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Sample records for abnormal glucose metabolism

  1. Cerebral glucose metabolic abnormality in patients with congenital scoliosis

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    Nam, H. Y.; Seo, G. T.; Lee, J. S.; Kim, S. C.; Kim, I. J.; Kim, Y. K.; Jeon, S. M. [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    A possible association between congenital scoliosis and low mental status has been recognized, but there are no reports describing the mental status or cerebral metabolism in patients with congenital scoliosis in detail. We investigated the mental status using a mini-mental status exam as well as the cerebral glucose metabolism using F-18 fluorodeoxyglucose brain positron emission tomography in 12 patients with congenital scoliosis and compared them with those of 14 age-matched patients with adolescent idiopathic scoliosis. The mean mini-mental status exam score in the congenital scoliosis group was significantly lower than that in the adolescent idiopathic scoliosis group. Group analysis found that various brain areas of patients with congenital scoliosis showed glucose hypometabolisms in the left prefrontal cortex (Brodmann area 10), right orbitofrontal cortex (Brodmann area 11), left dorsolateral prefrontal cortex (Brodmann area 9), left anterior cingulate gyrus (Brodmann area 24) and pulvinar of the left thalamus. From this study, we could find the metabolic abnormalities of brain in patients with congenital scoliosis and suggest the possible role of voxel-based analysis of brain fluorodeoxyglucose positron emission tomography.

  2. Persistent abnormal coronary flow reserve in association with abnormal glucose metabolism affects prognosis in acute myocardial infarction

    DEFF Research Database (Denmark)

    Løgstrup, Brian B; Høfsten, Dan E; Christophersen, Thomas B

    2011-01-01

    Objectives: To evaluate changes in coronary flow reserve (CFR) over time after acute myocardial infarction (AMI) in relation to left ventricular (LV) function and glucometabolic state and prognostic implication of abnormal CFR. Methods: 154 patients with first time AMI had a comprehensive...... baseline CFR (P = 0.004), S' (P = 0.045) and abnormal glucose metabolism (P = 0.001) were predictors of a decreased CFR at 3 months of follow-up. In multivariate analyses abnormal glucose metabolism (OR: 5.3; 95%CI: 1.9-14.4; P = 0.001) remained a predictor of decreased CFR at follow-up, furthermore...... baseline CFR (OR: 0.5; 95%CI: 0.25-0.94; P = 0.032) and S' (OR: 0.67; 95% CI: 0.47-0.94; P = 0.021) was predictors of decreased CFR. Finally, CFR was associated with a lower risk of cardiac events in patients with normal glucose metabolism (HR: 0.64; 95% CI: 0.22-1.9; P = 0.42) than in patients...

  3. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy.

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    Tricò, Domenico; Baldi, Simona; Frascerra, Silvia; Venturi, Elena; Marraccini, Paolo; Neglia, Danilo; Natali, Andrea

    2016-01-01

    Dilated cardiomyopathy (DCM) is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT). In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT) and 5 with AGT (DCM-AGT), and 5 non-DCM subjects with AGT (N-AGT), we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min), and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA) myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p equivalents, p metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.

  4. Abnormal glycosylated hemoglobin as a predictive factor for glucose metabolism disorders in antipsychotic treatment

    Institute of Scientific and Technical Information of China (English)

    XU Leping; JI Juying; DUAN Yiyang; SHI Hui; ZHANG Bin; SHAO Yaqin; SUN Jian

    2007-01-01

    The aim of this study was to observe the changes in glucose metabolism after antipsychotic(APS)therapy,to note the influencing factors,as well as to dicuss the relationship between the occurrence of glucose metabolism disorders of APS origin and abnormal glycosylated hemoglobin(HbA1c)levels.One hundred and fifty-two patients with schizophrenia,whose fasting plasma glucose(FPG)and 2-h plasma glucose (2hPG)in the oral glucose tolerance test(2HPG)were normal,were grouped according to the HbA1c levels,one normal and the other abnormal,and were randomly enrolled into risperidone,clozapine and chlorpromazine treatment for six weeks.The FPG and 2hPG were measured at the baseline and at the end of the study.In the group with abnormal HbA1c and clozapine therapy,2HPG was higher after the study[(9.5±1.8)mmol/L]than that before the study[(7.2±1.4)mmol/L]and the difierence was statistically significant(P<0.01).FPG had no statistically significant difference before and after the study in any group(P>0.05).HbA1c levels and drugs contributing to 2HPG at the end of study had statistical cross-action(P<0.01).In the abnormal HbA1c group,2HPG after the study was higher in the clozapine treatment group [(9.5±1.8)mmol/L]than in the risperidone treatment group [(7.4±1.7)mmol/L]and the chlorpromazine treatment group[(7.3±1.6)mmol/L].The differences were statistically significant(P<0.01).In the normal HbA1c group there was no statistically significant difierence before and after the study in any group(P>0.05).2HPG before[(7.1±1.6)mmol/L]and after the study[(8.1±1.9)mmol/L]was higher in the abnormal HbA1c group than in the normal HbA1c group[(6.2±1.4)mmol/L vs(6.5±1.4)mmol/L]with the difierence being statistically significant(P<0.01 vs P<0.001).As compared with normal HbA1c group,the relative risk (RR)of glucose metabolism disease occurrence was 4.7 in the abnormal HDA1C group wlth the difierence being statistically significant(P<0.001).Patients with abnormal HbA1c

  5. Abnormal Glucose Tolerance Is Associated with a Reduced Myocardial Metabolic Flexibility in Patients with Dilated Cardiomyopathy

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    Domenico Tricò

    2016-01-01

    Full Text Available Dilated cardiomyopathy (DCM is characterized by a metabolic shift from fat to carbohydrates and failure to increase myocardial glucose uptake in response to workload increments. We verified whether this pattern is influenced by an abnormal glucose tolerance (AGT. In 10 patients with DCM, 5 with normal glucose tolerance (DCM-NGT and 5 with AGT (DCM-AGT, and 5 non-DCM subjects with AGT (N-AGT, we measured coronary blood flow and arteriovenous differences of oxygen and metabolites during Rest, Pacing (at 130 b/min, and Recovery. Myocardial lactate exchange and oleate oxidation were also measured. At Rest, DCM patients showed a reduced nonesterified fatty acids (NEFA myocardial uptake, while glucose utilization increased only in DCM-AGT. In response to Pacing, glucose uptake promptly rose in N-AGT (from 72 ± 21 to 234 ± 73 nmol/min/g, p<0.05, did not change in DCM-AGT, and slowly increased in DCM-NGT. DCM-AGT sustained the extra workload by increasing NEFA oxidation (from 1.3 ± 0.2 to 2.9 ± 0.1 μmol/min/gO2 equivalents, p<0.05, while DCM-NGT showed a delayed increase in glucose uptake. Substrate oxidation rates paralleled the metabolites data. The presence of AGT in patients with DCM exacerbates both the shift from fat to carbohydrates in resting myocardial metabolism and the reduced myocardial metabolic flexibility in response to an increased workload. This trial is registered with ClinicalTrial.gov NCT02440217.

  6. Abnormal glucose metabolism in acute myocardial infarction: influence on left ventricular function and prognosis

    DEFF Research Database (Denmark)

    Høfsten, Dan E; Løgstrup, Brian B; Møller, Jacob E

    2009-01-01

    tolerance test before discharge. LV function was assessed using echocardiographic measurements (LV end-diastolic volume, LV end-systolic volume, LV ejection fraction, restrictive diastolic filling pattern, early transmitral flow velocity to early diastolic mitral annular velocity ratio [E/e'], and left...... atrial volume index) and by measuring plasma N-terminal pro-B-type natriuretic peptide levels. RESULTS: After adjustment for age and gender, a linear relationship between the degree of abnormal glucose metabolism was observed for each marker of LV dysfunction (p(trend)

  7. Abnormal Glucose Metabolism in Alzheimer’s Disease: Relation to Autophagy/Mitophagy and Therapeutic Approaches

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    Banerjee, Kalpita; Munshi, Soumyabrata; Frank, David E.; Gibson, Gary E.

    2015-01-01

    Diminished glucose metabolism accompanies many neurodegenerative diseases including Alzheimer’s disease. An understanding of the relation of these metabolic changes to the disease will enable development of novel therapeutic strategies. Following a metabolic challenge, cells generally conserve energy to preserve viability. This requires activation of many cellular repair/regenerative processes such as mitophagy/autophagy and fusion/fission. These responses may diminish cell function in the long term. Prolonged fission induces mitophagy/autophagy which promotes repair but if prolonged progresses to mitochondrial degradation. Abnormal glucose metabolism alters protein signaling including the release of proteins from the mitochondria or migration of proteins from the cytosol to the mitochondria or nucleus. This overview provides an insight into the different mechanisms of autophagy/mitophagy and mitochondrial dynamics in response to the diminished metabolism that occurs with diseases, especially neurodegenerative diseases such as Alzheimer's disease. The review discusses multiple aspects of mitochondrial responses including different signaling proteins and pathways of mitophagy and mitochondrial biogenesis. Improving cellular bioenergetics and mitochondrial dynamics will alter protein signaling and improve cellular/mitochondrial repair and regeneration. An understanding of these changes will suggest new therapeutic strategies. PMID:26077923

  8. Plasma myeloperoxidase is inversely associated with endothelium-dependent vasodilation in elderly subjects with abnormal glucose metabolism.

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    van der Zwan, Leonard P; Teerlink, Tom; Dekker, Jacqueline M; Henry, Ronald M A; Stehouwer, Coen D A; Jakobs, Cornelis; Heine, Robert J; Scheffer, Peter G

    2010-12-01

    Myeloperoxidase (MPO), a biomarker related to inflammation, oxidative stress, and nitric oxide scavenging, has been shown to impair endothelium-dependent vasodilation. Because elevated hydrogen peroxide concentrations in diabetic vessels may enhance MPO activity, we hypothesized that a stronger association of MPO with flow-mediated dilation (FMD) may be found in subjects with abnormal glucose metabolism. Myeloperoxidase concentrations were measured in EDTA plasma samples from participants of a population-based cohort study, including 230 subjects with normal glucose metabolism and 386 with abnormal glucose metabolism. Vascular function was expressed as FMD and nitroglycerin-mediated dilation of the brachial artery. In subjects with abnormal glucose metabolism, MPO was negatively associated with FMD (-20.9 [95% confidence interval {CI}, -41.7 to -0.2] -μm change in FMD per SD increment of MPO). This association remained significant after adjustment for nitroglycerin-mediated dilation (-31.1 [95% CI, -50.0 to -12.3]) and was not attenuated after further adjustment for established risk factors. In subjects with normal glucose metabolism, MPO was not significantly associated with FMD (2.0 [95% CI, -16.0 to 20.0]). In conclusion, in subjects with abnormal glucose metabolism, plasma levels of MPO are inversely associated with endothelium-dependent vasodilation, possibly reflecting enhancement of MPO activity by vascular oxidative stress.

