Insulin binding and insulin response of adipocytes from rats adapted to fat feeding1

The effect of fat feeding on adipocyte insulin binding was examined to expand a study of adaptive changes in plasma membrane functions. Cells from rats fed a high fat (L) diet for five to seven days bound less insulin and showed a decreased response to insulin (glucose oxidation) compared to those from rats fed a high glucose (G) diet. Both high and low affinity sites were influenced; the extent of the binding difference increased as increasing concentrations of insulin were present in the assay medium. Diet did not change hormone degradation or the capacity of phospholipase C to increase binding. Concanavalin A effects on fat cells were also decreased by L diet both in inhibition of insulin binding and its insulin-like effect on glucose oxidation. Spermine, which had no effect on insulin binding, also had a smaller insulin-like effect on glucose oxidation by L cells than by G cells. Serum insulin was significantly lower (30 * 3.7 pU/ml) in L than in G (43 f 3.1 pU/ml) groups. Dietary fat produces alterations in fat cells that decrease insulin binding as a part of a complex overall adaptation to the diet. Supplementary key words fat cell size * phospholipase C . serum insulin levels concanavalin A * spermine The present study was designed to investigate the possibility that a plasma membrane-associated function, insulin binding capacity, can fluctuate in response to changes in diet composition. Reports that insulin binding capacity is altered by certain hormones ( I ) , and in obesity (2, 3) in association with changes in insulin sensitivity indicate that such adaptation to environmental changes can occur. In a previous report from this laboratory (4) we demonstrated that both a decreased plasma membrane adenylate cyclase response to epinephrine and glucagon in fat cell ghosts and decreased lipolytic response of fat tissue were found in rats fed high fat diets. It seemed of interest, therefore, to study the effect of feeding a high fat diet to rats on the capacity of their fat cells to bind insulin. It has already been reported that fat feeding decreases adipose tissue response to insulin as measured by its effect on glucose uptake (5), glucose oxidation (6) or lipolysis (7). Serum insulin and glucose concentrations in rats fed high fat or high carbohydrate diets were also measured. Concanavalin A (8 ,9) has been reported to have an insulin-like effect on fat cells and to decrease insulin binding (8). It seemed possible that changes in the function of fat cell membranes induced by diet might influence the availability of the concanavalin A binding sites. Therefore the effects of this agent on glucose oxidation and on insulin binding by fat cells from rats on the various diets were investigated. In preliminary experiments, it was found that spermine, which also mimics the action of insulin on fat cells (lo), does not inhibit binding of the hormone. Fat cells from rats fed each of the diets were tested for their response to spermine as a measure of diet effects on glucose oxidation that do not involve insulin binding. MATERIALS AND METHODS