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Biochemistry. Biokhimiia Nov 20183-Deoxyglucosone (3DG) is a highly reactive dicarbonyl species, and its accumulation evokes carbonyl and oxidative stress. Our recent data reveal the role of 3DG as an...
3-Deoxyglucosone (3DG) is a highly reactive dicarbonyl species, and its accumulation evokes carbonyl and oxidative stress. Our recent data reveal the role of 3DG as an independent factor for the development of prediabetes and suggest that intestine could be its novel target tissue. The present study investigated whether exogenous 3DG increases intestinal permeability by triggering carbonyl and oxidative stress, thus contributing to β-cell dysfunction. Rats were administered 3DG for two weeks by gastric gavage. Then levels of insulin, ROS, MDA, SOD, NLRP3, TNF-α and IL-1β in blood plasma as well as the ROS level and content of TNF-α and IL-1β in pancreas were assessed. Also, the expression of E-cadherin and ZO-1 as well as levels of 3DG, protein carbonylation, ROS, TNF-α and IL-1β in colon were determined. The 3DG-treated rats showed an elevation in systemic oxidative stress (ROS, MDA and SOD) and in inflammation (TNF-α and IL-1β), decreased plasma insulin level 15 min after the glucose load, and increased levels of TNF-α, IL-1β and ROS in pancreatic tissue. In colon tissues of the 3DG-treated rats, decreased E-cadherin expression and increased ROS production as well as an elevation of TNF-α and IL-1β levels were observed. Interestingly, elevation of colon protein carbonylation was observed in the 3DG-treated rats that displayed 3DG deposition in colon tissues. We revealed for the first time that 3DG deposition in colon triggers carbonyl and oxidative stress and, as a consequence, impairs gut permeability. The enhanced intestinal permeability caused by 3DG deposition in colon results in systemic and pancreatic oxidative stress and inflammatory process, contributing to the development of β-cell dysfunction.
Topics: Animals; Colon; Deoxyglucose; Gene Expression Regulation; Insulin-Secreting Cells; Permeability; Protein Carbonylation; Rats; Rats, Sprague-Dawley
PubMed: 30482147
DOI: 10.1134/S0006297918110068 -
American Journal of Physiology.... Dec 2019These studies test, using intravital microscopy (IVM), the hypotheses that perfusion effects on insulin-stimulated muscle glucose uptake (MGU) are ) capillary...
These studies test, using intravital microscopy (IVM), the hypotheses that perfusion effects on insulin-stimulated muscle glucose uptake (MGU) are ) capillary recruitment independent and ) mediated through the dispersion of glucose rather than insulin. For , capillary perfusion was visualized before and after intravenous insulin. No capillary recruitment was observed. For , mice were treated with vasoactive compounds (sodium nitroprusside, hyaluronidase, and lipopolysaccharide), and dispersion of fluorophores approximating insulin size (10-kDa dextran) and glucose (2-NBDG) was measured using IVM. Subsequently, insulin and 2[C]deoxyglucose were injected and muscle phospho-2[C]deoxyglucose (2[C]DG) accumulation was used as an index of MGU. Flow velocity and 2-NBDG dispersion, but not perfused surface area or 10-kDa dextran dispersion, predicted phospho-2[C]DG accumulation. For , microspheres of the same size and number as are used for contrast-enhanced ultrasound (CEU) studies of capillary recruitment were visualized using IVM. Due to their low concentration, microspheres were present in only a small fraction of blood-perfused capillaries. Microsphere-perfused blood volume correlated to flow velocity. These findings suggest that ) flow velocity rather than capillary recruitment controls microvascular contributions to MGU, ) glucose dispersion is more predictive of MGU than dispersion of insulin-sized molecules, and ) CEU measures regional flow velocity rather than capillary recruitment.
Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Blood Flow Velocity; Carbon Radioisotopes; Deoxyglucose; Dextrans; Glucose; Hypoglycemic Agents; Insulin; Intravital Microscopy; Mice; Microcirculation; Microspheres; Muscle, Skeletal; Ultrasonography
PubMed: 31526289
DOI: 10.1152/ajpendo.00260.2019 -
Zhonghua Yi Xue Za Zhi Nov 2020To evaluate the consistency of different measurement methods of saliva 1,5-anhydroglucitol (1,5-AG) in different glucose metabolism populations. From January 2018 to...
To evaluate the consistency of different measurement methods of saliva 1,5-anhydroglucitol (1,5-AG) in different glucose metabolism populations. From January 2018 to June 2019, 175 healthy volunteers (21-65 years, 58 males and 117 females) with normal glucose tolerance (NGT) and 80 diabetic patients (18-70 years, 44 males and 36 females) were enrolled in Shanghai Jiao Tong University Affiliated Sixth People's Hospital. Saliva was collected by saliva collection tube, and 1,5-AG was measured using both enzymatic and mass spectrometry methods. Serum 1,5-AG was determined by enzymatic method. In NGT subjects, both serum and saliva 1,5-AG levels detected by enzymatic method were positively correlated with the saliva 1,5-AG levels detected by liquid chromatography-mass spectrometry (=0.247 and 0.523, respectively, both <0.05). However, there was no significant correlation between saliva and serum 1,5-AG levels detected by enzymatic method (=-0.074, =0.333). In diabetic patients, both serum and saliva 1,5-AG levels detected by enzymatic method were positively correlated with the saliva 1,5-AG levels detected by gas chromatography-mass spectrometry (=0.284 and 0.423, respectively, both <0.05). However, there was no significant correlation between saliva and serum 1,5-AG levels detected by enzymatic method (=-0.079, =0.487). Both serum and saliva 1,5-AG levels detected by enzymatic method have a good consistency with saliva 1,5-AG levels detected by mass spectrometry method. The saliva and serum 1,5-AG levels detected by enzymatic method are not well correlated, and thus the enzymatic detection of saliva 1,5-AG needs further improvement in clinical practice.
Topics: China; Deoxyglucose; Diabetes Mellitus; Female; Humans; Male; Saliva
PubMed: 33202489
DOI: 10.3760/cma.j.cn112137-20200312-00726 -
International Journal of Molecular... Aug 2018Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in...
Cancer metabolism is characterized by extensive glucose consumption through aerobic glycolysis. No effective therapy exploiting this cancer trait has emerged so far, in part, due to the substantial side effects of the investigated drugs. In this study, we examined the side effects of a combination of isocaloric ketogenic diet (KD) with the glycolysis inhibitor 2-deoxyglucose (2-DG). Two groups of eight athymic nude mice were either fed a standard diet (SD) or a caloric unrestricted KD with a ratio of 4 g fat to 1 g protein/carbohydrate. 2-DG was investigated in commonly employed doses of 0.5 to 4 g/kg and up to 8 g/kg. Ketosis was achieved under KD (ketone bodies: SD 0.5 ± 0.14 mmol/L, KD 1.38 ± 0.28 mmol/L, < 0.01). The intraperitoneal application of 4 g/kg of 2-DG caused a significant increase in blood glucose, which was not prevented by KD. Sedation after the 2-DG treatment was observed and a behavioral test of spontaneous motion showed that KD reduced the sedation by 2-DG ( < 0.001). A 2-DG dose escalation to 8 g/kg was lethal for 50% of the mice in the SD and for 0% of the mice in the KD group ( < 0.01). A long-term combination of KD and an oral 1 or 2 g 2-DG/kg was well-tolerated. In conclusion, KD reduces the sedative effects of 2-DG and dramatically increases the maximum tolerated dose of 2-DG. A continued combination of KD and anti-glycolytic therapy is feasible. This is, to our knowledge, the first demonstration of increased tolerance to glycolysis inhibition by KD.
