¹Departments of Medicine and Biochemistry and Molecular Biology, Medical University of South Carolina, Charleston, SC 29425, USA and

²Departments of Psychiatry and Behavioral Sciences and Pharmacology, and the Sarah Stedman Center for Nutrition, Duke University Medical Center, Durham NC 27710, USA

Correspondence: TW Gettys, 652 Thurmond Building, MUSC, 171 Ashley Avenue, Charleston, SC 29425, USA

OBJECTIVE: To investigate the role of hypercorticism in the development of compromised -adrenergic signalling in adipocytes of mature C57BL/6J-ob/ob mice. DESIGN AND EXPERIMENTAL UNITS: Mature male ob/ob mice and their lean littermates were treated with vehicle or the specific glucocorticoid receptor (GR) antagonist, RU-486 (30 mg/kg bw/d) for 21 d. MEASUREMENTS: Blood glucose, serum insulin, adipocyte Glut-4 expression, adipocyte G_s expression, adenylylcyclase activation by -adrenergic receptor (-AR) agonists in adipocyte membranes and mRNA levels for ₁-, ₂- and ₃-adrenergic receptor subtypes in adipocytes. RESULTS: RU-486 reduced blood glucose levels in ob/ob mice to levels that were not different from lean mice. RU-486 also reduced serum insulin by approximately 50% in ob/ob mice, but failed to restore depressed G_s or GLUT-4 expression in adipocytes of ob/ob mice. RU-486 produced a two-fold increase in ₃-AR mRNA in ob/ob mice and a small but significant improvement in isoprenaline-mediated adenylylcyclase activation. CONCLUSIONS: The present results indicate that glucocorticoid antagonism ameliorates diabetic symptoms of the mature ob/ob mouse, but does not lessen their obesity or fully reverse deficient expression and function of components of the adipocyte -adrenergic signalling cascade.

obesity; adenylylcyclase; G proteins; receptor signalling