title: Anakinra Protects Against Serum Deprivation-Induced Inflammation and Functional Derangement in Islets Isolated From Nonhuman Primates.
abstract: We investigated whether serum deprivation induces islet amyloid polypeptide (IAPP) oligomer accumulation and/or a proinflammatory response and, if so, whether the addition of interleukin (IL)-1 receptor antagonist to the culture medium can relieve the proinflammatory response during serum-deprived culture of nonhuman primate (NHP) islets. After culture in medium with and without Ana under serum-deprived culture conditions, IAPP oligomer/amyloid accumulation, in vitro viability, islet function, cytokine secretion, and posttransplantation outcome in streptozotocin-induced diabetic nude mice were determined in islets isolated from heterozygote human IAPP transgenic (hIAPP+/-) mice and/or NHP islets. Serum deprivation induced accumulation of IAPP oligomer, but not amyloid, in NHP islets. Anakinra (Ana) protected islets from the serum deprivation-induced impairment of in vitro viability and glucose-stimulated insulin secretion and attenuated serum deprivation-induced caspase-1 activation, transcription, and secretion of IL-1β, IL-6, and tumor necrosis factor-α in hIAPP+/-mice and NHP islets. Supplementation of medium with Ana during serum-deprived culture also improved posttransplantation in vivo outcomes of NHP islets. In conclusion, serum deprivation induced accumulation of IAPP oligomers and proinflammatory responses in cultured isolated islets. Supplementation of the culture medium with Ana attenuated the functional impairment and proinflammatory responses induced by serum deprivation in ex vivo culture of NHP islets.
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Diabetes and Endocrinology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: S-M
authors.initials: SM
authors.lastname: Jin
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.|Molecular Science and Technology Research Center, Ajou University, Suwon, Korea.
authors.forename: W
authors.initials: W
authors.lastname: Shim
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Diabetes and Endocrinology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: B J
authors.initials: BJ
authors.lastname: Oh
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: S-H
authors.initials: SH
authors.lastname: Oh
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: S J
authors.initials: SJ
authors.lastname: Yu
authors.affiliation: Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea.
authors.forename: J M
authors.initials: JM
authors.lastname: Choi
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Park
authors.affiliation: Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: J B
authors.initials: JB
authors.lastname: Park
authors.affiliation: Division of Endocrinology and Metabolism, Department of Medicine, Diabetes and Endocrinology Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.|Department of Health Sciences and Technology, SAIHST (Samsung Advanced Institute for Health Sciences & Technology), Seoul, Korea.
authors.forename: J H
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D018501:Antirheumatic Agents / Q000494:pharmacology*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D016895:Culture Media, Serum-Free / Q000633:toxicity*; D006801:Humans; D007249:Inflammation / Q000139:chemically induced / Q000517:prevention & control*; D053590:Interleukin 1 Receptor Antagonist Protein / Q000494:pharmacology*; D007515:Islets of Langerhans / Q000187:drug effects* / Q000473:pathology; D008252:Macaca fascicularis; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude
chemical_list: D018501:Antirheumatic Agents; D016895:Culture Media, Serum-Free; D053590:Interleukin 1 Receptor Antagonist Protein
keywords: basic (laboratory) research/science; diabetes; endocrinology/diabetology; innate immunity; islet transplantation; islets of Langerhans; translational research/science