Prostaglandin E2 differentiates between two forms of glucose transport inhibition by lipolytic agents

Summary The inhibition of insulin-stimulated glucose transport by lipolytic agents was studied in isolated rat adipose cells. Two different mechanisms for the inhibition of glucose transport by lipolytic hormones and agents were distinguished by use of the antilipolytic agent prostaglandin E₂ (PGE₂). The inhibition of glucose transport induced by lipolytic hormones such as glucagon, catecholamines or ACTH in the presence of adenosine deaminase was antagonized by PGE₂. In contrast, inhibition of hexose transport by alkylxanthines was only partially (20–30%) attenuated by PGE₂, although the eicosanoid had antagonized cyclic AMP accumulation and stimulation of lipolysis in response to all tested lipolytic agents. The inhibition of glucose transport by IBMX was immediate, whereas the lipolytic hormones (isoprenaline and ACTH) exhibited a latency of 2–3 min. In addition, the inhibition induced by the lypolytic hormones disappeared after cooling of the cells to 22°C, at which temperature IBMX was still inhibitory. Thus, the PGE₂-sensitive component of the effect of lipolytic agents on glucose transport appears to be mediated by adenylate cyclase or its subunits N_s/N_i. The PGE₂-insensitive effect of alkylxanthines probably reflects a direct interaction of the agents with a regulatory site at the transporter or a related protein.Send offprint requests to H. J. Steinfelder at the above address