Insulin concentration in each sample of dog urine, carotid artery plasma, or renal vein plasma was estimated following the infusion of bovine insulin-I-125, unlabeled bovine insulin, or glucose. Insulin was estimated by immunoassay and by TCA insoluble radioactivity. Whenever insulin-I-125 and unlabeled insulin were infused together both methods were used on each sample. In agreement with the conclusions of others, who have used less direct technics, it was found that the use of plasma TCA insoluble radioactivity to determine radio-insulin degradation in vivo results in an underestimate of insulin removal, and hence an overestimate of insulin half life. This finding was shown to apply not only to the whole animal but also to the kidney. All forms of insulin were removed by the kidney but the radioactive estimate of kidney insulin removal was less than that by immunoassay. Data from experiments in which radioactive insulin was bound to guinea pig anti-insulin serum prior to infusion and from experiments in which ureteral ligation was performed prior to infusion indicated that the kidney removed insulin primarily by glomerular filtration but that direct absorption also played a role.

INSULIN-IMMUNOASSAY ESTIMATED RECOVERY nomena are related. Perhaps the large initial inhibition of leucine catabolism compensates for whatever anabolic inhibition is occurring. Since less leucine i s being degraded, more is available for incorporation and this effect counteracts the process of inhibition of protein synthesis. Once the catabolic inhibition reaches a plateau, the compensation no longer exists, and the inhibition of protein anabolism can assert itself. This hypothesis represents one possibility.Another explanation is offered for the peculiar instance of PEBG-induced inhibition of protein incorporation. I t is possible that there is present in the medium an unknown substance which reacts with the PEBG to form an inactive complex ; inactive toward inhibition of protein synthesis, it would be active toward inhibition of COa release. Once 8 pmoles of PEBG were added, all of the unknown substance would be complexed and further addition of PEBG would result in the sudden drop in incorporation seen in Fig. 2. It was originally thought that this unknown substance might be glucose, since there are 8 pmoles of glucose present in each incubation flask. The data in Table IV show the fallacy of this assumption.Summary. Leucine-C14 was utilized to study the affects of 2 oral hypoglycemic agents (tolbutamide and phenethylbiguanide) on protein metabolism. Both compounds were seen to inhibit CI4O2 production and incorporation of the amino acid into protein by rat liver homogenate. Differences in the mode of inhibition are noted and discussed. Neither compound appears to be dependent on the presence of glucose for its in vitro affects on protein metabolism.

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