Non-suppressible insulin-like activity of human serum: II. Biological properties of plasma extracts with non-suppressible insulin-like activity

Abstract

1. 1. Extracts of human plasma globulins with 52 (extract B) to 1775 (purified extract B) μU non-suppressible insulin-like activity (ILA) per mg protein were tested with regard to their biological properties in several insulin-assay procedures in vitro and in vivo. 2. 2. The effects of purified extract B on glucose metabolism of rat and human adipose tissue and on isolated fat cells in vitro were the same as those of crystalline insulin. Extract B stimulated the transport of glucose from the extracellular into the intracellular space of rat adipose tissue. Glycerol release of adipose tissue of fasted-refed rats was inhibited by extract B as well as by crystalline insulin in the absence of glucose in the medium. 3. 3. Incorporation of uniformly labelled [ 14C]glucose into glycogen of mouse diaphragm in vitro was stimulated by extract B as well as by crystalline insulin. 4. 4. When injected intraperitoneally into mice, extract B enhanced [ 14C]glucose incorporation into muscle glycogen and adipose tissue lipids. 5. 5. Purified extract B administered intravenously to rats lowered their serum glucose, decreased the biological half-life of serum glucose from a basal level of 18 to 9 min and enhanced the incorporation of [6- 14C]glucose into the glycogen of the diaphragm and into the total lipids of adipose tissue. Compared with crystalline insulin, the effects of purified extract B on the diaphragm clearly surpassed those on adipose tissue. 6. 6. Whereas the effects of crystalline insulin were inhibited by the simulataneous injection of anti-insulin serum, those of purified extract B were not. 7. 7. The increase of glucose assimilation brought about by these small doses of insulin and purified extract B subsided 15 min after injection, whereas the effects on the tissues remained more or less constant up to 30 min. 8. 8. The apparent inefficacy of unaltered non-suppressible ILA in human serum in vivo contrasts with its effectiveness in vitro and with the effects of extracted non-suppressible ILA in vivo. These phenomena are discussed with regard to a possible physiological role of non-suppressible ILA.