title: The efficacy of SPA0355 in protecting β cells in isolated pancreatic islets and in a murine experimental model of type 1 diabetes.
abstract: Cytokines activate several inflammatory signals that mediate β-cell destruction. We recently determined that SPA0355 is a strong anti-inflammatory compound, thus reporting its efficacy in protecting β cells from various insults. The effects of SPA0355 on β-cell survival were studied in RINm5F cells and primary islets. The protective effects of this compound on the development of type 1 diabetes were evaluated in non-obese diabetic (NOD) mice. SPA0355 completely prevented cytokine-induced nitric oxide synthase (iNOS) expression and cytotoxicity in RINm5F cells and isolated islets. The molecular mechanism of SPA0355 inhibition of iNOS expression involves the inhibition of nuclear factor κB and Janus kinase signal transducer and activator of transcription pathways. The protective effects of SPA0355 against cytokine toxicity were further demonstrated by normal insulin secretion and absence of apoptosis of cytokine-treated islets. In experiments with NOD mice, the occurrence of diabetes was efficiently reduced when the mice were treated with SPA0355. Therefore, SPA0355 might be a valuable treatment option that delays the destruction of pancreatic β cells in type 1 diabetes.
authors.affiliation: Department of Biochemistry, Chonbuk National University Medical School, Jeonju, Jeonbuk, Republic of Korea.
authors.forename: Ui-Jin
authors.initials: UJ
authors.lastname: Bae
authors.forename: Mi-Young
authors.initials: MY
authors.lastname: Song
authors.forename: Hyun-Young
authors.initials: HY
authors.lastname: Jang
authors.forename: Hyo Jin
authors.initials: HJ
authors.lastname: Gim
authors.forename: Jae-Ha
authors.initials: JH
authors.lastname: Ryu
authors.forename: Sang-Myeong
authors.initials: SM
authors.lastname: Lee
authors.forename: Raok
authors.initials: R
authors.lastname: Jeon
authors.forename: Byung-Hyun
authors.initials: BH
authors.lastname: Park
mesh_terms: D000818:Animals; D017209:Apoptosis; D048588:Benzoxazines / Q000494:pharmacology / Q000627:therapeutic use*; D002460:Cell Line; D002470:Cell Survival; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000517:prevention & control*; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000378:metabolism; D053612:Janus Kinases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D016688:Mice, Inbred NOD; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II / Q000235:genetics / Q000378:metabolism; D051381:Rats; D013890:Thiourea / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D048588:Benzoxazines; D016328:NF-kappa B; C570784:SPA0355; D052247:Nitric Oxide Synthase Type II; D053612:Janus Kinases; D013890:Thiourea