  9. High incidence of abnormal glucose metabolism in acute coronary syndrome patients at a moderate altitude: A sub-Himalayan study

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    Mokta, Jitender; Kumar, Subash; Ganju, Neeraj; Mokta, Kiran; Panda, Prashant Kumar; Gupta, Swatantra

    2017-01-01

    Background: Abnormal glucose metabolic status at admission is an important marker of future cardiovascular events and long-term mortality after acute coronary syndrome (ACS), whether or not they are known diabetics. Objective: The aims were to study the prevalence of abnormal glucose metabolism in ACS patients and to compare the different methods of diagnosing diabetes in ACS patients. Methods: We did a prospective study. About 250 consecutive nondiabetic patients (200 men and 50 women) with ACS admitted to a tertiary care institute of Himachal Pradesh in 1 year were enrolled. Admission plasma glucose, next morning fasting plasma glucose (FPG), A1C, and a standardized 75-g oral glucose tolerance test (OGTT) 72 h after admission were done. Glucose metabolism was categorized as normal glucose metabolism, impaired glucose metabolism (impaired fasting glucose or impaired glucose tolerance [IGT]), and diabetes. Diabetes was arbitrarily classified further as undiagnosed (HBA1c ≥6.5%) or possibly stress diabetes (HBA1c <6.5%). A repeat OGTT after 3 months in objects with IGT and stress hyperglycemia at a time of admission was done. Results: The mean age was 54 ± 12.46 years. The mean plasma glucose at admission was 124 ± 53.96 mg/dL, and the mean FPG was 102 ± 27.07 mg/dL. The mean 2-h postglucose load concentration was 159.5 ± 56.58 mg/dL. At baseline, 95 (38%) had normal glucose metabolism, 95 (38%) had impaired glucose metabolism (IGT and or IGT) and 60 (24%) had diabetes; 48 (19.2%) were undiagnosed diabetes and 12 (4.8%) had stress hyperglycemia. At follow up 58.66% and 55.55% of patients with impaired glucose tolerance and stress hyperglycemia continued to have impaired glucose tolerance respectively. About 75 gm OGTT has highest sensitivity and specificity to diagnose diabetes, whereas A1C most specific to rule out stress hyperglycemia. Conclusions: In this small hilly state of India, abnormal glucose metabolism (previously undiagnosed diabetes and IGT) is

  10. Morphological and glucose metabolism abnormalities in alcoholic Korsakoff's syndrome: group comparisons and individual analyses.

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    Anne-Lise Pitel

    Full Text Available BACKGROUND: Gray matter volume studies have been limited to few brain regions of interest, and white matter and glucose metabolism have received limited research attention in Korsakoff's syndrome (KS. Because of the lack of brain biomarkers, KS was found to be underdiagnosed in postmortem studies. METHODOLOGY/PRINCIPAL FINDINGS: Nine consecutively selected patients with KS and 22 matched controls underwent both structural magnetic resonance imaging and (18F-fluorodeoxyglucose positron emission tomography examinations. Using a whole-brain analysis, the between-group comparisons of gray matter and white matter density and relative glucose uptake between patients with KS and controls showed the involvement of both the frontocerebellar and the Papez circuits, including morphological abnormalities in their nodes and connection tracts and probably resulting hypometabolism. The direct comparison of the regional distribution and degree of gray matter hypodensity and hypometabolism within the KS group indicated very consistent gray matter distribution of both abnormalities, with a single area of significant difference in the middle cingulate cortex showing greater hypometabolism than hypodensity. Finally, the analysis of the variability in the individual patterns of brain abnormalities within our sample of KS patients revealed that the middle cingulate cortex was the only brain region showing significant GM hypodensity and hypometabolism in each of our 9 KS patients. CONCLUSIONS/SIGNIFICANCE: These results indicate widespread brain abnormalities in KS including both gray and white matter damage mainly involving two brain networks, namely, the fronto-cerebellar circuit and the Papez circuit. Furthermore, our findings suggest that the middle cingulate cortex may play a key role in the pathophysiology of KS and could be considered as a potential in vivo brain biomarker.

  11. Preliminary validation of an exercise program suitable for pregnant women with abnormal glucose metabolism: inhibitory effects of Tai Chi Yuttari-exercise on plasma glucose elevation

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    Yamamoto, Sachina; Kagawa, Kyoko; Hori, Naohi; Akezaki, Yoshiteru; Mori, Kohei; Nomura, Takuo

    2016-01-01

    [Purpose] There is insufficient evidence related to exercise programs that are safe and efficacious for pregnant women with abnormal glucose metabolism. Tai Chi Yuttari-exercise is an exercise program with validated safety and efficacy in improving physical function in the elderly. In this study, we investigated this program’s inhibitory effects on plasma glucose elevation when it was adapted to a pregnancy model. [Subjects and Methods] Twelve 18- to 19-year-old females without a history of pregnancy were randomly assorted into two groups: an intervention group, for which six subjects were outfitted with mock-pregnancy suits and asked to perform Tai Chi Yuttari-exercise, and a control group who did not perform exercise. The intervention group had a mean Borg Scale score of 11.1 ± 0.9 during the exercise. [Results] No significant intragroup differences were observed in fasting, baseline, or post-intervention/observation plasma glucose levels. On the other hand, the intergroup change in plasma glucose levels after intervention/observation was significant when comparing the intervention and control groups: −1.66 ± 7.0 and 9.42 ± 6.57 mg/dl, respectively. [Conclusion] Tai Chi Yuttari-exercise appears to effectively inhibit plasma glucose elevation at intensity and movement levels that can be safely applied to pregnant women with abnormal glucose metabolism. PMID:28174463

  12. Evaluation of glucose metabolic abnormality in postlingually deaf patients using F-18-FDG positron emission tomography and statistical parametric mapping

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    Lee, Jae Sung; Lee, Dong Soo; Oh, Seung Ha; Kim, Chong Sun; Park, Kwang Suk; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2000-07-01

    We have previously reported the prognostic relevance of cross-modal cortical plasticity in prelingual deaf patients revealed by F-18-FDG PET and SPM analysis. In this study, we investigated metabolic abnormality in postlingual deaf patients, whose clinical features are different from prelingual deafness. Nine postlingual deaf patients (age: 30.5 {+-}14.0) were performed on F-18-FDG brain PET. We compared their PET images with those of age-matched 20 normal controls (age: 27.1 {+-}8.6), and performed correlation analysis to investigate the relationship between glucose metabolism and deaf duration using SPM99. Glucose metabolism of deaf patients was significantly (p<0.05, corrected) decreased in both anterior cingulate, inferior frontal cortices, and superior temporal cortices, and left hippocampus. Metabolism in both superior temporal cortices and association area in inferior parietal cortices showed significant (p<0.01, uncorrected) positive correlation with deaf duration. Decreased metabolism in hippocampus accompanied with hypometabolism in auditory related areas can be explained by recent finding of anatomical connectivity between them, and may be the evidence indicating their functional connectivity. Metabolism recovery in auditory cortex after long deaf duration suggests that cortical plasticity takes place also in postlingual deafness.

  13. Dietary antioxidants: Do they have a role to play in the ongoing fight against abnormal glucose metabolism?

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    Avignon, Antoine; Hokayem, Marie; Bisbal, Catherine; Lambert, Karen

    2012-07-01

    Overfeeding, an increased intake of saturated fatty acids, and sugary foods are key dietary changes that have occurred in recent decades in addition to the emergence of the obesity epidemic. In addition to an increase in energy storage as fat, these dietary changes are accompanied by an increase in mitochondrial macronutrient oxidation, leading to an excessive free radical production and, hence, oxidative stress. The latter has long been considered a central mechanism linking nutrient overload, insulin resistance, the metabolic syndrome, and diabetes. However, food, through fruit and vegetable consumption, also can be a great source of antioxidants that protect the body against oxidative damage and insulin resistance and thus help cope with the metabolic backlash of the energy-dense Westernized diet. Experimental data are in favor of the beneficial role conveyed by antioxidants in glucose metabolism, but clinical data in humans remain controversial. This review therefore aimed to sort out any underlying discrepancies and provide an overall clear view of the role of antioxidants in the ongoing fight against abnormal glucose metabolism.

  14. Objective 3D surface evaluation of intracranial electrophysiologic correlates of cerebral glucose metabolic abnormalities in children with focal epilepsy.

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    Jeong, Jeong-Won; Asano, Eishi; Kumar Pilli, Vinod; Nakai, Yasuo; Chugani, Harry T; Juhász, Csaba

    2017-03-21

    To determine the spatial relationship between 2-deoxy-2[(18) F]fluoro-D-glucose (FDG) metabolic and intracranial electrophysiological abnormalities in children undergoing two-stage epilepsy surgery, statistical parametric mapping (SPM) was used to correlate hypo- and hypermetabolic cortical regions with ictal and interictal electrocorticography (ECoG) changes mapped onto the brain surface. Preoperative FDG-PET scans of 37 children with intractable epilepsy (31 with non-localizing MRI) were compared with age-matched pseudo-normal pediatric control PET data. Hypo-/hypermetabolic maps were transformed to 3D-MRI brain surface to compare the locations of metabolic changes with electrode coordinates of the ECoG-defined seizure onset zone (SOZ) and interictal spiking. While hypometabolic clusters showed a good agreement with the SOZ on the lobar level (sensitivity/specificity = 0.74/0.64), detailed surface-distance analysis demonstrated that large portions of ECoG-defined SOZ and interictal spiking area were located at least 3 cm beyond hypometabolic regions with the same statistical threshold (sensitivity/specificity = 0.18-0.25/0.94-0.90 for overlap 3-cm distance); for a lower threshold, sensitivity for SOZ at 3 cm increased to 0.39 with a modest compromise of specificity. Performance of FDG-PET SPM was slightly better in children with smaller as compared with widespread SOZ. The results demonstrate that SPM utilizing age-matched pseudocontrols can reliably detect the lobe of seizure onset. However, the spatial mismatch between metabolic and EEG epileptiform abnormalities indicates that a more complete SOZ detection could be achieved by extending intracranial electrode coverage at least 3 cm beyond the metabolic abnormality. Considering that the extent of feasible electrode coverage is limited, localization information from other modalities is particularly important to optimize grid coverage in cases of large hypometabolic cortex. Hum Brain Mapp, 2017. © 2017

  15. Abnormal glucose metabolism is associated with reduced left ventricular contractile reserve and exercise intolerance in patients with chronic heart failure

    DEFF Research Database (Denmark)

    Egstrup, M; Kistorp, C N; Schou, M;

    2013-01-01

    years, 69% male, 59% had ischaemic heart disease, mean LV ejection fraction (LVEF) 37 ± 9%). Thirty-four (21%) patients had known diabetes mellitus (DM). Oral glucose tolerance testing (OGTT) classified patients without a prior DM diagnosis as normal glucose tolerance (NGT), impaired glucose tolerance......AIMS: To investigate the associations between glucose metabolism, left ventricular (LV) contractile reserve, and exercise capacity in patients with chronic systolic heart failure (HF). METHODS AND RESULTS: From an outpatient HF clinic, 161 patients with systolic HF were included (mean age 70 ± 10...... detected by OGTT, is independently associated with reduced LV contractile reserve and exercise...

  16. Burden and Socio-Behavioral Correlates of Uncontrolled Abnormal Glucose Metabolism in an Urban Population of India

    Science.gov (United States)

    Mahapatra, Tanmay; Chakraborty, Kaushik; Mahapatra, Sanchita; Mahapatra, Umakanta; Pandey, Naren; Thomson, Peter L.; Musk, Arthur W.; Mitra, Ramendra N.

