Effect of Human Serum Albumin on the Glucose Metabolism of Isolated Rat Diaphragm and Its Response to Insulin

The effect of human serum albumin prepared by Cohn method 6 on the glucose metabolism of isolated rat diaphragms was studied. In the absence of insulin 5 per cent albumin slightly inhibited glucose uptake and lactate production but not glycogen synthesis. Albumin partially inhibited the stimulatory effect of insulin on glucose uptake, lactate production and glycogen synthesis. The insulin antagonistic effect of 5 per cent albumin was due in part only to increased H+ ion concentration in the medium. Albumin (1.25 per cent) did not affect glucose utilization or lactate production with or without insulin. Albumin (5 per cent) alone slightly but significantly augmented the penetration of d-xylose into “intact” diaphragms. In the presence of insulin and albumin the space of distribution of d-xylose was significantly less than with insulin alone. The albumin preparations contained free fatty acids and citrate; however, the insulin antagonism of 5 per cent albumin could not be reproduced with palmitate or citrate. Following dialysis and lyophilization 5 per cent albumin assayed at controlled pH did not affect glucose uptake, lactate production or glycogen synthesis either in the presence or absence of insulin. The noninhibitory albumin was extracted with TCA-ethanol, dialyzed, lyophilized and assayed as above. It significantly inhibited the stimulatory effect of insulin on glucose uptake, lactate production and glycogen synthesis. It is suggested that several factors can be associated with albumin and antagonize the stimulatory effect of insulin on muscles in vitro. These factors will have to be separated and characterized before the biological significance of the “synalbumin antagonist” of insulin can be evaluated.