Expression Of Glucose Transporter Research Articles

Abstract 3317: Expression of glucose transporter-1 in follicular lymphoma affected tumor-infiltrating immunocytes and was related to progression of disease within 24 months

Abstract Objective Follicular lymphoma (FL) occurring progression within 24 months (POD24) after initial immunochemotherapy has poor prognosis. GLUT1 affects glycolysis within tumor microenvironment (TME) and promotes tumor progression. However, its specific mediated mechanism remains unclear in FL. Methods Baseline GLUT1 expression, infiltrations of M2 macrophage, and CD8+ T-cells were assessed by immunohistochemistry in FL with POD24 and long-term remission respectively. The spatial features of TME were assessed by MIBI-TOF and proteomics. Predictive immunophenotypes for POD24 occurrence was analyzed by random forest algorithm. The lactate production and the induction of M2 macrophages were detected when GLUT1 was transfected or knocked down in DOHH2. The activation of PI3K/Akt/mTOR signaling in DOHH2 and WSU-FSCCL cells co-cultured with induced inhibitory immunocytes was tracked by western blotting. Results The FL with POD24 exhibited higher baseline GLUT1 expression and increased infiltration of various inhibitory immunocytes. Spatial signatures of 69 immunophenotypes could predict POD24 occurrence. The activation of PI3K/Akt/mTOR signaling pathway was not significant in both groups. The supernatant of DOHH2-GLUT1 cells which had more lactate content could induce more M2-type macrophages than that of DOHH2/siRNA GLUT1 cells. When co-cultured with exhausted CD8+ T cells, M2-type macrophages and Tregs, compared with WSU-FSCCL cells, DOHH2 cells with high GLUT1 expression induced more M2-type macrophages and was triggered activation of PI3K/Akt/mTOR signaling pathway. Conclusion Tumor cells overexpressing GLUT1 could domesticate immunocytes to form an immunosuppressive TME, which promotes occurrence of POD24 and gradually activates PI3K/Akt/mTOR pathway of tumor cells in FL. Clinical correlation between GLUT1 expression and tumor-infiltrating macrophages and CD8+ T cells GLUT1 expression High n(%) Low n(%) P value CD206 expression High 16(43.2) 5(18.5) 0.037 Low 21(56.8) 22(81.5) CD8 expression High 27(73.0) 12(44.4) 0.021 Low 10(27.0) 15(55.6) Citation Format: Jianli Ma, Yuwei Deng, Shu Zhao, Ming Yang, Yutian Yu, Qingyuan Zhang, Jinming Yu. Expression of glucose transporter-1 in follicular lymphoma affected tumor-infiltrating immunocytes and was related to progression of disease within 24 months [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2023; Part 1 (Regular and Invited Abstracts); 2023 Apr 14-19; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2023;83(7_Suppl):Abstract nr 3317.

Lignans from Patrinia scabiosaefolia improve insulin resistance by activating PI-3K/AKT pathway and promoting GLUT4 expression

Patrinia scabiosaefolia, is used as wild vegetable in China for more than 2 000 years, with a variety of pharmacological activities, including anti-inflammatory, anti-tumor and hypoglycemic. Based on our ongoing research on chemical constituents and hypoglycemic activity of P. scabiosaefolia, 4 lignan compounds, (+)-isolariciresinol (1), 7R,7'R,8S,8'S-(+)-neo-olivil-4-O-β-D-glucopyranoside (2), 4-O-methylcedrusin (3) and patrinian A (4), were isolated and identified. The hypoglycemic activity showed that compounds 2 and 3 could extremely significantly improve insulin resistance at 100 (P < 0.001), 50 (P < 0.001) and 25 µmol/L (P < 0.01) in IR 3T3-L1 cells. While compound 4 only promoted glucose uptake by IR 3T3-L1 cells at 100 µmol/L (P < 0.01). Western blotting experiments showed that compounds 2 and 4 up-regulated the protein expressions of p-IRS, PI-3K, p-AKT and glucose transporter 4 (GLUT4), and promoted the transcription of GLUT4 mRNA. Therefore, the mechanisms of compounds 2 and 4 were presumed to improve IR by activating PI-3K/AKT signaling pathway.

