Metabolic Perturbation Associated With COVID-19 Disease Severity and SARS-CoV-2 Replication.

Viruses hijack host metabolic pathways for their replicative advantage. In this study, using patient-derived multiomics data and in vitro infection assays, we aimed to understand the role of key metabolic pathways that can regulate severe acute respiratory syndrome coronavirus-2 reproduction and their association with disease severity. We used multiomics platforms (targeted and untargeted proteomics and untargeted metabolomics) on patient samples and cell-line models along with immune phenotyping of metabolite transporters in patient blood cells to understand viral-induced metabolic modulations. We also modulated key metabolic pathways that were identified using multiomics data to regulate the viral reproduction in vitro. Coronavirus disease 2019 disease severity was characterized by increased plasma glucose and mannose levels. Immune phenotyping identified altered expression patterns of carbohydrate transporter, glucose transporter 1, in CD8+ T cells, intermediate and nonclassical monocytes, and amino acid transporter, xCT, in classical, intermediate, and nonclassical monocytes. In in vitro lung epithelial cell (Calu-3) infection model, we found that glycolysis and glutaminolysis are essential for virus replication, and blocking these metabolic pathways caused significant reduction in virus production. Taken together, we therefore hypothesized that severe acute respiratory syndrome coronavirus-2 utilizes and rewires pathways governing central carbon metabolism leading to the efflux of toxic metabolites and associated with disease severity. Thus, the host metabolic perturbation could be an attractive strategy to limit the viral replication and disease severity.

Aerobic exercise improves LPS-induced sepsis via regulating the Warburg effect in mice.

We investigated the impact of aerobic exercise (AE) on multiple organ dysfunction syndrome (MODS), aortic injury, pathoglycemia, and death during sepsis. ICR mice were randomized into four groups: Control (Con), Lipopolysaccharide (LPS), Exercise (Ex), and Exercise + LPS (Ex + LPS) groups. Mice were trained with low-intensity for 4 weeks. LPS and Ex + LPS mice received 5 mg/kg LPS intraperitoneally for induction of sepsis. Histopathological micrographs showed the organ morphology and damage. This study examined the effects of AE on LPS-induced changes in systemic inflammation, pulmonary inflammation, lung permeability, and bronchoalveolar lavage fluid (BALF) cell count, oxidative stress-related indicators in the lung, blood glucose levels, plasma lactate levels, serum insulin levels, plasma high-mobility group box 1 (HMGB1) levels, glucose transporter 1 (Glut1) and HMGB1, silent information regulator 1 (Sirt-1), and nuclear factor erythroid 2-related factor 2 (Nrf-2) mRNA expression levels in lung tissue. AE improved sepsis-associated multiple organ dysfunction syndrome (MODS), aortic injury, hypoglycemia, and death. AE prominently decreased pulmonary inflammation, pulmonary edema, and modulated redox balance during sepsis. AE prominently decreased neutrophil content in organ. AE prominently downregulated CXCL-1, CXCL-8, IL-6, TNF-α, Glu1, and HMGB1 mRNA expression but activated IL-1RN, IL-10, Sirt-1, and Nrf-2 mRNA expression in the lung during sepsis. AE decreased the serum levels of lactate and HMGB1 but increased blood glucose levels and serum insulin levels during sepsis. A 4-week AE improves sepsis-associated MODS, aortic injury, pathoglycemia, and death. AE impairs LPS-induced lactate and HMGB1 release partly because AE increases serum insulin levels and decreases the levels of Glut1. AE is a novel therapeutic strategy for sepsis targeting aerobic glycolysis.

Evaluation of GLUT1, IGF-2, VEGF, FGF 1, and angiopoietin 2 in infantile hemangioma.

