Effect of vinblastine on the insulin-receptor interaction in mammalian heart muscle.
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Animals↗
Biomedical subjects
H Reinauer
Publications and source records attributed to H Reinauer.
Metabolic performance and insulin binding of mammary cells isolated from Wistar and Zucker rats.
A method for the isolation of cells from lactating mammary gland tissue of rats is described. Metabolic properties of mammary cells isolated by the described method either from Wistar of Zucker rats as well as insulin binding were studied. Whereas synthesis of protein and lipid showed no significant differences, the rate of glucose oxidation is slightly increased in cells isolated from Zucker rats. Incorporation of (14)C-uridine in the RNA-fraction is stimulated by insulin; the half-maximal concentration is given by 5 x 10(-10) mol/1). Specific binding of insulin to both types of cells can be described by a nonlinear Scatchard-plot. The apparent affinity constants for the high affinity receptors (1 x 10(-10) mol/1) correlate well with the described metabolic effect of insulin on RNA-synthesis. The total capacity for insulin binding is reduced in cells isolated from Zucker rats when compared to those from Wistar rats.
Animals↗
[The effect of insulin on the metabolism of isolated rat glomeruli (author's transl)].
Glomeruli isolated from the kidneys of metabolically normal and diabetic rats were investigated morphologically and metabolically. Glomeruli from chronically diabetic animals showed significantly increased contents of DNA and protein, and an altered DNA/protein ratio. These changes were prevented by insulin treatment in vivo of diabetic rats. Insulin had no effect on glucose degradation by the glomeruli of normal or diabetic rats. Protein synthesis is unchanged in the glomeruli from acutely diabetic rats, but shows a significant increase in those from chronically diabetic animals. In the glomeruli of normal animals, both protein synthesis and RNA synthesis are increased in vitro by insulin, but this effect is absent from the glomeruli of diabetic rats. Under in vitro conditions there is a resistance to insulin. Changes in protein and RNA synthesis can be prevented by insulin only when it is administered in vivo. In addition, the incorporation of lysine and uridine in the glomeruli of normal animals was dependent on the glucose concentration. It is concluded from these results that insulin deficiency and increased blood sugar level are accompanied by characteristic changes in the metabolism of protein and RNA, which are related to morphologically and biochemically detectable structural changes.
Animals↗
Effect of phenformin on the metabolism of glucose, pyruvate and acetate in guinea-pig heart.
In the isolated perfused heart of the guinea-pig, phenformin could be shown to have a characteristic effect on cardiac performance and metabolism. In the working heart, phenformin (1 mmol1/1) decreased dp/dt and increased the end diatolic pressure; this reduced heart performance could not be explained by changes in the content of energy-rich compounds. Furthermore, phenformin increased lactate production in hearts perfused with glucose as substrate and inhibited the utilisation of pyruvate, but not of acetate. The activity of the purified pyruvate dehydrogenase complex was not influenced by phenformin, but the active form of the pyruvate dehydrogenase complex (PDHa) was diminished. This effect may be explained by an inhibition of the pyruvate dehydrogenase phosphatase. An inhibition of pyruvate dehydrogenase and, coincidently, of oxygen consumption might contribute to the development of lactic acidoses and, particularly, might be deleterious for the heart.
Adenine Nucleotides↗
[Localization of the degradation of injected maltose].
The major maltase activity was found in the kidneys, followed by liver, muscle and blood. Only low maltase activity has been found in adipose tissue, muscle, and brain. The pH-optimum of kidney maltase was at pH = 6.0, the Michaelis-Menten Constant was measured to be 15.6 X 10(-3) mol/l. Even with a dose of 200 mg maltose/100 g body weight saturation of the hydrolysing system could not be attained in living rats. In nephrectomized rats the maltose oxidation was reduced to 55%. Only 0.2% of the applied maltose is excreted into the bile. According to our results the following main pathway of metabolism of maltose is suggested: glomerular filtration of maltose, hydrolysis of maltose to glucose by maltases which are localized in the membrane of the kidney brush borders, absorption of glucose, oxidation of glucose to CO2. In addition an extrarenal maltase activity is considered in the liver. The metabolism of injected trehalose was only 10% when compared with the metabolism of maltose.
Animals↗
Myofibrillar protein degradation and muscle proteinases in normal and diabetic rats.
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Aminopeptidases↗
[Use of maltose and a mixture of maltose, fructose and xylitol in parenteral feeding].
Maltose or maltose in combination with fructose and xylitol was administered intravenously to eight healthy male subjects. Constant maltose levels could not be attained in the blood at an infusion rate of 0.125 g maltose/kg body-weight and hour. Maximal concentrations of maltose were found at the end of the infusion period. 8.6 +/- 1.2% of the administered radioactivity was excreted into urine within 8 hours. Regarding the enzymatically determined maltose and glucose, the maltose balance was more favorable with the loss of only 3--3.5% carbohydrates into urine. The highest oxidation rate of the administered maltose was 1.5 g maltose/human volunteer and hour. During the experimental period of 8 hours 7.4 g maltose, corresponding to 37% of the applied dosis of the disaccharid, has been oxidized to and excreted as 14CO2. Xylitol and fructose did not effect utilisation and balance of maltose. Only the urinary excretion of glucose was higher when the combined solution was applied. At a limited infusion rate (0.125 g maltose/kg body-weight and hour) maltose or the combined solution maltose--xylitol--fructose may be recommended for parenteral nutrition.
