title: The antioxidant HDL-associated paraoxonase-1 (PON1) attenuates diabetes development and stimulates β-cell insulin release.
abstract: OBJECTIVE
  To analyze the direct effects of paraoxonase-1 (PON1) on diabetes development and on β-cell insulin release.
  
  
  RESULTS
  Injection of rePON1 to mice, prior to STZ-induced diabetes, resulted in reduced incidence of diabetes, as well as, in higher serum insulin levels. Incubation of β-cells with PON1 also dose-dependently increased insulin secretion and its cellular content. PON1 increased cell survival under high glucose levels, but not under high STZ concentrations. The addition of the PON1 carrier in the circulation - HDL, to βTC3 cell line, had an additive effect on PON1-induced insulin secretion. PON1 administration to mice or incubation with β-cells was associated with a substantial decreased oxidative stress. Just like PON1, the dietary anti-oxidants, pomegranate juice, punicalagin (major polyphenol in pomegranate) or vitamin E, also increased insulin release from βTC3, but unlike PON1, failed to increase insulin cellular content, suggesting a possible role for PON1 in insulin biosynthesis, separately from PON1 antioxidative effect. Both, PON1 catalytic activity and PON1 association to HDL, were not required for PON1 stimulation of insulin release from β-cells. However, the PON1 free sulfhydryl group was shown to be essential for insulin release by PON1, as blocking the PON1 SH group, abolished PON1 stimulatory effect on insulin secretion.
  
  
  CONCLUSIONS
  PON1 is a potent anti-diabetic enzyme that exerts this protection against diabetes through its antioxidative, as well as via its insulin stimulation properties on β-cells.
authors.affiliation: The Lipid Research Laboratory, Technion Faculty of Medicine, The Rappaport Family Institute for Research in the Medical Sciences, Rambam Medical Center, Haifa 31096, Israel.
authors.forename: Marie
authors.initials: M
authors.lastname: Koren-Gluzer
authors.forename: Michael
authors.initials: M
authors.lastname: Aviram
authors.forename: Edna
authors.initials: E
authors.lastname: Meilin
authors.forename: Tony
authors.initials: T
authors.lastname: Hayek
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage*; D043303:Aryldialkylphosphatase / Q000008:administration & dosage* / Q000172:deficiency / Q000235:genetics; D001786:Blood Glucose / Q000187:drug effects / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007274:Injections, Intraperitoneal; D007328:Insulin / Q000097:blood / Q000378:metabolism*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000378:metabolism; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009154:Mutation; D018384:Oxidative Stress / Q000187:drug effects; D011994:Recombinant Proteins / Q000008:administration & dosage; D013997:Time Factors
chemical_list: D000975:Antioxidants; D001786:Blood Glucose; D007004:Hypoglycemic Agents; D007328:Insulin; D008075:Lipoproteins, HDL; D011994:Recombinant Proteins; D043303:Aryldialkylphosphatase; C560867:PON1 protein, mouse