INTRODUCTION: Infantile hemangioma (IH) is a common vascular tumor in children. It is reported that IHs are associated with immunochemical markers such as vascular endothelial growth factor (VEGF)-A, glucose transporter isoform 1 (GLUT1), and insulin-like growth factor-2 (IGF-2). MATERIAL AND METHODS: This cross-sectional study focused on pediatric patients with IH. A total of 46 patients (mean age 14.2±21.9 months) with IH and 45 healthy controls (mean age 21.8±15.08 months) were enrolled. Demographic data, clinical findings, and laboratory parameters were recorded. Blood samples were collected. Serum GLUT1, IGF-2, VEGF-A, fibroblast growth factor 1 (FGF1), and angiopoietin 2 levels were assessed by enzyme-linked immunosorbent assay. RESULTS: Serum GLUT1, IGF-2, and VEGF-A levels were significantly higher in patients with IH than in healthy controls (8.80±4.07pg/mL vs. 5.66±4.34pg/mL, 281.10±84.12pg/mL vs. 234.19±75.38pg/mL, 1196.99±389.34pg/mL vs. 996.99±349.16pg/mL, respectively, p=0.026, p=0.030, and p=0.036). Serum GLUT1, IGF-2, and VEGF-A levels in patients with complicated hemangioma were significantly higher than in healthy controls (9.69±3.94pg/mL vs. 5.66±4.34pg/mL, 289.94±83.18pg/mL vs. 234.19±75.38pg/mL, 1276.22±388.24pg/mL vs. 996.99±349.16pg/mL, respectively, p=0.017, p=0.022, and p=0.011). Serum GLUT1, IGF-2, and VEGF-A levels in patients with hemangioma receiving propranolol treatment were significantly higher than in healthy controls. Serum FGF1 levels were higher in patients with IH, complicated hemangioma, and hemangioma receiving propranolol treatment than in healthy controls but the difference was not statistically significantly. CONCLUSION: Serum GLUT1, IGF-2, and VEGF-A levels were positively correlated with disease severity in patients with hemangioma, for example, in complicated hemangioma and hemangioma requiring propranolol treatment. However, further research on larger and different age subgroups is warranted to assess these markers.

Effects of feeding high volumes of milk replacer on reproductive performance and on concentrations of metabolites and hormones in blood of Japanese black heifer calves.

We evaluated the effects of feeding high volumes of milk replacer on growth and reproductive performances in Japanese black heifers. Fifty-one heifers were fed milk replacer at 9 L/day for 60 days (9 L × 60 days; n = 18) or 41 days (9 L × 41 days; n = 15), or at 7 L/day for 40 days (7 L × 40 days; n = 18). Artificial insemination (AI) was performed on heifers with ≥270 kg body weight and ≥116 cm body height at 300 days of age. The age at the first AI was 0.35 month later for 7 L × 40 days than the other groups (p < .01). However, age at calving did not differ among treatments (22.1 months). The interval from the first AI to pregnancy tended to be ~2 months longer for the 9 L × 60 days than the other groups (p = .07). Our results showed that feeding high volumes of milk replacer may reduce the age at calving via an improved rate of growth. In addition, we propose that feeding a maximum of 7 L milk replacer for 40 days may be the most appropriate rearing regime because the success of pregnancy per AI may be reduced in calves fed a maximum of 9 L for 41 and 60 days.

Decreased GLUT1/NHE1 RNA expression in whole blood predicts disease severity in patients with COVID-19.