    2016-01-01

    Background Progressive burden of diabetes mellitus is a major concern in India. Data on the predictors of poor glycemic control among diabetics are scanty. A population-based cross-sectional study nested in an urban cohort was thus conducted in West Bengal, India to determine the burden and correlates of total and uncontrolled abnormalities in glucose metabolism (AGM) in a representative population. Methods From 9046 adult cohort-members, 269 randomly selected consenting subjects (non-response = 7.24%) were interviewed, examined [blood pressure (BP), anthropometry], tested for fasting plasma glucose (FPG) and glycosylated hemoglobin (HbA1C). Those having pre-diagnosed diabetes or FPG ≥126 or HbA1c≥6.5 were defined as diabetic. Among non-diabetics, subjects with FPG (mg/dl) = 100–125 or HbA1C(%) = 5.7–6.4 were defined as pre-diabetic. Pre-diagnosed cases with current FPG ≥126 were defined as uncontrolled AGM. Descriptive and regression analyses were conducted using SAS-9.3.2. Results Among participants, 28.62% [95% Confidence Interval (95%CI) = 23.19–34.06)] were overweight [body mass index(BMI) = (25–29.99)kg/meter2], 7.81% (4.58–11.03) were obese(BMI≥30kg/meter2), 20.82% (15.93–25.70) were current smokers, 12.64% (8.64–16.64) were current alcohol-drinkers and 46.32% of responders (39.16–53.47) had family history of diabetes. 17.84% (13.24–22.45) had stage-I [140≤average systolic BP (AvSBP in mm of mercury)business-owners [OR = 25.53(24.91–16.18)], retired [OR = 46.53(45.38–47.72)], ex-smokers [OR = 4.75(1.09–20.78)], ex-drinkers [OR = 22.43(4.62–108.81)] and hypertensives [ORStage II = 13.17(1.29–134.03)] were more likely to have uncontrolled AGM. Conclusions Burden of uncontrolled AGM was high among participants. Efforts to curb the diabetes epidemic in urban India should include interventions targeting appropriate diabetic control among relatively older persons, unemployed, business-owners, retired, ex-smokers, ex

  17. Metabolic Abnormalities in Children with Asthma

    OpenAIRE

    2010-01-01

    Rationale: Childhood asthma and obesity have reached epidemic proportions worldwide, and the latter is also contributing to increasing rates of related metabolic disorders, such as diabetes. Yet, the relationship between asthma, obesity, and abnormal lipid and glucose metabolism is not well understood, nor has it been adequately explored in children.

  18. Long-term exposure to abnormal glucose levels alters drug metabolism pathways and insulin sensitivity in primary human hepatocytes

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    Davidson, Matthew D.; Ballinger, Kimberly R.; Khetani, Salman R.

    2016-06-01

    Hyperglycemia in type 2 diabetes mellitus has been linked to non-alcoholic fatty liver disease, which can progress to inflammation, fibrosis/cirrhosis, and hepatocellular carcinoma. Understanding how chronic hyperglycemia affects primary human hepatocytes (PHHs) can facilitate the development of therapeutics for these diseases. Conversely, elucidating the effects of hypoglycemia on PHHs may provide insights into how the liver adapts to fasting, adverse diabetes drug reactions, and cancer. In contrast to declining PHH monocultures, micropatterned co-cultures (MPCCs) of PHHs and 3T3-J2 murine embryonic fibroblasts maintain insulin-sensitive glucose metabolism for several weeks. Here, we exposed MPCCs to hypo-, normo- and hyperglycemic culture media for ~3 weeks. While albumin and urea secretion were not affected by glucose level, hypoglycemic MPCCs upregulated CYP3A4 enzyme activity as compared to other glycemic states. In contrast, hyperglycemic MPCCs displayed significant hepatic lipid accumulation in the presence of insulin, while also showing decreased sensitivity to insulin-mediated inhibition of glucose output relative to a normoglycemic control. In conclusion, we show for the first time that PHHs exposed to hypo- and hyperglycemia can remain highly functional, but display increased CYP3A4 activity and selective insulin resistance, respectively. In the future, MPCCs under glycemic states can aid in novel drug discovery and mechanistic investigations.

  19. 冠心病糖代谢异常患者血浆Ghrelin水平及临床意义%Plasma ghrelin level in patients with coronary heart disease with abnormal glucose metabolism and its clinical significance

    Institute of Scientific and Technical Information of China (English)

    庞军刚; 徐新; 唐良秋; 张社兵; 江志平

    2012-01-01

    目的:探讨冠心病糖代谢异常患者血浆胃饥饿素(Ghrelin)水平及其相关临床意义.方法:将纳入研究对象依据相关检验及检查结果分为正常对照组、冠心病组(冠心病糖代谢正常组和冠心病糖代谢异常组)、单纯糖代谢异常组.收集所有入选对象人院第2天清晨空腹血样,采用ELISA方法同批检测血浆Ghrelin水平.结果:①冠心病组及单纯糖代谢异常组血浆Ghrelin水平均显著低于正常对照组.②冠心病糖代谢异常组血浆Ghrelin水平显著低于冠心病糖代谢正常组及单纯糖代谢异常组.③析因分析结果显示:冠心病与糖代谢异常在对血浆Ghrelin水平影响方面不存在交互作用.然而,糖代谢异常比冠心病对血浆Ghrelin水平的影响更明显.结论:冠心病糖代谢异常患者血浆Ghrelin水平显著下降,且糖代谢异常对Ghrelin的影响更明显.%AIM: To study plasma ghrelin level distribution in patients with coronary heart disease (CHD) with abnormal glucose metabolism and to discuss its clinical significance. METHODS; According to laboratory examination results, subjects were divided into control group, coronary heart disease with normal glucose metabolism group, coronary heart disease with abnormal glucose metabolism group and abnormal glucose metabolism group. Fasting blood samples were collected the morning after admission with EDTA-2K anticoagulation tubes. Blood samples were then transferred to centrifuge tubes containing aprotinin and were centrifuged to extract plasma for cryopreservation. All blood plasma ghrelin levels were tested with ELISA. RESULTS: Compared with those in control group, ghrelin levels were significantly reduced in the group with CHD with normal glucose metabolism, group of CHD with abnormal glucose metabolism and group with abnormal glucose metabolism. Compared with those in the group of CHD with normal glucose metabolism, levels of ghrelin were significantly reduced in patients with

  20. 妊娠期糖代谢异常的相关危险因素分析%Risk Factors of Abnormal Glucose Metabolism in Gestation Period

    Institute of Scientific and Technical Information of China (English)

    代明甫; 李倩; 钟思燕; 杨霜雪; 邬小臣

    2015-01-01

    Objective:To explore risk factors of abnormal glucose metabolism in gestation period, and provide the theory basis for the clinical prevention and treatment of gestational diabetes mellitus ( GDM ) . Method:A case-control study was conducted on 100 pregnant women with clinically confirmed gestational abnormal glucose metabolism as study group, and 100 pregnant women of same gestational weeks with normal glucose metabolism as control group from Jun.2011 to May 2014.The general information, gestational mate-rials and behaviors of the two groups were investigated and the risk factors of abnormal glucose metabolism in gestation period were analyzed.Result:Multi-factor logistic regression analysis showed that diabetes family history ( OR =2.398, 95%CI 1.042~5.012) , age was more than 28 years ( OR=1.413, 95%CI 1.322~4. 352) , BMI>24 ( OR=6.543, 95%CI 0.782~2.320) , abortion history ( OR=0.212, 95%CI 0.025~2. 256) , smoking history ( OR=0.246, 95%CI 0.045~3.452) were the risk factor of GDM morbidity.Con-clusion:Pregnant women with diabetes family history,>28 years, BMI>24,history of abortion and smoking should undergo gestational diabetes screening during early trimester of pregency.%目的:探讨妇女妊娠期糖代谢异常分布情况及发病的相关危险因素,为预防和控制妊娠期糖尿病提供理论依据。方法:以我院2011年6月至2014年5月保健门诊确诊的妊娠期糖代谢异常的孕产妇100例为病例组,以糖代谢正常及孕周相同的孕产妇100例为对照组。调查两组孕产妇一般情况,分析妊娠期糖代谢异常相关因素。结果:Logistic回归分析发现糖尿病遗传史( OR=2.398,95%, CI:1.042~5.012)、年龄>28岁( OR=1.413,95%,CI:1.322~4.352)、体质指数>24( OR=6.543,95%, CI:0.782~2.320)、流产史( OR=0.212,95%,CI:0.025~2.256)、吸烟史( OR=0.246,95%,CI:0.045~3.452)是妊娠

  1. Antihypertensive drugs and glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    Christos; V; Rizos; Moses; S; Elisaf

    2014-01-01

    Hypertension plays a major role in the development and progression of micro-and macrovascular disease.Moreover,increased blood pressure often coexists with additional cardiovascular risk factors such as insulin resistance.As a result the need for a comprehensive management of hypertensive patients is critical.However,the various antihypertensive drug categories have different effects on glucose metabolism.Indeed,angiotensin receptor blockers as well as angiotensin converting enzyme inhibitors have been associated with beneficial effects on glucose homeostasis.Calcium channel blockers(CCBs)have an overall neutral effect on glucose metabolism.However,some members of the CCBs class such as azelnidipine and manidipine have been shown to have advantageous effects on glucose homeostasis.On the other hand,diuretics andβ-blockers have an overall disadvantageous effect on glucose metabolism.Of note,carvedilol as well as nebivolol seem to differentiate themselves from the rest of theβ-blockers class,being more attractive options regarding their effect on glucose homeostasis.The adverse effects of some blood pressure lowering drugs on glucose metabolism may,to an extent,compromise their cardiovascular protective role.As a result the effects on glucose homeostasis of the various blood pressure lowering drugs should be taken into account when selecting an antihypertensive treatment,especially in patients which are at high risk for developing diabetes.

  2. 丙型肝炎病毒感染致糖代谢异常的相关机制研究进展%Progress in mechanisms of abnormal glucose metabolism in patients with hepatitis C virus infection

    Institute of Scientific and Technical Information of China (English)

    康姚洁(综述); 王煊(审校)

    2014-01-01

    丙型肝炎病毒感染者糖代谢异常的发病率有不同程度的升高。除了肝源性糖尿病共有的发病机制外,胰岛β细胞功能的减低和胰岛素抵抗(IR)在丙型肝炎病毒感染者糖代谢异常的发病机制中起着重要作用。但IR可能更为重要,而肝脂肪变性、肿瘤坏死因子-α过表达、脂联素水平下降、细胞因子信号抑制因子合成以及铁代谢异常等都可能参与了IR的形成。%The morbidity of abnormal glucose metabolism in patients with hepatitis C infection increases gradually. In addition to the common pathogenesis similar to hepatogenous diabetes,malfunciton in pancreaticβ-cell and insulin resistance (IR) play important roles in the pathogenesis of abnormal glucose metabolism in pa-tients with hepatitis C virus infection. IR may be more important,and hepatic steatosis, tumor necrosis factor-αoverexpression,decreased adiponectin, abnormality in synthesis of cytokine signaling inhibitory factors and in iron metabolism may all be involved in IR.

