THE SPECIFICITY OF THE INTERACTION OF INSULIN-I131WITH TISSUE

Abstract

Insulin-I¹³¹ possessing full hypoglycemic activity and insulin-I¹³¹ totally inactivated either by treatment with dilute NaOH at 37° or by heavy iodine substitution (5.6 I atoms⁄molecule) were intravenously injected into male albino rats. The following results were demonstrated 5 minutes later. 1) Inactivation caused a marked reduction in the concentration of the labeled protein by the liver and, in marked contrast to the active hormone, permitted large quantities to be removed by perfusion. 2) The proportion of inactivated insulin-I¹³¹ bound to intracellular structures was reduced by alkali inactivation and increased by heavy iodine substitution; specific alterations were also observed in the pattern of distribution among the intracellular structures (nuclei, mitochondria and microsomes). 3) Degradation by liver and kidney was different for both inactivated insulin preparations. These results support the thesis that the metabolic fate of hormonally intact insulin-I¹³¹ in the liver is specific. The data are discussed in relation to the validity of the use of insulin-I¹³¹ as a biological tracer and the relationship between molecular structure and tissue interactions.