Nuciferine relieves type 2 diabetes mellitus via enhancing GLUT4 expression and translocation

Nuciferine contained in lotus leaves have been confirmed to have the effect of ameliorating hyperlipemia and hyperglycemia. A laser scanning confocal microscope was used to track the translocation of glucose transporter 4 (GLUT4) in L6 cells and the changes in intracellular Ca2+ levels in real time, and related protease inhibitors combined with western blotting were used to explore the mechanism of nuciferine. Meanwhile, KK-Ay mice, the spontaneous type 2 diabetic mice, were used to evaluate the in vivo activity of nuciferine. In this study, the in vitro studies indicated that nuciferine-induced GLUT4 translocation was regulated by G protein-PLC-PKC and AMPK pathways and nuciferine-enhanced intracellular Ca2+ was mediated by G protein-PLC-IP3-IP3R pathway, the increase in intracellular Ca2+ caused by nuciferine was not directly related to GLUT4 translocation, but both promote glucose uptake. The in vivo results suggested that nuciferine ameliorated weight gain induced by high-fat diet, abnormal lipid metabolism and the symptoms of insulin resistance in KK-Ay diabetic mice. Western blot results suggested that nuciferine increased AMPK and PKC phosphorylation levels in skeletal muscle and liver, and enhanced GLUT4 expression in skeletal muscle. Taken together, this research showed that nuciferine has the non-negligible potential in the treatment of type 2 diabetes mellitus.

Evaluation of the Expression Intensity of Glucose Transporter-1 Marker and its Diagnostic Value in Differentiating Between Borderline and Malignant Ovarian Epithelial Tumors

Background: Ovarian cancer ranks second among gynecological cancers worldwide. This study aimed to compare the glucose transporter-1 (GLUT-1) expression in benign, borderline, and malignant ovarian epithelial tumors and evaluate GLUT-1 expression as a diagnostic tool for distinguishing tumors in the ovary. Materials and Methods: This descriptive-analytical cross-sectional study analyzed 69 pathological samples of patients diagnosed with ovarian epithelial tumors who underwent oophorectomy. Immunohistochemical staining was performed using GLUT-1 antibody. The intensity of cell membrane staining and the proportion of positive neoplastic cells were graded to score immunostaining. Chi-square/Fisher’s exact test was used to analyze the data. The sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV), and staining accuracy for GLUT-1 in distinguishing borderline from invasive tumors were calculated by standard methods (P&lt;0.05). Results: In all benign tumors, GLUT-1 staining was negative. In addition, weak staining intensity was observed in 38.5% of borderline tumors, and 96% of invasive tumors had strong staining intensity (P&lt;0.001). Strong GLUT-1 staining was found in 94.7% of Papillary Serous Carcinoma, 9/1% of Borderline Serous tumors, 100% of Brenner tumors, and clear cell carcinoma. The results demonstrated a high diagnostic value of GLUT-1 expression intensity in differentiating between borderline and malignant ovarian epithelial tumors (Accuracy: 97.10, Sensitivity: 96%, Specificity: 97.73). Conclusion: Overall, GLUT-1 expression could help distinguish benign from borderline, especially borderline from malignant ovarian epithelial tumors. Thus, it seems that it provides useful prognostic information, particularly for the borderline category.

Antimutagenic 1,4-Dihydropyridine AV-153 Normalizes Expression of GLUT1, GLUT4, INOS, PARP1, and Gamma H2AX Histone in Myocardium of Rats with Streptozotocin Model of Diabetes Mellitus

Abstract Diabetic cardiomyopathy increases the risk of heart failure and worsens prognosis for diabetes mellitus (DM) patients. Its development depends on many factors, including modification of nitric oxide production and impaired DNA repair. The goal of the present work was to study in vivo effects of a 1,4-dihydropyridine AV-153, known as antimutagen and DNA-binder, on DNA integrity, and on the expression of several proteins involved in glucose transport, nitric oxide metabolism, and DNA repair in myocardium in diabetic rats. DM was induced in rats by streptozotocin (STZ) injection. Expression of proteins was studied by means of immunohistochemistry. Development of the STZ-induced DM significantly induced PARP1 and gamma H2AX histone, markers of DNA breakage, protein expression in heart tissue, while AV-153 administration decreased PARP1 and H2AX protein expression. In this model of diabetes, myocardial expression of iNOS was also significantly increased, but administration of AV-153 reduced it to normal levels. AV-153 also upregulated the expression of insulin-dependent GLUT4 and insulin-independent GLUT1 glucose transporters up to normal level in diabetic rats. Thus, AV-153 appears to be prospective for creation of a remedy for prevention of diabetic cardiomyopathy.

PD38-04 METABOLIC HETEROGENEITY OF HUMAN PROSTATE CANCER BASED ON 18 F-PSMA-1007 AND 18 F-FDG PET/CT AND ITS CLINICOPATHOLOGIC CHARACTERISTICS

