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; Amilcar Flores-Morales; Thomas Nyström; Antonio Castrillo; Anneli Bjorklund; Gunnar Norstedt; Leandro Fernández-Perez

doi:10.1515/hmbci-2015-0036

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, Amilcar Flores-Morales, Thomas Nyström, Antonio Castrillo, Anneli Bjorklund, Gunnar Norstedt^*, Leandro Fernández-Perez

^*Corresponding author for this work

5 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 language	English
Journal	Hormone Molecular Biology and Clinical Investigation
Volume	26
Issue number	1
Pages (from-to)	67-76
Number of pages	10
ISSN	1868-1883
DOIs	https://doi.org/10.1515/hmbci-2015-0036
Publication status	Published - Apr 2016

Keywords

beta cells
growth hormone and prolactin
pancreas
SOCS2

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1515/hmbci-2015-0036

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Alkharusi, A., Mirecki-Garrido, M., Ma, Z., Flores-Morales, A., Nyström, T., Castrillo, A., Bjorklund, A., Norstedt, G., & Fernández-Perez, L. (2016). Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice. Hormone Molecular Biology and Clinical Investigation, 26(1), 67-76. https://doi.org/10.1515/hmbci-2015-0036

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 et al.

In: Hormone Molecular Biology and Clinical Investigation, Vol. 26, No. 1, 04.2016, p. 67-76.

Research output: Contribution to journal › Journal article › Research › peer-review

Alkharusi, A, Mirecki-Garrido, M, Ma, Z, Flores-Morales, A, Nyström, T, Castrillo, A, Bjorklund, A, Norstedt, G & Fernández-Perez, L 2016, 'Suppressor of cytokine signaling 2 (SOCS2) deletion protects against multiple low dose streptozotocin-induced type 1 diabetes in adult male mice', Hormone Molecular Biology and Clinical Investigation, vol. 26, no. 1, pp. 67-76. https://doi.org/10.1515/hmbci-2015-0036

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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.",

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AU - Mirecki-Garrido, Mercedes

AU - Ma, Zuheng

AU - Flores-Morales, Amilcar

AU - Nyström, Thomas

AU - Castrillo, Antonio

AU - Bjorklund, Anneli

AU - Norstedt, Gunnar

AU - Fernández-Perez, Leandro

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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

Abstract

Keywords

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