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Exp Clin Endocrinol Diabetes 2005; 113(8): 418-422
DOI: 10.1055/s-2005-865771
Article

J. A. Barth Verlag in Georg Thieme Verlag KG Stuttgart · New York

The β3-Adrenergic Agonist CL316,243 Inhibits Insulin Signaling but not Glucose Uptake in Primary Human Adipocytes

M. M. Jost1 , P. Jost2 , J. Klein3 , H. H. Klein4
  • 1BioVisioN AG, Medical Research, Hannover, Germany
  • 2Department of Radiology, University of Bonn, Bonn, Germany
  • 3Department of Internal Medicine I, Medical University of Lübeck, Lübeck, Germany
  • 4Chairman of the Department of Internal Medicine 1, Berufsgenossenschaftliche Kliniken Bergmannsheil, Ruhr-University Bochum, Bochum, Germany
Further Information

Publication History

Received: June 10, 2004 First decision: October 14, 2004

Accepted: May 13, 2005

Publication Date:
08 September 2005 (online)

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Abstract

Insulin resistance and obesity are central components of the metabolic syndrome which has become the leading cause of cardiovascular morbidity and mortality worldwide. Direct interactions of the β3-adrenoceptor system with adipocyte signaling and function in humans remain poorly understood. However, this might have important consequences for the regulation of energy homeostasis and insulin resistance in states of hyperinsulinemia and sympatho-adrenergic overactivity. We therefore investigated β3-adrenoceptor-mediated effects on insulin signaling and glucose uptake in mammary adipocytes of healthy women that underwent breast reduction surgery. Glucose uptake was strongly induced by insulin stimulation. This was paralleled by robust induction of insulin receptor kinase activity, insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity, and protein kinase B phosphorylation. Treatment with the β3-adrenoceptor-selective agonist CL316,243 alone, neither induced alterations in the early insulin signaling cascade nor changed the basal level of glucose uptake. By contrast, pretreatment with the β3-adrenoceptor agonist inhibited the insulin-induced insulin receptor substrate-1-associated phosphatidylinositol-3 kinase activity by 50 % and protein kinase B phosphorylation by 40 % without affecting insulin receptor kinase activity upstream. However, on the functional level insulin-induced glucose uptake remained unchanged by β3-adrenoceptor stimulation. Our data demonstrate an insulin receptor-independent negative influence of β3-adrenoceptor stimulation on proximal insulin signaling. This inhibition is apparently dissociated from glucose uptake in human adipocytes.

Key words

Insulin receptor - obesity - PD151746 - PI3 kinase - protein kinase B

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Ph.D. Marco M. Jost

Medical Research
BioVisioN AG

Feodor-Lynen-Str. 5

30625 Hannover

Germany

Phone: + 4951153889672

Fax: + 49 5 11 53 88 96 66

Email: m.jost@biovision-discovery.de

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