The results of chemical, biologic, and clinical studies of the interaction between insulin and zinc were published in 1951 and 1952 by K. Hallas-Møller, P. M. Jersild, K. Petersen, and J. Schlichtkrull. It was reported that insulin is insoluble at blood pH in the presence of zinc ions, since at this pH a slowly soluble and slowly resorbable insulin-zinc compound is formed. The degree of retardation of an insulin-zinc suspension is governed first and foremost by the physical state of the suspended insulin. As seen in figure I, a suspension of the amorphous modification, Semilente, has a somewhat longer action than ordinary insulin, whereas the crystalline modification, Ultralente, may be compared to protamine-zinc insulin.

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