Joseph A. Glennon

Comparative aspects of lipogenesis in mammalian tissues

Abstract Human adipose tissue, unlike that of the rat, has a poor capacity to synthesize fatty acids de novo. The citrate cleavage enzyme is essentially absent from human adipose tissue, and other related lipogenic enzymatic activities are considerably lower and less adaptive than in rat epididymal fat. Studies carried out with monkey liver indicate, indirectly at least, a closer relationship of primate and rat liver. Comparison of lipogenesis in a number of animals indicates that the rat may be a poor experimental model to study the carbon pathway and regulation of lipogenesis.

Failure of trivalent chromium to improve hyperglycemia in diabetes mellitus

Abstract Through the use of a double-blind cross-over investigative method, the effect of trivalent chromium supplements on blood sugar concentrations of normal and diabetic human subjects was evaluated. Four normal and 10 diabetic subjects took 50 μg. of trivalent chromium and a chromium-placebo thrice daily by mouth for 16-week periods. Chromium did not improve hyperglycemia in diabetic patients, and there was no difference in diabetic glucose tolerance measured after placebo and chromium treatment. Normal glucose tolerance was also unaffected. Despite evidence that trivalent chromium may be an essential micronutrient for maintenance of normal glucose tolerance in rats, results of this investigation do not support suggestions of a similar role in man.

Comparison of some metabolic responses in normal and asthmatic subjects to epinephrine and glucagon

Abstract Nine asymptomatic asthmatic men and 9 normal men were given an intravenous infusion of epinephrine 0.1 μg per kilogram per minute for 10 minutes. Blood samples were taken every 10 minutes for an hour and analyzed for glucose, free fatty acids, and glycerol. Initial values of these metabolites were similar in both groups, but the rise in glucose was smaller in the asthmatic group. There was no difference in the rise in free fatty acid and glycerol. Six asthmatic men and 9 normal men were given 7 μg per kilogram glucagon intravenously. The blood glucose response was smaller in the asthmatic group, but the difference was not statistically significant. The diminished hyperglycemic response to epinephrine in patients with asthma who were not receiving sympathomimetics or corticosteroid drugs and who were asymptomatic at the time of the study indicates that asthma itself is associated with a diminished glycemic response to epinephrine.

Effect of a short period of cold exposure on plasma FFA level in lean and obese humans.

Abstract Plasma FFA level rose in normal weight control and to a lesser degree in obese women when they were exposed to cold at 4–6°C for a period of 30 minutes. This rise, in lean subjects, of plasma FFA was eliminated by pretreatment with either nicotinic acid or propranolol. The response to cold was a biphasic one with an early fall in plasma FFA level followed by a rise. The rise in plasma FFA appears to be catecholamine induced, and the absence of significant change in blood glucose would suggest that norepinephrine may be the stimulus. The biphasic nature of the response to cold suggests a favoring of utilization to mobilization of FFA early and the reverse later. The difference in the response noted in obese women may represent a decreased responsiveness, but possibly may be due to an insulating effect of adipose tissue mass.

Enzyme Studies in Human Liver and Adipose Tissue

DURING an investigation of metabolic and hormonal control mechanisms in humans, a number of potentially adaptive enzymes in human liver and adipose tissue were investigated with regard to their possible regulatory function.

Evaluation of an epinephrine test in obesity

In 38 healthy normal weight controland 106 obese subjects measurements were made of serum PBI, fasting plasma free fatty acid (FFA) level and level of FFA 30 minutes after injecting 0.5 mg. aqueous epinephrine subcutaneously. Serum PBI level did not significantly differ in the groups suggesting independence from body weight. Fasting FFA level increased with weight, a finding not exlained by this study. The rise in FFA following epinephrine decreased as body weight increased. The proportion of control and obese subjects with a rise in FFA less than 300–400 μEq./L. was the same. It has been claimed that a diminished or absent response of FFA to a fixed subcutaneous dose of epinephrine defines a category of “metabolic” obesity. On the basis of this study it would appear that decreased response in a similar number of control and obese indicates the variation inherent in a test of this kind rather than a metabolic defect. The diminished response with increasing weight appears to reflect the response of larger subjects to a fixed dose of epinephrine rather than impaired mobilization of FFA.

