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(2016)
摘要
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 beta-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 beta-cell survival may be of relevance to islet regeneration and survival in transplantation.
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关键词
beta cells, growth hormone and prolactin, pancreas, SOCS2
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