| First Author | Chai SP | Year | 2015 |
| Journal | Biochim Biophys Acta | Volume | 1852 |
| Issue | 10 Pt A | Pages | 2048-55 |
| PubMed ID | 26143144 | Mgi Jnum | J:231199 |
| Mgi Id | MGI:5767065 | Doi | 10.1016/j.bbadis.2015.06.026 |
| Citation | Chai SP, et al. (2015) Synergistic induction of insulin resistance by endothelin-1 and cAMP in 3T3-L1 adipocytes. Biochim Biophys Acta 1852(10 Pt A):2048-55 |
| abstractText | Both endothelin-1 (ET-1) and cAMP are implicated for inducing insulin resistance. Since we have shown previously that there is a crosstalk between ET-1 and cAMP signaling pathways in regulating glucose uptake in 3T3-L1 adipocytes, we extended our investigation in this study on whether they may have a synergistic effect on inducing insulin resistance. Our results showed that it was indeed the case. Insulin-stimulated glucose uptake, phosphorylation of PKB, IRS-1-associated PI3K, and IRS-1 tyrosine phosphorylation were all inhibited by ET-1 and 8-bromo cAMP in a synergistic manner. IRS-1 protein levels were similarly decreased by ET-1 and 8-bromo cAMP, attributable to suppressed mRNA expression. In addition, after correction for the loss in IRS-1 protein, the inhibition of insulin-stimulated IRS-1 tyrosine phosphorylation or IRS-1-associated PI3K was mainly caused by cAMP. Moreover, whereas IRS-2 protein levels were increased by cAMP or ET-1 plus cAMP, insulin-stimulated IRS-2-associated PI3K activities were abolished by both treatments. Furthermore, ET-1 and beta-adrenergic agonists had similar synergistic inhibition on insulin-stimulated glucose uptake. In conclusion, we have shown that ET-1 and cAMP may synergistically induce insulin resistance in adipocytes via inhibiting IRS-1 expression as well as insulin-stimulated IRS-1/IRS-2 activities. |