Adult↗
Purification and some properties of an alkaline proteinase from rat skeletal muscle.
1. Rat skeletal muscle was homogenized in 0.05M-Tris/HCl, pH 8.5, containing 1M-KCl. Myofibrillar proteins were precipitated by addition of (NH4)2SO4 (33% saturation). 2. The alkaline proteolytic activity that was precipitated with the myofibrillar proteins was solubilized with trypsin (conjugated to Sepharose) and further purified by affinity chromatography, ion-exchange chromatography and gel filtration. 3. The purified enzyme migrates as a single band in polyacrylamide-disc electrophoresis, and has optimum hydrolytic activity with azocasein and [14C]haemoglobin as substrates at pH 9.4 and 9.6 respectively. Its apparent molecular weight, as determined by gel filtration on Sephadex G-75, is 30800. 4. The purified alkaline proteinase is strongly inhibited by equimolar amounts of soya-bean trypsin inhibitor and ovomucoid, whereas di-isopropyl phosphorofluoidate and alpha-toluenesulphonyl fluoride have no effect. On the other hand N-ethylmaleimide and p-chloromercuribenzoate have inhibitory effects on the enzyme activity. 5. Bivalent metal ions (Fe2+, Co2+, Zn2+, Mg2+, Mn2+) diminish the proteolytic activity, at 1mM concentrations. Ca2+ ions and the metal-ion-chelating agent EDTA are without effect on enzyme activity. 6. The enzyme is part of the alkaline proteolytic activity that appears to be associated with myofibrillar proteins.
Animals↗
Insulin effect on proteolytic activities in rat skeletal muscle.
Proteolytic activity has been measure in rat skeletal muscle by use of [14C]-hemoglobin as substrate. The activity of the alkaline proteinases increases during starvation and in diabetic state. In streptozotocin-diabetic animals the activity of alkaline proteases increases to 300% over a time of 21 days. Insulin treatment reverses the enhanced enzyme activity to normal level.
Adenosine Triphosphatases↗
[Human catabolism of medium and long chain triglycerides after intravenous infusion].
The metabolic rate of intravenously administered middle-chain and long-chain triglycerides has been tested in metabolically healthy adult subjects. After an infusion period of three hours (infusion rate 0.22 g triglyceride/kg body-weight and hour) the metabolic rate of long-chain triglycerides was 16.4 mg/kg body-weight and hour. The metabolic rate of the middle-chain triglycerides (infusion rate 0.056 g/kg body-weight and hour) administered in a mixture with long-chain triglycerides was slower: 4.8 mg/kg body-weight and hour. Even under these conditions, middle-chain triglycerides increased ketonemia and ketonuria. Furthermore, the acetate level in blood increased significantly. Infusion of lipids have a strong effect on amino-acid levels in blood. The concentration of alanine, leucine, isoleucine are decreased, whereas the concentration of glutamate increases at the same time. Under clinical parameters only a mild leucocytosis has been found. Our data suggest that the metabolic rate of middle-chain triglycerides is according to their low plasma concentration slow, nevertheless, the ketogenesis is significantly higher if middle-chain triglycerides are infused in a mixture with long-chain triglycerides.
Acetates↗
[Absorption and oxidation rate of arginine and malate (author's transl)].
Six normal volunteers received L-Arginin and DL-Malat p.o. in order to test absorption and utilisation of these compounds. Both compounds are almost completely reabsorbed from the intestine and then metabolized. Only about 2% of the arginine applied are recovered in the urine. 15% of arginine and 45% of malate applied are metabolized within 8 hours. If absorption is unimpaired oral therapy of hyperammoniemia would require application of the malate-arginine solution for every 3 hours, if constant plasma levels are to be achieved.
Adolescent↗
Utilization of maltose and oligosaccharides after intravenous infusion in man.
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Blood Glucose↗
Thiamine pyrophosphokinase activity in liver, heart and brain crude extracts of control and thiamine deficient rats.
The activity of thiamine pyrophosphokinase has been measured in liver, heart muscle and brain of normal and thiamine deficient rats. The activity measurement has been performed by use of thiamine-35S as substrate and separation of the reaction products by high voltage electrophoresis. KM has been determined as 7.1.10(-6) mol/l. The activity of thiamine pyrophosphokinase is reduced in liver and heart muscle of thiamine deficient rats significantly, whereas no decrease of the enzyme activity has been found in the brain. The content of thiamine pyrophosphate has been measured in the liver of normal and thiamine deficient rats. Injection of thiamine to deficient rats normalized the content of thiamine pyrophosphate in the liver within 6 hours. Our data suggest that thiamine pyrophosphokinase is an adaptive enzyme, the activity of which depends on the thiamine content of the cells.
