The Removal of Infused Leucine after Injury, Starvation and other Conditions in Man

1980 ◽  
Vol 59 (4) ◽  
pp. 275-283 ◽  
Author(s):  
M. Elia ◽  
Rose Farrell ◽  
Vera Ilic ◽  
R. Smith ◽  
D. H. Williamson
Keyword(s):  
Muscular Dystrophy ◽  
Blood Concentration ◽  
Ketone Bodies ◽  
Elective Surgery ◽  
Metabolic Effects ◽  
Accidental Injury ◽  
Sufficient Energy ◽  
Branched Chain ◽  
Clinical Conditions ◽  
Basal Concentration

1. To investigate the effects of starvation, elective surgery, accidental injury and other clinical conditions on the metabolism of branched-chain amino acids in man, we have measured the basal concentration of leucine and the removal and metabolic effects of infused l-leucine. 2. The blood concentration of leucine was significantly increased by surgery, starvation and accidental injury, and decreased in cirrhosis. It tended to increase in diabetes and was unaffected by muscular dystrophy. 3. The half-life of infused leucine was nearly doubled by 4 days of complete starvation, unaltered by surgery and decreased by severe accidental injury. Infusion with Intralipid, which increased free fatty acid and ketone-body concentrations, had no effect on the removal of a leucine load. The clearance rate of infused leucine was reduced in diabetes and muscular dystrophy and increased in cirrhosis. 4. The effects of infused leucine on blood glucose and ketone bodies differed according to the groups studied. 5. Since the traumatized patients were given sufficient energy and nitrogen and disposed of a leucine load at a different rate from the starved patients, the causes of the increase in blood concentration of leucine in these two conditions are different.

scholarly journals Noninvasive evaluation of respiratory muscles in pre-clinical model of Duchenne Muscular Dystrophy

2016 ◽  
Vol 36 (4) ◽  
pp. 290-296
Author(s):  
Daniela M. Oliveira ◽  
Stefano C. Hagen ◽  
Amilton C. Santos ◽  
Maria A. Miglino ◽  
Antônio C. Assis Neto
Keyword(s):  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Respiratory Muscles ◽  
Experimental Models ◽  
Noninvasive Evaluation ◽  
Control Group ◽  
Clinical Model ◽  
Intercostal Muscles ◽  
Invasive Method ◽  
Clinical Conditions

Abstract Since respiratory insufficiency is the main cause of death in patients affected by Duchenne Muscular Dystrophy (DMD), the present study aims at establishing a new non-invasive method to evaluate the clinical parameters of respiratory conditions of experimental models affected by DMD. With this purpose in mind, we evaluated the cardiorespiratory clinical conditions, the changes in the intercostal muscles, the diaphragmatic mobility, and the respiratory cycles in Golden Retriever Muscular Dystrophy (GRMD) employing ultrasonography (US). A control group consisting of dogs of the same race, but not affected by muscular dystrophy, were used in this study. The results showed that inspiration, expiration and plateau movements (diaphragm mobility) were lower in the affected group. Plateau phase in the affected group was practically non-existent and showed that the diaphragm remained in constant motion. Respiratory rate reached 15.5 per minute for affected group and 26.93 per minute for the control group. Expiration and inspiration movements of intercostal muscles reached 8.99mm and 8.79mm, respectively, for control group and 7.42mm and 7.40mm, respectively, for affected group. Methodology used in the present analysis proved to be viable for the follow-up and evaluation of the respiratory model in GRMD and may be adapted to other muscular dystrophy experimental models.

scholarly journals Sexual dimorphism in hypothalamic inflammation in the offspring of dams exposed to a diet rich in high fat and branched-chain amino acids

2019 ◽  
Vol 317 (3) ◽  
pp. E526-E534 ◽  
Author(s):  
Marianna Sadagurski ◽  
Lucas Kniess Debarba ◽  
Joao Pedro Werneck-de-Castro ◽  
Abear Ali Awada ◽  
Tess A. Baker ◽  
...  
Keyword(s):  
Energy Homeostasis ◽  
Maternal Nutrition ◽  
Inflammatory Responses ◽  
Maternal Diet ◽  
Female Offspring ◽  
Metabolic Effects ◽  
Standard Diet ◽  
High Fat ◽  
Hypothalamic Inflammation ◽  
Branched Chain