  3. ANALYSIS OF THE PREVALENCE RATE AND RISK FACTOR OF ABNORMAL GLUCOSE METABOLISM IN CADRE MEMBERS%副厅级以上干部人群糖代谢异常患病情况及危险因素分析

    Institute of Scientific and Technical Information of China (English)

    杨英; 曾莉; 吴琴琴; 张帆; 秦恳; 邹天富; 黄燕; 王佑娟

    2011-01-01

    [Objective]To realize the prevalence rate and analyse the risk factor of abnormal glucose metabolism in cadre members in Sichuan province to provide scientific evidence to set up the preventive strategies.[Methods]Information were collected in the cadre menbers checked in our hospital and medical examination including height, weight, blood pressure, oral glucose tolerance test (OGTT) and biochemical test, etc.Abnormal glucose metabolism was based on the diagnosis criteria in 1999.The relationships between risk factors and IGR were analyzed by unconditional multivariate logistic regression.[Results](1) The detection rate of total abnormal glucose metabolism was 33.2%, with 7.3% of DM.The detection rate of IGR was 25.8%.The detection rate of I-IFG, I-IGT, IFG/IGT was 1.9%, 20.3%, 3.6%, respectively, (2) Compared with the NGT group, the IGR group had higher body mass index (BMI) , waist-to-hip ratio (WHR), triglyceride (TG) , systolic blood pressure (SBP), serum creatinine (Cr) , lower high density lipoprotein with statistical significance (P < 0.01 or P < 0.05).(3) Age, BMI, WHR, TG were risk factors of abnormal glucose metabolism (P< 0.01 or P< 0.05).[Conclusion]The abnormality rare of glucose metabolism in cadre menbers in Sichuan province is high.Age, BMI, WHR, TG are main risk factors of abnormal glucose metabolism.%[目的]了解四川省干部人群糖代谢异常的患病情况并分析其危险因素,为制定适宜的干预措施提供依据.[方法]选用2009年在某院健康体检的干部人群,分别进行身高体重血压测定、糖耐量试验(OGTT)及生化指标检查等.糖代谢异常的诊断依据WHO1999年糖尿病的诊断标准.运用多因素非条件Logistic回归分析,探讨影响糖代谢异常发生的危险因素.[结果](1)糖代谢异常总检出率为33.2%,其中DM的检出率7.3%,糖调节受损(IGR,糖尿病前期)总的检出率为25.8%,IGR各亚组的检出率分别为:I-IFG1.9%、I-IGT20.3%及IFG/IGT3

  4. 多囊卵巢综合征患者糖代谢异常发生率及其特点%Characteristics and prevalence of abnormal glucose metabolism in patients with polycystic ovary syndrome

    Institute of Scientific and Technical Information of China (English)

    倪仁敏; 钟俊敏; 陈晓莉; 李琳; 李予; 陈亚肖; 刘雯; 杨冬梓

    2009-01-01

    目的 探讨多囊卵巢综合征患者糖代谢异常特点及其发生率.方法 回顾性分析2006年6月1日至2009年2月1日广州中山大学孙逸仙纪念医院妇产科收治的初诊多囊卵巢综合征患者654例(青春期101例,成人553例),以120名年龄匹配的健康志愿者为对照组(青春期40名,成人80名).病例和对照组均行口服葡萄糖耐量试验和胰岛素释放试验,比较病例组和对照组、成人多囊卵巢综合征与青春期多囊卵巢综合征、不同体重指数亚组中糖代谢异常的特点及其发生率.结果 多囊卵巢综合征患者糖代谢异常的发生率为24.5%(160/654),显著高于对照组的3.3%(4/120)(χ2=27.11,P7.0 mmol/L,9例(69.2%)通过口服葡萄糖耐量试验筛查发现.多囊卵巢综合征组糖代谢异常的发生率随体重指数升高而升高(χ2=53.71,P<0.0001).结论 多囊卵巢综合征患者为糖代谢异常的高危人群,其糖代谢异常以糖耐量受损为主,空腹血糖受损次之.多囊卵巢综合征患者(尤其是肥胖者)应行口服葡萄糖耐最试验,以早期发现其糖代谢异常.%Objective To evaluate the characteristics and prevalence of abnormal glucose metabolism in polycystic ovary syndrome (PCOS) patients. Methods A retrospective case-control study was performed in 654 PCOS patients (101 were in adolescence, 553 were adults) and 120 healthy controls (40 were in adolescence, 80 were adults). Oral glucose tolerance test (OGTT), insulin releasing test (IRT), and other biochemical testing were underwent in all patients and controls. The characteristics and prevalence of abnormal glucose metabolism were analyzed and compared. Results The prevalence of abnormal glucose metabolism, including impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and diabetes mellitus (DM), was 24.5% in PCOS patients, which was significantly higher than that in the controls (χ2 = 27.11, P < 0.0001). The prevalence of abnormal glucose metabolism in

  5. 妊娠期糖代谢异常162例母儿预后分析%Analysis on the outcomes of 162 maternal and fetal with abnormal glucose metabolism during pregnancy

    Institute of Scientific and Technical Information of China (English)

    徐亚萍

    2011-01-01

    Objective: To investigate the effect of abnormal glucose metabolism during pregnancy on maternal and fetal outcomes.Methods: 162 patients were diagnosed definitely in our hospital from June 2003 to August 2007.They were divided into Gestational Diabetes Mellitus (GDM) group (58 cases) and gestational impaired glucose tolerance (GIGT) group (104 cases).150 pregnant women of normal blood glucose were taken as normal glucose tolerance (GNGT) group, maternal and fetal outcomes were compared in three groups.Results: The incidences of postpartum hemorrhage, cesarean section, pregnancy - induced hypertension, polyhydramnios, fatal macrosomia, premature delivery, neonatal hypoglycemia were higher in GDM group than in GNGT group (P < 0.05 ).The incidences of cesarean section, polyhydramnios, fatal acrosomia were higher in the GIGT group than in GNGT group (P <0.05).Conclusion: Abnormal glucose metabolism during pregnancy can produce adverse effect on mothers and neonates.It is very important to positive treatment the pregnant women of abnormal glucose metabolism during pregnancy.%目的:探讨妊娠期糖代谢异常对母儿预后的影响.方法:2003年6月~2007年8月在大同市第一人民医院诊断为妊娠期糖代谢异常的孕妇162例,其中妊娠期糖尿病(GDM)组58例,妊娠期糖耐量减低(GIGT)组104例,另选择150例血糖值正常孕妇作为血糖正常(GNGT)组,比较3组的母儿预后.结果:GDM组孕妇产后即时出血、剖宫产、妊娠期高血压疾病、羊水过多、巨大儿、早产儿和新生儿低血糖的发生率均显著高于GNGT组(P<0.05);GIGT组剖宫产、羊水过多、巨大儿的发生率显著高于GNGT组(P<0.05).结论:妊娠期糖代谢异常对孕产妇和围生儿的预后有不良影响,应对妊娠期糖代谢异常的孕产妇进行积极干预.

  6. Establishment and Evaluation of Rat Model of Metabolic Syndrome with Abnormal Glucose Metabolism%糖代谢异常的代谢综合征大鼠模型的建立及评价

    Institute of Scientific and Technical Information of China (English)

    姜楠; 石岩; 蒲纪; 张文顺; 张冰冰; 马贤德

    2011-01-01

    Objective:To establish and to evaluate rat model of metabolic syndrome (MS) with abnormal glucose metablism. Method: Wistar male rats were fed with a diet of high fat, salt and sugar for 12 weeks.Afterwards, body weight, blood pressure, blood glucose, triglycerides, high density lipoprotein and insulin level were determined. According to the MS diagnostic criteria established by Chinese Diabetes Society (CDS) and statistical theory, the model was evaluated. Result: In the first 8 weeks, rats were significantly increased body weight and systolic blood pressure; in the first 12 weeks, fasting blood glucose, triglycerides, insulin level were significantly elevated, high-density lipoprotein significantly reduced. Based on the evaluation criteria, a success rate of 80% for the model was found. Conclusion: We successfully established the rat model of MS with abnormal glucose metabolism, and also the preliminary evaluation criteria for the model.%目的:建立糖代谢异常的代谢综合征大鼠模型及其评价标准.方法:采用高脂高盐高糖饮食配合饮用蔗糖水喂养Wistar雄性大鼠12周,喂养结束后检测其体重、血压、血糖、甘油三酯、高密度脂蛋白及胰岛素水平.根据中华医学会糖尿病学分会关于代谢综合征(MS)的诊断标准和统计学原理建立模型评价标准.结果:第8周开始,高脂高糖高盐膳食组大鼠体重(367±17)g和收缩压(130.67±4.31)mmHg与普通膳食对照组比较显著升高(P<0.01);第12周时,大鼠空腹血糖(10.51±0.89)mmol·L-1、甘油三酯(1.63±0.23)mmol·L-1、胰岛素水平(1.97±1.07)mmol·L-1显著升高(P<0.01或P<0.05),高密度脂蛋白(0.54±0.07)mmol·L-1显著降低(P<0.01).根据评价标准,模型成功率达到80%.结论:实验成功建立了糖代谢异常的MS大鼠模型,并初步建立了该模型的评价标准.

  7. Glucose metabolism and hyperglycemia.

    Science.gov (United States)

    Giugliano, Dario; Ceriello, Antonio; Esposito, Katherine

    2008-01-01

    Islet dysfunction and peripheral insulin resistance are both present in type 2 diabetes and are both necessary for the development of hyperglycemia. In both type 1 and type 2 diabetes, large, prospective clinical studies have shown a strong relation between time-averaged mean values of glycemia, measured as glycated hemoglobin (HbA1c), and vascular diabetic complications. These studies are the basis for the American Diabetes Association's current recommended treatment goal that HbA1c should be regulation is accompanied by a significant improvement of many pathways supposed to be involved in diabetic complications, including oxidative stress, endothelial dysfunction, inflammation, and nuclear factor-kappaB activation. The goal of therapy should be to achieve glycemic status as near to normal as safely possible in all 3 components of glycemic control: HbA1c, fasting glucose, and postmeal glucose peak.

  8. Abnormal brain glucose metabolism and depressive mood in patients with pre-dialytic chronic kidney disease: SPM analysis of F-18 FDG positron emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Jun, Sung Min; Song, Sang Heon; Kim, Seong Jang; Kim, Ji Hoon; Kwak, Ihm Soo; Kim, In Ju; Kim, Yong Ki [Pusan National University Hospital, Pusan (Korea, Republic of)

    2007-07-01

    The aim of this study was to investigate the relationship between depressive mood and pre-dialytic CKD, to localize and quantify depressive mood -related lesions in pre-dialytic CKD patients through statistical parametric mapping (SPM) analysis of brain positron emission tomography (PET), and to examine the usefulness of brain PET for early detection and proper treatment of depressive mood. Twenty one patients with stage 5 CKD and 22 healthy volunteers were analyzed by depressive mood assessment and statistical parametric mapping (SPM) analysis of 18F-FDG PET. Depressive mood assessment was done by Beck Depression Inventory (BDI) and Hamilton Depression Rating Scale (HDRS). The largest clusters were areas including precentral gyrus, prefrontal cortex, and anterior cingulated cortex of left hemisphere. Other clusters were left transverse temporal gyrus, left superior temporal gyrus, right prefrontal cortex, right dorsolateral prefrontal cortex (BA 46, 44), right inferior frontal gyrus, right inferior parietal lobule, left angular gyrus. In addition, correlation was found between hypometabolized areas and HDRS scores of CKD patients in right prefrontal cortex (BA 11) and right anterior cingulated gyrus (BA 24). In conclusion, this study demonstrated specific depressive mood-related abnormal metabolic lesion. Interestingly, in CKD patients with severe depressive mood, cerebral metabolism was similar to that of MDD.

