Wolfgang J. Brech

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.

Studies on pyruvate carboxylase in rat and human liver

Abstract Pyruvate carboxylase in rat and human liver was assayed by a sensitive and specific [2-14C]pyruvate-oxaloacetate exchange reaction. The final product [2-14C]-aspartate was identified by high-voltage electrophoresis and autoradiography. Studies on the subcellular distribution of pyruvate carboxylase indicated that the majority, if not the entire enzyme activity, was located in the mitochondrial fraction of both rat and human liver. Phosphoenolpyruvate carboxykinase was identified in both the mitochondrial and cytosol fractions of human liver which is in contrast to the specific cytosol location in rat liver. The activity of pyruvate carboxylase in rat-liver mitochondria and cytosol was not influenced by the production of alloxan diabetes.

Die physiologische Rolle des Fettgewebes

ZusammenfassungDas Fettgewebe stand in jüngerer Zeit aufgrund seiner hohen Aktivität im Kohlenhydrat- und Fettstoffwechsel im Mittelpunkt zahlreicher Forschungsarbeiten. Es wird versucht, die physiologische und biochemische Rolle des Fettgewebes zu umreißen. In einem Organismus, der auf eine diskontinuierliche Zufuhr von Nahrung eingestellt ist, muß ein Gewebe, dessen Spezialität die Speicherung und Mobilisierung von Energie ist, einen hervorragenden Platz im Stoffwechselgeschehen einnehmen. Insulin, das Hormon der Lipogenese par excellence, kontrolliert beide Vorgänge, die Speicherung und Mobilisierung von Fett, und verknüpft sie eng mit dem Stoffwechsel der Kohlenhydrate. Dies geschieht auf der einen Seite durch eine Steigerung der Glucoseverwertung und damit erhöhte Bildung von Acetyl-CoA und Co-Fermenten zur Fettsäuresynthese sowie von α-Glycerophosphat, das die Veresterung der Fettsäuren und ihre Deponierung als Triglyceride ermöglicht, auf der anderen Seite durch einen direkten hemmenden Einfluß auf das lipolytische System des Fettgewebes. Dem Insulin stehen zahlreiche Faktoren gegenüber, die eine Mobilisierung von Fettsäuren bewirken, wie das sympathische Nervensystem, Adrenalin und Noradrenalin, ACTH und das Wachstumshormon. Ein ausgewogenes Gleichgewicht von Fettsäureveresterung und -freigabe, das sich je nach Stoffwechsellage nach beiden Seiten verschieben läßt, ermöglicht es dem tierischen Organismus, sich an extreme Schwankungen der Energieversorgung und des Energiebedarfs zu adaptieren. Die biochemischen Grundlagen dafür werden ausführlich dargelegt und die Rolle der Fettsäuren im Energiehaushalt unterstrichen.Die Kenntnis dieser Stoffwechselzusammenhänge ermöglicht das Verständnis der verschiedensten Stoffwechselerkrankungen. Es werden besonders die Verhältnisse bei Fettsucht und Diabetes mellitus hervorgehoben und die Entstehung der diabetischen Ketoacidose beschrieben.SummaryIn recent years, the high activity of adipose tissue in fat and carbohydrate metabolism has been increasingly emphasized in scientific studies. It is conceivable that a tissue specialized in storage and release of energy-rich material will be of extreme importance to an organism adapted to discontinuous food supply. Both storage and mobilization of fat are under the immediate control of insulin, the hormone of lipogenesis par excellence, and are thus closely related to carbohydrate metabolism. Stimulation of glucose metabolism by insulin results in an increased formation of acetyl-CoA and of Co-factors necessary for fatty acid synthesis as well as of α-glycerophosphate for fatty acid esterification and deposition. Insulin also shows a direct inhibitory action on the lipolytic system of adipose tissue. There are, on the other hand, numerous factors promoting fatty acid mobilization, such as the sympathetic nervous system, epinephrine and norepinephrine, ACTH and growth hormone. A close equilibrium — which may be shifted into either direction to enable the organism to adapt to extreme changes in energy supply and energy need — has been established between fatty acid esterification and fatty acid release. The biochemical background of these regulations is discussed in detail and the role of fatty acids in energy metabolism is pointed out.The knowledge of these metabolic events is necessary to understand diseases related to fat metabolism, such as obesity, diabetes mellitus and the development of diabetic ketoacidosis.

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.

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.