Branched-chain amino acid (BCAAs: leucine, isoleucine, and valine) contribute to the development of obesity-associated insulin resistance in the context of consumption of a high-fat diet (HFD) in humans and rodents. Maternal diet is a major determinant of offspring health, and there is strong evidence that maternal HFD alters hypothalamic developmental programming and disrupts offspring energy homeostasis in rodents. In this study, we exposed pregnant and lactating C57BL/6JB female mice to either HFD, HFD with supplemented BCAA (HFD+BCAA), or standard diet (SC), and we studied offspring metabolic phenotypes. Both maternal HFD and HFD supplemented with BCAA had similar effect rendering the offspring metabolic imbalance and impairing their ability to cope with HFD when challenged during aging. The metabolic effects of HFD challenge were more profound in females, worsening female offspring ability to cope with an HFD challenge by activating hypothalamic inflammation in aging. Moreover, the sex differences in hypothalamic estrogen receptor α (ER-α) expression levels were lost in female offspring upon HFD challenge, supporting a link between ER-α levels and hypothalamic inflammation in offspring and highlighting the programming potential of hypothalamic inflammatory responses and maternal nutrition.

scholarly journals Metabolic effects of low cortisol during exercise in humans

1998 ◽  
Vol 84 (3) ◽  
pp. 939-947 ◽  
Author(s):  
Pedro Del Corral ◽  
Edward T. Howley ◽  
Mike Hartsell ◽  
Muhammad Ashraf ◽  
Mary Sue Younger
Keyword(s):  
Amino Acids ◽  
Growth Hormone ◽  
Plasma Glucose ◽  
Respiratory Exchange Ratio ◽  
Branched Chain Amino Acids ◽  
Physiological Effect ◽  
Metabolic Effects ◽  
Whole Body ◽  
Branched Chain ◽  
Exercise In Humans

This study examined the physiological effect of reduced plasma cortisol (C) during prolonged exercise in humans. The effects of normal C (NC) were compared with metyrapone-induced low C (LC) on plasma substrate availability and the respiratory exchange ratio during 2 h of exercise at ∼60% peak O2 consumption in nine subjects. The C responses were compared with preexercise (Pre) levels and with a rest day (Con). At rest, C was attenuated by ∼70% for LC compared with NC. At rest, plasma glucose, lactate, glycerol, β-hydroxybutyrate, alanine, branched-chain amino acids, insulin, glucagon, growth hormone, epinephrine, and norepinephrine were similar under LC and NC ( P > 0.05). During exercise under NC, plasma C increased compared with Pre, whereas it remained unchanged during LC. During NC, plasma C was elevated at 90 min (compared with Con) and at 120 min (compared with Con and Pre). During exercise, plasma glucose decreased to the same extent and lactate was similar under both conditions, whereas plasma glycerol, β-hydroxybutyrate, alanine, and branched-chain amino acids were higher ( P < 0.01) under NC. Plasma insulin declined ( P = 0.01) to a greater extent under LC, whereas growth hormone, epinephrine, and norepinephrine tended to be higher (0.05 ≤ P ≤ 0.10). Plasma glucagon increased under both conditions ( P < 0.01). The respiratory exchange ratio did not differ between conditions. We conclude that, during exercise, 1) C accelerates lipolysis, ketogenesis, and proteolysis; 2) under LC, glucoregulatory hormone adjustments maintain glucose homeostasis; and 3) LC does not alter whole body substrate utilization or the ability to complete 2 h of moderate exercise.

scholarly journals Anti-Inflammatory and General Glucocorticoid Physiology in Skeletal Muscles Affected by Duchenne Muscular Dystrophy: Exploration of Steroid-Sparing Agents

2020 ◽  
Vol 21 (13) ◽  
pp. 4596 ◽  
Author(s):  
Sandrine Herbelet ◽  
Arthur Rodenbach ◽  
Boel De Paepe ◽  
Jan L. De Bleecker
Keyword(s):  
Skeletal Muscle ◽  
Duchenne Muscular Dystrophy ◽  
Muscular Dystrophy ◽  
Metabolic Effects ◽  
Growth Delay ◽  
Secondary Effects ◽  
Cellular Pathways ◽  
Anti Inflammatory ◽  
Steroid Sparing ◽  
Synthetic Glucocorticoid

