Please use this identifier to cite or link to this item: http://hdl.handle.net/10553/52582
Title: Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice
Authors: Alkharusi, Amira
Mirecki-Garrido, Mercedes 
Ma, Zuheng
Zadjali, Fahad
Flores-Morales, Amilcar 
Nyström, Thomas
Castrillo, Antonio 
Bjorklund, Anneli
Norstedt, Gunnar
Fernandez-Perez, Leandro 
UNESCO Clasification: 32 Ciencias médicas
Keywords: Beta cells
Growth hormone and prolactin
Pancreas
SOCS2
Issue Date: 2016
Project: "Evaluación Preclinica de Nuevas Estructuras Quimicas Diseñadas Para Inhibir la Ruta Oncogenica Jak-Stat O Como Moduladores Selectivos de Los Receptores Estrógenos" 
Journal: Hormone Molecular Biology and Clinical Investigation 
Abstract: Background: Diabetes type 1 is characterized by the failure of beta cells to produce insulin. Suppressor of cytokine signaling (SOCS) proteins are important regulators of the Janus kinase/signal transducer and activator of transcription (JAK-STAT) pathway. Previous studies have shown that GH can prevent the development of type I diabetes in mice and that SOCS2 deficiency mimics a state of increased GH sensitivity. Methodology: The elevated sensitivity of SOCS2-/- mice to GH and possibly to PRL was the rationale to analyze the effects of multiple low dose streptozotocin (MLDSTZ)-induced diabetes in SOCS2-/- mice. Results: We show that 6-month-old SOCS2-/- mice, but not 2-month-old mice, were less sensitive to MLDSTZ-induced diabetes, compared to controls. MLDSTZ treatment induced glucose intolerance in both SOCS2+/+ and SOCS2-/- mice, as shown by glucose tolerance tests, with SOCS2+/+ mice showing a more marked intolerance, compared to SOCS2-/- mice. Furthermore, insulin tolerance tests showed that the SOCS2-/- mice have an improved hypoglycemic response to exogenous insulin, compared to SOCS2+/+ mice. Moreover, in isolated islets, lipotoxic effects on insulin release could partly be overcome by ligands, which bind to GH or PRL receptors. Conclusion: Knockdown of SOCS2 makes mice less sensitive to MLDSTZ. These results are consistent with the proposal that elimination of SOCS2 in pancreatic islets creates a state of β-cell hypersensitivity to GH/PRL that mimics events in pregnancy, and which is protective against MLDSTZ-induced type I diabetes in mice. SOCS2-dependent control of β-cell survival may be of relevance to islet regeneration and survival in transplantation.
URI: http://hdl.handle.net/10553/52582
ISSN: 1868-1883
DOI: 10.1515/hmbci-2015-0036
Source: Hormone Molecular Biology and Clinical Investigation [ISSN 1868-1883], v. 26 (1), p. 67-76
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