You have accessJournal of UrologyCME1 Apr 2023PD38-04 METABOLIC HETEROGENEITY OF HUMAN PROSTATE CANCER BASED ON 18F-PSMA-1007 AND 18F-FDG PET/CT AND ITS CLINICOPATHOLOGIC CHARACTERISTICS Sungun Bang, Hyun Ho Han, Dongwoo Kim, Mijin Yun, and Seung Hwan Lee Sungun BangSungun Bang More articles by this author , Hyun Ho HanHyun Ho Han More articles by this author , Dongwoo KimDongwoo Kim More articles by this author , Mijin YunMijin Yun More articles by this author , and Seung Hwan LeeSeung Hwan Lee More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003336.04AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: 18F-FDG Positron emission tomography/computed tomography (PET/CT) is limited in evaluating prostate cancer (PCa) due to low glycolysis in the primary tumor. Recently, PET/CT targeting the prostate specific membrane antigen (PSMA) has been useful for the diagnosis of biochemical recurrence and subsequent radioligand therapy (RLT). So far, there are limited reports on the value of PSMA PET/CT in detecting primary tumors of the prostate gland. We conducted this study to evaluate the values of 18F-PSMA-1007 and 18F-FDG PET/CT in the primary tumor detection and understand metabolic heterogeneity and related clinicopathologic characteristics at initial presentation. METHODS: This prospective study included 73 tumor regions from 42 patients who underwent both 18F-PSMA-1007 and 18F -FDG PET/CT and subsequent radical prostatectomy. SUVmax of the primary tumors on 18F-PSMA-1007 PET/CT were compared with the histological subtype and Gleason score (GS) by Kruskal-Wallis test with Bonferroni correction and with tumor size, serum PSA, and pathological stage (pStage). GS 6 and 7 were considered low and 8 to 10 were high. pStage I and II were considered early and the rest was advanced. Immunohistochemistry (IHC) was done for glucose transporter, PSMA, and androgen receptor (AR) expression. RESULTS: 18F-PSMA-1007 PET/CT detected all primary tumors with a detection sensitivity of 100% (73/73) whereas 18F-FDG PET/CT detected only 16% (12/73). When tumors were classified into low-GS acinar, high-GS acinar, and high-GS ductal types, SUVmax of 18F-PSMA-1007 uptake was significantly different among the three groups (SUVmax 8.9 in low-GS acinar, 14.7 in high-GS ductal, and 33.9 in high-GS acinar, all p values<0.05). In addition, high 18F-PSMA-1007 uptake was correlated with high serum PSA level, and advanced pStage. There were 12 primary lesions with both 18F-PSMA and 18F-FDG uptake demonstrating a flip-flop phenomenon between the two radiotracer uptake; the foci of increased 18F-FDG uptake showed low 18F-PSMA-1007 uptake and vice versa. All were advanced in pStage with low AR expression on IHC and most of them (9/12) were large ductal tumors. CONCLUSIONS: 18F-PSMA-1007 PET/CT was excellent in detecting primary tumors of all GS in the prostate gland. Some primary tumors showed a reciprocal pattern of 18F-PSMA-1007 and 18F-FDG uptake which were mostly large ductal type with low AR expression. Further studies are needed to see whether tumors with 18F-FDG uptake may predict treatment resistance to androgen deprivation therapy and PSMA RLT. Source of Funding: None © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e994 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Sungun Bang More articles by this author Hyun Ho Han More articles by this author Dongwoo Kim More articles by this author Mijin Yun More articles by this author Seung Hwan Lee More articles by this author Expand All Advertisement PDF downloadLoading ...

Perturbated glucose metabolism augments epithelial cell proinflammatory function in chronic rhinosinusitis

Glucose concentrations are increased in nasal secretions in chronic rhinosinusitis (CRS). However, the glucose metabolism and its contribution to disease pathogenesis in CRS remain unexplored. We sought to explore the glucose metabolism and its effect on the function of nasal epithelial cells in CRS with and without nasal polyps (CRSwNP and CRSsNP). Glucose metabolites were detected with mass spectrometry. The mRNA levels of glucose transporters (GLUTs), metabolic enzymes, and inflammatory mediators were detected by quantitative RT-PCR. The protein expression of GLUTs was studied by immunofluorescence staining, Western blotting, and flow cytometry. Glucose uptake was measured by using fluorescent glucose analog. Human nasal epithelial cells (HNECs) were cultured. Bioenergetic analysis was performed with Seahorse XF analyzer. Gene expression in HNECs was profiled by RNA sequencing. Increased glucose concentrations in nasal secretions was confirmed in both CRSsNP and CRSwNP. GLUT4, GLUT10, and GLUT11 were abundantly expressed in HNECs, whose expression was upregulated by inflammatory cytokines and D-glucose and was increased in CRS. Glucose uptake, glycolysis and tricarboxylic acid cycle metabolites, metabolic enzymes, and extracellular acidification rate and oxygen consumption rates were increased in HNECs in CRSsNP and CRSwNP, with a predominant shift to glycolysis. HNECs treated with high-level apical D-glucose showed enhanced glucose uptake, predominant glycolysis, and upregulated production of IL-1α, IL-1β, TNF-α, CCL20, and CXCL8, which was suppressed by 2-deoxy-D-glucose, an inhibitor of glycolysis. Increased glucose in nasal secretions promotes glucose uptake and predominant glycolysis in epithelial cells, augmenting the proinflammatory function of epithelial cells in CRS.

