Energy Metabolism In Leukocytes Research Articles

The evaluation of intracellular energy metabolism in prediabetic patients and patients newly diagnosed with type 2 diabetes mellitus

Background/aimIncreased susceptibility to infections is a serious problem in diabetics. Impairment in the energy metabolism of the immune system is the main source of the problem. Early diagnosis of the impairment in energy metabolism is crucial. Our study aimed to investigate the energy metabolism in leukocytes in patient groups such as prediabetics and patients newly diagnosed with type 2 diabetes mellitus. Materials and methods Our study included 21 newly diagnosed type 2 diabetic patients (NDDP), 30 prediabetic patients, and 22 adult volunteers. 75 g oral glucose tolerance test (OGTT) was applied to all patients included in the study. Blood samples were taken after 9-16 h of fasting and fasting blood glucose (FBG), postprandial blood glucose (PBG) levels, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), fasting serum insulin, and hemoglobin A1c (HbA1c) levels were evaluated. After the cells were completely lysed, citrate levels from the released mononuclear leukocyte cells (MNC) content were manually studied, and lactate levels were applied to the autoanalyzer with the lactate kit. Lactate and citrate results were calculated as µg/mL. Statistical comparisons were done using Chi-square test, Mann-Whitney U test and student’s t test, and P < 0.05 values were accepted as significant. ResultsA significant difference was found between the controls and the other groups (newly diagnosed diabetic patients (NDDP), impaired fasting glucose (IFG), and impaired glucose tolerance (IGT)) in terms of FBG levels (P < 0.001, P < 0.001 and P < 0.001, respectively). IFG and IGT patients had significantly higher PBG levels compared to the control group (P = 0.009 and P < 0.001, respectively). There was a significant difference between the IFG and IGT patients in terms of insulin levels (P = 0.019). There was a significant relationship between FBG levels and lactate production only in the NDDP group (r = 0.610, P = 0.003)ConclusionThe metabolic effects of hyperglycemia on leukocytes is in direction of anaerobic glycolysis. The increased anaerobic pathway is closely related to blood glucose levels and insulin resistance.

Immune and inflammatory responses in subjects with stable angina and acute myocardial infarction.

associated with systemic inflammation also appear to increase the likelihood of clinically manifest atherosclerotic vascular disease. Acute myocardial infarction (AMI) triggers an intense acute inflammatory response both locally and systemically. However, the differences in systemic immune and inflammatory response between AMI and chronic phase of atherosclerosis are not fully understood. Two papers in the current issue of the journal by Wang and colleagues have used genome wide gene expression in peripheral leukocytes to examine the differences in several inflammation and immunologic related genes between subjects with and without atherosclerosis and, for those with atherosclerosis between those with and without AMI. In the paper by Yan, et al, [2] there was evidence of impaired regulation of T cell activation and proliferation in the AMI group compared with a group of well matched subjects with stable angina (SA), suggesting disregulated immune response in AMI. Given the cross-sectional nature of the study, it is not clear whether any of these changes preceded the acute event. Genes related to mitochondria, electron transport chain, and cellular cation homeostasis were down-regulated, indicating an impaired energy metabolism in leukocytes. In contrast, genes related to inflammatory response, macrophage activation, neutrophil mediated immunity and response to bacterium and DNA damage stimulus were up-regulated in the AMI group compared to the SA group, suggesting an increased inflammatory response and an intense response to tissue damage in AMI. In addition, the up-regulation of positive regulation of the IκB kinase (IKK)/nuclear factor (NF) κB cascade found in the study

Стимулирующее действие низкомолекулярной фракции кордовой крови на энергетический обмен в лейкоцитах

Стимулирующее действие низкомолекулярной фракции кордовой крови на энергетический обмен в лейкоцитах

FETAL MALNUTRITION

Fetal malnutrition has been associated with maturational defect in cell metabolism. A series of studies on anthropometric and clinical aspects of patients with intrauterine malnutrition was conducted to establish the relationship between intrauterine growth failure and cell function. The 1st study assessed intrauterine growth in 128 cases. 36 infants were found to be small for gestational age and exhibited usual signs of fetal growth retardation. The mothers of these infants were similar with respect to age, weight, height, nutritional patterns, and prior pregnancy histories. The 2nd study determined whether there was a unique pattern for certain cell energy function in leukocytes of mothers and their small-for-gestational age infants at the time of birth, and whether this pattern was the same as that found in infants with severe postnatal protein-calorie malnutrition. The findings showed that the altered pattern of energy metabolism in leukocytes of infants with intrauterine growth retardation was the same as that found in young infants with postnatal protein-calorie malnutrition. The similarity of enzyme pattern in the adenine nucleotide contents of maternal and cord blood leukocytes at time of delivery also supported the interrelationship between energy metabolisms of mothers and their fetuses. The 3rd study suggested that fetal malnutrition may be reflected in placental tissues. These studies may prove useful in developing diagnostic tools for monitoring fetal growth and for establishing criteria for intervention.

