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Journal of the American College of... Sep 2019
Topics: Fluorodeoxyglucose F18; Humans; Plaque, Atherosclerotic; Positron-Emission Tomography
PubMed: 31466621
DOI: 10.1016/j.jacc.2019.07.009 -
Nature Metabolism May 2023
Topics: Positron-Emission Tomography; Fluorodeoxyglucose F18
PubMed: 37231249
DOI: 10.1038/s42255-023-00795-x -
Proceedings of the National Academy of... Aug 2021The amino acid and oligopeptide transporter Solute carrier family 15 member A4 (SLC15A4), which resides in lysosomes and is preferentially expressed in immune cells,...
The amino acid and oligopeptide transporter Solute carrier family 15 member A4 (SLC15A4), which resides in lysosomes and is preferentially expressed in immune cells, plays critical roles in the pathogenesis of lupus and colitis in murine models. Toll-like receptor (TLR)7/9- and nucleotide-binding oligomerization domain-containing protein 1 (NOD1)-mediated inflammatory responses require SLC15A4 function for regulating the mechanistic target of rapamycin complex 1 (mTORC1) or transporting L-Ala-γ-D-Glu-meso-diaminopimelic acid, IL-12: interleukin-12 (Tri-DAP), respectively. Here, we further investigated the mechanism of how SLC15A4 directs inflammatory responses. Proximity-dependent biotin identification revealed glycolysis as highly enriched gene ontology terms. Fluxome analyses in macrophages indicated that SLC15A4 loss causes insufficient biotransformation of pyruvate to the tricarboxylic acid cycle, while increasing glutaminolysis to the cycle. Furthermore, SLC15A4 was required for M1-prone metabolic change and inflammatory IL-12 cytokine productions after TLR9 stimulation. SLC15A4 could be in close proximity to AMP-activated protein kinase (AMPK) and mTOR, and SLC15A4 deficiency impaired TLR-mediated AMPK activation. Interestingly, SLC15A4-intact but not SLC15A4-deficient macrophages became resistant to fluctuations in environmental nutrient levels by limiting the use of the glutamine source; thus, SLC15A4 was critical for macrophage's respiratory homeostasis. Our findings reveal a mechanism of metabolic regulation in which an amino acid transporter acts as a gatekeeper that protects immune cells' ability to acquire an M1-prone metabolic phenotype in inflammatory tissues by mitigating metabolic stress.
Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Cell Differentiation; Cell Line; Dendritic Cells; Deoxyglucose; Energy Metabolism; Gene Expression Regulation; Gene Silencing; Humans; Macrophages; Membrane Transport Proteins; Mice; Mice, Knockout; Nerve Tissue Proteins; Oligodeoxyribonucleotides
PubMed: 34385317
DOI: 10.1073/pnas.2100295118 -
Biomedicine & Pharmacotherapy =... Dec 2022Chronic exposure to high glucose inside the human body helps in the progression of cancer by activating various signaling pathways including PI3K, Akt, mTOR, Ras, Raf,... (Review)
Review
Chronic exposure to high glucose inside the human body helps in the progression of cancer by activating various signaling pathways including PI3K, Akt, mTOR, Ras, Raf, MAPK, and PKC. Hyperglycemia induces ROS and AGE production and decreases the functional activities of the cellular antioxidant system. By downregulating the prolyl hydroxylase, it stabilizes HIF-α leading to EMT-induced cancer progression and inhibition of apoptosis. High glucose level increases inflammation by creating a pro-inflammatory environment through the production of certain pro-inflammatory mediators (cytokines, chemokines, leukotrienes), and by influencing the recruitment of immune cells, leukocytes in the inflamed region. High glucose impairs the immune response and dysregulates ROS formation through the alteration in ETC and glutaminolysis which makes hyperglycemic patients more susceptible to viral infection. 2-DG is a modified form of D-glucose, that shows anticancer, anti-inflammatory, and anti-viral effects. It enters the cells through GLUT transporters and is converted into 2-deoxy-D-glucose-6-phosphate with the help of hexokinase. It inhibits the glycolysis, the TCA cycle, and the pentose phosphate pathway leading to ATP depletion. By downregulating glucose uptake and energy (ATP) production it halts various pathways responsible for cancer progression. It promotes the formation of anti-inflammatory mediators, and macrophage polarization, and also modulates immune function, which decreases inflammation. 2-DG inhibits PI3K/Akt/mTOR and upregulates the AMPK pathway, causing activation of the SIRT-4 gene that reduces lipogenesis, glucose uptake, nucleotide formation, and alters viral replication thus reducing the chances of infection.