Dynamic evolution and mechanism of myocardial glucose metabolism in different functional phenotypes of diabetic cardiomyopathy — a study based on 18 F-FDG microPET myocardial metabolic imaging

PurposeTo use 18 F-FDG microPET dynamic imaging to preliminarily identify the changes of myocardial glucose metabolism corresponding to different functional phenotypes of diabetic cardiomyopathy (DCM) in mice and elucidate their relationships.MethodsLeft ventricular function was measured by echocardiography in C57BL/KsJ-db/db (db/db) mice and their controls at 8, 12, 16, and 20 weeks of age to divide DCM stages and functional phenotypes. Myocardial histopathology was used to verify the staging accuracy and list-mode microPET dynamic imaging was conducted. The myocardial metabolic rate of glucose (MRglu) and the glucose uptake rate constant (Ki) were derived via Patlak graphical analysis, and the differences in myocardial glucose metabolism levels in different DCM stages were compared. The key proteins involved in myocardial glucose metabolism signaling pathway were analyzed by Western blotting to elucidate the underlying mechanism of abnormal glucose metabolism in DCM.ResultsCompared with the controls, the ratio of early diastolic transmitral flow velocity to early diastolic mitral annular tissue velocity (E/e’) of db/db mice was significantly increased from the age of 12 weeks, while the left ventricular ejection fraction (LVEF) was significantly decreased from the age of 16 weeks (all P < 0.05). Based on the staging criteria, 8 and 12 weeks (8/12w) db/db mice were in DCM stage 1 (diastolic dysfunction with normal LVEF), and 16 and 20 weeks (16/20w) db/db mice were in DCM stage 2/3 (diastolic and systolic dysfunction). The degree of myocardial fibrosis, glycogen deposition and ultrastructural damage in 16/20w db/db mice were more obvious than those in 8/12w group. The myocardial MRglu, Ki of db/db mice in 8/12w group or 16/20w group were significantly lower than those in the control group (all P < 0.05), while the myocardial standard uptake value (SUV) was not significantly reduced in the 8/12w group compared with the control group (P > 0.05). MRglu and SUV were moderately negatively correlated with the E/e’ ratio (r=-0.539 and − 0.512, P = 0.007 and 0.011), which were not significantly correlated with LVEF (P > 0.05). Meanwhile, Ki was not significantly correlated with LVEF or E/e’ ratio. The decreased expression of glucose transporter (GLUT) -4 in db/db mice preceded GLUT-1 and was accompanied by decreased phosphorylated AMP-activated protein kinase (p-AMPK) expression. Myocardial MRglu, Ki and SUV were significantly positively correlated with the expression of GLUT-4 (MRglu: r = 0.537; Ki: r = 0.818; SUV: r = 0.491; P = 0.000 ~ 0.046), but there was no significant correlation with GLUT-1 expression (P = 0.238 ~ 0.780).ConclusionsDuring the progression of DCM, with the changes of left ventricular functional phenotype, abnormal and dynamic changes of myocardial glucose metabolism can occur in the early stage.

Retraction notice to Glucose transporter-1 gene expression is associated with pancreatic cancer invasiveness and MMP-2 activity [Surgery -September 2004, Pages 548-556

This article has been retracted: please see Elsevier Policy on Article Withdrawal (https://www.elsevier.com/about/our-business/policies/article-withdrawal). This article has been retracted at the request of the Editors-in-Chief, because an investigation by Harvard Medical School and the Brigham and Women’s Hospital has concluded that Figure 3 is invalid and no underlying research data are available to resolve the discrepancies or validate the reported results. Glucose transporter-1 gene expression is associated with pancreatic cancer invasiveness and MMP-2 activitySurgeryVol. 136Issue 3PreviewOverexpression of the facilitative glucose transporter-1 (GLUT-1) has been observed for a wide range of human cancers, with the degree of overexpression generally being inversely correlated with prognosis. We tested the effects of modulating GLUT-1 expression on pancreatic cancer cellular invasiveness. Full-Text PDF

Plant Polyphenol Gossypol Induced Cell Death and Its Association with Gene Expression in Mouse Macrophages

