Theodore E. Weichselbaum

Comparative utilization of fructose and glucose given intravenously.

Summary In 10 experiments on human subjects comparative intravenous injections of 10% glucose and 10% fructose were carried out. Even at rapid rates of infusion very little fructose appeared in the urine as compared to the amount of glucose. Diuresis was also less pronounced with fructose. Moreover, the fructose infusions were not followed by either hyperglycemia nor by an excessive rise in the blood fructose level, thus indicating a more rapid utilization of fructose and presumably more rapid glycogenesis.

A New Method of Flame Photometry.

Summary A new type of atomizer-burner system is described for use in flame photometry which accomplishes consistently accurate quantitative chemical analysis of sodium, potassium, and other cations.

Isolation and identification of adrenocortical steroids in human peripheral blood: II. Isolation of the Naturally Occurring Acetates of Cortisol and Corticosterone and the Quantitative Distribution of Cortisol Acetate, Cortisol and Corticosterone in Normal Human Blood

Abstract Cortisol acetate and corticosterone acetate were isolated from large quantities of normal human peripheral blood and identified by infrared spectroscopy. It has been demonstrated that 50% or more of the “Porter-Silber chromogens” present in circulating whole blood are cortisol acetate. Heparinized whole blood, when collected in glass containers and allowed to stand for 30 minutes at room temperature, contains only 15–30% of the cortisol acetate present in whole blood shed directly into a protein precipitating solvent mixture. Results are presented which indicate that free cortisol is present only in plasma, while cortisol acetate and 17-deoxycorticosteroids are distributed between red cells and plasma.

A method for the enzymic determination of corticosteroids in extracts from whole blood, plasma and urine

An enzymic procedure based on the reduction of the 20-oxo group of corticosteroids by 20β-hydroxysteroid dehydrogenase (20β-SD) and the simultaneous oxidation of stoichiometric amounts of DPNH to DPN has been modified and applied to the quantitative measurement of corticosteroids in extracts from biological fluids. Experimental data are presented concerning the specificity, sensitivity and accuracy of this procedure. Selective solvent partition techniques allow to differentiate between 17-hydroxycorticosteroids and 17-deoxycorticosteroids, possessing the C-20-oxo group. Esterification at carbon 21 prevents the enzymic reaction. Certain applications and advantages over other methods of corticosteroid analysis are discussed.

Human Metabolism of Orally Ingested Glycyrrhetinic Acid and Monoammonium Glycyrrhizinate.

Summary Orally administered glycyrrhetinic acid and monoammonium glycyrrhizinate were poorly absorbed from the gastrointestinal tract as indicated by blood, bile and urine levels of radioactivity. The bulk of fed materials are excreted directly in the feces, and, in the case of G.A., at least in part as unchanged compound. Small quantities of glycyrrhetinic acid have been isolated from urines of subjects fed each of above compounds. Many problems relating to stereoisomerism of G.A. remain to be clarified.

Effect of citrus bioflavonoids on metabolism of hydrocortisone in man.

Summary Administration to normal humans of certain phenolic compounds, such as citrus bioflavonoids and N-acetyl-p-aminophenol (NAPA) significantly decreased the rate of disappearance from the plasma of parenterally administered hydrocortisone. The authors acknowledge the cooperation of Drs. H. H. Weathers, J. E. White and L. M. Harlow, Jr. and thank Joanne Roberts, Christine Olah, Leon Ashford and Lawrence La Valle for valuable technical assistance.

Hyperglycemia in Response to Hypoglycemia in Normal and Hypophysectomized Dogs

Somogyi 1 has observed on diabetic as well as on non-diabetic human beings that hypoglycemia is followed by a compensatory hyperglycemia, After hypoglycemia in the postabsorptive state the blood sugar rises and in many cases temporarily exceeds the fasting level. In other words, there is a hyperglycemia relative to the fasting blood sugar. This phenomenon has not been generally noted because most workers do not observe the course of the blood sugar level long enough following hypoglycemia. We report here the occurrence of the same phenomenon in normal and in hypophysectomized dogs, observed during studies of their carbohydrate metabolism. Hypoglycemia was produced by 2 different procedures: (1) by oral or intravenous administration of glucose; (2) by intravenous injection of moderate doses of insulin. In the first type of experiment, several hours after the administration of glucose the blood sugar fell below the fasting level, and this hypoglycemia was followed by hyperglycemia within 6 hours after the administration. It may be seen in Table I that the compensatory hyperglycemic response after hypoglycemia occurred in hypophysectomized animals about as in the normals. In the second group of experiments, hypoglycemia that did not reach the convulsive level was the result of the injection of insulin in moderate doses. As shown in Table II, the compensatory hyperglycemic response again appeared, as after the hypoglycemia elicited by the administration of glucose, both in normal and in hypophysectomized dogs. Instances of hyperglycemia in response to hypoglycemia are to be found in blood sugar curves after the injection of insulin, in experiments reported by Lucke, Heydeman and Hechler.