Topics: Animals; Antimetabolites; Blood Glucose; Deoxyglucose; Diet, Ketogenic; Female; Glucose; Glycolysis; Ketone Bodies; Ketosis; Mice, Nude; Neoplasms
PubMed: 30127309
DOI: 10.3390/ijms19082462 -
Biological & Pharmaceutical Bulletin 2018Glucose, one of the most fundamental sugar elements, has either D- or L-conformation. Of these, most cells preferentially take up D-glucose as an essential energy/carbon... (Review)
Review
Glucose, one of the most fundamental sugar elements, has either D- or L-conformation. Of these, most cells preferentially take up D-glucose as an essential energy/carbon source. Such stereoselective uptake of glucose has been explored by fluorophore-bearing D- and L-glucose analogues. 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-D-glucose (2-NBDG), the most widely used fluorescent D-glucose analogue, was abundantly taken up into living Escherichia coli cells, whereas no detectable uptake was obtained for 2-[N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-L-glucose (2-NBDLG), the antipode of 2-NBDG developed as a fluorescent L-glucose analogue (fLG). Interestingly, we found three-dimensionally accumulating tumor cell aggregates taking up 2-NBDLG when they expressed nuclear heterogeneity, one of the major cytological criteria for cells suspected of high-grade malignancy in clinical diagnosis. 2-NBDLG uptake was not detected in aggregates consisting of homogeneous cells and was specifically abolished by phloretin, a broad-spectrum inhibitor against transporters/channels. Preliminary studies have suggested that a combined use of 2-NBDLG, which emits green fluorescence, with 13-[4-[(2-deoxy-D-glucopyranose-2-yl)aminosulfonyl]-2-sulfonatophenyl]-4,5-trimethylene-7,8-trimethylene-1,2,3,4,6,9,10,11-octahydro-4-aza-6-oxa-8-azoniapentacene (2-TRLG), a membrane-impermeable fLG bearing a large red fluorophore, is effective for discriminating malignant tumor from benign cells both in living biopsy specimens endoscopically dissected from patients with early-stage gastric cancer and in ascites fluid of patients with gynecological cancers. Confocal endomicroscopic imaging of a carcinogen-induced cancer in bile duct of hamsters indicated that the fLG uptake pattern well correlated with pathological diagnosis for carcinoma. Safety tests according to Good Laboratory Practice regulations have been successfully completed so far. fLGs are unique fluorescent glucose analogues for identifying and characterizing living cancer cells based on derangements in their transport function.
Topics: 4-Chloro-7-nitrobenzofurazan; Animals; Deoxyglucose; Diagnostic Imaging; Filaggrin Proteins; Fluorescence; Fluorescent Dyes; Glucose; Humans; Neoplasms; Stereoisomerism
PubMed: 30270319
DOI: 10.1248/bpb.b18-00089 -
Journal of Veterinary Science Jul 2021Naringenin and its glycoside naringin are well known citrus flavonoids with several therapeutic benefits. Although the anti-adipogenic effects of naringenin and naringin...
BACKGROUND
Naringenin and its glycoside naringin are well known citrus flavonoids with several therapeutic benefits. Although the anti-adipogenic effects of naringenin and naringin have been reported previously, the detailed mechanism underlying their anti-adipogenesis effects is poorly understood.
OBJECTIVES
This study examined the anti-adipogenic effects of naringenin and naringin by determining differential gene expression patterns in these flavonoids-treated 3T3-L1 adipocytes.
METHODS
Lipid accumulation and triglyceride (TG) content were determined by Oil red O staining and TG assay. Glucose uptake was measured using a 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)amino]-2-deoxy-d-glucose fluorescent d-glucose analog. The phosphorylation levels of AMP-activated protein kinase (AMPK) and acetyl Co-A carboxylase (ACC) were observed via Western blot analysis. Differential gene expressions in 3T3-L1 adipocytes were evaluated via RNA sequencing analysis.
