INSULIN DEGRADATION BY ADIPOSE-TISSUE IS INCREASED IN HUMAN OBESITY

White adipose tissue samples from obese and lean patients were used fo r the estimation of insulin protease and insulin:glutathione transhydr ogenase using I-125-labeled insulin. There was no activity detected in the absence of reduced glutathione, which indicates that insulin is c leaved in human adipose tissue through reduction of the disulfide brid ge between the chains. Obese patients showed higher transhydrogenase a ctivity (per U tissue protein wt, per U tissue wt, and in the total ad ipose tissue mass) than the lean group. There is a significant correla tion between the activity per U tissue wt, and protein and total activ ity in the whole adipose tissue with respect to body mass index, with a higher activity in obese patients. The potential of insulin cleavage by adipose tissue in obese patients was a mean 5.6-fold higher than t hat in controls. The coexistence of high insulinemia and high cleavage capability implies that insulin secretion and turnover are increased in the obese. Thus, white adipose tissue may be crucial in the control of energy availability through modulation of insulin cleavage.