| First Author | Fève B | Year | 1994 |
| Journal | Proc Natl Acad Sci U S A | Volume | 91 |
| Issue | 12 | Pages | 5677-81 |
| PubMed ID | 8202547 | Mgi Jnum | J:18751 |
| Mgi Id | MGI:66990 | Doi | 10.1073/pnas.91.12.5677 |
| Citation | Feve B, et al. (1994) Transcriptional down-regulation by insulin of the beta 3-adrenergic receptor expression in 3T3-F442A adipocytes: a mechanism for repressing the cAMP signaling pathway. Proc Natl Acad Sci U S A 91(12):5677-81 |
| abstractText | Modulation of the three beta-adrenergic receptor subtypes (beta-ARs) by insulin was investigated in mouse 3T3-F442A adipocytes. Saturation and competition experiments measuring binding of 125I-labeled (-)-cyanopindolol to adipocyte membranes demonstrated that cell exposure to insulin for 4 days caused a 3.5-fold decrease in the density of the major beta-AR component of the adipocyte, the beta 3-AR, while beta 1-AR sites remained unchanged and beta 2-ARs were undetectable. This correlated with a lower potency of the beta 3-AR-selective agonists CGP12177, ICI201651, and BRL37344 in stimulating adenylate cyclase. Northern blotting analysis indicated that insulin induced a rapid and sharp decrease in beta 3-AR mRNA levels. This effect was detectable at low insulin concentrations (EC50 = 3 nM) and was not observed in the presence of insulin-like growth factor I, suggesting an insulin receptor-mediated phenomenon. Reverse transcriptase-PCR analysis showed that, in contrast to its dramatic down-regulatory effect on beta 3-AR mRNA, insulin did not modify the levels of beta 1- and beta 2-AR transcripts. As assessed by nuclear run-on assays, insulin inhibited the beta 3-AR gene transcription rate by 90% within 30 min. mRNA turnover experiments showed that the half-life of beta 3-AR mRNA was short (90 min) and remained unaffected by insulin. These findings demonstrate the genetic control of a beta-AR subtype expression by insulin and reveal a mechanism for the regulation by this hormone of cAMP-dependent biological processes in adipocytes. |