Gossypol is a complex plant polyphenol reported to be cytotoxic and anti-inflammatory, but little is known about its effect on gene expression in macrophages. The objective of this study was to explore gossypol's toxicity and its effect on gene expression involved in the inflammatory response, glucose transport and insulin signaling pathways in mouse macrophages. Mouse RAW264.7 macrophages were treated with multiple concentrations of gossypol for 2-24 h. Gossypol toxicity was estimated by MTT assay and soluble protein content. qPCR analyzed the expression of anti-inflammatory tristetraprolin family (TTP/ZFP36), proinflammatory cytokine, glucose transporter (GLUT) and insulin signaling genes. Cell viability was greatly reduced by gossypol, accompanied with a dramatic reduction in soluble protein content in the cells. Gossypol treatment resulted in an increase in TTP mRNA level by 6-20-fold and increased ZFP36L1, ZFP36L2 and ZFP36L3 mRNA levels by 26-69-fold. Gossypol increased proinflammatory cytokine TNF, COX2, GM-CSF, INFγ and IL12b mRNA levels up to 39-458-fold. Gossypol treatment upregulated mRNA levels of GLUT1, GLUT3 and GLUT4 genes as well as INSR, AKT1, PIK3R1 and LEPR, but not APP genes. This study demonstrated that gossypol induced macrophage death and reduced soluble protein content, which was accompanied with the massive stimulation of anti-inflammatory TTP family and proinflammatory cytokine gene expression, as well as the elevation of gene expression involved in glucose transport and the insulin signaling pathway in mouse macrophages.

A glucose-sensing mechanism with glucose transporter 1 and pyruvate kinase in the area postrema regulates hepatic glucose production in rats

The area postrema (AP) of the brain is exposed to circulating metabolites and hormones. However, whether AP detects glucose changes to exert biological responses remains unknown. Its neighboring nuclei, the nucleus tractus solitarius (NTS), responds to acute glucose infusion by inhibiting hepatic glucose production, but the mechanism also remains elusive. Herein, we characterized AP and NTS glucose-sensing mechanisms. Infusion of glucose into the AP, like the NTS, of chow rats suppressed glucose production during the pancreatic (basal insulin)-euglycemic clamps. Glucose transporter 1 or pyruvate kinase lentiviral-mediated knockdown in the AP negated AP glucose infusion to lower glucose production, while the glucoregulatory effect of NTS glucose infusion was also negated by knocking down glucose transporter 1 or pyruvate kinase in the NTS. Furthermore, we determined that high-fat (HF) feeding disrupts glucose infusion to lower glucose production in association with a modest reduction in the expression of glucose transporter 1, but not pyruvate kinase, in the AP and NTS. However, pyruvate dehydrogenase activator dichloroacetate infusion into the AP or NTS that enhanced downstream pyruvate metabolism and recapitulated the glucoregulatory effect of glucose in chow rats still failed to lower glucose production in HF rats. We discovered that a glucose transporter 1- and pyruvate kinase-dependent glucose-sensing mechanism in the AP (as well as the NTS) lowers glucose production in chow rats and that HF disrupts the glucose-sensing mechanism that is downstream of pyruvate metabolism in the AP and NTS. These findings highlight the role of AP and NTS in mediating glucose to regulate hepatic glucose production.

Overexpression of facilitative glucose transporter-3 and membrane procoagulation in maternal platelets of preeclamptic pregnancy

BackgroundPreeclampsia (PE) is a hypertensive disorder during pregnancy that results in significant adverse maternal and neonatal outcomes. Platelet activation is present in PE and contributes to the thrombo-hemorrhagic states of the disorder. However, the mechanisms that initiate and/or sustain platelet activation in PE are ill-defined. ObjectivesWe aimed to characterise this mechanism and the procoagulant potentials of platelets in PE. MethodsIn this quantitative observational study, we analyzed platelet procoagulant membrane dynamics in patients with PE (n = 21) compared with age-matched normotensive pregnancies (n = 20), gestational hypertension (n = 10), and non-pregnant female controls (n = 19). We analyzed fluorescently labeled indicators of platelet activation, bioenergetics, and procoagulation (phosphatidylserine exposure and thrombin generation), coupled with high-resolution imaging and thrombelastography. We then validated our findings using flow cytometry, immunoassays, classical pharmacology, and convolutional neural network analysis. ResultsPE platelets showed significant ultra-structural remodeling, are more extensively preactivated than in healthy pregnancies and can circulate as microaggregates. Preactivated platelets of PE externalized phosphatidylserine and thrombin formed on the platelet membranes. Platelets’ expression of facilitative glucose transporter-1 increased in all pregnant groups. However, PE platelets additionally overexpress glucose transporter-3 to enhance glucose uptake and sustain activation and secretion events. Although preeclampsia platelets exposed to subendothelial collagen showed incremental activation, the absolute hemostatic response to collagen was diminished, and likely contributed to greater blood loss perioperatively. ConclusionsWe revealed 2 bioenergetic mediators in the mechanism of sustained platelet procoagulation in preeclampsia. Although glucose transporter-1 and glucose transporter-3 remain elusive antiprocoagulant targets, they may be sensitive monitors of PE onset and progression.

Role of myeloid cells in system-level immunometabolic dysregulation during prolonged successful HIV-1 treatment.