Activities of enzymes in the malate–aspartate shuttle and the isoenzyme pattern of lactate dehydrogenase in plasma and peripheral leukocytes of lactating Holstein cows and riding horses

The activities of the enzymes involved in the malate–aspartate shuttle and lactate dehydrogenase (LDH) and the pattern of the isoenzymes of LDH were determined in plasma and peripheral leukocytes of lactating Holstein cows and thoroughbred riding horses as representative herbivorous animals. In the horse plasma, LDH activities were significantly lower and AST activities were significantly higher than those in the cow plasma. The specific activities of cytosolic malate dehydrogenase (MDH), LDH and AST in the horse leukocytes were higher than those in the cows. The cytosolic ratio of MDH/LDH activity (ML ratio) in the horse leukocytes was significantly lower than that in the cow leukocytes owing to significantly higher activities of LDH. The ML ratio was considered to reflect the difference in energy metabolism in leukocytes between cows and horses. The plasma LDH isoenzyme patterns of cow and horse showed the characteristic as herbivorous animals with dominance of LDH-1, -2 and -3. The LDH isoenzyme patterns with dominance of LDH-3 and -4 in the horse leukocytes were remarkably different from those in the cow leukocytes. There were significant differences in activities of malate–aspartate shuttle enzymes, ML ratio and LDH isoenzyme patterns in the cytosolic fractions of leukocytes between the lactating cows and the riding horses.

HUMAN FETAL GROWTH RETARDATION: II. ENERGY METABOLISM IN LEUKOCYTES

This study was initiated to determine if there was a unique pattern for certain cell energy functions in leukocytes of mothers and their small for gestational age (IUM) infants at the time of birth. Further, the study attempted to determine if these patterns of cell energy functions were similar to those found in infants with severe postnatal protein-calorie malnutrition. In leukocytes, the protein/DNA ratio (cell size) was larger in the IUM infants (cord blood) and their mothers than in those of the full-term (FT) and premature (AGA) groups. The contents of ATP, total adenine nucleotides, pyruvic kinase (PK), and adenylate kinase (AK) in leukocytes of IUM infants were significantly lower than those of the ACA and FT infants. The energy charge of the adenylate system was calculated from the content of adenine nucleotides (ATP + ½ ADP) ÷ (ATP + ADP + AMP). There was no statistically significant difference between the groups. A new parameter of cellular energy metabolism was suggested, based on the functional relationship between ATP and ADP which can be partially regulated by AK. Tentatively, this relationship is called the "energy capacity" and is quantified as (ATP + ½ ADP) x AK. The energy capacity in leukocytes of the IUM infants and their mothers was significantly lower than that of the FT and AGA infants and their mothers, respectively. On the whole, the altered pattern of energy metabolism in leukocytes of the IUM infants was similar to that found in young infants with severe postnatal protein-calorie malnutrition, thus adding further support to the concept that fetal growth retardation is a manifestation of malnutrition in utero. The similarity of enzyme pattern and adenine nucleotide contents between maternal and cord blood leukocytes at the time of delivery suggests some interrelation between energy metabolism in mothers and their fetuses.

Leukocyte Energy Metabolism III. Anaerobic and Aerobic ATP Production and Related Enzymes

We have measured anaerobic and aerobic energy metabolism in leukocytes from human and animal blood, using several methods. We have taken special care to correct our results for an unavoidable contamination with thrombocytes, which has been neglected in all previous work. White cells were isolated by a method combining sedimentation through Dextran with low speed centrifugations. A pellet of thrombocytes was prepared in parallel from the same blood. Mitochondria were isolated by differential centrifugation in 0.25 M sucrose. Firstly, we have specially studied two cytosolic glycolytic enzymes, phosphoglycerate kinase and pyruvate kinase, both of which catalyze a reaction producing ATP. These two enzymes are very active in leukocytes. Other nucleotides, such as CDP, GDP and UDP can also be phosphorylated. Secondly, we have measured the activity of several mitochondrial enzymes, the most active being α-glycerophosphate oxidase. Using an enzymatic test, we have measured the amount of ATP produced in oxidative phosphorylation; in these experiments it was necessary to consider the activity of adenylate kinase as well as correcting for thrombocyte contamination. Several metabolites in direct or indirect relation with the Krebs cycle were used as oxidizable substrates: glutamate, succinate and α-glycerophosphate gave the best results. Except for amytal, inhibitors of oxidative phosphorylation also inhibit ATP production in leukocyte mitochondria. In conclusion, it can be said that oxidative phosphorylation exists in leukocytes, but that the phosphorylation steps in glycolysis produce 1,000 to 10,000 times more ATP than aerobic energy metabolism.