Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice

Amira Alkharusi, Mercedes Mirecki-Garrido, Zuheng Ma, Fahad Zadjali, Amilcar Flores-Morales, Thomas Nyström, Antonio Castrillo, Anneli Bjorklund, Gunnar Norstedt*, Leandro Fernandez-Pérez

*المؤلف المقابل لهذا العمل

نتاج البحث: المساهمة في مجلةمراجعة النظراء

5 اقتباسات (Scopus)

ملخص

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.

اللغة الأصليةEnglish
الصفحات (من إلى)67-76
عدد الصفحات10
دوريةHormone Molecular Biology and Clinical Investigation
مستوى الصوت26
رقم الإصدار1
المعرِّفات الرقمية للأشياء
حالة النشرPublished - أبريل 1 2016

ASJC Scopus subject areas

  • ???subjectarea.asjc.2700.2712???
  • ???subjectarea.asjc.2700???
  • ???subjectarea.asjc.1300.1312???
  • ???subjectarea.asjc.1300.1310???

بصمة

أدرس بدقة موضوعات البحث “Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice'. فهما يشكلان معًا بصمة فريدة.

قم بذكر هذا