In Duchenne muscular dystrophy (DMD), the activation of proinflammatory and metabolic cellular pathways in skeletal muscle cells is an inherent characteristic. Synthetic glucocorticoid intake counteracts the majority of these mechanisms. However, glucocorticoids induce burdensome secondary effects, including hypertension, arrhythmias, hyperglycemia, osteoporosis, weight gain, growth delay, skin thinning, cushingoid appearance, and tissue-specific glucocorticoid resistance. Hence, lowering the glucocorticoid dosage could be beneficial for DMD patients. A more profound insight into the major cellular pathways that are stabilized after synthetic glucocorticoid administration in DMD is needed when searching for the molecules able to achieve similar pathway stabilization. This review provides a concise overview of the major anti-inflammatory pathways, as well as the metabolic effects of glucocorticoids in the skeletal muscle affected in DMD. The known drugs able to stabilize these pathways, and which could potentially be combined with glucocorticoid therapy as steroid-sparing agents, are described. This could create new opportunities for testing in DMD animal models and/or clinical trials, possibly leading to smaller glucocorticoids dosage regimens for DMD patients.

scholarly journals A Clinical Case of Clozapine-Induced Fatal Diabetic Ketoacidosis

2016 ◽  
Vol 7 ◽  
pp. CMPsy.S30532
Author(s):  
Eric Romney ◽  
Vinay J. Nagaraj ◽  
Amie Kafer
Keyword(s):  
Fatty Acids ◽  
Weight Gain ◽  
Free Fatty Acids ◽  
Diabetic Ketoacidosis ◽  
Ketone Bodies ◽  
Pancreatic Beta Cell ◽  
Metabolic Effects ◽  
Psychotic Symptoms ◽  
Life Threatening ◽  
Altered Metabolism

Introduction Clozapine, a second generation medication, has become the atypical antipsychotic drug of choice for refractory or treatment-resistant schizophrenia. In addition to the high risk of agranulocytosis and seizures, clozapine treatment is increasingly associated with significant metabolic effects, such as hyperglycemia, central weight gain and adiposity, hypertriglyceridemia, and elevated low-density lipoprotein cholesterol. A potentially life-threatening complication of altered metabolism is diabetic ketoacidosis (DKA). This report details a case of fatal DKA in a schizophrenic patient undergoing treatment with clozapine. Case Description An African–American male in his 20s with a medical history significant for schizophrenia was presented to the psychiatric inpatient ward with severe paranoid thoughts and aggressive behavior. After trials of risperidone, olanzapine, and haloperidol—all of which failed to adequately control his psychotic symptoms—clozapine titration was initiated and he showed significant improvement. Weight gain was observed throughout hospitalization, but all blood and urine test results showed no metabolic or hematological abnormalities. The patient was discharged for outpatient treatment on clozapine (125 mg morning and 325 mg evening) along with divalproex sodium and metoprolol. Six days post-discharge, the patient died. A medical autopsy later ruled that the death was due to DKA without any evidence of contributory injuries or natural disease. Results and Conclusion Significant increase in body mass index from 28.7 to 33.5 was observed during hospitalization. The blood glucose level, measured after his death, was found to be 500 mg/dL. Altered metabolism due to clozapine can lead to dyslipidemia-mediated-pancreatic-beta-cell damage, decreased insulin secretion as well as insulin resistance. In DKA, low levels of insulin lead to an increased release of free fatty acids from adipose tissue. Acetyl coenzyme A (CoA), derived from the breakdown of free fatty acids, is metabolized by the Kreb's cycle. In hepatocytes, excess acetyl-CoA is converted into ketone bodies (acetoacetate and β-hydroxybutyrate) and released into circulation. Ketone bodies have a low p Ka value and their high serum concentrations lead to DKA. In this patient, DKA was most probably clozapine induced and had fatal consequences. Thus, recognizing potential risk factors, providing patient education, and increasing monitoring of patients on clozapine and other atypical antipsychotics are critical to prevent the life-threatening effects of DKA.

scholarly journals Metabolic consequences of methylenecyclopropylglycine poisoning in rats

1991 ◽  
Vol 274 (2) ◽  
pp. 395-400 ◽  
Author(s):  
K Melde ◽  
S Jackson ◽  
K Bartlett ◽  
H S A Sherratt ◽  
S Ghisla
Keyword(s):  
Amino Acids ◽  
Ketone Bodies ◽  
Blood Glucose Concentration ◽  
Plasma Concentrations ◽  
Liver Mitochondria ◽  
Branched Chain Amino Acids ◽  
Oxidation Products ◽  
Rat Liver Mitochondria ◽  
Toxic Metabolite ◽  
Branched Chain