Animals↗
Regulation of the pyruvate dehydrogenase activity in the isolated perfused heart of guinea-pigs.
The activity and the interconversion of the between the pyruvate after pyruvate should read: utilization in the perfused hearts and the pyruvate dehydrogenease complex has been measured in the isolated perfused working hearts of guinea-pigs. 1. The pyruvate dehydrogenase complex is transferred into the active form by high work, in anoxia, with 2,4-dinitrophenol and by perfusion without substrate. The rate of interconversion is faster in the perfused heart than in the homogenate. 2. The active form of the pyruvate dehydrogenase complex limits the pyruvate oxidation. There is a close correlation between the pyruvate utilization in the perfused hearts and the pyruvate dehydrogenase of the active form in the homogenates of the same hearts. 3. The "adenylate energy charge" of the cells is considered as the main regulating factor of the interconversion of the pyruvate dehydrogenase complex as seen in experiments with anoxia, dinitrophenol and high work. The inactivation of the pyruvate dehydrogenase complex by acetyl CoA can be overcome by decreasing ATP/ADP ratios.
Acetates↗
Activity of pyruvate dehydrogenase complex in the mammary gland of normal and diabetic rats.
After parturition there is a 10 fold increase in the actual and total activity of the PDH complex in the mammary gland, which can be explained by an increased amount of enzyme protein. There is a marked difference between the activity state of the PDH complex in the suckled and unsuckled gland of the same animals. In fasting rats the active form of the PDH complex is decreased. This effect is further enhanced by inhibition of suckling. In the diabetic state the PDHa activity is reduced, but the change is statistically insignificant. The decreased milk production during diabetes results from the reduction of the total mass of gland. The total activity of the PDH complex is the same in fetal and neonatal liver of the rat. Whereas the PDH complex is fully activated before parturition, there is a significant decrease in the active form of the pyruvate dehydrogenase complex in the liver of the newborn rats.
Animals↗
[The catabolism of infused maltose in man].
The use of intravenously administered maltose was tested in 9 healthy human subjects and 3 insulin-dependent diabetic patients. The concentration of the blood sugar has not been influenced by the administered maltose. The concentration of maltose in the blood increases up to 170 mg/100 ml blood depending on the rate of the maltose infusion. The excretion of maltose in the urinis correlated with the applied dosis and with the blood maltose concentration. Under our experimental conditions 20 to 30% of the administered maltose have been excreted and 7.5 to 23.4% have been oxidized within 8 hours. The highest rate of degradation was about 40 mg maltose/min/human subject and is reached 2 hours later than the peak concentration of maltose in the blood. The metabolism of maltose is reduced in insulin-dependent diabetic patients. In these patients only 3% of the applied maltose have been oxidized and 51% excreted in the urin within 8 hours. Therefore, this disaccharide cannot be recommended as carbohydrate source of parenteral nutrition in insulin-dependent diabetic patients. The balance of intravenously administered maltose is not satisfactory in healthy adult humans, too. Infusion of maltose solutions have no real advantages over the infusions of oligosaccharide solutions.
Adult↗
[Utilization of xylitol in the isolation-perfused myocardium of the rat].
1. In the rat heart muscle, only 3 to 4% of the oxygen-consumption can be referred to xylitol utilization. With xylitol as only substrate the heart is working under substrate deficiency conditions. 2. Diabetes mellitus does not improve the xylitol utilization in the rat heart muscle. 3. The data are compared with the activities of xylitol degrading enzymes in the heart muscle.
Animals↗
[Influence of heart work and substrate uptake on the regulation of pyruvate dehydrogenase activity in isolated guinea pig hearts (author's transl)].
In isolated guinea pig hearts performing a defined stroke work, the influence of heart work and substrate uptake on the interconversion of pyruvate dehydrogenase (PDH) was studied. When hearts from fasted animals are perfused with a salt solution containing 10mM glucose, an increase in cardiac output and aortic pressure effects an increase in active PDH from 50 to 74% of total PDH activity and a decrease in tissue content of energy-rich phosphates. Pyruvate turnover calculated from oxygen consumption corresponds with PDH activity. Under these experimental conditions, PDH activity might either represent the rate limiting step of oxidative glucose breakdown, or it might be adjusted to a flux rate controlled by other factors. In fed animals, PDH activity exceeds the pyruvate turnover. However, an increase of heart work raises the active PDH from 76 to 95%. Addition of 10 mM acetate to the perfusion medium decreases PDH activity and glucose uptake. In fed animals, an increase of heart work raises the active PDH from 43 to 59% only, whereas in fasted animals this effect is abolished. The effect of changes in heart work on PDH interconversion might be explained by changes in energy-rich phosphate concentrations. However, substrate uptake and nutritional state may interfere or even abolish this effect.
Acetates↗