RESULTS
Naringenin and naringin inhibited both lipid accumulation and TG content, increased phosphorylation levels of both AMPK and ACC and decreased the expression level of 3-hydroxy-3-methylglutaryl CoA reductase (HMGCR) in 3T3-L1 adipocytes. RNA sequencing analysis revealed that 32 up-regulated (> 2-fold) and 17 down-regulated (< 0.6-fold) genes related to lipid metabolism, including , , , , , , , and , were normalized to the control level in naringenin-treated adipocytes. In addition, 25 up-regulated (> 2-fold) and 25 down-regulated (< 0.6-fold) genes related to lipid metabolism, including , , , , , , , , and , were normalized to the control level by naringin.
CONCLUSIONS
The results indicate that naringenin and naringin have anti-adipogenic potentials that are achieved by normalizing the expression levels of lipid metabolism-related genes that were perturbed in differentiated 3T3-L1 cells.
Topics: 3T3-L1 Cells; 4-Chloro-7-nitrobenzofurazan; Adipocytes; Adipogenesis; Animals; Biological Transport; Deoxyglucose; Flavanones; Gene Expression Regulation; Mice
PubMed: 34313040
DOI: 10.4142/jvs.2021.22.e55 -
Asian Pacific Journal of Cancer... 2015Different types of treatment are available for patients with breast cancer, the most being radiotherapy, chemotherapy, hormonal therapy and combination therapy.... (Review)
Review
Different types of treatment are available for patients with breast cancer, the most being radiotherapy, chemotherapy, hormonal therapy and combination therapy. Recently, nanoparticles have been emerging as promising agents for cancer therapy and are being investigated as contrast agents, drug carriers, radiosensitizers and also for hyperthermia effects. In this review the focus is on approaches for targeted treatment of breast cancer by combining nanoparticles, chemodrugs and radiation. The availble data suggest the possibility of increased roles for combined therapy, particularly by reducing the dose of each treatment modality, and consequently minimizing related side effects.
Topics: Antineoplastic Agents; Breast Neoplasms; Combined Modality Therapy; Contrast Media; Deoxyglucose; Doxorubicin; Drug Carriers; Female; Humans; Hyperthermia, Induced; Nanoparticles; Radiation-Sensitizing Agents
PubMed: 25773810
DOI: 10.7314/apjcp.2015.16.5.1683 -
Journal of Science and Medicine in Sport Oct 2017Dicarbonyl stress and high concentrations of advanced glycation endproducts (AGEs) relate to an elevated risk for cardiovascular diseases (CVD). Exercise training lowers...
OBJECTIVES
Dicarbonyl stress and high concentrations of advanced glycation endproducts (AGEs) relate to an elevated risk for cardiovascular diseases (CVD). Exercise training lowers the risk for future CVD. We tested the hypothesis that lifelong endurance athletes have lower dicarbonyl stress and AGEs compared to sedentary controls and that these differences relate to a better cardiovascular health profile.
DESIGN
Cross-sectional study.
METHODS
We included 18 lifelong endurance athletes (ATH, 61±7years) and 18 sedentary controls (SED, 58±7years) and measured circulating glyoxal (GO), methylglyoxal (MGO) and 3-deoxyglucosone (3DG) as markers of dicarbonyl stress. Furthermore, we measured serum levels of protein-bound AGEs N-(carboxymethyl)lysine (CML), N-(carboxyethyl)lysine (CEL), methylglyoxal-derived hydroimidazolone-1 (MG-H1), and pentosidine. Additionally, we measured cardiorespiratory fitness (VOpeak) and cardiovascular health markers.
RESULTS
ATH had lower concentrations of MGO (196 [180-246] vs. 242 [207-292] nmol/mmol lysine, p=0.043) and 3DG (927 [868-972] vs. 1061 [982-1114] nmol/mmol lysine, p<0.01), but no GO compared to SED. ATH demonstrated higher concentrations CML and CEL compared to SED. Pentosidine did not differ across groups and MG-H1 was significantly lower in ATH compared to SED. Concentrations of MGO en 3DG were inversely correlated with cardiovascular health markers, whereas CML and CEL were positively correlated with VOpeak and cardiovascular health markers.
