beta-Adrenergic dependent downregulation of insulin binding in rat adipocytes.

In order to study factors regulating insulin binding to rat adipocytes short- and long-term incubations were performed in the presence or absence of noradrenaline (NA) at a concentration of 3 microM. Culture with NA for 24 hours resulted in a significant decrease (30%) of insulin binding due to a reduced number of binding sites. This reduction was dose-dependent and completely prevented by the addition of timolol, a beta-adrenergic blocking agent, but not by the alpha-blocking agent phentolamine. Addition of 1.0 mM db cAMP to the culture medium resulted in a similar reduction in insulin binding. Also short-term incubations with NA resulted in a downregulation of insulin binding; reproducible reductions seen already after 20 min and about 30% reduction achieved after 2 hours' preincubation. Thus, beta-adrenergic stimulation and subsequent cAMP elevation results in a rapid reduction in the number of insulin binding sites.