AIMS: We aimed to assess whether expression of whole-blood RNA of sodium proton exchanger 1 (NHE1) and glucose transporter 1 (GLUT1) is associated with COVID-19 infection and outcome in patients presenting to the emergency department with respiratory infections. Furthermore, we investigated NHE1 and GLUT1 expression in the myocardium of deceased COVID-19 patients. METHODS AND RESULTS: Whole-blood quantitative assessment of NHE1 and GLUT1 RNA was performed using quantitative PCR in patients with respiratory infection upon first contact in the emergency department and subsequently stratified by SARS-CoV-2 infection status. Assessment of NHE1 and GLUT1 RNA using PCR was also performed in left ventricular myocardium of deceased COVID-19 patients. NHE1 expression is up-regulated in whole blood of patients with COVID-19 compared with other respiratory infections at first medical contact in the emergency department (control: 0.0021 ± 0.0002, COVID-19: 0.0031 ± 0.0003, P = 0.01). The ratio of GLUT1 to NHE1 is significantly decreased in the blood of COVID-19 patients who are subsequently intubated and/or die (severe disease) compared with patients with moderate disease (moderate disease: 0.497 ± 0.083 vs. severe disease: 0.294 ± 0.0336, P = 0.036). This ratio is even further decreased in the myocardium of patients who deceased from COVID-19 in comparison with the myocardium of non-infected donors. CONCLUSIONS: NHE1 and GLUT1 may be critically involved in the disease progression of SARS-CoV-2 infection. We show here that SARS-CoV-2 infection critically disturbs ion channel expression in the heart. A decreased ratio of GLUT1/NHE1 could potentially serve as a biomarker for disease severity in patients with COVID-19.

Oral glucose tolerance test does not affect degree of hemoglobin glycation as measured by routine assay.

BACKGROUND: Hemoglobin A1c (HbA1c) is an accurate index of fluctuation in glycemia over the 2-3 months prior to quantitative assessment. During this time, hemoglobin (Hb) slowly glycates until it shows the properties of advanced glycation end-products. Glycation kinetics is intensified by prolonged glucose exposure. In subjects undergoing oral glucose tolerance testing (OGTT), immediately after ingestion, glucose is ostensibly transported by the glucose transporter 1 (GLUT1) to erythrocyte corpuscular hemoglobin. The earliest significant measurable level of hemoglobin glycation associated with this transportation is still not clear. SUBJECTS AND METHODS: We attempted to explore the early impact of short-term glucose load on HbA1c levels, because it is now known that transmembrane GLUT1-mediated glucose transport occurs immediately. A total of 88 participants (46 patients and 42 clinically healthy controls) underwent fasting plasma glucose quantitation during an OGTT. HbA1c, revealed by a monoclonal anti-glycation epitope antibody and adiponectin, was quantitated before (T0) and 2 hours (T120) after 80 g glucose ingestion. RESULTS: Wilcoxon test revealed that the HbA1c values did not significantly vary (P=0.15) during the OGTT, whereas glucose concentration varied strongly between T0 and T120. DISCUSSION: It is well known that quantitative estimation of HbA1c is informative for clinical care, independently of glucose level. The molecular mechanisms and dynamics by which glucose enters/exits red blood cells are incompletely known and may differ between individuals. We here show, for the first time, that HbA1c levels do not significantly increase during OGTT, supporting the view that non-enzymatic glycation of hemoglobin occurs slowly and that glycation during the 2 hours of an OGTT is insignificant.

An olaparib window-of-opportunity trial in patients with early-stage endometrial carcinoma: POLEN study.

OBJECTIVE: Olaparib is a potent inhibitor of poly(ADP-ribose) polymerase (PARP)-1, 2, and 3 with potential activity in endometrial cancer (EC). METHODS: In this window-of-opportunity trial, women with operable type 1 EC received olaparib oral tablets (300mg) twice daily for 28days before surgery. The primary objective was to evaluate the effects of olaparib on EC in tissue samples taken at baseline and at treatment completion. Signal of activity was defined as significant changes in the expression of the cell cycle-related proteins cyclin D1, Ki67, and cleaved caspase-3. RESULTS: A total of 31 patients were included in the biomarker analysis. The median time of olaparib exposure was 24 days (1-39). Significant inhibition was found for cyclin D1 (p < 0.01), but not for Ki67 and active caspase 3 immunostaining. PARP-1 levels positively correlated with cyclin D1 levels (rho = 0.661, p = 0.0001). Both PARP-1 and cyclin D1 levels were significantly lower (p = 0.022 and p = 0.004, respectively) in patients with ARID1A[-] tumors than ARID1A[+] tumors. A significant relationship between plasma olaparib concentrations and decreased GLUT1 activity was observed (r = -0.5885; p < 0.05). Drug-related toxicity consisted mostly of gastrointestinal and grade 1 or 2 adverse events. CONCLUSIONS: Olaparib reduced expression of cyclin D1, which positively correlated with PARP-1 levels. This effect was more evident in ARID1A-deficient tumors. Olaparib further induced inhibition of GLUT1 plasma activity. Our findings could have noteworthy implications in predicting which patients with EC would benefit from olaparib-based strategies.

