Pharmacological Profile of GPD-1116, an Inhibitor of Phosphodiesterase 4.

We have previously reported that GPD-1116, an inhibitor of phosphodiesterase (PDE) 4, exhibits anti-inflammatory effects in a model of cigarette smoke-induced emphysema in senescence-accelerated P1 mice. In the present study, we further characterized the pharmacological profile of GPD-1116 in several experiments in vitro and in vivo. GPD-1116 and its metabolite GPD-1133 predominantly inhibited not only human PDE4, but also human PDE1 in vitro.

Activation of peroxisome proliferator-activated receptor delta induces fatty acid beta-oxidation in skeletal muscle and attenuates metabolic syndrome.

In this study, we defined the role of peroxisome proliferator-activated receptor beta/delta (PPARdelta) in metabolic homeostasis by using subtype selective agonists. Analysis of rat L6 myotubes treated with the PPARdelta subtype-selective agonist, GW501516, by the Affymetrix oligonucleotide microarrays revealed that PPARdelta controls fatty acid oxidation by regulating genes involved in fatty acid transport, beta-oxidation, and mitochondrial respiration. Similar PPARdelta-mediated gene activation was observed in the skeletal muscle of GW501516-treated mice.