Inhibition of the action of nonsuppressible insulin-like activity on isolated rat fat cells by binding to its carrier protein

extracted and purified from human serum (NSILA-S) mimics all insulin-like effects in vitro and, after injec-tion, in vivo in the presence of excess insulin anti-bodies. However, there is no evidence that it exerts acute insulin-like effects in its native form in the cir-culation, where it is almost completely bound to a specific large molecular weight carrier protein. In this paper we show that partially purified NSILA-S-car-rier protein, devoid ofendogenous insulin-like activity, inhibits the stimulatory effect of NSILA-S, but not of insulin, on 3-0-methylglucose transport and on lipo-genesis from [U-14C]glucose in isolated rat fat cells. Concomitantly, it prevents binding of 125I-labeled NSILA-S to the insulin receptor and to the NSILA-S-binding site. The following explanation is, therefore, offered for the absence of acute insulin-like effects of native NSILA-S in vivo: In native serum NSILA-S occurs alfmost exclusively as NSILA-S-carrier complex. Ac-cording to recent findings the passage of this complex through blood capillaries is restricted. The present results indicate that, in addition, it is metabolically in-active, or, at least, possesses reduced metabolic ac-tivity. The well-known phenomenon that whole serum, nevertheless, exerts pronounced nonsuppressible in-sulin-like effects on adipose tissue in vitro seems, therefore, to be mainly caused by the presence of a large molecular weight insulin-like protein not identi-cal to the NSILA-S-carrier complex