Topics: Humans; Glucose; Phosphatidylinositol 3-Kinases; Proto-Oncogene Proteins c-akt; Reactive Oxygen Species; TOR Serine-Threonine Kinases; Cell Proliferation; Glycolysis; Neoplasms; Deoxyglucose; Inflammation; Adenosine Triphosphate; Virus Diseases
PubMed: 36228369
DOI: 10.1016/j.biopha.2022.113801 -
Seminars in Nuclear Medicine Sep 2021In neurodegenerative diseases, positron emission tomography (PET) imaging plays an important role in the early identification and differential diagnosis in particular in... (Review)
Review
In neurodegenerative diseases, positron emission tomography (PET) imaging plays an important role in the early identification and differential diagnosis in particular in clinically challenging patients. F-FDG is still the most widely used and established tracer in this patient group, with different cortical and subcortical regions being preferentially affected in different neurodegenerative diseases, such as frontotemporal dementia, Alzheimer's disease or Lewy Body dementia, resulting in typical hypometabolic patterns. Over the last decades, however, the implementation of tracers specific for the pathological deposits characteristic of the different diseases, such as amyloid and tau, has revolutionized the way of classifying and reporting cases of cognitive impairment of neurodegenerative origin, providing complementary information to F-FDG PET. In neuro-oncology, PET imaging can be performed in several clinical indications, as highlighted in the joint European Association of Nuclear Medicine (EANM)/European Association of Neuro-Oncology (EANO)/Response assessment in neuro-oncology (RANO) practice guidelines on imaging in neuro-oncology. For assessment of glioma, amino-acid analogues, such as C-methionine or F-FET, are used whenever clinically available, as they offer excellent tumor-to-background ratios in malignant tumors. Moreover, dynamic acquisition of amino-acid analogue tracers and assessment of the shape of the time-activity curve can be used to perform noninvasive grading of brain gliomas, differentiating low from high grade presentations. In both settings, however, thorough knowledge of the normal physiological tracer distribution and the variants and pitfalls that can occur during image acquisition, processing and interpretation is mandatory in order to provide optimal diagnostic information to referring physicians and patients. Especially in neuro-oncology, this process can be aided by the active use of coregistered magnetic resonance imaging to accurately identify the imaging correlates of developmental origin, acute and chronic stroke, inflammation, infection and seizure related activity.
Topics: Fluorodeoxyglucose F18; Glioma; Humans; Magnetic Resonance Imaging; Nuclear Medicine; Positron-Emission Tomography
PubMed: 33820651
DOI: 10.1053/j.semnuclmed.2021.03.003 -
Journal of Psychiatric Research Feb 2022Individuals with suicidal behaviours are increasingly recognized as having impairments in brain metabolism. However, these are not well delineated.
BACKGROUND
Individuals with suicidal behaviours are increasingly recognized as having impairments in brain metabolism. However, these are not well delineated.
AIM
To evaluate regional cerebral glucose metabolism (rCMglu) in subjects with suicidal behaviours and assess differences in rCMglu between depressed and non-depressed suicidal subjects.
METHODS
Thirty-three subjects with suicidal behaviours were assessed using Columbia Suicide Severity Rating scale (CSSRS) and Beck's Depression Inventory (BDI). Brain metabolism was assessed using [F]Fluoro,Deoxy-Glucose Positron Emission Tomography (FDG-PET).
RESULTS
Of 33 subjects, eighteen had depression. FDG-PET findings revealed that in comparison to mean asymptomatic controls, subjects had decreased rCMglu in right inferior frontal, left Broca's, left inferiolateral andsuperiolateral temporal, right inferior parietal and left posterior cingulate cortex. Increased rCMglu was seen in bilateral superior and medial frontal, right inferiolateral and posteriomedial temporal cortex, and midbrain. CSSRS total intensity inversely correlated with rCMglu in medial frontal cortex, left Broca's and superiolateral temporal cortex and directly correlated with rCMglu in right cerebellum. There was no significant difference in rCMglu between depressed and non depressed group.
CONCLUSIONS
Significant differences exist in rCMglu of suicidal individuals, chiefly in frontal and temporal regions. Understanding these would help us identify individuals more at risk for suicidal behaviours.
