4.5 Article

Activation of Akt through 5-HT2A receptor ameliorates serotonin-induced degradation of insulin receptor substrate-1 in adipocytes

期刊

MOLECULAR AND CELLULAR ENDOCRINOLOGY
卷 365, 期 1, 页码 25-35

出版社

ELSEVIER IRELAND LTD
DOI: 10.1016/j.mce.2012.08.022

关键词

Serotonin; 5-HT2A receptor; IRS-1 ubiquitination; Low density microsome; Insulin resistance; Sarpogrelate

资金

  1. Ministry of Education, Science, and Culture of Japan
  2. Tokushima Prefecture, Japan
  3. Grants-in-Aid for Scientific Research [22616005] Funding Source: KAKEN

向作者/读者索取更多资源

Serotonin (5-hydroxytryptamine, 5-HT) was found to be elevated in the serum of diabetic patients. In this study, we investigate the mechanism of insulin desensitization caused by 5-HT. In 3T3-L1 adipocytes, 5-HT treatment induced the translocation of insulin receptor substrate-1 (IRS-1) from low density microsome (LDM), the important intracellular compartment for its functions, to cytosol, inducing IRS-1 ubiquitination and degradation. Moreover, inhibition of 5-HT-stimulated Akt activation by either ketanserin (a specific 5-HT2A receptor antagonist) or knocking-down the expression of 5-HT2A receptor promoted 5-HT-stimulated IRS-1 dissociation from 14-3-3 beta in LDM, leading to drastic ubiquitination. Interestingly, sarpogrelate, another antagonist of 5-HT2A receptor, protected IRS-1 from degradation through activation of Akt. This implicates the importance of Akt activation in extending IRS-1 life span through maintaining their optimal sub-location into adipocytes. Taken together, this study suggest that activation of Akt may be able to compensate the adverse effects of 5-HT by stabilizing IRS-1 in LDM. (C) 2012 Elsevier Ireland Ltd. All rights reserved.

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