Anakinra Protects Against Serum Deprivation-Induced Inflammation and Functional Derangement in Islets Isolated From Nonhuman Primates

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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 vitroviability, 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 ofin vitroviability 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 inhIAPP+/−mice and NHP islets. Supplementation of medium with Ana during serum-deprived culture also improved posttransplantationin vivooutcomes 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 inex vivoculture of NHP islets.

Serum deprivation induces accumulation of islet amyloid polypeptide oligomers and proinflammatory responses in cultured isolated islets, and supplementing the culture medium with anakinra attenuates the functional impairment and proinflammatory responses induced by serum deprivation in ex vivo culture of nonhuman primate islets.

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