forename: S
authors.initials: S
authors.lastname: Soltani
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors.forename: J J
authors.initials: JJ
authors.lastname: Wilhelm
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, Minnesota. Electronic address: bala@umn.edu.
authors.forename: A N
authors.initials: AN
authors.lastname: Balamurugan
authors.affiliation: Schulze Diabetes Institute, Department of Surgery, University of Minnesota, Minneapolis, Minnesota.
authors.forename: B J
authors.initials: BJ
authors.lastname: Hering
mesh_terms: D000818:Animals; D002452:Cell Count; D002469:Cell Separation; D059305:Diet, High-Fat; D007515:Islets of Langerhans / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D016381:Islets of Langerhans Transplantation; D009929:Organ Size; D010179:Pancreas / Q000166:cytology* / Q000254:growth & development* / Q000378:metabolism; D013024:Soybean Oil / Q000008:administration & dosage*; D013552:Swine
chemical_list: D013024:Soybean Oil