Journal article

Publication year: 2002

Pages: E146-E153

Journal: American Journal of Physiology-Endocrinology and Metabolism

Volume number: 283

Issue number: 1

ISSN: 0193-1849

DOI Link: https://doi.org/10.1152/ajpendo.00531.2001

Publisher: American Physiological Society

Abstract: 
Cross talk between adrenergic and insulin signaling systems may represent a fundamental molecular basis of insulin resistance. We have characterized a newly established beta(3)-adrenoceptor-deficient (beta(3)-KO) brown adipocyte cell line and have used it to selectively investigate the potential role of novel-state and typical beta-adrenoceptors (beta-AR) on insulin signaling and action. The novel-state beta(1)-AR agonist CGP-12177 strongly induced uncoupling protein-1 in beta(3)-KO brown adipocytes as opposed to the beta(3)-selective agonist CL-316,243. Furthermore, CGP-12177 potently reduced insulin-induced glucose uptake and glycogen synthesis. Neither the selective beta(1)- and beta(2)-antagonists metoprolol and ICI-118,551 nor the nonselective antagonist propranolol blocked these effects. The classical beta(1)-AR agonist dobutamine and the beta(2)-AR agonist clenbuterol also considerably diminished insulin-induced glucose uptake. In contrast to CGP-12177 treatment, these negative effects were completely abrogated by metoprolol and ICI-118,551. Stimulation with CGP-12177 did not impair insulin receptor kinase activity but decreased insulin receptor substrate-1 binding to phosphatidylinositol (PI) 3-kinase and activation of protein kinase B. Thus the present study characterizes a novel cell system to selectively analyze molecular and functional interactions between novel and classical beta-adrenoceptor types with insulin action. Furthermore, it indicates insulin receptor-independent, but PI 3-kinase- dependent, potent negative effects of the novel beta(1)-adrenoceptor state on diverse biological end points of insulin action.

Harvard Citation style: Jost, P., Fasshauer, M., Kahn, C., Benito, M., Meyer, M., Ott, V., et al. (2002) Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytes, Endocrinology and Metabolism, 283(1), pp. E146-E153. https://doi.org/10.1152/ajpendo.00531.2001

APA Citation style: Jost, P., Fasshauer, M., Kahn, C., Benito, M., Meyer, M., Ott, V., Lowell, B., Klein, H., & Klein, J. (2002). Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytes. Endocrinology and Metabolism. 283(1), E146-E153. https://doi.org/10.1152/ajpendo.00531.2001