[Parameters of energy and nitrogen metabolism in rats under insulin-induced hypoglycemia].

Repeated severe insulin-induced hypoglycemia in rats has led to an increase in aminotransferase, glutaminase, and glutamate dehydrogenase activities in the liver; protease activities in tissues; and in blood serum levels of free fatty acids, urea, and uric acid. These changes are indicative of gluconeogenesis activation in animals exposed to hyperinsulinization. Decreased rates of glycolysis and glycogenolysis, reduced activities of NADP-dependent dehydrogenases, and substantial changes in the activities of enzymes responsible for metabolism of nucleotides and transmitter amino acids have been observed in the brain. All these changes are mainly associated with hypoglycemia and activation of the contrainsular system and can play a significant role in pathogenesis of posthypoglycemic encephalopathy.

[Changes of some energy exchange parameters in the rat heart under insulin hypoglycemia].

Hypoglycemic coma induced by administration of a large dose of insulin, was accompanied by the increased rates of glycolysis, glycogenolysis, activity of lactate dehydrogenase, succinate dehydrogenase, isocitrate dehydrogenase, and increased concentration of glycogen. Under these conditions triacylglycerol content decreased administration of the large dose of insulin to rats with alloxan diabetes increased not only rates of glycolysis, glycogenolysis and lactate dehydrogenase activity and also activities of aspartate transaminase and glutamate dehydrogenase. Data obtained suggest the increased utilization of amino acids for energy supply of myocardium under conditions of hypoglycemia induced by insulin adminisration to diabetic animals.

[Rat metabolic parameters in multiple insulin hy- 44poglycemia].

Hypoglycemic coma was induced with 40 U of insulin per kg body weight. The animals experiencing 7 hypoglycemic comas at 2-day intervals and killed during the last coma were found to have elevated serum levels of free fatty acids, urea, and uric acid; hepatic glycogen levels remained normal. In the liver, the activities of aspartate aminotransferase (EC 2.6.1.1), alanine aminotransferase (EC 2.6.1.2), glutaminase (EC 3.5.1.2), glutamate dehydrogenase (EC 1.4.1.3), succinate dehydrogenase (EC 1.3.99.1), and lactate dehydrogenase (EC 1.1.1.27) were enhanced and the rate of lactate generation increased when glucose and glycogen were used as substrates. Such changes were absent in initially healthy animals during the first hypoglycemic coma. They are indicative of increases in the catabolism of amino acids and in the activation of gluconeogenesls in the rats experiencing insulin hypoglycemia many times and they are associated with the stimulation of the contramsular apparatus in hypoglycemia.

[Energy metabolic changes and nerve cell damage in rats exposed to multiple administration of large-dose insulin].

The brains of rats that had experienced 5-7 hypoglycemic comas on day 2 of the rehabilitative period after the last coma showed increases in the activity NAD-isocitrate dehydrogenase and in the catabolism of adenylonucleotides and decreases in the activities ofNADH dehydrogenase, mitochondrial NADP-isocitrate dehydrogenase, glucose-6-phosphate dehydrogenase, glutathione reductase, and superoxide dismutase, and no changes in the rate of glycolysis. Placing the brain slices in the hypoosmolar medium added by Fe2+ and ascorbate caused the higher yield oflactate dehydrogenase into the incubation medium. In this case, there was a significant elevation in the concentration ofmalonic dialdehyde in the brain slices from the experimental rats. The findings suggest that energy metabolic disturbances and activated lipid peroxidation are involved in the pathogenesis of postglycemic encephalopathy.

Glycolysis and oxidtion enzyme activity in rat brain during insulin-induced hypoglycemia against the background of alloxan-induced diabetes mellitus.

Insulin-induced hypoglycemic coma in animals with alloxan diabetes was observed at a higher basal glucose level in the blood compared to healthy animals. It was associated with inhibition of glycolysis and glycogenolysis and decreased activities of succinate dehydrogenase and glutamate dehydrogenase in the cerebral hemispheres and brainstem.

