Abstract
Studies previously reported 1 , 2 have established the fact that trypsin can inactivate insulin both in vitro and in vivo. It has also been ascertained that dissociation of insulin 3 from its inactivate combination with trypsin is possible in vitro by proper adjustment of the hydrogen ion concentration of the substance in solution, i. e., by shifting the pH to the acid side of 4.6. It became desirable to ascertain whether or not dissociation of insulin from trypsin could be effected in vivo. It is obvious that the hydrogen ion concentration of the body fluids could not be altered to the point necessary for the dissociation of insulin. Other means were therefore tried, and the following results obtained:
1. Upon the addition, in vitro, of such substances as pepsin, safranin and cryogenin (M-Benzaminosemicarbazide) to the solutions of inactivated insulin (trypsulin), liberation of the insulin takes place. This is evidenced by the result of injection of these mixtures into suitable test animals.
2. These agents (pepsin, safranin and cryogenin) can cause dissociation of insulin from trypsin directly in vivo. Injection of adequate amounts of these substances into animals (subcutaneously or intravenously) made just prior to the parenteral administration of inactivated insulin, cause liberation of the insulin and the production of its physiological effects.
The accompanying tables illustrate the effect on the blood sugar of one of the reactivating substances used:
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