We describe the effects of methylenecyclopropylglycine in fasted rats. A 75% decrease in the blood glucose concentration and an increase of lactate and pyruvate were observed 6 h after administration of 100 mg of this amino acid/kg. By contrast with the effects reported for hypoglycin [Williamson & Wilson (1965) Biochem. J. 94, 19c-21c], the plasma concentrations of ketone bodies decreased after administration of methylenecyclopropylglycine and the concentrations of branched-chain amino acids in the plasma were increased 6-fold. The oxidation of decanoylcarnitine or of palmitate was nearly completely inhibited in rat liver mitochondria from methylenecyclopropylglycine-poisoned rats. The activities of acetoacetyl-CoA and of 3-oxoacyl-CoA thiolase were decreased to 25% and less than 10% of the controls. There was a pronounced aciduria, due to the excretion of dicarboxylic acids and of oxidation products of branched-chain amino acids. The accumulation of the toxic metabolite methylenecyclopropylformyl-CoA in the mitochondrial matrix was detected after administration of methylenecyclopropylglycine. Similarly we confirmed experimentally that methylenecyclopropylacetyl-CoA accumulates in mitochondria incubated with methylenecyclopropylpyruvate.

scholarly journals Effects of starvation on intermediary metabolism in the lactating cow. A comparison with metabolic changes occurring during bovine ketosis

1972 ◽  
Vol 128 (5) ◽  
pp. 1311-1318 ◽  
Author(s):  
G. D. Baird ◽  
R. J. Heitzman ◽  
K. G. Hibbitt
Keyword(s):  
Fatty Acids ◽  
Plasma Concentration ◽  
Dairy Cows ◽  
Blood Concentration ◽  
Ketone Bodies ◽  
Fat Metabolism ◽  
Metabolic Changes ◽  
Initial Increase ◽  
Blood Concentrations ◽  
Lactating Dairy Cows

1. The purpose of this study was to determine the nature of the metabolic changes associated with carbohydrate and fat metabolism that occurred in the blood and liver of lactating dairy cows during starvation for 6 days. 2. During starvation, the blood concentrations of the free fatty acids and ketone bodies increased, whereas that of citrate decreased. After an initial increase, the blood concentration of glucose subsequently declined as starvation progressed. Starvation caused a significant decrease in the plasma concentration of serine and a significant increase in that of leucine. 3. After 6 days of starvation the hepatic concentrations of oxaloacetate, citrate, phosphoenolpyruvate, 2-phosphoglycerate, 3-phosphoglycerate, glucose, glycogen, ATP and NAD+ had all decreased, as had the hepatic activities of phosphopyruvate carboxylase (EC 4.1.1.32) and pyruvate kinase (EC 2.7.1.40). 4. The above metabolic changes are similar to those previously found to occur in cows suffering from spontaneous ketosis (Baird et al., 1968; Baird & Heitzman, 1971). 5. Milk yield decreased progressively during starvation. 6. There were marked differences in the ability of individual animals to resist the onset of severe starvation ketosis.

scholarly journals Mitochondrial and Metabolic Effects of Nucleoside Reverse Transcriptase Inhibitors (NRTIs) in Mice Receiving One of Five Single- and Three Dual-NRTI Treatments

2003 ◽  
Vol 47 (11) ◽  
pp. 3384-3392 ◽  
Author(s):  
Reine Note ◽  
Caroline Maisonneuve ◽  
Philippe Lettéron ◽  
Gilles Peytavin ◽  
Fatima Djouadi ◽  
...  
Keyword(s):  
Mitochondrial Dna ◽  
Reverse Transcriptase ◽  
Ketone Bodies ◽  
Metabolic Effects ◽  
Reverse Transcriptase Inhibitors ◽  
Nucleoside Reverse Transcriptase Inhibitors ◽  
Aminoisobutyric Acid ◽  
Mitochondrial Fatty Acid ◽  
High Doses ◽  
Cpt I

ABSTRACT Although treatments with nucleoside reverse transcriptase inhibitors (NRTIs) can modify fat metabolism and fat distribution in humans, the mechanisms of these modifications and the roles of diverse NRTIs are unknown. We studied the mitochondrial and metabolic effects of stavudine (d4T), zidovudine (AZT), didanosine (ddI), lamivudine (3TC), zalcitabine (ddC), and three combinations (AZT-3TC, d4T-3TC, and d4T-ddI) in mice treated for 2 weeks with daily doses equivalent to the human dose per body area. Concentrations of AZT and d4T in plasma were lower when these drugs were administered with 3TC or ddI. Whatever the treatment, mitochondrial DNA was not significantly decreased in muscle, heart, brain, or white adipose tissue but was moderately decreased in liver tissue after the administration of AZT, 3TC, or d4T alone. Blood lactate was unchanged, even when NRTIs were administered at supratherapeutic doses. In contrast, the level of plasma ketone bodies increased with the administration of AZT or high doses of d4T but not with ddC, 3TC, or ddI, suggesting that the thymine moiety could be involved. Indeed, the levels of plasma ketone bodies increased in mice treated with β-aminoisobutyric acid, a thymine catabolite. Treatment with AZT, d4T, or β-aminoisobutyric acid increased hepatic carnitine palmitoyltransferase I (CPT-I) mRNA expression and the mitochondrial generation of ketone bodies from palmitate. In conclusion, therapeutic doses of NRTIs have no or moderate effects on mitochondrial DNA and no effects on plasma lactate in mice. However, AZT and high doses of d4T increase the levels of hepatic CPT-I, mitochondrial fatty acid β-oxidation, and ketone bodies, and these catabolic effects are reproduced by β-aminoisobutyric acid, a thymine metabolite.