Kinetische Untersuchungen des Glucosestoffwechsels: II. Glucosepool, Glucoseumsatz und Cori-Cyclus bei Adipositas

ZusammenfassungKinetische Untersuchungen des Glucosestoffwechsels wurden bei 18 fettsüchtigen Patienten durchgeführt. Wie bei normalen Versuchspersonen zeigte auch bei der Adipositas der Glucosepool eine direkte Abhängigkeit vom Körpergewicht, war jedoch berechnet als g/kg signifikant erniedrigt. Eine solche Berechnung erscheint wegen der großen Verschiebung in den Proportionen des fettsüchtigen Körpers zugunsten des Fettgewebes nicht zulässig. Bezogen auf fettfreies Körpergewicht war der Glucosepool bei der Fettsucht normal, der Glucoseumsatz war jedoch erniedrigt, obwohl kein manifester Diabetes mellitus nachweisbar war. Fettsüchtige Diabetiker hatten gegenüber normalen und fettsüchtigen nichtdiabetischen Patienten einen vergrößerten Glucosepool und zwar nicht aufgrund eines erweiterten Poolvolumens, sondern aufgrund einer erhöhten Poolkonzentration. Der Glucoseumsatz war jedoch insgesamt pro Person und Stunde bei allen fettsüchtigen Individuen normal, gleichgültig, ob ein Diabetes mellitus bestand oder nicht. Offenbar stellt die erhöhte Glucosekonzentration im Pool des Diabetikers einen kompensatorischen Mechanismus dar, der einen normalen Ruheumsatz erlaubt.SummaryKinetic studies of glucose metabolism were performed in 18 obese patients. The size of the glucose pool was directly related to body weight as it was the case in normal subjects, but significantly smaller per kg of body weight. However, these calculations seemed not to be valid since in obesity the proportions of the body are — due to the accumulation of fat — distorted in such a way that they cannot be compared to normal. For this reason, the lean body weight has been determined and was used as a basis for calculating the metabolic data. Then, the glucose pool was normal in obesity, the glucose turnover was, however, significantly reduced.In obese diabetic patients glucose pool size was expanded due to an elevation of pool concentration rather than to an increased pool volume. Total glucose turnover was normal (12 gms/hr). This suggestes that the higher glucose concentration in the diabetic pool may represent a compensatory mechanism to shift a normal glucose turnover across an increased metabolic threshold.

Protein Metabolism in Thyroid Glands of Euthyroid, Thiouracil-fed and Hypophysectomized Rats after Cortisone Treatment

Summary Chronic administration of cortisone (5 mg/day) to hypophysectomized pituitary replaced rats resulted in decreased: (a) body weight; (b) thyroid weight; (c) incorporation of 3H-leucine into thyroid protein; and (d) an increase in liver weight similar to that seen in unoperated rats injected with adrenocorticoids. These data indicate that cortisone is equally effective in intact and hypophysectomized rats receiving pituitary replacement therapy but argue against a major pituitary involvement. Incubation of thyroid gland lobes in vitro with 3H-inulin indicated that the extracellular gland space of thiouracil-fed rats was markedly reduced below that of either euthyroid or euthyroid plus cortisone animals (p>0.01). When thiouracil-fed rats were given cortisone their gland inulin space was not reduced as much, although it was still significantly smaller (p>0.05) than that of glands from rats of either euthyroid group. Cortisone treatment, however, had no effect on the inulin space in glands of euthyroid animals. The ability of 3H-cycloleucine to enter the thyroid gland intracellular pool under in vitro incubation condition was unaffected by any of the prior in vivo treatments. It is suggested that chronic cortisone treatment may affect thyroid gland protein biosynthesis indirectly by altering its available supply and pattern of amino acids.

Kinetische Untersuchungen des Glucosestoffwechsels bei der Adipositas

Im Jahre 1962 wurde von Gordon u. Mitarb. [1] berichtet, das die Ausatmung von radioaktivem Kohlendioxyd nach der Injektion von Glucose-C14 bei fettsuchtigen Personen erniedrigt sei. Die enge Beziehung zwischen Diabetes mellitus und Adipositas ist allgemein bekannt: altersdiabetische Patienten sind haufig ubergewichtig, fettleibige Personen weisen in 60 bis 70% einen pathologischen Glucosetoleranztest (GTT) auf [2, 3]. Als es sich zeigte, das Insulinspiegel und Insulinsekretion nach Glucose [4] oder Glucagon [5] bei der Adipositas erhoht waren, lag es nahe, im Zusammenhang mit dem von Vallance-Owen [6] beschriebenen erhohten Synalbumin-Insulinantagonismus, der sich gegenuber der Muskulatur, nicht aber gegenuber dem Fettgewebe nachweisen last, einen verstarkten lipogenetischen Stimulus auf das Fettgewebe abzuleiten. Isolierte Fettzellen fettsuchtiger Patienten sind jedoch relativ unempfindlich gegenuber Insulin und die erhohten Insulinspiegel in ihrem Plasma scheinen sich nach Gewichtsreduktion zu normalisieren [7], so das die Beziehungen zwischen Fettsucht, Hyperinsulinismus und Diabetes mellitus erneuter Uberlegungen bedurfen.