Non-Suppressible Insulin-Like Activity and Sulphation Activity in Serum Extracts of Normal Subjects, Acromegalics and Pituitary Dwarfs

Abstract

Non-suppressible insulin-like activity (NSILA) is a term used for a variety of substances in serum, excluding insulin, which promote glucose uptake of adipose tissue and diaphragm in vitro. NSILA-S is a peptide with a mole¬ cular weight of 7000 which is soluble in acid ethanol and which has been purified on a large scale from human serum. This study describes a simple Chromatographie one step procedure by which NSILA-S can be extracted and quantitatively measured in individual sera. Using Sephadex G-75 equilibrated with 1 M acetic acid, NSILA-S was detected only in one peak containing small molecular peptides. NSILA-S obtained with this one step Chromatographie procedure exerted all the effects of purified NSILA-S including sulphation activity on the rat cartilage. All Chromatographie fractions with NSILA-S also had sul¬ phation activity. Both, NSILA-S and sulphation activity were increased in acromegalics and decreased in pituitary dwarfs. It is suggested that one molecule in serum is responsible for both activities which are, at least in part, under the control of growth hormone.

Evidence for the existence in human serum of large molecular weight nonsuppressible insulin‐like activity (NSILA) different from the small molecular weight forms

“…This procedure has been shown to result in dissociation of small mol. wt NSILA from its carrie r protein [ 11,12,[17][18][19].…”

“…Unextracted normal whole serum contains ~200 ~uU/ml of NSILA as determined in the fat pad assay [11,21]. The serum pool used in this study contained 195/aU/ml.…”

“…It has been shown to contain 2 insulin-like polypeptides (termed insulin-like growth factors, IGF I and II) whose chemical [6][7][8] and biological properties [9] have been defined. The 2 polypeptides occur in human serum in tight association with a specific carrier protein [ 10] from which they dissociate under acidic conditions [ 11,12]. Doubts have, however, been raised about the existence of NSILA-P. Chromatography of human serum on Sephadex G-75 in 1 M acetic acid, did not reveal measurable amounts of large mol.…”

“…wt fraction 0nol. wt <10 000) [ 11 ]. Recently, Poffenbarger, using Dowex.50 ion exchange chromatography as the first purification step, isolated a large mol.…”

“…In this work we tried to reassess the problem with the methods applied in our earlier studies [11,12]. Avoiding lyophilization of the large mol.…”