Destruction of insulin effector system of adipose tissue cells by proteolytic enzymes.

Insulin did not stimulate glucose utilization or inhibit lipolysis in adipose tissue cells previously incubated with trypsin. The acceleration of glucose oxidation by insulin was also reduced by prior incubation of cells with chymotrypsin, papain, or ficin, but not with purified collagenases or an acidic proteinase of Closfridium hisfolyficum. The loss of insulin effects was not due to destruction of the hormone. Furthermore, it appeared that trypsin did not digest cells nonspecifically since the treated tissue retained (a) a substantial lipolytic activity that was still responsive to epinephrine and adrenocorticotropin, (b) the capacity to oxidize glucose rapidly when sugar transport was stimulated by a high glucose concentration in the incubation medium, (c) a cell membrane that was not leaky to fat, glucose, or lactate dehydrogenase, and (d) a stereospecific sugar transport mechanism. These results suggest that a site (or sites) on the cell surface containing peptide components is necessary for the action of insulin on glucose transport and lipolysis. The site is probably distinct from the elements involved directly in glucose transport, lipolysis, and turnover of cyclic AMP.