Why people with HIV-1 on ART (PWH ART ) display convoluted metabolism and immune cell functions during prolonged suppressive therapy is not well evaluated. In this study, we aimed to address this question using multiomics methodologies to investigate immunological and metabolic differences between PWH ART and HIV-1 negative individuals (HC). Cross-sectional study. Untargeted and targeted metabolomics was performed using gas and liquid chromatography/mass spectrometry, and targeted proteomics using Olink inflammation panel on plasma samples. The cellular metabolic state was further investigated using flow cytometry and intracellular metabolic measurement in single-cell populations isolated by EasySep cell isolation. Finally, flow cytometry was performed for deep-immunophenotyping of mononuclear phagocytes. We detected increased levels of glutamate, lactate, and pyruvate by plasma metabolomics and increased inflammatory markers (e.g. CCL20 and CCL7) in PWH ART compared to HC. The metabolite transporter detection by flow cytometry in T cells and monocytes indicated an increased expression of glucose transporter 1 (Glut1) and monocarboxylate transporter 1 (MCT-1) in PWH ART . Single cell-type metabolite measurement identified decreased glucose, glutamate, and lactate in monocytic cell populations in PWH ART . Deep-immunophenotyping of myeloid cell lineages subpopulations showed no difference in cell frequency, but expression levels of CCR5 were increased on classical monocytes and some dendritic cells. Our data thus suggest that the myeloid cell populations potentially contribute significantly to the modulated metabolic environment during suppressive HIV-1 infection.

TXNIP loss expands Myc-dependent transcriptional programs by increasing Myc genomic binding

The c-Myc protooncogene places a demand on glucose uptake to drive glucose-dependent biosynthetic pathways. To meet this demand, c-Myc protein (Myc henceforth) drives the expression of glucose transporters, glycolytic enzymes, and represses the expression of thioredoxin interacting protein (TXNIP), which is a potent negative regulator of glucose uptake. A Mychigh/TXNIPlow gene signature is clinically significant as it correlates with poor clinical prognosis in triple-negative breast cancer (TNBC) but not in other subtypes of breast cancer, suggesting a functional relationship between Myc and TXNIP. To better understand how TXNIP contributes to the aggressive behavior of TNBC, we generated TXNIP null MDA-MB-231 (231:TKO) cells for our study. We show that TXNIP loss drives a transcriptional program that resembles those driven by Myc and increases global Myc genome occupancy. TXNIP loss allows Myc to invade the promoters and enhancers of target genes that are potentially relevant to cell transformation. Together, these findings suggest that TXNIP is a broad repressor of Myc genomic binding. The increase in Myc genomic binding in the 231:TKO cells expands the Myc-dependent transcriptome we identified in parental MDA-MB-231 cells. This expansion of Myc-dependent transcription following TXNIP loss occurs without an apparent increase in Myc's intrinsic capacity to activate transcription and without increasing Myc levels. Together, our findings suggest that TXNIP loss mimics Myc overexpression, connecting Myc genomic binding and transcriptional programs to the nutrient and progrowth signals that control TXNIP expression.

Inhibiting NLRP3 Inflammasome Activation by CY-09 Helps to Restore Cerebral Glucose Metabolism in 3×Tg-AD Mice

The reduction of the cerebral glucose metabolism is closely related to the activation of the NOD-like receptor protein 3 (NLRP3) inflammasome in Alzheimer's disease (AD); however, its underlying mechanism remains unclear. In this paper, 18F-flurodeoxyglucose positron emission tomography was used to trace cerebral glucose metabolism in vivo, along with Western blotting and immunofluorescence assays to examine the expression and distribution of associated proteins. Glucose and insulin tolerance tests were carried out to detect insulin resistance, and the Morris water maze was used to test the spatial learning and memory ability of the mice. The results show increased NLRP3 inflammasome activation, elevated insulin resistance, and decreased glucose metabolism in 3×Tg-AD mice. Inhibiting NLRP3 inflammasome activation using CY-09, a specific inhibitor for NLRP3, may restore cerebral glucose metabolism by increasing the expression and distribution of glucose transporters and enzymes and attenuating insulin resistance in AD mice. Moreover, CY-09 helps to improve AD pathology and relieve cognitive impairment in these mice. Although CY-09 has no significant effect on ferroptosis, it can effectively reduce fatty acid synthesis and lipid peroxidation. These findings provide new evidence for NLRP3 inflammasome as a therapeutic target for AD, suggesting that CY-09 may be a potential drug for the treatment of this disease.

Effects of Stevioside on the Expressions of GLUT 1, GLUT 3, and GLUT 4 Proteins in Diabetic Rat Placenta.