[Hypoglycemia and the brain: metabolism and the mechanisms of neuronal damage]. / Gipoglikemiia i mozg: metabolizm i mekhanizmy povrezhdeniia neironov.

Hypoglycaemia is a widely distributed pathological state, which develops in case of insulinoma of pancreas, alcohol intoxication, lever and gastrointestinal problems [2, 4, 7, 8, 9, 11, 28]. The most important clinic aspect is that it is associated with treatment of diabetes [2, 7, 8, 19, 28]. Hypoglycaemia may lead to irrecoverable damage to neurons and persistent disruption of the cerebral functions--post-hypoglycaemic encephalopathy; therefore, the metabolic changes resulting from neuroglycopenia and their relationship with neurotic disturbances, as well as the biochemical mechanisms leading to irrecoverable damage to cells are of special interest. Hypoglycaemia is a unique possibility to study these mechanisms, because it leads to cell damage even if there is no disturbance of oxygen supply to brain and intracellular acidosis [35, 38, 133].

[Glutamate and peroxidation in the pathogenesis of CNS diseases]. / Glutamat i peroksidnoe okislenie v patogeneze zabolevanii TsNS.

The review summarises literature data on the interrelationship between glutamate and oxidative stress. Certain attention is paid to nitric oxide and its contribution to the oxidative stress. Free radical scavenges attenuate brain damage caused by glutamate neurotoxicity.

[Enzyme activity and level of GABA-shunt substrates in rat brain during repeated exposure to hypoglycemic doses of insulin]. / Aktivnost' fermentov i soderzhanie substratov GAMK-shunta v mozge krys pri mnogokratnom vozdeistvii gipoglikemicheskikh doz insulina.

The activity of glutamate decarboxylase, GABA-, aspartate-and alanine aminotransferases, the content of GABA, glutamate, aspartate and alanine were studied in the brain hemispheres and stem of rats that were undergoing the hypoglycemic coma as well as those rats had undergone 7-9 comas on the second day after the last coma. In hypoglycemia, the brain's content of glutamate, alanine and GABA decreased and content of aspartate increased; the activity of enzymes investigated did not change. On the second day after 7-9th hypoglycemic coma, the decrease of activity of glutamate decarboxylase in hemispheres and the decrease of GABA amount in brain stem were detected. This can be an evidence of decrease of GABA amount produced and secreted by nerve ends of the pathways leading from striata to substantia nigra. The detected changes result from multiple influence of hypoglycemia to the brain and may by important in the development of posthypoglycemic encephalopathy.

[Changes in indices of carbohydrate metabolism in suspended rats]. / Izmeneniia pokazatelei uglevodnogo obmena u krys pri vyveshivanii.

In the experiments with 35 white rats, it is found that on Days 7 and 14 of rat suspension in the head-down position the content of glycogen in both ventricles of the heart is significantly reduced. On Day 7 of the experiment, the glycogen content in m.gastrocnemius and concentration of glucose in the blood are lessened. The level of lactate in the blood and glycogen in the liver and m.soleus is not changed. The mass of body and skeletal muscles is diminished and the mass of ventricles of the heart is not changed.

[Activity of NADP-dependent dehydrogenases and level of recovery of pyridine nucleotides in the rat brain in insulin hypoglycemia and in the recuperative period]. / Aktivnost' NADF-zavisimykh degidrogenaz i uroven' vosstanovlennosti piridinovykh nukleotidov v mozge krys pri insulinovoi gipoglikemii i v vosstanovitel'nom periode.

Activity of NADP-dependent isocitrate- and malate dehydrogenases and the rate of NADP reduction into NAD+ were studied in various rat brain compartments during the hypoglycemic coma and within various periods after the coma cupping using glucose administration. Severe hypoglycemia was accompanied by distinct decrease in content of NADH x H+ in nervous tissue, while the enzymatic activity studied was not altered and content of NADPH x H+ was not decreased. Within the early restoration period activity of cytoplasmic NADP-malate dehydrogenase and content of NADPH x H+ were increased in brain tissue. Production of NADPH x H+ during hypoglycemic coma and after its cupping was maintained in nervous tissue at the adequately high level and did not affect the restoration-related synthesis.