  9. 出生体重与成年期肥胖指标联合效应对糖代谢异常的影响%Joint effect of birth weight and obesity measures on abnormal glucose metabolism at adulthood

    Institute of Scientific and Technical Information of China (English)

    席波; 程红; 陈芳芳; 赵小元; 米杰

    2016-01-01

    Objective To investigate the joint effect of birth weight and each of obesity measures (body mass index (BMI) and waist circumference (WC)) on abnormal glucose metabolism (including diabetes) at adulthood. Methods Using the historical cohort study design and the convenience sampling method, 1 921 infants who were born in Beijing Union Medical College Hospital from June 1948 to December 1954 were selected to do the follow-up in 1995 and 2001 respectively. Through Beijing Household Registration and Management System, they were invited to participate in this study. A total of 972 subjects (627 were followed up in 1995 and 345 were followed up in 2001) with complete information on genders, age, birth weight, family history of diabetes, BMI, WC, fasting plasma glucose (FPG) and 2-hour plasma glucose (2 h PG) met the study inclusion criteria at the follow-up visits. In the data analysis, they were divided into low, normal, and high birth weight, respectively. The ANOVA and Chi-squared tests were used to compare the differences in their characteristics by birth weight group. In addition, multiple binary Logistic regression model was used to investigate the single effect of birth weight, BMI, and waist circumference on abnormal glucose metabolism at adulthood. Stratification analysis was used to investigate the joint effect of birth weight and each of obesity measures (BMI and WC) on abnormal glucose metabolism. Results There were 972 subjects (males:50.7%, mean age:(46.0±2.2) years) included in the final data analysis. The 2 h PG in low birth weight group was (7.6±3.2) mmol/L , which was higher than that in normal birth weight group (6.9± 2.1) mmol/L and high birth weight group (6.4±1.3) mmol/L (F=3.88, P=0.021). After adjustment for genders, age, body length, gestation age, family history of diabetes, physical activity, smoking and alcohol consumption, and duration of follow-up, subjects with overweight and obesity at adulthood had 2.73 (95%confidence interval (CI

  10. Efficacy and safety of 131Ⅰ in treating hyperthyroidism combined with abnormal glucose metabolism%131Ⅰ治疗甲亢合并糖代谢异常的有效性和安全性

    Institute of Scientific and Technical Information of China (English)

    劳丹华; 叶学和; 黄庆娟; 梁深; 谭宗连

    2011-01-01

    Objective To evaluate the efficacy and safety of 131Ⅰ in treating hyperthyroidism combined with abnormal glucose metabolism. Methods 108 patients with hyperthyroidism combined with abnormal glucose metabolism were divided into 131 Ⅰ group of 55 cases and antithyroid drug(ATD) group of 53 cases as contrast group. Compared the curative effect of hyperthyroidism, blood sugar,glycosylated hemoglobin(HbAlc), β-cell function and adverse reaction between the two groups. Results The total efficiency of hyperthyroidism in 131 Ⅰ group was obviously higher than that of the contrast group (P=0. 008). The hyperthyroidism recurrence rate of 131 Ⅰ group was evidently much lower than the contrast group (P=0. 001). The occurring rate of hypothyroidism in 131 Ⅰ group was evidently higher than the contrast group (P=0. 031). After treatment, fasting plasma glucose(FPG), two hour plasma glucose after breakfast (2hPG), bAlc and HOMA-IR in the 131Ⅰ group were evidently under than those in the contrast group (P <0.05). HOMA-IS was distinctly higher than that in the contrast group (P<0. 05). There was no other adverse reaction in 131 Ⅰ group, while diabetic ketoacidosis, hypoglycemia and other adverse reaction in the contrast group. Conclusion 131 Ⅰ has a good curative effect in treating hyperthyroidism combined with abnormal glucose metabolism,with little adverse reaction.%目的 评价131Ⅰ治疗甲状腺功能亢进症(甲亢)合并糖代谢异常的疗效及安全性.方法 108例甲亢合并糖代谢异常患者分为131Ⅰ治疗组55例和抗甲状腺药物(ATD)对照组53例,比较两组甲亢的疗效、血糖、糖化血红蛋白(HbA1c)、胰岛β细胞功能及不良反应.结果 治疗组甲亢总有效率显著高于对照组(P=0.008),复发率显著低于对照组(P=0.001),甲状腺功能减退症(甲减)发生率高于对照组(P=0.031),治疗后治疗组的空腹血糖(FPG)、餐后2 h血糖(2hPG)、HbA1c及胰岛素抵抗指数显著低于对照组(P<0

  11. [Glucose Metabolism: Stress Hyperglycemia and Glucose Control].

    Science.gov (United States)

    Tanaka, Katsuya; Tsutsumi, Yasuo M

    2016-05-01

    It is important for the anesthesiologists to understand pathophysiology of perioperative stress hyperglycemia, because it offers strategies for treatment of stress hyperglycemia. The effect of glucose tolerance is different in the choice of the anesthetic agent used in daily clinical setting. Specifically, the volatile anesthetics inhibit insulin secretion after glucose load and affects glucose tolerance. During minor surgery by the remifentanil anesthesia, the stress reaction is hard to be induced, suggesting that we should consider low-dose glucose load. Finally it is necessary to perform the glycemic control of the patients who fell into stress hyperglycemia depending on the individual patient. However, there are a lot of questions to be answered in the future. The prognosis of the perioperative patients is more likely to be greatly improved if we can control stress hyperglycemia.

  12. Investigation and analysis of risk factors of abnormal glucose metabolism in pregnant women%妊娠期糖代谢异常相关因素调查分析

    Institute of Scientific and Technical Information of China (English)

    吴红媛; 刘春燕

    2014-01-01

    目的:探讨妊娠期糖代谢异常发病的高危因素,为制定有效干预措施提供科学依据。方法采用前瞻性对照研究方法,收集2011年4至9月在珠海市妇幼保健院产科门诊行产前检查诊断的糖代谢异常孕妇(研究组)共108例,其中妊娠期糖尿病(GDM)75例、妊娠糖耐量异常(GIGT)33例;收集同期糖代谢正常孕妇91例(对照组),对两组孕妇的临床资料进行单因素及多因素回归分析,探讨各因素对妊娠期糖代谢异常发病的影响。结果一般情况分析显示,糖代谢异常孕妇年龄、孕前身体质量指数( BMI)、孕期体重增长、孕次及产次均大于正常孕妇( t 值分别为-6.567、-4.818、-1.929、-3.231、-3.270,均P<0.05);糖代谢异常孕妇高中以下文化程度的比例较对照组高,差异有统计学意义(χ2=5.642,P<0.05)。单因素分析发现,孕次、产次、文化程度、年龄≥30岁、孕前BMI≥24kg/m2、糖尿病家族史、不良孕产史、高脂血症、反复发生霉菌性阴道炎( VCC)、孕期大量甜食、孕期大量水果、孕期锻炼等因素与糖代谢异常的发生相关。多因素Logistic回归分析表明,孕期大量甜食、孕期大量水果、糖尿病家族史、孕前BMI≥24kg/m2、VCC、年龄≥30岁、孕期锻炼7个因素进入主效应模型,其中孕期锻炼为保护性因素,其他为危险因素。结论不合理饮食、糖尿病家族史、孕前超重、年龄≥30岁、反复发生霉菌性阴道炎为影响妊娠期糖代谢异常发生的高危因素,孕期锻炼为保护性因素。对存在高危因素的妇女在产前检查时应加强监护和指导。%Objective To explore the risk factors of abnormal glucose metabolism during pregnancy , so as to provide evidence for effective intervention .Methods A prospective case-control study was performed among 108 women with abnormal glucose metabolism

  13. Sex steroids and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Carolyn A Allan

    2014-04-01

    Full Text Available Testosterone levels are lower in men with metabolic syndrome and type 2 diabetes mellitus (T2DM and also predict the onset of these adverse metabolic states. Body composition (body mass index, waist circumference is an important mediator of this relationship. Sex hormone binding globulin is also inversely associated with insulin resistance and T2DM but the data regarding estrogen are inconsistent. Clinical models of androgen deficiency including Klinefelter's syndrome and androgen deprivation therapy in the treatment of advanced prostate cancer confirm the association between androgens and glucose status. Experimental manipulation of the insulin/glucose milieu and suppression of endogenous testicular function suggests the relationship between androgens and insulin sensitivity is bidirectional. Androgen therapy in men without diabetes is not able to differentiate the effect on insulin resistance from that on fat mass, in particular visceral adiposity. Similarly, several small clinical studies have examined the efficacy of exogenous testosterone in men with T2DM, however, the role of androgens, independent of body composition, in modifying insulin resistance is uncertain.

  14. Degree of abnormality is associated with rate of change in measures of beta-amyloid, glucose metabolism and cognition in an autopsy-verified Alzheimer's disease case.

    Science.gov (United States)

    Almkvist, Ove; Kadir, Ahmadul; Nordberg, Agneta

    2015-01-01

    The degree of abnormality and rate of change in cognitive functions, positron emission tomography Pittsburg compound B (PET PIB), and fluorodeoxyglucose (FDG) measures were studied for 8 years in an autopsy-confirmed Alzheimer's disease (AD) patient, who died 61 years old (Mini-Mental State Examination (MMSE) score 7). At first encounter with medical care, the patient was very mildly demented (MMSE score 27). She had four cognitive assessments and two examinations with PET PIB and FDG in 23 bilateral brain regions. The onset of cognitive decline was retrospectively estimated to have started in the early forties. The degree of impairment was inversely related to the rate of decline. A similar relationship was seen between the rate of change and the level of abnormality in both PIB and FDG. To conclude, rate of change in cognition, PIB, and FDG was associated with the degree of abnormality.

  15. Genetic determinants for metabolic abnormalities

    NARCIS (Netherlands)

    Risselada, A.J.

    2012-01-01

    Psychiatric patients often use psychotropic drugs. Apart from frequent problems regarding lack of efficacy, use of these drugs also often results in (severe) adverse effects. The use of (atypical) antipsychotic drugs in particular can give rise to weight gain and metabolic deregulation regarding glu

  16. Impacts of Abnormal Glucose Metabolism on Chronic Ischemic Leukoaraiosis%糖代谢异常对慢性缺血性脑白质疏松的影响

    Institute of Scientific and Technical Information of China (English)

    王君梅; 李静; 金桂花; 田沈

    2014-01-01

    目的:探究糖代谢异常对慢性缺血性脑白质疏松(LA)的影响。方法回顾性分析2013年6月~12月中国医科大学附属第四医院神经内科收治的258例缺血性脑血管疾病患者的临床资料。根据病史及化验结果将糖代谢情况分为正常糖代谢、2型糖尿病以及前驱期糖尿病,依据头MRI结果对LA严重程度进行分级,分析比较不同糖代谢情况以及不同血糖化验指标(包括FPG、2hPG及HbA1c)对慢性缺血性脑白质疏松及其严重程度的影响。结果单因素分析显示,慢性缺血性脑白质疏松的相关危险因素有年龄、高血压病史、糖尿病病史、糖代谢异常、甘油三酯、2hPG(OR>1,P<0.05)。Logistic回归分析显示脑白质疏松与年龄、高血压病史、2hPG相关(P<0.05)。Spearman秩相关检验显示LA严重程度分级与年龄大小、高血压病史时长、2hPG水平呈正相关,与HDL、apoA、腔梗病史呈负相关(P<0.05,r=0.402、0.227、0.135、-0.154、-0.147、-0.312)。结论年龄、高血压病史、糖尿病病史、糖代谢异常、2hPG、甘油三酯是脑白质疏松的危险因素;年龄越大、高血压病史时间越长、2hPG越高、HDL及apoA越低,脑白质疏松越严重;而FPG、HbA1c、前驱期糖尿病、糖尿病及其时长与脑白质疏松的严重程度无相关性。%Objective To explore the impacts of abnormal glucose metabolism on chronic ischemic leukoaraiosis (LA).Methods The clinical data of 258 patients with ischemic cerebrovascular disease were analyzed who were cured in the Fourth Affi liated Hospital of China Medical University from Jun to December in 2013. According to the medical history and laboratory reports, these patients were divided into normal glucose metabolism group, type 2 diabetes group and pre-diabetes group. Based on the results of head MRI, the severity of leukoaraiosis was graded. Then we compared and analyzed the impacts of

  17. 农村高血压患者血糖与血脂参数改变的调查%Investigation on abnormality of glucose and lipid metabolism in patients with hypertension in rural area

