On Insulin Immunologic Activity in Livers and Kidneys of Mice Injected with Beef Insulin.

Abstract

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.

Evidence from Combined Immunoassay and Radioautography Procedures That Intact Insulin-125I Molecules Are Concentrated by Mouse Kidney Proximal Tubule Cells

“…In respect to simplicity, AIS-i25 I estimations are practically as easy to secure as are estimations of TCA insoluble radioiodine, the criterion which has been so much used for "estimation" of "intact radioiodoinsulin" [for references cf Lee (8)]. Good specificity is indicated both by theory and by present findings that AIS-m I disappeared from mouse plasma, kidney and liver appreciably more rapidly than did TCA insoluble 125 I; this agrees with literature reports that no matter whether tissue "insulin" was estimated as insulin radioiodine peaks on paper (7,9), through bio-assay (9), or through immunoassay (10,11), this tissue "insulin" always disappeared more rapidly than did TCA insoluble radioidoine derived from iv injected insulin-131 ! or -125 I.…”

Insulin delivery rate into plasma in normal and diabetic subjects

“…Elgee and Williams (25) have shown that preloading with insulin diminished the rate of insulin-131I degradation in vivo, and that the extent of inhibition was the same regardless of whether the preloading was accomplished with labeled or unlabeled insulin, implying that both types of insulin competed equally well for the degradation system. Beck, Roberts, Blanken-baker, and King (26) have shown that the distribution and rates of accumulation of labeled and unlabeled insulin in various organs and subcellular fractions were similar. Finally, Samols and Ryder (27) have shown that hepatic clearance of exogeneously administered beef insulin was similar to the clearance of endogenous human insulin in human subjects.…”

Degraded and Undegraded Insulin in the Bile of Rabbits After Intravenous Administration of Tracer Amounts of Labeled Insulin

“…Beck et QZ. (15) have recently shown that intact insulin molecules can penetrate the liver cells of mammals. The degradation of insulin in the liver apparently is not total, and this suggests that the liver not only shows a capacity for "taking up" radioactivity from the blood, but can also retain undegraded insulin.…”