CONCLUSION
Lifelong exercise training relates to lower dicarbonyl stress (MGO and 3DG) and the AGE MG-H1. The underlying mechanism and (clinical) relevance of higher CML and CEL concentrations among lifelong athletes warrants future research, since it conflicts with the idea that higher AGE concentrations relate to poor cardiovascular health outcomes.
Topics: Aged; Athletes; Biomarkers; Case-Control Studies; Cross-Sectional Studies; Deoxyglucose; Exercise; Glycation End Products, Advanced; Glyoxal; Humans; Male; Middle Aged; Physical Endurance; Sedentary Behavior; Stress, Physiological; Sugar Alcohol Dehydrogenases; Surveys and Questionnaires
PubMed: 28416154
DOI: 10.1016/j.jsams.2017.03.011 -
Organic Letters Jul 2022Caldorazole () was isolated from the marine cyanobacterium sp. collected on Ishigaki Island, Okinawa, Japan. Its structure was determined to be a new polyketide that...
Caldorazole () was isolated from the marine cyanobacterium sp. collected on Ishigaki Island, Okinawa, Japan. Its structure was determined to be a new polyketide that contained two thiazole rings and an -methylenolpyruvamide moiety. Caldorazole () showed strong cytotoxicity toward tumor cells that had been seeded at a high density. Cell death induced by in HeLa and A431 cells was also observed only in the presence of the glycolysis blocker 2-deoxy-d-glucose (2DG). Co-treatment with and 2DG remarkably decreased ATP levels in these cells. Furthermore, selectively inhibited complex I in the mitochondrial respiratory chain. Thus, was demonstrated to exert cytotoxicity toward human tumor cells by blocking mitochondrial respiration.
Topics: Deoxyglucose; Glucose; Glycolysis; Humans; Polyketides; Thiazoles
PubMed: 35713373
DOI: 10.1021/acs.orglett.2c01566 -
Nuclear Medicine Communications Aug 2021Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Data are limited regarding 18F-labelled fluoro-2-deoxyglucose...
Comparison of 18F-labelled fluoro-2-deoxyglucose-PET with conventional computed tomography for staging and response assessment in paediatric and adult patients with nodular lymphocyte-predominant Hodgkin's lymphoma.
BACKGROUND
Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon subtype of Hodgkin lymphoma. Data are limited regarding 18F-labelled fluoro-2-deoxyglucose (FDG)-PET use in NLPHL. We are reporting our experience with FDG-PET utility in staging and response assessment NLPHL patients.
METHODS
We retrospectively studied a population of all newly diagnosed or relapsed/refractory patients who underwent both pre-treatment contrast-enhanced computed tomography (CeCT) and an FDG-PET and also at the end of planned treatment.
RESULTS
We identified 68 patients found to have in total 312 scans, 78 paired pre-therapeutic and post-treatment CeCT and FDG-PET scans. Among them, 55 were male, with a median follow-up was 48 months. Median SUV-max was 8.3 (2.0-21.0). FDG-PET and CeCT were concordant in 80% (62/78) of staging scans. In 20% (16/78) of patients in whom a discordance was observed, FDG-PET resulted in upstaging in 13 scans and downstaging in 3 scans. The sensitivity of CeCT was 92% for nodal staging and 42% for extralymphatic staging when compared to FDG-PET. The specificity of CeCT was 98% as compared to FDG-PET. For response assessment, there was poor agreement between the CeCT and FDG-PET in assigning complete remission of disease scores as FDG-PET was able to identify the absence of disease despite the presence of a radiologically evident residual mass on CeCT. The sensitivity for CeCT compared to FDG-PET was 100% while the specificity was 43% for detection of post-treatment response.
CONCLUSION
For NLPHL, pre-therapeutic FDG-PET scan is better than CeCT staging. FDG-PET has much better specificity for response assessment than CeCT.
Topics: Adult; Child; Fluorodeoxyglucose F18; Hodgkin Disease; Humans; Male; Middle Aged; Positron-Emission Tomography; Retrospective Studies
PubMed: 33852535
DOI: 10.1097/MNM.0000000000001406