title: 4-Deoxypyridoxine improves the viability of isolated pancreatic islets ex vivo.
abstract: The successful islet transplantation, for the treatment of type 1 diabetes, depends on the quantity and the quality of transplanted islets. Previously, it has reported that the significant loss of isolated islet mass could be prevented by sphingolipid metabolite, sphinogosine 1-phophate (S1P). This study was performed to elucidate whether the beneficial effects of S1P maintaining isolated pancreatic islets ex vivo are mimicked by modulation of intracellular S1P. We tested the in vitro effect of various agents that modulate intracellular S1P levels in insulinoma cell lines and isolated islets to compare their anti-apoptotic effects with that of S1P. As results, we discovered that 4-deoxypyridoxine (DOP), which inhibits the degradation of intracellular S1P by inhibiting S1P lyase (SPL) activity, minimized the chemically induced apoptosis of insulinoma cell lines as S1P did. Also, supplementation of DOP in the culture media protected the regression of isolated islets that have been maintained ex vivo at least for 18 h providing the evidence of increasing viability of isolated islets with DOP, which impaired SPL activity. In conclusion, these results suggest that the application of SPL inhibitors could be considered as a supplement for the maintenance of viable islets isolated from donor sources in the process of islet transplantation.
authors.affiliation: Department of Internal Medicine; Seoul National University College of Medicine; Seoul, Republic of Korea; Innovative Research Institute for Cell Therapy; Seoul National University Hospital; Seoul, Republic of Korea; Biomedical Research Institute; Seoul National University Hospital; Seoul, Republic of Korea.
authors.forename: Hakmo
authors.initials: H
authors.lastname: Lee
authors.forename: Ho Seon
authors.initials: HS
authors.lastname: Park
authors.forename: Shin Hee
authors.initials: SH
authors.lastname: Hong
authors.forename: Ok Kyung
authors.initials: OK
authors.lastname: Choi
authors.forename: Sung-Dae
authors.initials: SD
authors.lastname: Cho
authors.forename: Jongwoo
authors.initials: J
authors.lastname: Park
authors.forename: Ju Eun
authors.initials: JE
authors.lastname: Oh
authors.forename: Sung Soo
authors.initials: SS
authors.lastname: Chung
authors.forename: Hye Seung
authors.initials: HS
authors.lastname: Jung
authors.forename: Kyong Soo
authors.initials: KS
authors.lastname: Park
mesh_terms: D000446:Aldehyde-Lyases / Q000037:antagonists & inhibitors; D000818:Animals; D000963:Antimetabolites / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D007515:Islets of Langerhans / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism / Q000502:physiology; D008246:Lysophospholipids / Q000378:metabolism; D051379:Mice; D009994:Osmolar Concentration; D011736:Pyridoxine / Q000031:analogs & derivatives* / Q000494:pharmacology; D051381:Rats; D013110:Sphingosine / Q000031:analogs & derivatives / Q000378:metabolism; D034421:Sus scrofa; D013997:Time Factors; D046509:Tissue Culture Techniques; D014022:Tissue Survival / Q000187:drug effects; D025101:Vitamin B 6 / Q000037:antagonists & inhibitors
chemical_list: D000963:Antimetabolites; D004791:Enzyme Inhibitors; D007328:Insulin; D008246:Lysophospholipids; C060506:sphingosine 1-phosphate; C004675:4-deoxypyridoxine; D025101:Vitamin B 6; D000446:Aldehyde-Lyases; C022649:sphingosine 1-phosphate lyase (aldolase); D005947:Glucose; D011736:Pyridoxine; D013110:Sphingosine
keywords: 4-Deoxypyridoxine; pancreatic islet; transplantation; viability