    Institute of Scientific and Technical Information of China (English)

    鲁永华; 诸葛毅; 徐军

    2012-01-01

    Objective:To observe the abnormality of glucose and lipid metabolism in patients with hypertension in rural population in mountain area of Kaihua county and to provide a reference for the prevention and treatment of cardiovascular disease. Methods:298 cases of patients with hypertension in rural population in mountain area of Kaihua county as objective group and 291 cases of healthy people as control group were investigated with total cholesterol, triglyceride,high density lipoprotein cholesterol, low density lipoprotein cholesterol and fasting plasma glucose. The comparative study was done. Results:There were 84 cases of patients with hyperlipidemia in objective group and 21 cases with hyperlipidemia in control group, x =44.2,P<0.01. There was a low positive correlation( r = 0. 117, P < 0. 05 ) between diastolic pressure and total cholesterol of plasma in patients with hypertension. Conclusion:The fact showed that abnormality of glucose and lipid metabolism in patients with hypertension in rural population in mountain area of Kaihua county was present. Glucose, lipid parameters contributed to the clinical observation of disease in patients with hypertension. Health education should be carried out and rural population should be encouraged to cultivate a healthy mode of life. The measures to adjust the blood lipid levels should be carried out.%目的:调查开化山区高血压患者的血糖与血脂代谢异常,为心血管疾病的防治提供参考依据.方法:298例高血压患者为观察组,291例健康人为对照组,测定空腹血糖、总胆固醇、甘油三酯、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇,比较分析.结果:高血压观察组检出高血脂84例,对照组检出高血脂21例,x2=44.2,P<0.01.高血压组舒张压与血总胆固醇之间呈低度显著正相关(r为0.117,P<0.05).结论:开化山区高血压患者存在血糖、血脂参数的异常改变,测定血糖、血脂参数有助于临床观察高血压患者

  18. 不同糖代谢状态血管内皮功能变化及相关影响因素分析%Changes and influencing factors of vascular endothelial function in different abnormal glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    王蕾蕾; 张丽娜; 郭立新

    2015-01-01

    Objective To evaluate the vascular endothelial function and explore the related influencing factors in patients with abnormal glucose metabolism by use of ultrasound technology. Methods A total of 109 participants selected from endocrinology outpatients of Beijing Hospital from October 2011 to June 2013 were enrolled in this study. Oral glucose tolerance test(OGTT) was carried out, including fasting plasma glucose(FPG) and postprandial glucose(PPG), fasting and 2 hours after glucose load testing insulin, C-peptide, glycated hemoglobin A1c(HbA1c), glycated albumin(GA), lipids, liver and kidney function, blood uric acid,flow-mediated endothelium-dependent vasodilation (FMEDD), serum nitric oxide (NO), endothelin-1(ET-1), serum malondialdehyde(MDA) and superoxide dismutase(SOD).With the receiver operating characteristic (ROC)curve, the best critical points of fasting and glucose loading vascular endothelial function were obtained. Results (1)The critical points of FMEDD in the state of abnormal glucose metabolism: fasting FMEDD was 13.37%, Youden index was 0.467, and the area under the curve was 0.786 (95%CI:0.697⁃0.876);FMEDD of OGTT 2 h was 10.67%,Youden index was 0.458, and the area under the curve was 0.774(95% CI:0.687⁃0.861). (2)Body mass index(BMI), FPG, HbA1c, GA, triglyceride (TG), MDA in the patients withabnormal fasting FMEDD were significantly higher than those in the normalgroup(t=-3.013,-4.567,-3.487,-4.611,-2.309,-2.909, all P<0.05); and the homeostasis model assessment⁃β(HOMA⁃β), NO, SOD were significantly lower than those in the normal group(t=2.765,2.472, 5.937, all P<0.05). PPG, HbA1c, GA in the patients with abnormal FMEDD after glucose load were significantly higher than those in the normal group(t=-4.907,-4.236,-3.896, all P<0.05);and the HOMA⁃β, NO, SOD were all significantly lower than those in the normal group(t=2.704,4.675,4.633, all P<0.05).(3) FPG,HbA1c,GA were negatively correlated with fasting FMEDD(r=-0

  19. Evaluation of glucose metabolism in women with multiple ovarian follicles

    Institute of Scientific and Technical Information of China (English)

    Shulan Lü; Xiaoyan Guo; Zuansun Cao; Wenjun Mao

    2007-01-01

    Objective:To investigate glucose metabolism in women with multiple ovarian follicles (MOF) and explore the relationship between glucose metabolism, insulin resistance and body weight. Methods:We evaluated 46 women with MFO and 30 nor mal women as controls. All the subjects were given 75g of glucose orally in order to perform the oral glucose tolerance test(OGTT) and insulin releasing test(IRT), and they were also evaluated for insulin resistance using the insulin resistance index with homeostatic model assessment (HOMA). Results:The occurrence of impaired glucose tolerance in women with MOF was 10.87%, which was significantly higher than that in the control group (3.33% ,P < 0.05). The rate of insulin resistance was 30.43% in the study group as compared to 10.00% in the control group. The results showed that there was significant difference between the two groups(P < 0.05). The levels of FSH,LH,PRL,E2,T and P between the two groups had no significant difference (P > 0.05). BMI in women with impaired glucose tolerance was correlated positively to insulin resistance (r =0.567, P < 0.05). Conclusion :Abnormal glucose metabolism was observed in women with unitary multiple ovarian follicles,and this could be attributed to obesity and insulin resistance. Women with MOF and associated obesity should be subjected to OGTT so that their glucose levels can be monitored as a preventive measure.

  20. 糖脂代谢异常对肝硬化患者疾病进展的影响%Impact of abnormal glucose and lipid metabolism on the progression of disease in patients with cirrhosis

    Institute of Scientific and Technical Information of China (English)

    岑光力; 岑柏春

    2015-01-01

    ,triglycerides (TG) in patients with different Child-Pugh score had no statistically significant difference,P =0.558,0.169.The level of serum albumin (ALB) of patients with DM in cirrhosis was significantly lower than those without DM,P =0.009.The patients with DM in liver cirrhosis had higher incidence of complications such as ascites,gastro esophageal variceal bleeding(GEVB) or hepatic encephalopathy than those without DM,P =0.000.Conclusion The patients with cirrhosis had higher incidence of abnormal glucose metabolism,and DM lead to progression of liver disease in turn.

  1. Dietary Patterns and Glucose Tolerance Abnormalities in Chinese Adults

    NARCIS (Netherlands)

    He, Y.; Ma, G.; Zhai, F.; Li, Y.; Hu, Y.; Feskens, E.J.M.; Yang, X.

    2009-01-01

    OBJECTIVE To investigate the association of the dietary pattern with the presence of newly diagnosed glucose tolerance abnormalities among Chinese adults. RESEARCH DESIGN AND METHODS A total of 20,210 adults aged 45–69 years from the 2002 China National Nutrition and Health Survey were included. Inf

  2. Perturbed glucose metabolism: insights into Multiple Sclerosis pathogenesis

    Directory of Open Access Journals (Sweden)

    Deepali eMathur

    2014-12-01

    Full Text Available Multiple sclerosis (MS is a complex debilitating disease of the central nervous system perceived to result from the autoimmune effect of T cells in damaging myelin sheath. However, the exact pathogenesis of the disease remains elusive. Initial studies describing the possibility of defective pyruvate metabolism in MS were performed in 1950s. The group observed elevated blood pyruvate level in both fasting and postprandial times in MS patients with relapse. Similarly, other investigators also reported increased fasting pyruvate level in this disease. These reports hint to a possible abnormality of pyruvate metabolism in MS patients. In addition, increase in levels of Krebs cycle acids like alpha-ketoglutarate in fasting and citrate after glucose intake in MS patients further strengthened the connection of disturbed pyruvate metabolism with MS progression. These studies led the investigators to explore the role of disturbed glucose metabolism in pathophysiological brain function. Under normal circumstances, complex molecules are metabolized into simpler molecules through their respective pathways. Differential expression of genes encoding enzymes of the glucose metabolic pathway in central nervous system (CNS may result in neurological deficits. In this review article, we discussed the studies related to disturbed carbohydrate metabolism in MS and other neurodegenerative diseases. These observations open new perspectives for the understanding of metabolic dynamics in multiple sclerosis yet many puzzling aspects and critical questions need to be addressed. Much more research is required to fully unravel the disease mechanism, and a proper understanding of the disease could eventually lead to new treatments.

  3. A clinical analysis of abnormal gestational glucose metabolism and pregnancy outcome of the woman%妊娠期糖代谢异常与妊娠结局的临床分析

    Institute of Scientific and Technical Information of China (English)

    米阳; 闫坤; 黄谱; 苟文丽

    2009-01-01

    Objective To investigate relationship between abnormal gestational glucose metabolism and pregnancy outcome of the woman. Methods 1 636 pregnant women who received antenatal examination in Shannxi Provincial Maternal and Child Health Hospital in a period from January to June, 2008 were screened at their 24~28 weeks of gestation with 50g glucose challenge test (GCT). Those pregnant women with abnormal GCT results further received oral 75g glucose tolerance test (OGTT). According to OGTT results, the pregnant women were divided into 2 groups: GDM group (n=69) and gestational impaired glucose tolerance group (GIGT group, n=124). 300 pregnant women with normal glucose metabolism were as controls. All of them were followed up untill delivery and the perinatal outcomes in the 3groups were compared. Results The incidence of GDM was 4.21% and that of GIGT was 7.58%. The incidences of hypertensive disorder complicating pregnancy, polyhydramnios, premature rupture of membrane and premature delivery in GDM group were higher than those in the control group (χ2=4.660,11.530,5.193,4.661 respectively,all P<0.05).In GIGT group ,the incidences of polyhydramnios and premature rupture of membrane were significantly higher than those in the control group(χ2=12.450,6.325,respectively,both P<0.05). Conclusion The pregnant women with GDM or GIGT have significantly high incidences of obstetric complications and rate of cesarean section. So, screening of GDM should be strengthened and early diagnosis, early treatment, gestational supervision and guidance should be carried out in order to reduce incidence rates of maternal and infantile complications.%目的 探讨妊娠期糖代谢异常与妊娠结局的关系.方法 选取2008年1~6月在陕西省妇幼保健院进行产前检查的1 636名孕妇,于24~28周进行50g葡萄糖筛查试验,异常者行75g糖耐量试验,按糖代谢异常情况分为妊娠期糖尿病组(69例)和妊娠期糖耐量受损组(124例);

  4. Klinefelter syndrome: cardiovascular abnormalities and metabolic disorders.

    Science.gov (United States)

    Calogero, A E; Giagulli, V A; Mongioì, L M; Triggiani, V; Radicioni, A F; Jannini, E A; Pasquali, D

    2017-03-03

    Klinefelter syndrome (KS) is one of the most common genetic causes of male infertility. This condition is associated with much comorbidity and with a lower life expectancy. The aim of this review is to explore more in depth cardiovascular and metabolic disorders associated to KS. KS patients have an increased risk of cerebrovascular disease (standardized mortality ratio, SMR, 2.2; 95% confidence interval, CI, 1.6-3.0), but it is not clear whether the cause of the death is of thrombotic or hemorrhagic nature. Cardiovascular congenital anomalies (SMR, 7.3; 95% CI, 2.4-17.1) and the development of thrombosis or leg ulcers (SMR, 7.9; 95% CI, 2.9-17.2) are also more frequent in these subjects. Moreover, cardiovascular abnormalities may be at least partially reversed by testosterone replacement therapy (TRT). KS patients have also an increased probability of endocrine and/or metabolic disease, especially obesity, metabolic syndrome and type 2 diabetes mellitus. The effects of TRT on these abnormalities are not entirely clear.