Topics: Brain; Brain Mapping; Fluorodeoxyglucose F18; Glucose; Humans; Positron-Emission Tomography; Suicidal Ideation
PubMed: 35026694
DOI: 10.1016/j.jpsychires.2021.12.052 -
Epilepsy & Behavior : E&B Mar 20232-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of... (Review)
Review
2-deoxy-D-glucose (2DG) is a glucose analog differing from glucose only by removal of an oxygen atom at the 2 position, which prevents the isomerization of glucose-6-phosphate to fructose-6-phosphate, and thereby reversibly inhibits glycolysis. PET studies of regional brain glucose utilization positron-emitting 18F-2DG demonstrate that brain regions generating seizures have diminished glucose utilization during interictal conditions, but rapidly transition to markedly increased glucose delivery and utilization during seizures, particularly in status epilepticus (SE). 2-deoxy-D-glucose has acute antiseizure actions in multiple in vivo and in vitro seizure models, including models of SE induced by the chemo convulsants pilocarpine and kainic acid, suggesting that focal enhanced delivery of 2DG to ictal brain circuits is a potential novel anticonvulsant intervention for the treatment of SE.
Topics: Humans; Deoxyglucose; Status Epilepticus; Seizures; Glucose; Glycolysis; Pilocarpine
PubMed: 36804714
DOI: 10.1016/j.yebeh.2023.109108 -
European Radiology Nov 2023
Topics: Humans; Gallium Radioisotopes; Positron Emission Tomography Computed Tomography; Fluorodeoxyglucose F18
PubMed: 37171487
DOI: 10.1007/s00330-023-09715-9 -
In Vivo (Athens, Greece) 20231,5-Anhydro-d-fructose (1,5-AF, saccharide) and 1,5-anhydro-d-glucitol (1,5-AG) converted from 1,5-AF via the glycemic pathway have health benefits. However, this...
BACKGROUND/AIM
1,5-Anhydro-d-fructose (1,5-AF, saccharide) and 1,5-anhydro-d-glucitol (1,5-AG) converted from 1,5-AF via the glycemic pathway have health benefits. However, this metabolism has not been sufficiently elucidated. To clarify the in vivo metabolism of 1,5-AF to 1,5-AG, porcine (blood kinetics) and human (urinary excretion) studies were conducted.
MATERIALS AND METHODS
Microminipigs were administrated 1,5-AF orally or intravenously. Blood samples were obtained to analyse the kinetics of 1,5-AF and 1,5-AG. Urine samples were collected from human subjects who had orally ingested 1,5-AF, and the amounts of 1,5-AF and 1,5-AG excreted in the urine were analysed.
RESULTS
In blood kinetics analysis, the time to the maximum concentration of 1,5-AF after intravenous administration was 0.5 h, whereas 1,5-AF was not observed after oral administration. The times to the maximum concentration of 1,5-AG after intravenous and oral administration were 1.5 h and 2 h, respectively. In urinary excretion, the concentration of 1,5-AG in urine rapidly increased after the administration of 1,5-AF, peaked at 2 h, whereas 1,5-AF was not detected.
CONCLUSION
1,5-AF was rapidly metabolized to 1.5-AG in vivo in swine and human.
Topics: Humans; Animals; Swine; Sorbitol; Deoxyglucose; Fructose
PubMed: 37103066
DOI: 10.21873/invivo.13176 -
Current Protein & Peptide Science 2020It has been well established that advanced glycation end-products (AGEs) have a strong correlation with diabetes and its secondary complications. Moreover, dicarbonyls,... (Review)
Review
It has been well established that advanced glycation end-products (AGEs) have a strong correlation with diabetes and its secondary complications. Moreover, dicarbonyls, especially, methylglyoxal (MG) and glyoxal, accelerate AGEs formation and hence, have potential roles in the pathogenesis of diabetes. They can also induce oxidative stress and concomitantly decrease the efficiency of antioxidant enzymes. Increased proinflammatory cytokines (tumor necrosis factor-α and interleukin- 1β) are secreted by monocytes due to the dicarbonyl-modified proteins. High levels of blood dicarbonyls have been identified in diabetes and its associated complications (retinopathy, nephropathy and neuropathy). This review aims to provide a better understanding by including in-depth information about the formation of MG and glyoxal through multiple pathways with a focus on their biological functions and detoxifications. The potential role of these dicarbonyls in secondary diabetic complications is also discussed.
Topics: Deoxyglucose; Diabetes Mellitus, Type 2; Diabetic Nephropathies; Diabetic Neuropathies; Diabetic Retinopathy; Gene Expression Regulation; Glycation End Products, Advanced; Glyoxal; Humans; Insulin; Insulin Resistance; Isoenzymes; Lactoylglutathione Lyase; Oxidative Stress; Protein Carbonylation; Pyruvaldehyde; Signal Transduction
PubMed: 31660813
DOI: 10.2174/1389203720666191010155145