Showing papers by "Rosalyn S. Yalow published in 1960"

Immunoassay of Endogenous Plasma Insulin in Man

Abstract: For years investigators have sought an assay for insulin which would combine virtually absolute specificity with a high degree of sensitivity, sufficiently exquisite for measurement of the minute insulin concentrations usually present in the circulation. Methods in use recently depend on the ability of insulin to exert an effect on the metabolism of glucose in vivo or in excised muscle or adipose tissue. Thus, the insulin concentration in plasma has been estimated: a) from the degree of hypoglycemia produced in hypophysectomized, adrenalectomized, alloxan-diabetic rats (1); b) from the augmentation of glucose uptake by isolated rat hemidiaphragm (2); or c) from the increased oxidation of glucose-1-C14 by the rat epididymal fat pad (3). Since there have been reports indicating the presence, in plasma, of inhibitors of insulin action (4) and of noninsulin substances capable of inducing an insulin-like effect (5,6), these procedures, while yielding interesting information regarding the effects of various plasmas on glucose metabolism in tissues, are of doubtful specificity for the measurement of insulin per se (5).

Plasma insulin concentrations in nondiabetic and early diabetic subjects. Determinations by a new sensitive immuno-assay technic.

Abstract: For many years insulin was regarded as only weakly antigenic, or even, according to some, as essentially nonantigenic. However, a few years ago, during the course of investigations on the metabolism of I-labeled insulin, it was observed that the tagged insulin showed a prolonged retention in the blood stream of all subjects who had received insulin therapy, and it was demonstrated that this behavior was attributable to the presence of insulin-binding antibodies. Since the concentration of antibody is extremely low in most such patients and since the insulin-antibody complexes do not precipitate, certain special technics, including the use of an isotopically labeled insulin, are required for the detection of the antibody. Further extension of these technics has made possible an immunologic method for the assay of very small amounts of insulin.

Comparison of plasma insulin levels following administration of tolbutamide and glucose.

Abstract: The mechanism by which sulfonylureas induce hypoglycemia has been a subject of considerable debate. Since the literature in this field is already so vast that it can be touched upon only briefly here, the reader is referred to several excellent reviews.\" Whereas the bulk of evidence indicates that the hypoglycemic effect in mammals is dependent on the presence of functioning islet P cells and is therefore presumably a consequence of the stimulation of insulin secretion, it has not frequently been possible to demonstrate that the sulfonylureas produce the usual metabolic effects of injected insulin. Notably, studies with C-labeled glucose have generally revealed an unaltered rate of glucose utilization following administration of Na tolbutamide,*\" although slight increases were noted in one report. In contrast, insulin administration in similar experiments usually produces a marked increase in C-glucose utilization. However, one group of workers' has found that this effect may be absent if insulin is administered subcutaneously; hypoglycemia in the latter instance presumably results solely from the inhibition of hepatic release of glucose. Such a direct action of insulin on the liver has been disputed by Shoemaker et al. but the objections of the latter group have been overcome by the recent experiments of Madison and co-workers. It has long been known that the liver is capable of concentrating and destroying insulin. The rapid accumulation of insulin-I by the liver has been demonstrated in vivo by external counting technics, as well as by direct tissue analysis. It has been shown that the liver removes approximately 50 per cent of insulin-I administered into the portal vein in a single transhepatic circulation and the studies of Mirsky and others have demonstrated the marked insulin-degrading capacity of the liver in vitro. Furthermore, since the concentration of endogenous insulin would be higher

Correction of Sample Absorption of Radioactivity

Abstract: In the method presented here for the correction of sample absorption of C(14) activity, the only requirement is the availability of any C(14)-labeled compound of sufficiently high specific activity to permit addition, in negligible mass, of a number of counts equal to or greater than that in unknown samples and with solubility characteristics that exclude preferential layering during drying of samples. The principle may be applied to liquid scintillation counting. Absorption curves are dispensed with, and the weights of the assayed samples need not be determined.