Effect of diet on glucose tolerance of normal and hypophysectomized dogs.

Kageura 1 reported that dogs utilized glucose at a slower rate than normal following a high fat-low carbohydrate diet. Certain of the animals showed diabetic glucose-tolerance curves. The bearing of the results on problems of therapy in diabetes mellitus seemed of sufficient import to warrant repetition of the experiments. Accordingly 9 normal dogs were fed for 7 to 14 days on a diet consisting of 100 gm. of fat and 350 gm. raw lean meat daily. Six of the animals were then given 0.85 gm. of glucose per os and 3 of them 1.5 gm. of glucose intravenously per kilo of body weight and their glucose tolerance determined by blood analyses made according to the method of Shaffer and Somogyi 2 at the intervals indicated in the table. The same animals were then given a low fat diet consisting of 100 gm. cane sugar, one liter skimmed milk and 300 gm. whole wheat bread daily for 14 days. Then their glucose tolerance was again determined. The results are shown in Table I. They demonstrate that American dogs do not exhibit any consistent difference in their glucose tolerance after a high fat-low carbohydrate diet as contrasted with a low fat-high carbohydrate diet. In no instance in this small series was there any decrease in glucose tolerance on a high carbohydrate diet. In some of the animals there was a definite improvement. The suggestion that the difference in response of Japanese and American dogs may be related to a normal difference in their diets naturally presents itself. Japanese dogs are fed on a relatively high carbohydrate diet. The effect on glucose tolerance of a high fat-low carbohydrate and a low fat-high carbohydrate diet was determined in 8 hypophysectomized animals within 2 months following the operation in the same manner as outlined above for normal dogs. Four of these animals had been previously studied as normal dogs.

Quantitative Assay of Insulin Effect

In the post-absorptive state the constancy of the blood sugar level is an expression of a well-maintained balance between glycogenolysis and the withdrawal of sugar from the blood stream. The fall of the blood sugar level subsequent to an injection of insulin is regarded as the result of an inhibition of the glycogenolytic process, the withdrawal of blood sugar going on unaltered. 1 , 2 , 3 The degree to which the blood sugar is lowered is not in direct proportion to the insulin dosage. 4 One may increase the insulin dosage considerably in the lower and higher ranges with little or no increase in the degree of blood sugar depression. The effect of the larger dose expresses itself in a maintenance of the maximum depression for a longer time period and in a slowing of the rate of return to the initial level. It follows that the effect of injected insulin lasts as long as the blood sugar is below the post-absorptive level. The quantitative determination of insulin action must, therefore, involve the measurement of both the intensity of blood sugar depression and its duration. The times chosen by MacLeod and his coworkers 5 for determining blood sugar as a measure of insulin effect are suitable on the basis of the above postulate when relatively large doses are employed (0.5 units per kilo or over). Himsworth 6 has sought to measure the sensitivity of man to insulin by measuring the area enclosed by the depression curve below the resting level for the first 15 minutes. Scott and Dotti (loc. cit.) measured insulin response in terms of blood sugar depression at what they regard as optimum interval : 30 minutes after administration.

Effect of Diet on Insulin Response in Normal and Hypophy-sectomized Dogs

In another paper 1 are described the effects of high fat-low carbohydrate and low fat-high carbohydrate diets on the glucose tolerance in normal and hypophysectomized dogs. We report here the effect of similar diets on the insulin response of such animals. Ten normal dogs were fed from one to 3 weeks on a diet consisting of 100 gm. of fat and 350 gm. raw lean meat daily. The animals were then given 0.5 units of insulin per kilo of body weight intravenously and their response to insulin determined by blood sugar determinations made at the intervals indicated in the table. The same animals were then given a low fat-high carbohydrate diet consisting of 100 gm. cane sugar, one liter of skimmed milk and 300 gm. of whole wheat bread daily for a similar time period. Their insulin response was again determined. The results are presented in Table I. Their analysis shows no consistent effect of change in diet on insulin response. Six hypophysectomized dogs within 2 months following the operation were given the above diets for similar time periods and their insulin response again determined. Three of the dogs of this series had been used before in the normal series. The results are presented in Table II. The animals studied show definitely without exception better insulin response after the low fat-high carbohydrate than after high fat-low carbohydrate diet.