"Big, big insulin"

The presence of a new form of immunoreactive insulin, “big, big insulin”, was first detected in the plasma of an insuloma suspect. On Sephadex gel filtration the elution volume of this insulin is approximately that of ¹²⁵I-γ-globulin. Its sedimentation velocity on ultracentrifugation is between that of labeled albumin and labeled γ-globulin. Thus, it appears to have a molecular weight of about 100,000. Studies with starch gel and starch block electrophoresis reveal that it is a more basic protein than porcine or crystalline human insulin. It is immunochemically identical with crystalline human insulin, maintains its identity on refractionation on Sephadex gel filtration and is rapidly transformed by trypsin to an insulin-like component. “Big, big insulin” is a minor component (<1%) in extracts of normal pancreas and of insulomas. These observations suggest that insulin is the daughter product not only of proinsulin but of an even larger precursor, “big, big insulin”.