Biological Activity of Porcine Proinsulin (3)

Abstract

It is of high interest to know whether the biological activity of purified porcine proinsulin (Eli Lilly Co.) is due to the effect of proinsulin itself or to the effect of insulin produced from proinsulin, both in vitro and in vivo. From this point of view, the influence of a broad spectrum proteolytic trypsin inhibitor, Kunitz pancreatic trypsin inhibitor (KPTI), on the biological activity of proinsulin was investigated in the normal rat. The results obtained were as follows.
1. The degree of hypoglycemia induced by the combined administration of proinsulin and KPTI was significantly lower than that of proinsulin in single intraperitoneal injection. These results suggest indirectly that it is possible that proinsulin is converted to insulin in vivo.
2. KPTI added in the incubation medium with proinsulin did not show any influence on the glucose uptake by proinsulin itself in the hemidiaphragm and epididymal adipose tissues excised from rats. These results indicate that there is extremely little possibility of conversion from proinsulin to insulin in the in vitro system.