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Type: Artigo de periódico
Title: Ciliary Neurotrophic Factor Protects Mice Against Streptozotocin-induced Type 1 Diabetes through SOCS3 THE ROLE OF STAT1/STAT3 RATIO IN beta-CELL DEATH
Author: Rezende, LF
Santos, GJ
Carneiro, EM
Boschero, AC
Abstract: Type 1 diabetes is characterized by a loss of islet beta-cells. Ciliary neurotrophic factor (CNTF) protects pancreatic islets against cytokine-induced apoptosis. For this reason, we assessed whether CNTF protects mice against streptozotocin-induced diabetes (a model of type 1 diabetes) and the mechanism for this protection. WT and SOCS3 knockdown C57BL6 mice were treated for 5 days with citrate buffer or 0.1 mg/kg CNTF before receiving 80 mg/kg streptozotocin. Glycemia in non-fasted mice was measured weekly from days 0-28 after streptozotocin administration. Diabetes was defined as a blood glucose > 11.2 mmol/liter. Wild-type (WT) and SOCS3 knockdown MIN6 cells were cultured with CNTF, IL1 beta, or both. CNTF reduced diabetes incidence and islet apoptosis in WT but not in SOCS3kd mice. Likewise, CNTF inhibited apoptosis in WT but not in SOCS3kd MIN6 cells. CNTF increased STAT3 phosphorylation in WT and SOCS3kd mice and MIN6 cells but reduced STAT1 phosphorylation only in WT mice, in contrast to streptozotocin and IL1 beta. Moreover, CNTF reduced NF kappa B activation and required down-regulation of inducible NO synthase expression to exert its protective effects. In conclusion, CNTF protects mice against streptozotocin-induced diabetes by increasing pancreatic islet survival, and this protection depends on SOCS3. In addition, SOCS3 expression and beta-cell fate are dependent on STAT1/STAT3 ratio.
Country: EUA
Editor: Amer Soc Biochemistry Molecular Biology Inc
Rights: fechado
Identifier DOI: 10.1074/jbc.M112.358788
Date Issue: 2012
Appears in Collections:Unicamp - Artigos e Outros Documentos

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