Metabolically inactive insulin analog prevents type I diabetes in prediabetic NOD mice

D. G. Karounos, J. S. Bryson, D. A. Cohen

Research output: Contribution to journalArticlepeer-review

74 Scopus citations


The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administering insulin or an inactive insulin analog by daily subcutaneous injections to prediabetic mice: A recombinant monomeric human insulin analog, which does not bind to the insulin receptor as a consequence of an alteration of a single amino acid at position 25 of the B chain, was shown to be equally effective at diabetes prevention as was intact insulin. In contrast to native insulin, the insulin analog did not cause hypoglycemia after subcutaneous injection. The insulin analog, however, protected young adult mice from diabetes, even when it was initiated after the onset of extensive lymphocytic infiltration of the islets. Thus, preventative therapy by daily subcutaneous injections of insulin does not require the hypoglycemic response, or binding to the insulin receptor to prevent the onset of type I diabetes.

Original languageEnglish
Pages (from-to)1344-1348
Number of pages5
JournalJournal of Clinical Investigation
Issue number6
StatePublished - Sep 15 1997


  • Autoimmunity
  • Immunotherapy
  • Synthetic hormones
  • Type I diabetes mellitus

ASJC Scopus subject areas

  • General Medicine


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