scholarly journals Cardioprotective mechanisms of sodium-glucose cotransporter 2 inhibitors

2021 ◽  
Vol 24 (3) ◽  
pp. 291-299
Author(s):  
A. M. Mkrtumyan ◽  
T. N. Markova ◽  
N. K. Mishchenko
Keyword(s):  
Large Scale ◽  
Troponin I ◽  
Ketone Bodies ◽  
Cardiovascular Effects ◽  
Metabolic Effects ◽  
Atp Production ◽  
Cardiovascular Outcome Trials ◽  
Sodium Glucose Cotransporter ◽  
Myocardial Energetics ◽  
Highly Sensitive Troponin

The findings of large-scale cardiovascular outcome trials have been demonstrated that sodium-glucose cotransporter 2 ­inhibitors (iSGLT-2) have shown beneficial cardiovascular effects. In this review proposed mechanisms underlying iSGLT-2-associated cardiovascular benefits have been discussed: haemodynamic and intracellular effects, including metabolic effects and electrolyte changes; and also, the effect on markers of cardiovascular disease (CVD). The hemodynamic effects of SGLT-2 are characterized by reduction of cardiac preload and afterload as a result of osmotic diuresis, a decrease in blood pressure and arterial stiffness. The metabolic effects of this medicine are accompanied by an increase the production of ketone bodies, followed by improving ATP production and myocardial energetics. Also, iSGLT-2 modulate ion transporters (NHE1 and NHE3). A reduction of cytoplasmic sodium and calcium levels and increasing mitochondrial calcium levels in the cardiomyocytes enhances the synthesis of ATP and increases cell viability. Effect of iSGLT-2 on CVD markers showed a decrease in the levels of the N-terminal pro-B-type natriuretic peptide and highly sensitive troponin I in elderly patients with type 2 diabetes mellitus (T2DM). Thus, this class of agents has a multifactorial effect on the functioning of cardiovascular system. Further studies will help to explain the all possible cardioprotective effects of iSGLT-2 in individuals with and without T2DM.

Food intake in diabetic rats: isolation of primary metabolic effects of fat feeding

1985 ◽  
Vol 249 (1) ◽  
pp. R44-R51 ◽  
Author(s):  
M. I. Friedman ◽  
I. Ramirez ◽  
N. K. Edens ◽  
J. Granneman
Keyword(s):  
Food Intake ◽  
Food Consumption ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Metabolic Effects ◽  
Carbohydrate Consumption ◽  
Plasma Triglycerides ◽  
Urinary Glucose ◽  
Ad Libitum ◽  
Fat Feeding

The effects of varying dietary fat content on food intake and metabolism in streptozotocin-diabetic rats were examined. The metabolic consequences of fat feeding were separated from the marked adjustments in voluntary food consumption that occur when diabetic rats are fed diets containing different amounts of fat by feeding rats a fixed ration of food in which either fats or carbohydrates were reduced by equicaloric amounts, or in which only the concentration of fat, but not other dietary nutrients, was varied systematically. Resulting changes in metabolism and subsequent ad libitum food intake on refeeding were then measured. Rats did not increase their food intake after a prior reduction in carbohydrate consumption but did so after an equicaloric reduction in fat consumption. Urinary glucose excretion during rationing was a function of carbohydrate consumption and was not predictive of changes in food intake during refeeding. The more fat that rats consumed during rationing, the higher their levels of plasma triglycerides and ketone bodies were at the time of refeeding and the less they ate when allowed to eat ad libitum. The orderly changes in food consumption and in plasma triglycerides and ketones observed with variations in fat intake suggest that the effects of fat feeding on food intake in diabetic rats are mediated through the oxidation of ingested fat.

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