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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 EMAIL logo and Leandro Fernandez-Pérez
Published/Copyright: November 12, 2015
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Hormone Molecular Biology and Clinical Investigation
From the journal Hormone Molecular Biology and Clinical Investigation Volume 26 Issue 1

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.

Keywords: beta cells; growth hormone and prolactin; pancreas; SOCS2
Corresponding author: Gunnar Norstedt, Karolinska Institutet, Center for Molecular Medicine, Karolinska Hospital M103, 171 76 Stockholm, Sweden, Phone: +46-704848548, E-mail: ; and Karolinska Institutet, Department of Women’s and Children’s Health, Stockholm, Sweden
aAmira Alkharusi and Mercedes Mirecki-Garrido: These authors contributed equally to this work.

Disclosure statement: All authors declare no conflict of interest.

Funding: The Spanish Ministry of Science and Innovation, with the European Regional Development Fund, supported this research by grants-in-aid to L.F.-P. (SAF2012–37344). L.F.-P. was also supported by grants-in-aid from ACIISI (PI2010/0110) and Alfredo Martin-Reyes Foundation (Arehucas)-FICIC. The Danish Council for Independent Research and the Novo Nordisk Foundation supports A.F-M. G.N. is supported by a grant from Swedish Heart and Lung Foundation. A.A is supported by a fellowship from Sultan Qaboos University, Muscat, Oman. M.M-G. is a recipient of predoctoral fellowship from ULPGC-MEC (AP2001–3499) and Fundación Universitaria de Las Palmas (INNOVA).

Authors’ contributions: Alkharusi A and Mirecki-Garrido M: Data acquisition, analysis and interpretation, drafting the article, and final approval of the submitted version. Castrillo A., Ma Z and Björklund A: Data acquisition and analysis, drafting the article, and final approval of the submitted version. Alzadjali F, Flores-Morales A, Nyström T, Norstedt G, and Fernández-Pérez L: Study design, analysis and interpretation, drafting the article and final approval of the submitted version.

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Supplemental Material:

The online version of this article (DOI: 10.1515/hmbci-2015-0036) offers supplementary material, available to authorized users.

Received: 2015-8-2
Accepted: 2015-10-8
Published Online: 2015-11-12
Published in Print: 2016-4-1

©2016 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Editorial Preface
  3. Preface to special issue on “Hormones and Diabetes”
  4. Topic A: Insulin Resistance, Pre-Diabetes and Diabetes Status: Endocrine and Molecular Mechanisms
  5. Mini-Review Article
  6. The role of ghrelin in the regulation of glucose homeostasis
  7. Review Articles
  8. Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle
  9. Adipose tissue: an endocrine organ playing a role in metabolic regulation
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  11. Aldosterone and type 2 diabetes mellitus
  12. 1,25-Dihydroxyvitamin D3 and type 2 diabetes: Ca2+-dependent molecular mechanisms and the role of vitamin D status
  13. Original Article
  14. Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice
https://doi.org/10.1515/hmbci-2015-0036
Keywords for this article
beta cells; growth hormone and prolactin; pancreas; SOCS2

Articles in the same Issue

  1. Frontmatter
  2. Editorial Preface
  3. Preface to special issue on “Hormones and Diabetes”
  4. Topic A: Insulin Resistance, Pre-Diabetes and Diabetes Status: Endocrine and Molecular Mechanisms
  5. Mini-Review Article
  6. The role of ghrelin in the regulation of glucose homeostasis
  7. Review Articles
  8. Insulin-stimulated glucose uptake in healthy and insulin-resistant skeletal muscle
  9. Adipose tissue: an endocrine organ playing a role in metabolic regulation
  10. Intramyocellular fat storage in metabolic diseases
  11. Aldosterone and type 2 diabetes mellitus
  12. 1,25-Dihydroxyvitamin D3 and type 2 diabetes: Ca2+-dependent molecular mechanisms and the role of vitamin D status
  13. Original Article
  14. Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice
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