No abstract available.
Deoxyglucose* ; Shock*

The conventional glycemic indices used in management of diabetic patients includes A1c, fructosamine, 1,5-anhydroglucitol, and glycated albumin (GA). Among these indices, A1c is currently used as the gold standard. However, A1c cannot reflect the glycemic change over a relatively short period of time, and its accuracy is known to decrease when abnormalities in hemoglobin metabolism, such as anemia, coexist. When considering these weaknesses, there have been needs for finding a novel glycemic index for diagnosing and managing diabetes, as well as for predicting diabetic complications properly. Recently, several studies have suggested the potential of GA as an intermediate-term glycation index in covering the short-term effect of treatment. Furthermore, its role as a pathogenic protein affecting the worsening of diabetes and occurrence of diabetic complications is receiving attention as well. Therefore, in this article, we wanted to review the recent status of GA as a glycemic index and as a pathogenic protein.
Anemia ; Deoxyglucose ; Diabetes Complications ; Diabetes Mellitus ; Fructosamine ; Glycemic Index ; Hemoglobins ; Humans ; Serum Albumin

BACKGROUND: Hypoxic pulmonary vasoconstriction (HPV) is a defense mechanism to maintain adequate oxygenation. It has been reported that metabolism inhibition augments HPV. The purpose of the present study was, therefore, to determine the effect of metabolism inhibition on HPV in a rabbit model of isolated lung perfusion with exclusion of the influential factors on HPV. METHODS: In adult rabbits, lungs were isolated and perfused with a constant pulmonary perfusate flow. Acid-base status and temperature of perfusate was also constantly maintained. Thirty minutes after, the baseline hypoxic pressor response (HPR) was measured as the difference of pulmonary artery pressure (PAP) between a period of 21% normoxic gas inhalation and that of 3% hypoxic gas inhalation. After another thirty minutes, 2-deoxy-D-glucose 100 mg was mixed with the perfusate, and then HPR was measured three times. After checking metabolism inhibition effects, D-glucose 300 mg was mixed to the perfusate to reverse metabolism inhibition, and then HPR was measured three times again. RESULTS: Metabolism inhibition increased the basal PAP compared to the noninhibition state, but it didn't increase HPV response, so the peak PAP responding to hypoxic gas was the same as the noninhibition state. The absolute HPV response was decreased. After reversal of the inhibition state with a large amount of glucose, the basal PAP decreased to the original value and the HPV response recovered to the previous value. CONCLUSIONS: Deoxyglucose-induced metabolism inhibition increased the PAP ventilated with 21% O2, but it didn't increase the PAP ventilated with 3% O2. As a result, the absolute HPV response was decreased.
Adult ; Deoxyglucose* ; Glucose ; Humans ; Inhalation ; Lung* ; Metabolism* ; Oxygen ; Perfusion ; Pulmonary Artery ; Rabbits ; Vasoconstriction*

PURPOSE: To characterize the effects of 2-deoxy-D-glucose (2-DG) and quercetin (QCT) on gene expression of osteonectin (ON) and osteopontin (OP) in irradiated MC3T3-E1 cells. MATERIALS AND METHODS: When MC3T3-E1 osteoblastic cells had reached 70-80% confluence, cultures were transferred to a differentiating medium supplemented with 5 mM 2-DG or 10 micrometer QCT and then irradiated with 2, 4, 6, and 8 Gy. At various times after irradiation, the cells were analyzed for the expression of bone mineralization genes such as ON and OP. RESULTS: The mRNA expression of both ON and OP was increased according to the culture time in the differentiation medium, and the increase of the genes peaked at 14 days after the differentiation induction. In the case of OP, the increase of mRNA expression was maintained to 28 days after the differentiation, while the mRNA level of ON was reduced to the basal level at the same time. Irradiation adding 2-DG showed a significant peak value in the expression pattern of ON at 4 Gy 7 days after irradiation. Irradiation adding QCT increased the mRNA expression of ON and OP in a dose-dependant manner, but irradiation adding 2-DG did not show any differences between the control and experiments 14 days after irradiation. Irradiation adding QCT increased significantly the expression patterns of ON 21 days after irradiation. CONCLUSION: The results showed that QCT acted as a radiosensitizer in the gene expression of ON and OP during differentiation of the late stage of irradiated MC3T3-E1 osteoblastic cells in vitro.
Calcification, Physiologic ; Deoxyglucose ; Gene Expression ; Osteoblasts ; Osteonectin ; Osteopontin ; Quercetin ; RNA, Messenger

