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

Research output: Contribution to journalArticle

3 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)67-76
Number of pages10
JournalHormone Molecular Biology and Clinical Investigation
Volume26
Issue number1
DOIs
Publication statusPublished - Apr 1 2016

Fingerprint

Streptozocin
Type 1 Diabetes Mellitus
Cytokines
Insulin
Experimental Diabetes Mellitus
Suppressor of Cytokine Signaling Proteins
Prolactin Receptors
Janus Kinases
Glucose Intolerance
Glucose Tolerance Test
Transducers
Islets of Langerhans
Hypoglycemic Agents
Regeneration
Cell Survival
Hypersensitivity
Transplantation
Ligands

Keywords

  • beta cells
  • growth hormone and prolactin
  • pancreas
  • SOCS2

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Medicine(all)
  • Molecular Biology
  • Endocrinology

Cite this

Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice. / Alkharusi, Amira; Mirecki-Garrido, Mercedes; Ma, Zuheng; Zadjali, Fahad; Flores-Morales, Amilcar; Nyström, Thomas; Castrillo, Antonio; Bjorklund, Anneli; Norstedt, Gunnar; Fernandez-Pérez, Leandro.

In: Hormone Molecular Biology and Clinical Investigation, Vol. 26, No. 1, 01.04.2016, p. 67-76.

Research output: Contribution to journalArticle

Alkharusi, Amira ; Mirecki-Garrido, Mercedes ; Ma, Zuheng ; Zadjali, Fahad ; Flores-Morales, Amilcar ; Nyström, Thomas ; Castrillo, Antonio ; Bjorklund, Anneli ; Norstedt, Gunnar ; Fernandez-Pérez, Leandro. / Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice. In: Hormone Molecular Biology and Clinical Investigation. 2016 ; Vol. 26, No. 1. pp. 67-76.
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AU - Flores-Morales, Amilcar

AU - Nyström, Thomas

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