METABOLICALLY INACTIVE INSULIN ANALOG PREVENTS TYPE-I DIABETES IN PREDIABETIC NOD MICE

The purpose of this study was to determine the relative importance of the metabolic effects of insulin for diabetes prevention by administer ing insulin or an inactive insulin analog by daily subcutaneous inject ions to prediabetic mice, A recombinant monomeric human insulin analog , which does not bind to the insulin receptor as a consequence of an a lteration of a single amino acid at position 25 of the B chain, was sh own to be equally effective at diabetes prevention as was intact insul in. In contrast to native insulin, the insulin analog did not cause hy poglycemia after subcutaneous injection. The insulin analog, however, protected young adult mice from diabetes, even when it was initiated a fter the onset of extensive lymphocytic infiltration of the islets. Th us, preventative therapy by daily subcutaneous injections of insulin d oes not require the hypoglycemic response, or binding to the insulin r eceptor to prevent the onset of type I diabetes.