Endocrinology, Vol 115, 1787-1791, Copyright © 1984 by Endocrine Society
Differential effects of two phosphodiesterase inhibitors on fat cell metabolism
Y Shechter
The various effects of the phosphodiesterase inhibitor D-4-(3-butoxy-4-
methoxybenzyl)-2-imidazolidinone (RO-20-1724) on fat cell metabolism were
examined and compared to those obtained with 1-methyl-3- isobutylxanthine
(IBMX). Like IBMX, RO-20-1724 increased the rate of lipolysis, suppressed
the incorporation of glucose into fat, did not increase the basal rate of
cAMP production, but induced fast linear accumulation of the nucleotide
when combined with a lipolytic agent. The time scale and the effective
concentrations of both reagents in exerting these effects were similar.
Both inhibitors were also equally potent in inhibiting the low
Michaelis-Menten constant (Km) cAMP phosphodiesterase activity in fat cell
homogenate. A fundamental difference between both inhibitors however did
exist. Whereas the addition of IBMX abolished the ability of insulin to
inhibit lipolysis as previously reported, insulin is fully functional in
inhibiting the increased rate of lipolysis in the presence of RO-20-1724.
Also, RO-20- 1724 does not interfere with the ability of insulin to inhibit
fully cholera toxin-mediated lipolysis. It is concluded that under these
conditions the antilipolytic effect of insulin may be produced without
demonstrable activation of cAMP phosphodiesterase. The effects of the
methylxanthines in abolishing insulin action probably relates to
interference with insulin-dependent intracellular enzymic activity other
than cAMP phosphodiesterase.