Cancer cells typically display increased rates of aerobic glycolysis that are correlated with tumor aggressiveness and a poor prognosis. Targeting the glycolytic pathway has emerged as an attractive therapeutic route mainly because it should spare normal cells. Here, we evaluate the effects of combining the inhibition of glycolysis with application of the polyphenolic compound resveratrol (RSV) in neuroblastoma (NB) cancer cell lines. Inhibiting glycolysis with 2-deoxy-D-glucose (2-DG) significantly reduced NB cell viability and was associated with increased endoplasmic reticulum (ER) stress and Akt activity. Administration of 2-DG increased the expression of the ER molecular chaperones GRP78 and GRP94, the prodeath protein C/EBP homology protein (CHOP) and the phosphorylation of Akt at S473, T450 and T308. Combined treatment with both RSV and 2-DG reduced GRP78, GRP94 and Akt phosphorylation but increased CHOP and NB cell death when compared with the administration of 2-DG alone. The selective inhibition of Akt activity also decreased 2-DG-induced GRP78 and GRP94 expression and increased CHOP expression, suggesting that Akt can modulate ER stress. Protein phosphatase 1α (PP1α) was activated by RSV, as indicated by a reduction in PP1α phosphorylation at T320. Pretreatment of cells with tautomycin, a selective PP1α inhibitor, prevented the RSV-mediated decrease in Akt phosphorylation, suggesting that RSV enhances 2-DG-induced cell death by activating PP1 and downregulating Akt. The RSV-mediated inhibition of Akt in the presence of 2-DG was not prevented by the selective inhibition of SIRT1, a known target of RSV, indicating that the effects of RSV on this pathway are independent of SIRT1. We propose that RSV inhibits Akt activity by increasing PP1α activity, thereby potentiating 2-DG-induced ER stress and NB cell death.
Cell Death ; Cell Line ; Cell Survival ; Deoxyglucose ; Endoplasmic Reticulum ; Glycolysis ; Molecular Chaperones ; Neuroblastoma* ; Phosphorylation ; Prognosis

PURPOSE: To investigate the in vitro response of MC3T3-E1 osteoblastic cells to X-ray in the presence and absence of 2 deoxy-D-glucose (2-DG) and quercetin (QCT). MATERIALS AND METHODS: The MC3T3-E1 cells were cultured in an alpha-MEM supplemented with 5 mM 2-DG or 10 micrometer QCT and then the cells were incubated for 12 h prior to irradiation with 2, 4, 6, and 8 Gy using a linear accelerator (Mevaprimus, Germany) delivered at a rate of 1.5 Gy/min. At various times after the irradiation, the cells were processed for the analyses of proliferation, viability, cytotoxicity, and mineralization. RESULTS: Exposure of the cells to X-ray inhibited the tritium incorporation, 3-(4, 5-dimethylthiazol-2yl-)-2, 5- diphenyl tetrazolium bromide (MTT)-reducing activity, and alkaline phosphatase (ALP) activity, and caused cytotoxicity and apoptosis in a dose-dependent manner of the X-ray. This effect was further apparent on day 3 and 7 after the irradiation. RA+2-DG showed the decrease of DNA content, cell viability, and increase of cytotoxicity rather than RA. ALP activity increased on day 7 and subsequently its activity dropped to a lower level. 2-DG suppressed the calcium concentration, but visual difference of number of calcified nodules between RA and RA+2-DG was not noticed. RA+QCT showed the increase of DNA content, cell viability, but decrease of cytotoxicity and subG1 stage cells in the cell cycle, and increased calcified nodules in von Kossa staining rather than the RA. ALP activity showed significant increases on day 7 and subsequently its activity dropped to a lower level. CONCLUSION: The results showed that the 2-DG acted as a radiosensitizing agent and QCT acted as a radioprotective agent respectively in the irradiated MC3T3-E1 osteoblast-like cells.
Alkaline Phosphatase ; Apoptosis ; Calcium ; Cell Cycle ; Cell Survival ; Deoxyglucose* ; DNA ; Osteoblasts* ; Particle Accelerators ; Quercetin* ; Tritium

BACKGROUND: The isolated lung model is a very useful model in investigation of hypoxic pulmonary vasoconstriction (HPV), and angiotensin II is extensively used in this model. But the exact role of angiotensin II in HPV is not clear in the isolated rabbit lung. Thus we were concerned about the role of angiotensin II in the blood-perfused rabbit lung. METHODS: New Zealand white rabbits (n = 28) lungs were isolated and perfused with a constant pulmonary perfusate flow; acid-base status and temperature were maintained at constant levels. Deoxyglucose (DOG group, n = 7), angiotension II and deoxyglucose (AG-DOG group, n = 7), calcium (CA group, n = 7), angiotensin II and calcium (AG-CA group, n = 7) were administered, and then hypoxic responses were measured. Three ratios were calculated and compared (P alpha: ratio of hypoxic response to pulmonary arterial pressure at normoxia, P beta: ratio of hypoxic response to baseline hypoxic response, P gamma: ratio of pulmonary arterial pressure at hypoxia to pulmonary arterial pressure at baseline). RESULTS: Angiotensin II increased the pulmonary arterial pressure by 14%, and increased HPV. Baseline pulmonary pressure was increased in the AG-DOG group and in the AG-CA group (P<0.05). P gamma significantly increased in the AG-DOG and AG-CA groups (P<0.05). The first HPV increased but the second HPV decreased in the AG-DOG group (P alpha: P<0.05) and in the AG-CA group. P beta showed no difference between groups. CONCLUSIONS: Angiotensin II resulted in an increase of pulmonary arterial pressure in the isolated rabbit lung. One may misinterpret this as an potentiation of HPV, but HPV was not changed by angiotensin II. Therefore we deny the necessity for angiotensin II in the isolated rabbit lung model.
Angiotensin II* ; Angiotensins* ; Anoxia ; Arterial Pressure ; Calcium ; Deoxyglucose ; Lung* ; Rabbits ; Vasoconstriction*