Basal Sodium-Dependent Vitamin C Transporter 2 polarization in choroid plexus explant cells in normal or scorbutic conditions.

Vitamin C is incorporated into the cerebrospinal fluid (CSF) through choroid plexus cells. While the transfer of vitamin C from the blood to the brain has been studied functionally, the vitamin C transporter, SVCT2, has not been detected in the basolateral membrane of choroid plexus cells. Furthermore, it is unknown how its expression is induced in the developing brain and modulated in scurvy conditions. We concluded that SVCT2 is intensely expressed in the second half of embryonic brain development and postnatal stages. In postnatal and adult brain, SVCT2 is highly expressed in all choroidal plexus epithelial cells, shown by colocalization with GLUT1 in the basolateral membranes and without MCT1 colocalization, which is expressed in the apical membrane. We confirmed that choroid plexus explant cells (in vitro) form a sealed epithelial structure, which polarized basolaterally, endogenous or overexpressed SVCT2. These results are reproduced in vivo by injecting hSVCT2wt-EYFP lentivirus into the CSF. Overexpressed SVCT2 incorporates AA (intraperitoneally injected) from the blood to the CSF. Finally, we observed in Guinea pig brain under scorbutic condition, that normal distribution of SVCT2 in choroid plexus may be regulated by peripheral concentrations of vitamin C. Additionally, we observed that SVCT2 polarization also depends on the metabolic stage of the choroid plexus cells.

Relationship between plasma glycation with membrane modification, oxidative stress and expression of glucose trasporter-1 in type 2 diabetes patients with vascular complications.

BACKGROUND OF STUDY: Enhanced protein glycation in diabetes causes irreversible cellular damage through membrane modifications. Erythrocytes are persistently exposed to plasma glycated proteins; however, little are known about its consequences on membrane. Aim of this study was to examine the relationship between plasma protein glycation with erythrocyte membrane modifications in type 2 diabetes patients with and without vascular complications. METHOD: We recruited 60 healthy controls, 85 type 2 diabetic mellitus (DM) and 75 type 2 diabetic patients with complications (DMC). Levels of plasma glycation adduct with antioxidants (fructosamine, protein carbonyl, ß-amyloids, thiol groups, total antioxidant status), erythrocyte membrane modifications (protein carbonyls, ß-amyloids, free amino groups, erythrocyte fragility), antioxidant profile (GSH, catalase, lipid peroxidation) and Glut-1 expression were quantified. RESULT: Compared with controls, DM and DMC patients had significantly higher level of glycation adducts, erythrocyte fragility, lipid peroxidation and Glut-1 expression whereas declined levels of plasma and cellular antioxidants. Correlation studies revealed positive association of membrane modifications with erythrocyte sedimentation rate, fragility, peroxidation whereas negative association with free amino groups, glutathione and catalase. CONCLUSION: Our data suggest that plasma glycation is associated with oxidative stress, Glut-1 expression and erythrocyte fragility in DM patients. This may further contribute to progression of vascular complications.

Characteristics of noninvoluting congenital hemangioma: a retrospective review.