  5. Glucose abnormalities in Asian patients with chronic hepatitis C

    Directory of Open Access Journals (Sweden)

    Bo Q

    2015-11-01

    Full Text Available Qingyan Bo,1 Roberto Orsenigo,2 Junyi Wang,1 Louis Griffel,3 Clifford Brass3 1Beijing Novartis Pharma Co. Ltd., Shanghai, People’s Republic of China; 2Novartis Pharma AG, Basel, Switzerland; 3Novartis Pharmaceuticals Corporation, East Hanover, NJ, USA Abstract: Many studies have demonstrated a potential association between type 2 diabetes (T2D and hepatitis C virus infection in Western countries, while similar evidence is limited in Asia. We compared the prevalence of glucose abnormalities (impaired fasting glucose [IFG] and T2D and their risk factors between Asian and non-Asian chronic hepatitis C (CHC patients, and evaluated whether glucose abnormalities impacted the viral responses to peginterferon plus ribavirin treatment (current standard of care in most Asian countries. This study retrospectively analyzed data of 1,887 CHC patients from three Phase II/III studies with alisporivir (DEB025 as treatment for CHC. The chi-square test was used to compare the prevalence of IFG/T2D between Asian and non-Asian CHC patients, and logistic regression was used to adjust for sex, age, and cirrhosis status. Risk factors for IFG/T2D were evaluated using univariate and multivariate analysis. Our results indicated that the prevalence of IFG/T2D was high in both Asian and non-Asian CHC patients (23.0% vs 20.9%, and no significant difference was found between these two populations (adjusted odds ratio: 1.3, 95% confidence interval: 0.97, 1.7; P=0.08. Age, sex, and cirrhosis status were risk factors for IFG/T2D in both populations, while body mass index was positively associated with IFG/T2D in non-Asian but not in Asian participants. No significant differences in sustained virological response rates were seen between patients with normal fasting glucose and patients with IFG/T2D for both populations. These results demonstrate that the prevalence of glucose abnormalities in Asian CHC patients was similar to that in non-Asians, and glucose abnormalities had

  6. Glucose metabolism in rat retinal pigment epithelium.

    Science.gov (United States)

    Coffe, Víctor; Carbajal, Raymundo C; Salceda, Rocío

    2006-01-01

    The retinal pigment epithelium (RPE) is the major transport pathway for exchange of metabolites and ions between choroidal blood supply and the neural retina. To gain insight into the mechanisms controlling glucose metabolism in RPE and its possible relationship to retinopathy, we studied the influence of different glucose concentrations on glycogen and lactate levels and CO(2) production in RPE from normal and streptozotocin-treated diabetic rats. Incubation of normal RPE in the absence of glucose caused a decrease in lactate production and glycogen content. In normal RPE, increasing glucose concentrations from 5.6 mM to 30 mM caused a four-fold increase in glucose accumulation and CO(2) yield, as well as reduction in lactate and glycogen production. In RPE from diabetic rats glucose accumulation did not increase in the presence of high glucose substrate, but it showed a four- and a seven-fold increase in CO(2) production through the mitochondrial and pentose phosphate pathways, respectively. We found high glycogen levels in RPE which can be used as an energy reserve for RPE itself and/or neural retina. Findings further show that the RPE possesses a high oxidative capacity. The large increase in glucose shunting to the pentose phosphate pathway in diabetic retina exposed to high glucose suggests a need for reducing capacity, consistent with increased oxidative stress.

  7. Unmasking Glucose Metabolism Alterations in Stable Renal Transplant Recipients: A Multicenter Study

    Science.gov (United States)

    Delgado, Patricia; Diaz, Juan Manuel; Silva, Irene; Osorio, José M.; Osuna, Antonio; Bayés, Beatriz; Lauzurica, Ricardo; Arellano, Edgar; Campistol, Jose Maria; Dominguez, Rosa; Gómez-Alamillo, Carlos; Ibernon, Meritxell; Moreso, Francisco; Benitez, Rocio; Lampreave, Ildefonso; Porrini, Esteban; Torres, Armando

    2008-01-01

    Background and objectives: Emerging information indicates that glucose metabolism alterations are common after renal transplantation and are associated with carotid atheromatosis. The aims of this study were to investigate the prevalence of different glucose metabolism alterations in stable recipients as well as the factors related to the condition. Design, setting, participants, & measurements: A multicenter, cross-sectional study was conducted of 374 renal transplant recipients without pre- or posttransplantation diabetes. A standard 75-g oral glucose tolerance test was performed. Results: Glucose metabolism alterations were present in 119 (31.8%) recipients: 92 (24.6%) with an abnormal oral glucose tolerance test and 27 (7.2%) with isolated impaired fasting glucose. The most common disorder was impaired glucose tolerance (17.9%), and an abnormal oral glucose tolerance test was observed for 21.5% of recipients with a normal fasting glucose. By multivariate analysis, age, prednisone dosage, triglyceride/high-density lipoprotein cholesterol ratio, and β blocker use were shown to be factors related to glucose metabolism alterations. Remarkably, triglyceride levels, triglyceride/high-density lipoprotein cholesterol ratio, and the proportion of recipients with impaired fasting glucose were already higher throughout the first posttransplantation year in recipients with a current glucose metabolism alteration as compared with those without the condition. Conclusions: Glucose metabolism alterations are common in stable renal transplant recipients, and an oral glucose tolerance test is required for its detection. They are associated with a worse metabolic profile, which is already present during the first posttransplantation year. These findings may help planning strategies for early detection and intervention. PMID:18322043

  8. Metabolic abnormalities in adult and geriatric major depression with and without comorbid dementia.

    Science.gov (United States)

    Blank, Karen; Szarek, Bonnie L; Goethe, John W

    2010-06-01

    Metabolic abnormalities and metabolic syndrome (MetS) increasingly have been linked to depression. The authors studied examined inpatients 35 years and older with major depressive disorder (MDD) to determine the prevalence of component metabolic abnormalities and the full MetS with age, treatment, and comorbid dementia. Data analysis involved retrospective cross-sectional review from a nonprofit psychiatry inpatient service of all discharges 35 years and older with a diagnosis of MDD during a 3 year period (April 1, 2003 to March 31, 2006) (N=1718). Metabolic measures included waist circumference, lipid measurements, glucose, and hypertension diagnosis. Abnormal metabolic measures and MetS were highly prevalent in both young and old patients with MDD: one or more component was present in 87.6% of older (65-99 years old) and 79.9% of younger patients. Full MetS was present in 31.5% of older and 28.9% of younger patients (not significant, P=0.85). Metabolic abnormalities were not associated with atypical antipsychotics after controlling other variables. One-quarter (n=79, 24.9%) of older inpatients had a dementia co-diagnosis. Older patients with MDD and dementia had greater risk of elevated glucose while younger patients were more often hypertensive. Longitudinal studies are needed to determine the relationships of MDD with or without dementia with these highly prevalent abnormal metabolic measures and MetS.

  9. Abnormal tyrosine metabolism in chronic cluster headache.

    Science.gov (United States)

    D'Andrea, Giovanni; Leone, Massimo; Bussone, Gennaro; Fiore, Paola Di; Bolner, Andrea; Aguggia, Marco; Saracco, Maria Gabriella; Perini, Francesco; Giordano, Giuseppe; Gucciardi, Antonina; Leon, Alberta

    2017-02-01

    Objective Episodic cluster headache is characterized by abnormalities in tyrosine metabolism (i.e. elevated levels of dopamine, tyramine, octopamine and synephrine and low levels of noradrenalin in plasma and platelets.) It is unknown, however, if such biochemical anomalies are present and/or constitute a predisposing factor in chronic cluster headache. To test this hypothesis, we measured the levels of dopamine and noradrenaline together with those of elusive amines, such as tyramine, octopamine and synephrine, in plasma of chronic cluster patients and control individuals. Methods Plasma levels of dopamine, noradrenaline and trace amines, including tyramine, octopamine and synephrine, were measured in a group of 23 chronic cluster headache patients (10 chronic cluster ab initio and 13 transformed from episodic cluster), and 16 control participants. Results The plasma levels of dopamine, noradrenaline and tyramine were several times higher in chronic cluster headache patients compared with controls. The levels of octopamine and synephrine were significantly lower in plasma of these patients with respect to control individuals. Conclusions These results suggest that anomalies in tyrosine metabolism play a role in the pathogenesis of chronic cluster headache and constitute a predisposing factor for the transformation of the episodic into a chronic form of this primary headache.

  10. The Role of Helicobacter pylori Seropositivity in Insulin Sensitivity, Beta Cell Function, and Abnormal Glucose Tolerance

    Directory of Open Access Journals (Sweden)

    Lou Rose Malamug

    2014-01-01

    Full Text Available Infection, for example, Helicobacter pylori (H. pylori, has been thought to play a role in the pathogenesis of type 2 diabetes mellitus (T2DM. Our aim was to determine the role of H. pylori infection in glucose metabolism in an American cohort. We examined data from 4,136 non-Hispanic white (NHW, non-Hispanic black (NHB, and Mexican Americans (MA aged 18 and over from the NHANES 1999-2000 cohort. We calculated the odds ratios for states of glucose tolerance based on the H. pylori status. We calculated and compared homeostatic model assessment insulin resistance (HOMA-IR and beta cell function (HOMA-B in subjects without diabetes based on the H. pylori status. The results were adjusted for age, body mass index (BMI, poverty index, education, alcohol consumption, tobacco use, and physical activity. The H. pylori status was not a risk factor for abnormal glucose tolerance. After adjustment for age and BMI and also adjustment for all covariates, no difference was found in either HOMA-IR or HOMA-B in all ethnic and gender groups except for a marginally significant difference in HOMA-IR in NHB females. H. pylori infection was not a risk factor for abnormal glucose tolerance, nor plays a major role in insulin resistance or beta cell dysfunction.