The measure of HbA1c is the gold standard index of glycemic control in clinical practice for diabetes treatment and is well known as a risk marker for diabetes complications. However, HbA1C does not accurately reflect glucose fluctuations or the actual status of glycemic control for several days or weeks. HbA1c measurement can be confounded in the anemia, hemoglobinopathy, or renal impairment. In comparison, glycated albumin (GA), a ketoamine formed by binding of albumin and glucose, more accurately reflects short-term changes in plasma glucose and postprandial plasma hyperglycemia (PPH). GA is not affected by hemoglobin or dialysis. 1,5-Anhydroglucitol (1,5-AG), another glycemic marker, structurally resembles glucose and decreases with spikes of hyperglycemia exceeding the average renal threshold for glucose. Especially, 1,5-AG level is reflective of PPH or glycemic variability and becomes an increasingly important contributor in a moderately controlled glycemic state, even when HbA1c level is within the target range. Herein, the usefulness of and recent studies on GA and 1,5-AG are summarized. Further investigations about the associations between these glycemic markers and diabetes complications are needed.
Anemia ; Deoxyglucose ; Diabetes Complications ; Diabetes Mellitus ; Dialysis ; Glucose ; Hemoglobin A, Glycosylated ; Hemoglobinopathies ; Hemoglobins ; Hyperglycemia ; Plasma ; Serum Albumin

The effect of 2-deoxy-d-glucose (2-DDG) on C3H mouse fibrosarcoma (FSall) was studied. Metabolic status, especially for energy metabolism, was studied using in vivo 31P-MRS, proliferative capacity was observed on flow cytometry (FC) and growth rate was measured after transplantation of 106 viable tumor cells in the dorsum of foot of C3Hf/Sed mice. One gram of 2-DDG per kg of body weight was injected intraperitoneally on 12th day of implantation. Average tumor size on 12th day of implantation was 250mm3. Growth rate of FSall tumor was measured by tumor doubling time between tumor age 5-12 days was 0.84 days with slope 0.828 and tumor doubling time between tumor age 13-28 days was 3.2 days with slope 0.218 in control group. After 2-DDG injection, tumor doubling time was elongated to 5.1 days with slope 0.136. The effect of 2-DDG studied in vivo 31P-MRS suggested that the increase of phosphomonoester (PME) and inorganic phosphate (Pi) by increasing size of tumor, slowed down after 2-DDG injection. Flow cytometry showed significantly increased S-phase and G2+M phase fraction suggesting increased proliferative capacity of tumor cells in the presence of 2-DDG. Authors observed an interesting effect 2-DDG on FSall tumor and attempt to utilize as an adjunct for radiotherapy.
Animals ; Body Weight ; Deoxyglucose* ; Energy Metabolism ; Fibrosarcoma ; Flow Cytometry* ; Foot ; Magnetic Resonance Spectroscopy* ; Mice ; Mice, Inbred C3H ; Radiotherapy

BACKGROUND: The target of the treatment of metabolic syndrome and diabetes is an improvement of insulin resistance. D-chiro-inositol (DCI) plays a role in a phospholipid mediating intracellular insulin action. In the previous studies, the urine level of DCI were decreased in the diabetic animal with insulin resistance. Some clinical studies showed that DCI improved a glucose level and HbA1c. Therefore we studied the relationship between DCI and glucose metabolism, especially insulin resistance. METHODS: To investigate the mechanism of DCI affecting the glucose metabolism, we examined the effects of DCI on 2-deoxyglucose uptake, gene expression of adipocytokines and AMPK pathway by using RT-PCR and western blot in 3T3-L1 cells. RESULTS: Insulin-stimulated 2-deoxyglucose uptake increased in DCI-treated cells by about 1.2-fold (relative to the control) and was inhibited by phosphoinositide 3-kinase (PI3 Kinase) inhibitors (Wortmanin, LY294002) and AMPK inhibitor (STO-609). In Western blot analysis, it didn't show the difference of phosphorylation of Akt and AMPK between DCI-treated group and control in 3T3-L1 cells. However, DCI decreased the gene expression of resistin in 3T3-L1 cells. CONCLUSION: DCI may involve other pathway of insulin signaling, but not PI3 Kinase and AMPK signaling pathways and it may be useful in managing metabolic syndrome by improving insulin resistance through increasing glucose uptake and decreasing resistin relevant to insulin resistance.
3T3-L1 Cells ; Adipokines ; Animals ; Blotting, Western ; Deoxyglucose ; Gene Expression ; Glucose ; Insulin ; Insulin Resistance ; Negotiating ; Phosphorylation ; Phosphotransferases ; Resistin