Effects of insulin and proinsulin on isolated fat cells and hemidiaphragms from rats

The biological activities of purified porcine proinsulin and crystalline insulin were tested on isolated fat cells and hemidiaphragms from rats. With fat cells, proinsulin, like insulin, inhibited glycerol release in the presence of epinephrine, and stimulated conversion of glucose to CO₂ and lipids. For all effects studied, the dose-response curves for proinsulin were parallel to those for insulin. The ratio of the potency of bovine insulin to that of proinsulin was approximately 12.5/1 on a molar basis, corresponding to an apparent biological activity of 1.1 U/mg for proinsulin. Proinsulin did not affect the responses of cells which were maximally stimulated by insulin, nor did it antagonize the effects of submaximal concentrations of insulin. With hemidiaphragms in vitro, the dose-response curve for the stimulation of glucose uptake by proinsulin was parallel to that for insulin. The apparent biological activity of proinsulin was approximately 1.8 U/mg, in comparison with a standard solution of porcine insulin. Proinsulin did not inhibit the effects of submaximal concentrations of insulin. These results imply that, whether cells are exposed to proinsulin or insulin, the same effector systems are stimulated. Proinsulin is not an antagonist to insulin action.