The placenta provides maternal-fetal nutrient transport. The primary source of energy for fetus development is glucose and maternal-fetal glucose transport occurs through glucose transporters (GLUTs). Stevioside, a component of Stevia rebaudiana Bertoni, is used for medicinal and commercial purposes. We aim to determine the effects of stevioside on GLUT 1, GLUT 3, and GLUT 4 proteins expressions in diabetic rat placentas. The rats are divided into four groups. A single dose of streptozotocin (STZ) is administered to form the diabetic groups. Pregnant rats receive stevioside to form the stevioside and diabetic + stevioside groups. According to immunohistochemistry results, GLUT 1 protein is found in both the labyrinth and junctional zones. GLUT 3 protein is limited in the labyrinth zone. GLUT 4 protein is detected in trophoblast cells. According to Western blotting results, on the 15th and 20th days of pregnancy, there is no difference in the expression of GLUT 1 protein between groups. On the 20th day of pregnancy, the expression of GLUT 3 protein in the diabetic group is statistically higher compared to the control group. On the 15th day and 20th day of pregnancy, the expression of GLUT 4 protein in the diabetic group is statistically lower compared to the control group. Insulin levels in blood samples derived from rat abdominal aorta are determined by the ELISA method. According to the ELISA results, there is no difference in insulin protein concentration between groups. Stevioside treatment reduces GLUT 1 protein expression under diabetic conditions.

Relationship between Systemic Inflammatory Markers, GLUT1 Expression, and Maximum 18F-Fluorodeoxyglucose Uptake in Non-Small Cell Lung Carcinoma and Their Prognostic Significance

Factors involved in inflammation and cancer interact in various ways with each other, and biomarkers of systemic inflammation may have a prognostic value in cancer. Glucose transporter 1 (GLUT1) plays a pivotal role in glucose transport and metabolism and it is aberrantly expressed in various cancer types. We evaluated the differential expression of GLUT1, along with 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) in non-small-cell lung cancer (NSCLC), and then analyzed their prognostic significance. A total of 163 patients with resectable NSCLC were included in this study. Tumor sections were immunohistochemically stained for GLUT1 and GLUT3. Maximum standardized uptake value (SUVmax) was measured by preoperative FDG-PET, and neutrophil-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and lymphocyte-monocyte ratio (LMR) were derived from pretreatment blood count. GLUT1 and GLUT3 was positively expressed in 74.8% and 6.1% of the NSCLC tissues, respectively. GLUT1 expression was significantly correlated with squamous cell carcinoma histology, poor differentiation, high pathologic stage, old age, male, smoking, and high SUVmax (>7) (all p < 0.05). The squamous cell carcinoma and smoker group also showed significantly higher SUVmax (both p < 0.001). Systemic inflammation markers, including NLR, PLR, and LMR, were positively correlated with high SUVmax (all p < 0.05). High GLUT1 expression, high SUVmax, high NLR, and low LMR, were significantly associated with poor overall survival in patients with NSCLC. However, in the multivariate survival analysis, LMR was an independent prognostic factor overall (HR 1.86, 95% CI 1.05-3.3) and for the stage I/II cohort (HR 2.3, 95% CI 1.24-4.3) (all p < 0.05). Systemic inflammatory markers-NLR, PLR, and LMR are strongly correlated with the SUVmax and are indicators of aggressive tumor behavior. Specifically, LMR is a promising prognostic biomarker in NSCLC patients.

Predicting response to neoadjuvant therapy with glucose transporter-1 in breast cancer.

Glucose transporter-1 is a marker involved in energy transport in cancer cells. It has been shown to be a poor prognostic factor in many cancer types, including breast cancer. However, there is no satisfactory parameter predicting treatment in breast cancer patients receiving neoadjuvant therapy. This study investigated the effect of glucose transporter-1 in predicting the treatment response of patients receiving neoadjuvant therapy. In this study, glucose transporter-1 immunohistochemistry was applied to tru-cut biopsy of patients who were diagnosed with breast cancer and received neoadjuvant therapy between 2010 and 2021. A built-in scoring system was used to evaluate both the pattern and intensity of glucose transporter-1 immunohistochemistry staining. The relationship between glucose transporter-1 immunohistochemistry staining and other clinicopathological parameters was examined. In addition, the relationship of glucose transporter-1 with response to treatment was investigated. A relationship was found between high glucose transporter-1 expression and other clinicopathological parameters (such as estrogen and progesterone receptor negativity, high Ki-67, triple-negative, and Her2 status). Cases with high glucose transporter-1 expression had either a complete or a partial pathologic response. The result was statistically significant. Glucose transporter-1 has the potential to be a biomarker that can be evaluated more objectively as an alternative to Ki-67 labeling index in evaluating the response to treatment in patients receiving neoadjuvant therapy.