[Intensity of glycolysis and activity of energy metabolism enzymes in rat brain after multiple exposures to hypoglycemic doses of insulin]. / Intensivnost' glikoliza i aktivnost' fermentov énergeticheskogo obmena v mozge krys pri monogokratnom vozdeistvii gipoglikemicheskikh doz insulina.

Changes in the rates of glycolysis, glycogenolysis, activities of pyruvate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinate dehydrogenase, serum glutamic pyruvic and oxaloacetic transaminases in the brain hemispheres and stem of rats exposed to 5-7 hypoglycemic comas were studied. No noticeable changes were detected in glycolysis intensity or activities of Krebs' cycle enzymes in the large hemispheres. The intensity of glycogenolysis and activities of transaminases in the brain stem reduce on day 2 of repair period after the last hypoglycemic coma. The detected changes result from multiple exposures of the brain to hypoglycemia and may be important in the development of posthypoglycemic encephalopathy.

[Changes in some parameters of carbohydrate and lipid metabolism in rats with adrenaline administration in the rehabilitation period after hypokinesia]. / Izmeneniia nekotorykh pokazatelei uglevodnogo i lipidnogo obmena u krys pri vvedenii adrenalina v vosstanovitelnyi period posle gipokinezii.

Changes in the blood levels of glucose, lactate and free fatty acids, and glycogen in the livers and skeletal muscles of rats (n = 47) on epinephrine administration (150 mcg/kg body weight) were studied on Day 7 of a recovery period following hypokinesia of 15 and 30-day durations. In the animals exposed to restrained motor activity, as compared to normal rats, epinephrine has a less effect on glycogen content in the muscle, is not accompanied by increased serum levels of free fatty acids and results in more marked elevation of blood lactic acid levels. Adrenal control of lipolytic processes in the adipose tissue and of glycogenolytic processes in the muscles in the post-hypokinetic recovery period is reduced.

[Enzyme activity and substrate levels of the Krebs cycle in the brain tissue of rats with insulin-induced hypoglycemia and during the recovery period]. / Aktivnost' fermentov i soderzhanie substratov tsikla Krebsa v tkani golovnogo mozga krys pri insulinovoi gipoglikemii i v vosstanovitel'nom periode.

Alterations in enzymatic activity and in content of substrates involved in the Krebs cycle and in content of glutamate were studied in brain of rats with insulin-dependent coma and in various periods of the coma restoration with glucose. After administration of glucose content of the Krebs cycle substrates and succinate dehydrogenase activity, which were lowered during the coma, were not normalized, whereas the content of glutamate and activity of cytoplasmic NAD-dependent malate dehydrogenase were increased in brain. Functional impairments of the nervous system in hypoglycemia and the restoration effect of glucose appear to involve some alterations in glutamate metabolism in brain.

[Changes in the level of Krebs cycle metabolites in the brain tissue in the hypoglycemic nervous syndrome]. / Izmeneniia urovnia nekotorykh metabolitov tsikla Krebsa v tkani golovnogo mozga pri gipoglikemicheskom nervnom sindrome.

Different levels of pyruvate, citrate and alpha-ketoglutarate were investigated in the brain tissue of white rats exposed to insulin-induced coma or in various periods following its glucose-cutting. The emergence of pronounced hypoglycemic nervous disorders was followed by a significant decrease in the content of all mentioned acids. Glucose arrest of insulin-caused coma took place in the presence of inactive initial stages of Krebs cycle (citrate synthesis). Restoration of hypoglycemia-affected brain functions had no correlation with the activated citrate synthesis. The levels of citrate and alpha-ketoglutarate normalized 15 minutes after glucose injection and the pyruvate level augmented 30 minutes after the drug administration. It was suggested that the glucose arresting effect demonstrated in insulin coma was conditioned by transformations in glucose carbon lattice regarding pyruvate carboxylising into oxalacetate with further inclusion into brain amino acids and peptides.