Importance of phosphodiesterase 3 for the lipolytic response in adipose tissue during insulin-induced hypoglycemia in normal man.

The present investigation aimed to clarify the role of phosphodiesterase (PDE) type 3 for in vivo lipolysis in human adipose tissue during simultaneous insulin and catecholamine stimulation. Therefore, ten healthy subjects were investigated during insulin-induced hypoglycemia. Microdialysis probes were implanted in the subcutaneous adipose tissue and perfused by solvents with or without addition of the specific PDE 3 antagonist amrinone. Furthermore, changes in the local blood flow surrounding the dialysis probes were assessed by the ethanol escape technique. During the 60 min period before the start of the insulin infusion, adipose tissue glycerol levels (lipolysis index) increased significantly when amrinone was added to the perfusate (p = 0.0006, one-factor ANOVA). The antilipolytic response to the early phase of insulin infusion decreased (delta glycerol 9.0+/-3.5 vs. 29.9+/-6.0 micromol/l, p = 0.04) and the lipolytic response after hypoglycemia increased (AUC 122.4+/-18.0 vs. 13.4+/-16.3 micromol x l(-1) x h, p = 0.0001) comparing the experiments with or without amrinone, respectively. When amrinone was excluded from the perfusate, there was an increase in the nutritive blood flow during hypoglycemia, whereas there were no significant changes in the local blood flow surrounding the probe when amrinone was added to the perfusate. In conclusion, during insulin-induced hypoglycemia, PDE 3 activation clearly counteracts the lipolytic effect of catecholamines. When PDE 3 is specifically blocked, lipolysis increases greatly. Thus, PDE 3 is important for the in vivo regulation of the antilipolytic and lipolytic responses to hormones in human adipose tissue.