Differential regulatory effects of dietary lipid level on growth, antioxidant capacity and expression of genes involved in lipid and glucose metabolism of juvenile mud crab Scylla paramamosain

Three isonitrogenous diets (41% crude protein) with 4.87%, 10.75% and 16.10% lipid were designed to evaluate the effects of dietary lipid levels growth, antioxidant capacity, expression levels of genes related to lipid and glucose metabolism of juvenile Scylla paramamosain. Each diet was fed to four replicates of 32 crabs with initial weight 5.10 ± 0.05 g for 6 weeks. The results indicated that crabs fed diet with 10.75% lipid exhibited significantly higher percent weight gain (PWG) and specific growth rate (SGR) than those fed diet with 4.87% lipid (P < 0.05), and crabs fed diets with 10.75% and 16.10% lipid had significantly higher protein efficiency ratio (PER) and feed efficiency (FE) than those fed diet with 4.87% lipid (P < 0.05). Crabs fed diet with 4.87% lipid had the lowest concentrations of lipid and glycogen in muscle, lipid content in hepatopancreas and hemolymph glucose among all treatments (P < 0.05). The concentrations of free fatty acid (FFA), triglyceride (TG), total cholesterol (TCHO) and pyruvate in hemolymph and hepatopancreas increased significantly with the dietary lipid levels increasing from 4.87% to 16.10% (P < 0.05), while the concentration of crustacean insulin-like (INS) in hemolymph and crustacean hyperglycemic hormone (CHH) in hepatopancreas significantly decreased with the increase of dietary lipid levels (P < 0.05). In the hepatopancreas, The Oil Red-positive area significantly increased with increase of dietary lipid levels (P < 0.05). Crabs fed diet with 16.10% lipid showed the lowest concentration of glutathione peroxidase (GSH-Px) (P < 0.05). On the contrary, the highest concentration of malondialdehyde (MDA) was observed at crabs fed diet with 16.10% lipid (P < 0.05). Crabs fed diets with 10.75% and 16.10% lipid down-regulated expression of genes related to long-chain-PUFA biosynthesis and lipid synthesis in hepatopancreas than those fed diet with 4.87% lipid (P < 0.05). The mRNA level of cpt1 significantly up-regulated with the increase of dietary lipid levels, while the mRNA expression level cpt2, acox1 and fabp4 in hepatopancreas significantly down-regulated in crabs fed diets with 10.75% and 16.10% lipid (P < 0.05). The expression of gk and pfk in crabs fed diet with 16.10% lipid significantly down-regulated than those in other groups (P < 0.05). The expressions level of genes related to gluconeogenesis significantly down-regulated in crabs fed diets with 10.75% and 16.10% lipid (P < 0.05). The lowest mRNA expression of glucose transporter 4 (glut4) was occurred in crabs fed diet with 16.10% lipid (P < 0.05). Overall, the results of present study demonstrated that the dietary 10.75% lipid can improve the growth and feed utilization for juvenile mud crab, in addition, dietary lipid can affect the antioxidant capacity, lipid metabolism, glucose metabolism and insulin signaling pathway, dietary excessive lipid resulted in lipid deposition of hepatopancreas for juvenile mud crab.

Smilax china L. Polyphenols Improves Insulin Resistance and Obesity in High-fat Diet-induced Mice Through IRS/AKT-AMPK and NF-κB Signaling Pathways.

Smilax china L. is an important herb used in traditional Chinese medicine. In this study, the mechanism of Smilax china L. polyphenols (SCP) on insulin resistance and anti-obesity in mice induced by a high-fat diet (HFD) was investigated. Fifty female mice were randomly divided into five groups: control, HFD and low, medium, and high doses of SCP for 70 d. SCP significantly decreased intraperitoneal adipose tissue index, body weight gain, liver lipids, and serum inflammatory factor levels. Blood glucose and insulin concentrations, as well as insulin resistance index in SCP, were significantly lower than those in HFD. In addition, SCP markedly up-regulated the gene expression of glucose transporter 4 (GLUT4), insulin receptor substrate 1 (IRS1), insulin receptor substrate 2 (IRS2), serine-threonine kinase (AKT), Acyl-CoA oxidase (ACO), and protein kinase A (PKA), and down-regulated the expression of mammalian target of rapamycin complex 1 (mTORC1), sterol-responsive element-binding protein-1c (SREBP1c), fatty acid synthase (FAS), 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR), and forkhead box protein O1 (FOXO1). SCP significantly increased the protein expression of AKT, GLUT4, AMP-activated protein kinase (AMPK), phosphorylated-AMPK (p-AMPK), phosphorylated-AKT (p-AKT), and uncoupling protein 1 (UCP-1), and decreased the expression of SREBP1c, FAS, HMGCR, phosphorylation of IKBα (p-IKBα), and nuclear factor kappa B subunit p65 (P65) in the liver. Overall, SCP effectively reduced HFD-induced insulin resistance and obesity in mice, partly through NF-κB and IRS/AKT-AMPK signaling pathways to regulate inflammatory factors. Therefore, SCP may improve lifestyle diseases.