Antilipolytic effects of insulin and adenylate cyclase inhibitors on isolated human fat cells.
Antilipolysis induced by insulin by adenylate cyclase inhibitors was compared in isolated human fat cells when lipolysis was activated at well-defined steps in the cyclic AMP system. The latter was achieved with isoprenaline (beta-adrenoreceptor agonist), cholera toxin and pertussis toxin (acting on the GTP-sensitive coupling proteins), forskolin (stimulating the catalytic component of adenylate cyclase), enprofylline (selective phosphodiesterase inhibitor) and N6-monobutyryl-cyclic-AMP or 8-bromo cyclic-AMP (cyclic AMP analogues which are resistant or sensitive to phosphodiesterase, respectively). Clonidine (alpha 2-adrenoreceptor agonist), prostaglandin E2 and N6-(phenylisopropyl) adenosine (adenosine analogue) failed to inhibit lipolysis stimulated by cholera toxin or pertussis toxin, but were effective under all other conditions. Insulin failed to inhibit lipolysis stimulated by enprofylline or N6-monobutyryl cyclic AMP, but was effective under all other circumstances. In conclusion, insulin and adenylate cyclase inhibitors are antilipolytic in human fat cells through different mechanisms. Adenylate cyclase inhibitors act predominantly on the GTP-sensitive coupling proteins and, to a minor extent, at some yet unidentified distal step in the lipolytic machinery. As regards insulin, the major site of the antilipolytic action is phosphodiesterase.
Lönnqvist
F
F
Karolinska Institute, Department of Medicine, Stockholm, Sweden.
Wennlund
A
A
Arner
P
P
D000067956:Adenylyl Cyclase Inhibitors; D000273:Adipose Tissue / Q000166:cytology / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology; D000242:Cyclic AMP / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D008066:Lipolysis / Q000187:drug effects; D014970:Xanthines / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D007328:Insulin; D014970:Xanthines; D005576:Colforsin; C034347:enprofylline; D000242:Cyclic AMP