FORSKOLIN POTENTIATES ISOPRENALINE-INDUCED GLYCEROL OUTPUT AND LOCAL BLOOD-FLOW IN HUMAN ADIPOSE-TISSUE IN-VIVO

The synergistic action of forskolin on beta-adrenoceptor-mediated glyc erol output and changes in local blood flow were investigated in situ, in human adipose tissue of healthy subjects, by the use of microdialy sis. The addition of isoprenaline 0.1-1.0 mu M or forskolin 10-100 mu M to the perfusion solvent caused a concentration-dependent, marked an d sustained increase in the levels of glycerol in the dialysate (lipol ysis index) as compared to the solvent alone. On a molar basis, isopre naline was almost one thousand times more potent than forskolin. Isopr enaline caused a rapid and concentration-dependent decrease in the eth anol clearance ratio (index of local blood flow, i.e. a decrease in et hanol ratio implies an increase in blood flow). Forskolin had no effec t on the ethanol ratio at either 1.0 mu M or 10 mu M, while forskolin at 100 mu M induced a significant decrease in the ethanol ratio. When adipose tissue was pre-treated with forskolin, the subsequent addition of isoprenaline to the microdialysate resulted in a significantly hig her glycerol output and a significantly more prominent decease in the ethanol ratio than with isoprenaline alone. In conclusion, the data de monstrate that forskolin and the beta-adenoceptor-agonist both stimula te lipolysis and local blood flow in human adipose tissue in vivo. Fur thermore, forskolin, at concentrations that are ineffective alone, pot entiates the actions of isoprenaline on lipolysis and blood flow.