| First Author | Li Q | Year | 2013 |
| Journal | Mol Cell Endocrinol | Volume | 365 |
| Issue | 1 | Pages | 25-35 |
| PubMed ID | 22975078 | Mgi Jnum | J:193789 |
| Mgi Id | MGI:5469558 | Doi | 10.1016/j.mce.2012.08.022 |
| Citation | Li Q, et al. (2013) Activation of Akt through 5-HT2A receptor ameliorates serotonin-induced degradation of insulin receptor substrate-1 in adipocytes. Mol Cell Endocrinol 365(1):25-35 |
| abstractText | 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 14-3-3beta 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. |
