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Proinsulin — oder Insulingabe?

  • Conference paper
Diabetes mellitus

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Summary

Through recombinant DNA technology sufficient quantities of biosynthetic human proinsulin have become available. Therefore it was obvious to look for therapeutic benefits of human proinsulin or the advantages of human proinsulin over human insulin. By in vitro studies it could be demonstrated that human proinsulin binds to the same receptor as insulin, but the binding of human proinsulin is one hundred times less than that of human insulin. After binding the postreceptor effects of human insulin and proinsulin are indistinguishable.

The pharmacokinetics of human proinsulin and human insulin are different. The dominant biologic half-life of human proinsulin amounted to 1.54 h, and the metabolic clearance rate to 120 ml/min. Corresponding to the longer half-life and lower clearance rate, the blood glucose-lowering effect of human proinsulin lasted longer than that of human insulin. In this sense, human proinsulin could be said to have an its own depot effect. After s.c. injection the duration of the blood glucose-lowering effect of human proinsulin is longer than that of regular human insulin, but shorter than that of a formulation of NPH-modified human insulin.

Some problems concern the dosage of human proinsulin, as human proinsulin is, like human insulin, standardized in the rabbit hypoglycemia test. However, in this test procedure the different pharmacokinetics of human insulin and proinsulin are not considered. Therefore, the potency of 4 IU per mg for human proinsulin — in comparison, human proinsulin has a potency of 28 IU per mg — seems to be a slight underestimate.

Whether human proinsulin inhibits hepatic glucose output more than human insulin or not is under discussion. Indeed, a pronounced inhibition of hepatic glucose output could be of interest in treatment of diabetics. The results of several groups working on this field and clinical studies with human proinsulin in comparison to human insulin are equivocal. In treatment with insulin delivery devices human proinsulin could have advantages over insulin if it is used for substitution of the basal rate as, if the pump stops during the night, the longer half-life of human proinsulin will delay the glucose increase until the next morning.

(In the meantime, because of a suspected higher incidence of myocardial infarction in diabetics treated with human proinsulin, all clinical studies with human proinsulin have been interrupted).

Die Firma Lilly, die bisher Human-Proinsulin für klinische Studien zur Verfügung stellte, hat zwischenzeitlich weltweit alle klinischen Untersuchungen mit Proinsulin vorerst abgebrochen, da in einer von 5 Langzeitprüfungen in der mit Proinsulin behandelten Gruppe eine höhere Herzinfarktinzidenz als in der mit Insulin behandelten Vergleichsgruppe auftrat.

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  1. P. Bottermann
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Editors and Affiliations

  1. Medizinische Klinik III und Poliklinik, Klinikum der Justus-Liebig-Universität Gießen, Rodthohl 6, 6300, Gießen, Deutschland

    Reinhard G. Bretzel

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© 1990 Springer-Verlag · Heidelberg

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Bottermann, P. (1990). Proinsulin — oder Insulingabe?. In: Bretzel, R.G. (eds) Diabetes mellitus. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-74610-9_9

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  • DOI: https://doi.org/10.1007/978-3-642-74610-9_9

  • Publisher Name: Springer, Berlin, Heidelberg

  • Print ISBN: 978-3-642-74611-6

  • Online ISBN: 978-3-642-74610-9

  • eBook Packages: Springer Book Archive

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