title: Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice.
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.
  
  
  METHODS
  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.
  
  
  CONCLUSIONS
  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.
authors.forename: Amira
authors.initials: A
authors.lastname: Alkharusi
authors.forename: Mercedes
authors.initials: M
authors.lastname: Mirecki-Garrido
authors.forename: Zuheng
authors.initials: Z
authors.lastname: Ma
authors.forename: Fahad
authors.initials: F
authors.lastname: Zadjali
authors.forename: Amilcar
authors.initials: A
authors.lastname: Flores-Morales
authors.forename: Thomas
authors.initials: T
authors.lastname: Nyström
authors.forename: Antonio
authors.initials: A
authors.lastname: Castrillo
authors.forename: Anneli
authors.initials: A
authors.lastname: Bjorklund
authors.forename: Gunnar
authors.initials: G
authors.lastname: Norstedt
authors.forename: Leandro
authors.initials: L
authors.lastname: Fernandez-Pérez
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D003921:Diabetes Mellitus, Experimental / Q000235:genetics* / Q000378:metabolism; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000378:metabolism; D017353:Gene Deletion; D005947:Glucose / Q000378:metabolism; D013006:Growth Hormone / Q000494:pharmacology; D007328:Insulin / Q000378:metabolism; D050417:Insulin-Secreting Cells / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D011388:Prolactin / Q000494:pharmacology; D013311:Streptozocin / Q000633:toxicity; D050826:Suppressor of Cytokine Signaling Proteins / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; C491409:Socs2 protein, mouse; D050826:Suppressor of Cytokine Signaling Proteins; D013311:Streptozocin; D011388:Prolactin; D013006:Growth Hormone; D005947:Glucose