BACKGROUND: Noninvoluting congenital hemangioma (NICH) is a distinct vascular tumor of infancy. OBJECTIVE: We describe the clinical characteristics, histopathology, imaging, and natural history of NICH and compare our findings with previous reports. METHODS: We conducted a retrospective review of charts and photographic databases from 2 vascular anomaly centers over a 15-year period. RESULTS: Thirty cases of NICH were identified. All patients had fully formed vascular lesions at birth that demonstrated a nonprogressive course. The trunk and lower extremities were preferred sites and there was a female predominance. Thirteen of 30 patients reported pain. Focal necrosis and scarring was seen in a minority. Doppler studies, when performed, confirmed high vascular flow. Microscopic evaluation of 4 excised lesions showed lobular areas of endothelial cell proliferation directly adjacent to ectatic malformed vessels. Immunohistochemical studies demonstrated absence of glucose transporter-1 protein expression in every case. Wilms tumor-1 positivity was observed in lobular areas. The larger vessels did not stain with Wilms tumor-1, but some displayed D2-40 positivity. LIMITATIONS: Patients were referred to university-based pediatric vascular anomaly centers, with potential bias toward more severe or extensive cases. CONCLUSIONS: This retrospective study highlights the unique clinical and histopathologic features of NICH.

Adolescents with clinical type 1 diabetes display reduced red blood cell glucose transporter isoform 1 (GLUT1).

Type 1 diabetic (T1D) adolescent children on insulin therapy suffer episodes of both hyper- and hypoglycemic episodes. Glucose transporter isoform GLUT1 expressed in blood-brain barrier (BBB) and red blood cells (RBC) compensates for perturbed circulating glucose toward protecting the supply to brain and RBCs. We hypothesized that RBC-GLUT1 concentration, as a surrogate for BBB-GLUT1, is altered in T1D children. To test this hypothesis, we measured RBC-GLUT1 by enzyme-linked immunosorbent assay (ELISA) in T1D children (n = 72; mean age 15.3 ± 0.2 yr) and control children (CON; n = 11; mean age 15.6 ± 0.9 yr) after 12 h of euglycemia and during a hyperinsulinemic-hypoglycemic clamp with a nadir blood glucose of ~3.3 mmol/L for 90 min (clamp I) or ~3 mmol/L for 45 min (clamp II). Reduced baseline RBC-GLUT1 was observed in T1D (2.4 ± 0.17 ng/ng membrane protein); vs. CON (4.2 ± 0.61 ng/ng protein) (p < 0.0001). Additionally, baseline RBC-GLUT1 in T1D negatively correlated with hemoglobin A1c (HbA1c) (R = -0.23, p < 0.05) but not in CON (R = 0.06, p < 0.9). Acute decline in serum glucose to 3.3 mmol/L (90 min) or 3 mmol/L (45 min) did not change baseline RBC-GLUT1 in T1D or CON children. We conclude that reduced RBC-GLUT1 encountered in T1D, with no ability to compensate by increasing during acute hypoglycemia over the durations examined, may demonstrate a vulnerability of impaired RBC glucose transport (serving as a surrogate for BBB), especially in those with the worst control. We speculate that this may contribute to the perturbed cognition seen in T1D adolescents.

Hydration of AMP and ATP molecules in aqueous solution and solid films.

Water enables life and plays a critical role in biology. Considered as a versatile and adaptive component of the cell, water engages a wide range of biomolecular interactions. An organism can exist and function only if its self-assembled molecular structures are hydrated. It was shown recently that switching of AMP/ATP binding to the insulin-independent glucose transporter Human Erythrocyte Glucose Transport Protein (GLUT1) may greatly influence the ratio of bulk and bound water during regulation of glucose uptake by red blood cells. In this paper, we present the results on the hydration properties of AMP/ATP obtained by means of dielectric spectroscopy in aqueous solution and for fully ionized forms in solid amorphous films with the help of gravimetric studies.

A new class of drug for the management of type 2 diabetes: sodium glucose co-transporter inhibitors: 'glucuretics'.

