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Article

SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells

  • Authors:
    • Longzhen Piao
    • Jisoo Park
    • Yuwen Li
    • Sanghee Shin
    • Soyeon Shin
    • Gyeyeong Kong
    • Robin Shrestha
    • Quangdon Tran
    • Gang Min Hur
    • Jeong-Lan Kim
    • Jongsun Park
  • View Affiliations / Copyright

    Affiliations: Department of Pharmacology, Metabolic Diseases and Cell Signaling Laboratory, Research Institute for Medical Sciences, College of Medicine, Chungnam National University, Daejeon 301-747, Republic of Korea, Department of Psychiatry, College of Medicine, Chungnam National University, Daejeon 301-131, Republic of Korea
  • Pages: 1364-1370
    |
    Published online on: March 10, 2014
       https://doi.org/10.3892/ijmm.2014.1693
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Abstract

Antipsychotic drugs are regularly used for the treatment of many types of psychiatric disorders. The administration of second-generation antipsychotics is often associated with weight gain and the development of diabetes mellitus; however, the molecular mechanisms underlying the effects of these drugs remain poorly understood. Leptin and insulin play key roles in the regulation of energy balance and glucose homeostasis, and resistance to the actions of these hormones can occur with obesity and inflammation, resulting in the pathogenesis of obesity and type 2 diabetes. In this study, the effects of risperidone on the insulin-induced protein kinase B (PKB) phosphorylation and leptin-stimulated signal transducer and activator of transcription 3 (STAT3) phosphorylation were investigated in the human SH-SY5Y neuroblastoma cell line. The treatment of these cells with risperidone induced the activation of extracellular signal-related kinase (ERK) by cellular cyclic adenosine 3-monophosphate (cAMP)-dependent protein kinase (also known as protein kinase A; PKA) and the mechanisms involved include the induction of suppressor of cytokine signaling 3 (SOCS3) and suppressor of cytokine signaling 6 (SOCS6) expression. The risperidone-induced ERK activation induced an upregulation of SOCS3 and SOCS6 mRNA expression levels. Taken together, these results suggest that risperidone modulates SOCS3 and SOCS6 expression through adenylate cyclase-mediated ERK activation, which, in turn, leads to an inhibition of insulin-induced PKB phosphorylation and leptin-stimulated STAT3 phosphorylation. Eventually, these effects result in excessive body weight gain due to the inhibition of both the leptin and insulin signaling pathways.
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Copy and paste a formatted citation
Spandidos Publications style
Piao L, Park J, Li Y, Shin S, Shin S, Kong G, Shrestha R, Tran Q, Hur GM, Kim J, Kim J, et al: SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells. Int J Mol Med 33: 1364-1370, 2014.
APA
Piao, L., Park, J., Li, Y., Shin, S., Shin, S., Kong, G. ... Park, J. (2014). SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells. International Journal of Molecular Medicine, 33, 1364-1370. https://doi.org/10.3892/ijmm.2014.1693
MLA
Piao, L., Park, J., Li, Y., Shin, S., Shin, S., Kong, G., Shrestha, R., Tran, Q., Hur, G. M., Kim, J., Park, J."SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells". International Journal of Molecular Medicine 33.5 (2014): 1364-1370.
Chicago
Piao, L., Park, J., Li, Y., Shin, S., Shin, S., Kong, G., Shrestha, R., Tran, Q., Hur, G. M., Kim, J., Park, J."SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells". International Journal of Molecular Medicine 33, no. 5 (2014): 1364-1370. https://doi.org/10.3892/ijmm.2014.1693
Copy and paste a formatted citation
x
Spandidos Publications style
Piao L, Park J, Li Y, Shin S, Shin S, Kong G, Shrestha R, Tran Q, Hur GM, Kim J, Kim J, et al: SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells. Int J Mol Med 33: 1364-1370, 2014.
APA
Piao, L., Park, J., Li, Y., Shin, S., Shin, S., Kong, G. ... Park, J. (2014). SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells. International Journal of Molecular Medicine, 33, 1364-1370. https://doi.org/10.3892/ijmm.2014.1693
MLA
Piao, L., Park, J., Li, Y., Shin, S., Shin, S., Kong, G., Shrestha, R., Tran, Q., Hur, G. M., Kim, J., Park, J."SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells". International Journal of Molecular Medicine 33.5 (2014): 1364-1370.
Chicago
Piao, L., Park, J., Li, Y., Shin, S., Shin, S., Kong, G., Shrestha, R., Tran, Q., Hur, G. M., Kim, J., Park, J."SOCS3 and SOCS6 are required for the risperidone-mediated inhibition of insulin and leptin signaling in neuroblastoma cells". International Journal of Molecular Medicine 33, no. 5 (2014): 1364-1370. https://doi.org/10.3892/ijmm.2014.1693
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