In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 91, No. 12 ( 1994-06-07), p. 5677-5681
Abstract:
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.
Type of Medium:
Online Resource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.91.12.5677
Language:
English
Publisher:
Proceedings of the National Academy of Sciences
Publication Date:
1994
detail.hit.zdb_id:
209104-5
detail.hit.zdb_id:
1461794-8
SSG:
11
SSG:
12
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