BACKGROUND: Type 2 diabetes is a common, chronic disease with a prevalence that is increasing at epidemic proportions. Management involves advice on lifestyle changes, oral anti-hyperglycaemic agents and/or insulin. The kidneys play a major role in the regulation of glucose, re-absorbing 99% of the plasma glucose filtered through the renal glomeruli tubules. The glucose transporter, SGLT2, which is found primarily in the S1 segment of the proximal renal tubule accounts for 90% of glucose re-absorption. Competitive inhibition of SGLT2 induces glucosuria in a dose dependent manner and appears to have beneficial effects on glucose regulation in individuals with type 2 diabetes. O-glucoside phlorozin is the model substance for SGLT2 inhibitors: various O-, C-, N- and S-glucosides with varying affinity and specificity have been synthesised. AIMS: The aim of this review is to describe the background, the mechanism of action and the possible role for sodium glucose co-transporter inhibitors in the treatment of diabetes. MATERIALS AND METHODS: Databases, including MEDLINE, COCHRANE, EMBASE and EBM reviews were searched for literature relating to sodium glucose transport inhibitors and improvements in glycaemic control in patients with diabetes. RESULTS: The data suggest that sodium glucose transport inhibitors significantly improve glycaemic control by increasing glucosuria. Some studies described significant reductions in weight and improvement in blood pressure. The most common side effect was infection involving the urinary and genital tracts. CONCLUSIONS: Sodium glucose co-transport inhibitors appear to be an effective line of treatment, well tolerated and could be a further drug class in the armamentarium available for the management of type 2 diabetes.

Impact of diabetes in blood-testis and blood-brain barriers: resemblances and differences.

Blood-tissue barriers prevent an uncontrolled exchange of large molecules between adjacent but metabolically separated compartments. There are several known barriers and two of the most important and tightest blood-tissue barriers are the blood-testis barrier (BTB) and the blood-brain barrier (BBB). Under normal conditions these barriers, formed by tight junctions between adjacent cells, control the entry of substances and metabolites. However, hyperglycemia and other diabetes-related complications, such as hypertension, impair the function of these biological barriers with dramatic consequences. Although both, BBB and BTB, are responsible for the maintenance of different biological processes, they have some remarkable similarities not always explored when looking at metabolic-related diseases such as diabetes. These barriers possess their own glucose sensing machinery, suffer a tied hormonal control and have specific mechanisms to counteract hyper- and hypoglycemia. In BBB and BTB the insulin signaling is also distinct from other tissues and organs thus evidencing their importance in protecting against or exacerbating the effects of diabetes on glucose metabolism. The control of glucose and lactate levels in brain and testis highlights the role of these barriers in protecting against peripheral glucose and lactate fluctuations that occur in the diabetic individual. We review the role of BBB and BTB in the control of glucose and metabolic dysfunction caused by diabetes in the brain and seminiferous epithelium. Gaining a better understanding of the molecular mechanisms through which glucose metabolism disrupts BBB and BTB function may highlight new opportunities for the treatment of diabetic complications in brain and male reproductive function.

Biological role, clinical significance, and therapeutic possibilities of the recently discovered metabolic hormone fibroblastic growth factor 21.

Fibroblast growth factor 21 (FGF21), a 181 amino acid circulating protein, is a member of the FGF superfamily, with relevant metabolic actions. It acts through the interaction with specific FGF receptors and a cofactor called ß-Klotho, whose expression is predominantly detected in metabolically active organs. FGF21 stimulates glucose uptake in adipocytes via the induction of glucose transporter-1. This action is additive and independent of insulin. ß-Cell function and survival are preserved, and glucagon secretion is reduced by this protein, thus decreasing hepatic glucose production and improving insulin sensitivity. Lipid profile has been shown to be improved by FGF21 in several animal models. FGF21 increases energy expenditure in rodents and induces weight loss in diabetic nonhuman primates. It also exerts favorable effects on hepatic steatosis and reduces tissue lipid content in rodents. Adaptive metabolic responses to fasting, including stimulation of ketogenesis and fatty acid oxidation, seem to be partially mediated by FGF21. In humans, serum FGF21 concentrations have been found elevated in insulin-resistant states, such as impaired glucose tolerance and type 2 diabetes. FGF21 levels are correlated with hepatic insulin resistance index, fasting blood glucose, HbA1c, and blood glucose after an oral glucose tolerance test. A relationship between FGF21 levels and long-term diabetic complications, such as nephropathy and carotid atheromatosis, has been reported. FGF21 levels decreased in diabetic patients after starting therapy with insulin or oral agents. Increased FGF21 serum levels have also been found to be associated with obesity. In children, it is correlated with BMI and leptin levels, whereas in adults, FGF21 levels are mainly related to several components of the metabolic syndrome. Serum FGF21 levels have been found to be elevated in patients with ischemic heart disease. In patients with renal disease, FGF21 levels exhibited a progressive increase as renal function deteriorates. Circulating FGF21 levels seem to be related to insulin resistance and inflammation in dialysis patients. In summary, FGF21 is a recently identified hormone with antihyperglycemic, antihyperlipidemic, and thermogenic properties. Direct or indirect potentiation of its effects might be a potential therapeutic target in insulin-resistant states.

