Effect of p-chlorophenoxyisobutyrate on the antilipolytic action of insulin and insulin binding in isolated adipocytes

Abstract

The present study was undertaken to investigate the potentiation by p-chlorophenoxyisobutyrate (CPIB) of the antilipolytic effect of insulin in isolated adipocytes from rats fed a (1) sucrose diet, (2) glycerol-lard diet, or (3) chow diet. CPIB supplementation in the diet consistently resulted in decreased serum triglyceride levels in rats from the three dietary groups. The catecholamine-stimulated glycerol release was significantly depressed to a greater extent by insulin when the fat cells were obtained from rats given CPIB compared to those without drug treatment. The enhanced insulin sensitivity was, however, not accompanied by any changes in insulin binding to adipocytes. These two observations were found in cell preparations from rats fed any one of the diets, although differences among dietary groups could be detected. In an in vitro experiment, epinephrine-stimulated glycerol release was progressively inhibited by increasing concentrations of CPIB in the incubation medium. However, the antilipolytic response to an optimal concentration of insulin (100 muU/ml) was augmented in the presence of CPIB. Thus, it seems that CPIB can potentiate the action of insulin in inhibiting mobilization of free fatty acid from the adipose tissue, and the coordinated effect of both antilipolytic agents is important in lowering serum triglyceride concentration. The mechanism by which CPIB facilitates the effect of insulin is discussed.