Journalartikel

Jahr der Veröffentlichung: 1999

Seiten: 34795-34802

Zeitschrift: Journal of Biological Chemistry

Bandnummer: 274

Heftnummer: 49

ISSN: 0021-9258

DOI Link: https://doi.org/10.1074/jbc.274.49.34795

Verlag: Elsevier

Abstract: 
Activity of the sympathetic nervous system is an important factor involved in the pathogenesis of insulin resistance and associated metabolic and vascular abnormalities. In this study, we investigate the molecular basis of cross-talk between beta(2)-adrenergic and insulin signaling systems in mouse brown adipocytes immortalized by SV40 T infection. Insulin-induced tyrosine phosphorylation of the insulin receptor, insulin receptor substrate 1 (IRS-1), and IRS-S was reduced by prestimulation of beta(3)-adrenergic receptors (CL316243). Similarly, insulin-induced IRS-1-associated and phosphotyrosine-associated phosphatidylinositol S-kinase (PI 3-kinase) activity, but not IRS-2-associated PI 3-kinase activity, was reduced by beta(3)-adrenergic prestimulation, Furthermore, insulin-stimulated activation of Akt, but not mitogen-activated protein kinase, was diminished. Insulin-induced glucose uptake was completely inhibited by beta(3)-adrenersc prestimulation. These effects appear to be protein kinase A-dependent. Furthermore inhibition of protein kinase C restored the beta(3)-receptor-mediated reductions in insulin-induced IRS-1 tyrosine phosphorylation and IRS-1-associated PI 3-kinase activity. Together, these findings indicate cross-talk between adrenergic and insulin signaling pathways. This interaction is protein kinase A-dependent and, at least in part, protein kinase C-dependent, and could play an important role in the pathogenesis of insulin resistance associated with sympathetic overactivity and regulation of brown fat metabolism.

Harvard-Zitierstil: Klein, J., Fasshauer, M., Ito, M., Lowell, B., Benito, M. and Kahn, C. (1999) β3-Adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes, Journal of Biological Chemistry, 274(49), pp. 34795-34802. https://doi.org/10.1074/jbc.274.49.34795

APA-Zitierstil: Klein, J., Fasshauer, M., Ito, M., Lowell, B., Benito, M., & Kahn, C. (1999). β3-Adrenergic stimulation differentially inhibits insulin signaling and decreases insulin-induced glucose uptake in brown adipocytes. Journal of Biological Chemistry. 274(49), 34795-34802. https://doi.org/10.1074/jbc.274.49.34795