Correlations between SUVmax and expression of GLUT1 and growth factors inducing lymphangiogenesis.

RATIONALE AND OBJECTIVES: The purpose of this study was to assess the correlations between the maximum standardized uptake value (SUVmax) of colorectal carcinoma and hepatocyte growth factor (HGF), vascular endothelial growth factor C (VEGF-C), and their respective receptors using (18)F-fluorodeoxyglucose (FDG) positron emission tomography (PET)/computed tomography (CT). METHODS: Fluorine-18-FDG PET/CT scans were performed on 33 patients with colorectal carcinoma before any treatment. The SUVmax of colorectal carcinoma and the clinicopathologic data associated with lymphatic metastases were analyzed. The expression of glucose transporter 1 (GLUT1), HGF, c-Met, VEGF-C, and vascular endothelial growth factor receptor 3 (VEGFR-3) in tumor tissues was analyzed using immunohistochemical methods. Lymphatic endothelial cells were marked with D2-40, and lymphatic vessel density (LVD) was recorded. The correlations were analyzed among the SUVmax of colorectal carcinoma, LVD, and the expression of GLUT1, HGF, c-Met, VEGF-C, and VEGFR-3 in tumor tissues. RESULTS: SUVmax and LVD in 15 patients with lymphatic metastases were 13.00 ± 4.51 and 6.25 ± 1.54, respectively, whereas in 18 patients with nonmetastatic nodes, SUVmax and LVD were 9.66 ± 4.82 and 4.54 ± 1.02, respectively. The differences of SUVmax and LVD between metastatic and nonmetastatic patients were statistically significant (F = 4.153, P = .025, and F = 14.501, P = .001, respectively). There were no statistical differences of SUVmax and LVD in variably differentiated colorectal carcinoma (F = 0.708, P = .502, and F = 0.311, P = .735, respectively). The expression rates of GLUT1 in neoplastic and normal tissue were 72.7% (24 of 33) and 21.2% (seven of 33), respectively (P = .001). Moreover, the expression rates of GLUT1 in metastatic and nonmetastatic tissue were 93.33% (14 of 15) and 61.11% (11 of 18), respectively (P = .038). LVD and the integrated optical density of GLUT1 were 5.31 ± 1.53 and 8.21 × 10(4) ± 4.30 × 10(4), respectively, in tumor tissue, and there were linear correlations between SUVmax and LVD (r = 0.373, P = .033) and between SUVmax and expression of GLUT1 (r = 0.428, P = .013). The differences of SUVmax in HGF, c-Met, and VEGF-C groups with different expressions were statistically significant (P = .007, P = .009, and P = .030, respectively). No correlation was found between the expression of VEGFR-3 and SUVmax. The expression of GLUT1 and HGF as well as of GLUT1 and VEGF-C was rank correlated (r = 0.521, P = .002, and r = 0.505, P = .003, respectively). No rank correlations were found between the expression of GLUT1 and c-Met, GLUT1, and VEGFR-3. CONCLUSIONS: The SUVmax of colorectal carcinoma was significantly higher in metastatic patients; the uptake of colorectal carcinoma was associated with LVD and the expression of HGF and VEGF-C but not with the expression of VEGFR-3.