We have reported that normal human sera contain immunoactivity (IA) detected by a RIA directed against the first 21
amino acids of the E domain of
proinsulin-like growth factor-II (
pro-IGF-II). Marked elevations of E-21 IA were found in the serum of patients with nonislet cell
hypoglycemia (NICTH) and patients with
renal failure receiving chronic
hemodialysis. In this paper we describe some of the properties of the E-21 IA of normal and abnormal sera. The E-21 IA eluted from a calibrated
acid Sephadex G-50 column as two major peaks. In normal serum the first major peak had a mol wt (Mr) between 14,000-15,000, and the second peak had a Mr between 5,000-6,000. When E-21 IA from serum of a patient with NICTH was similarly studied, most of the IA was present as a Mr 11,000 peak and only a small amount was present as a 5,000-6,000 Mr peak. In contrast, most of the E-21 IA present in the sera of patients on
hemodialysis was present in the smaller molecular form, which eluted from a reverse phase column as a single component. This small Mr peak lacked determinants for the
IGF-II monoclonal antibody (Amano), for pooled serum
IGF-binding proteins, and for the
IGF-I receptors on human placental membranes. We suggest that the 15- and 11-kilodalton peaks represent the glycated and unglycated forms of
pro-IGF-II (E-21) reported by others. The glycated form appears to predominate in normal serum, whereas the nonglycated form predominates in the serum of patients with NICTH and
renal failure. The 5,000-6,000 Mr E-21 IA probably represents a fragment of the free E domain of
pro-IGF-II. Its size is consistent with cleavage of the free E domain between Arg46 and Arg47. The accumulation of this E-21 IA in
renal failure is evidence that the kidney has a major role in the clearance of this fragment, which is not accomplished by the membranes used in
hemodialysis.