  11. The clinical value of Mood glucose and insulin detection in early period of pregnancy on predicting abnormal glucose metabolism%妊娠初期检测血糖和胰岛素预测糖代谢异常的临床意义

    Institute of Scientific and Technical Information of China (English)

    陈丽萍

    2012-01-01

    Objective To investigate the correlation of fasting plasma glucose (FPG) in early period of pregnancy and abnormal glucose metabolism during gestation period.Methods Two hundred and seventy-seven women with single pregnancy and non-propregnant diabetes mellitus were selected.FPG,fasting insulin,insulin resistance index were detected in early period of pregnancy ( <19 weeks).One hundred g oral glucose tolerant test (OGTT) was taken during 24-36 weeks.According to OGTT,patients were divided into gestational impaired glucose tolerance (GIGT) group (24 cases),gestational diabetes mellitus(GDM) group(23 cases),OGTT 1 h higher blood glucose (HG-1) group (26 cases) and normal group (204 cases).Results FPG,fasting insulin and insulin resistance index of GDM group and HG-1 group were obviously higher than those of normal group [( 4.58 ± 0.36 ),( 4.58 ± 0.38) mmol/L vs.( 4.20 ±0.33) mmol/L,(9.4 ± 1.1),(9.3 ±2.1) U/L vs.(7.0 ± 2.1) U/L,2.0 ± 0.4,2.0 ± 0.3 vs.1.3 ± 0.4,P< 0.05].FPG of GIGT group [(4.45 ±0.36) mmol/L] was higher than that of normal group (P <0.05).After controlled age,body mass index,family history of type-2 diabetes mellitus and sport exercises,the relative risk degree of blood glucose metabolism had correlation with FPG,fasting insulin and insulin resistance index in early period of pregnancy (P < 0.05).Conclusion FPG,fasting insulin and insulin resistance index in early period of pregnancy can predict abnormal glucose metabolism.%目的 探讨妊娠初期空腹血糖(FPG)与妊娠期糖代谢异常的相关性.方法 单胎非孕前糖尿病孕妇277例,在妊娠初期(<19周)检测FPG、空腹血胰岛素、胰岛素抵抗指数.在妊娠24 ~ 36周行100 g口服葡萄糖耐量试验(OGTT),按OGTT结果进行分组,妊娠期糖耐量受损(GIGT)组24例,妊娠期糖尿病(GDM)组23例,OGTT1 h高血糖(HG-1)组26例,正常组204例.结果 GDM组和HG-1组FPG、空腹血胰岛素、胰岛素抵抗指数均明显高于正常组[(4.58±0

  12. 铬镁离子对糖代谢异常患者的影响及研究进展%Research progress and advances in chromium magnesium ion effect on patients with abnormal glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    周蒙蒙; 王会玲; 姚民秀

    2015-01-01

    血清镁离子及三价铬离子均是体内重要的阳性离子,2型糖尿病患者普遍存在血清铬及镁离子浓度的降低;铬镁离子可促进葡萄糖的利用,增加机体对胰岛素的敏感性,改善胰岛素抵抗,预防或延缓2型糖尿病的发生。铬镁离子可调节细胞内信号转导,降低血糖,保护组织器官,铬镁离子对脂质代谢也具有改善作用。下面就铬镁离子对糖尿病及糖耐量异常患者的影响做一综述。%Serum magnesium ion and trivalent chromium ion are important cations in body, magnesium ion and chromium ion are general deficiencies in type 2 diabetes mellitus. They can promote glucose metabolism, improve insulin sensitivity and beneficial to insulin resistance, prevent normal persons to diabetes. Magnesium ion and chromium ion can adjust the information transmission of intracellular, decrease the glucose, protect the tissues and organs. They are beneficial to the lipid metabolism. Here we made a review about the impact of chromium ion and magnesium ion in patients with diabetes and impaired glucose tolerance.

  13. Osteocalcin as a hormone regulating glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The number of patients with osteoporosis and diabetesis rapidly increasing all over the world. Bone is recentlyrecognized as an endocrine organ. Accumulatingevidence has shown that osteocalcin, which is specificallyexpressed in osteoblasts and secreted into the circulation,regulates glucose homeostasis by stimulating insulinexpression in pancreas and adiponectin expression inadipocytes, resulting in improving glucose intolerance.On the other hand, insulin and adiponectin stimulateosteocalcin expression in osteoblasts, suggesting thatpositive feedforward loops exist among bone, pancreas,and adipose tissue. In addition, recent studies haveshown that osteocalcin enhances insulin sensitivity andthe differentiation in muscle, while secreted factors frommuscle, myokines, regulate bone metabolism. Thesefindings suggest that bone metabolism and glucosemetabolism are associated with each other through theaction of osteocalcin. In this review, I describe the roleof osteocalcin in the interaction among bone, pancreas,brain, adipose tissue, and muscle.

  14. Melatonin and glucose metabolism: clinical relevance.

    Science.gov (United States)

    Lardone, P J; Alvarez-Sanchez, Sanchez N; Guerrero, J M; Carrillo-Vico, A

    2014-01-01

    The role of melatonin in glucose homeostasis is an active area of investigation. There is a growing body of evidence suggesting a link between disturbances in melatonin production and impaired insulin, glucose, lipid metabolism, and antioxidant capacity. Furthermore, melatonin has been found to influence insulin secretion both in vivo and in vitro, and night-time melatonin levels are related to night-time insulin concentrations in patients with diabetes. In several recent studies, a single nucleotide polymorphism of the human melatonin receptor 1B has been described as being causally linked to an increased risk of developing type 2 diabetes. Taken together, these data suggest that endogenous as well as exogenous melatonin may play a role in diabetes and associated metabolic disturbances not only by regulating insulin secretion but also by providing protection against reactive oxygen species, considering pancreatic β-cells are particularly susceptible to oxidative stress because they possess only low-antioxidative capacity.

  15. Noninvasive skin fluorescence spectroscopy for detection of abnormal glucose tolerance

    Directory of Open Access Journals (Sweden)

    Edward L. Hull, PhD

    2014-09-01

    Full Text Available The ENGINE study evaluated noninvasive skin fluorescence spectroscopy (SFS for detection of abnormal glucose tolerance (AGT. The AGT detection performance of SFS was compared to fasting plasma glucose (FPG and hemoglobin A1C (A1C. The study was a head-to-head comparison of SFS to FPG and A1C in an at-risk population of 507 subjects, with no prior diagnosis of diabetes, each of whom received a 75 g, two-hour oral glucose tolerance test (OGTT. Subjects were measured by SFS on multiple days in fasting and non-fasting states. SFS data were acquired and analyzed with the SCOUT DS® device (VeraLight, Albuquerque, NM, USA. Disease truth was AGT, defined as OGTT ≥ 7.8 mmol/L. Sensitivity, false positive rate (FPR, ROC area, and equal error rate (EER for detection of AGT were computed. The reproducibility of SFS and FPG was assessed. The AGT sensitivity of SFS at the device's recommended screening threshold of 50 was 75.2%, higher than that of FPG (thresholds of 5.6 mmol/L or 6.1 mmol/L and A1C (thresholds of 5.7% or 6.0%. The SFS FPR was 42.1%, comparable to an A1C threshold of 5.7% (FPR = 43.5%. The EERs of SFS, FPG and A1C were similar, as were the partial ROC areas for FPRs of 20–50%. The reproducibility of SFS was 7.7% versus 8.1% for FPG. SFS had similar AGT detection performance to FPG and A1C and is a viable alternative to screening individuals for AGT.

  16. Sudden infant death syndrome and abnormal metabolism of thiamin.

    Science.gov (United States)

    Lonsdale, Derrick

    2015-12-01

    Although it has been generally accepted that moving the infant from the prone to the supine position has solved the problem of sudden infant death syndrome (SIDS), it has been hypothesized that this is an insufficient explanation and that a mixture of genetic risk, some form of stressful incident and marginal brain metabolism is proportionately required. It is suggested that each of these three variables, with dominance in one or more of them, act together in the common etiology. Much has been written about the association of thiamin and magnesium but the finding of extremely high concentrations of serum thiamin in SIDs victims has largely caused rejection of thiamin as being involved in the etiology. The publication of abnormal brainstem auditory evoked potentials strongly suggests that there are electrochemical changes in the brainstem affecting the mechanisms of automatic breathing and the control of cardiac rhythm. The brainstem, cerebellum and limbic system of the brain are known to be highly sensitive to thiamin deficiency (pseudo-hypoxia) and the pathophysiology is similar to a mild continued deprivation of oxygen. Little attention has been paid to the complex metabolism of thiamin. Dietary thiamin requires the cooperation of the SLC19 family of thiamin transporters for its absorption into cells and recent information has shown that transporter SNPs may be relatively common and can be expected to increase genetic risk. Thiamin must be phosphorylated to synthesize thiamin pyrophosphate (TPP), well established in its vital action in glucose metabolism. TPP is also a cofactor for the enzyme 2-hydroxyacyl-CoA lyase (HACL1) in the peroxisome, emphasizing its importance in alpha oxidation and plasmalogen synthesis in cell membrane physiology. The importance of thiamine triphosphate (TTP) in energy metabolism is still largely unknown. Thiamin metabolism has been implicated in hyperemesis gravidarum and iatrogenic Wernicke encephalopathy has been reported when the

  17. 合并糖代谢异常的冠心病患者血浆脂联素水平变化及其临床意义%Plasma level of adiponectin in coronary heart disease patients combined with abnormal glucose metabolism

    Institute of Scientific and Technical Information of China (English)

    夏珂; 郭兰燕; 赵震宇; Ali Sheikh Md Sayed; 李非; 杨天伦

    2012-01-01

    Objective: To examine the plasma adiponectin concentration in coronary heart disease (CHD)patients combined with abnormal glucose metabolism, and to explore the clinical significance ofadiponectin.Methods: Eighty-seven hospitalized CHD patients confirmed by coronary angiography fromAugust 2009 to April 2010 at Xiangya Hospital were enrolled and divided into 3 groups according to their glucose metabolic state: 31 patients were selected as a simple CHD group, 28 were selected as a CHD combined with impaired glucose tolerance group (CHD+IGT group), and the other 28 as a CHD combined with diabetes mellitus group (CHD+DM group). The 31 healthy subjects who got health checkup at the same time were enrolled as a normal control group (NC group). Plasma adiponectin was measured by enzyme linked immunosorbent assay. The height, weight, waistline and blood pressure of all the subjects were checked, and the fasting blood glucose (FBG), insulin, lipids, high-sensitivity C-reactive protein (hs-CRP), free fatty acids (FFA), the liver function and the renal function were checked as well. The body mass index and the homeostasis model were assessed for insulin resistance.Results: 1) Plasma adiponectin in the CHD group, the CHD+IGT group, and the CHD+DM group was all lower than that in the NC group (P<0.05); 2) Compared with the CHD group, the plasma adiponectin in the CHD+DM group was the lowest, followed by the CHD+IGT group, and there was significant difference in the 3 groups (P<0.05); 3) Plasma adiponectin level was positively related with the high density lipoprotein cholesterol-C (HDL-C) (r=0.483, P<0.01), while it was negatively related with the hs-CRP and Gensini score (r=-0.489, P<0.05; r=-0.252, P<0.05). Conclusion: Plasma adiponectin concentration is reduced in the CHD patients, and significantly reduced in CHD patients combined with abnormal glucose metabolism. Plasma adiponectin concentration decreases significantly with the severity of abnormal glucose metabolism. CHD

  18. Analysis of Patients With Coronary Heart Disease Combined With Impaired Glucose Metabolism

    Institute of Scientific and Technical Information of China (English)

    Zhi-ping GAO; Li-wen LIE; Ying-ling ZHOU; Hao-jian DONG

    2009-01-01

    Objectives To study the morbidity of patients with coronary artery disease (CAD) combined with impaired glucose metabolism. Methods Retrospective analysis of clinical data about patients with CAD in 1997, 2002 and 2007, sepa-rately. A total of 2951 patients were enrolled, among whom had coexistence of 457 abnormal glycometabolism, inclu-ding impaired fasting glucose, impaired glucose tolerance and type 2 diabetes mellitus. Results The prevalence of ab-normal glycometabolism in patients with CAD was increasing year by year. The morbidity raised from 3.8% and 16. 5% to 10. 8% in these three years. Contusion It is more and more common to detect CAD with impaired glucose metabolism, and it should be emphasized in the secondary prevention of CAD.

  19. Effects of abnormal glucose metabolism during pregnancy on fetal body mass and incidence of neonatal complications%妊娠期糖代谢异常对胎儿体质量及新生儿并发症发生率的影响

    Institute of Scientific and Technical Information of China (English)

    李女好; 林碧绿; 曾胤; 庄泽吟

    2014-01-01

    Objective To investigate the effects of abnormal glucose tolerance during pregnancy on the incidence of fetal body mass and neonatal complications.Methods Oral 50g glucose challenge test (GCT)was done in 2502 cases of pregnant women,156 cases of abnormal 75g oral glucose tolerance retest (OGTT),diagnosed with gestational diabetes mellitus (GDM) in 86 cases,gestational impaired glucose tolerance (GIGT) in 70 cases,and 300 cases of the control group,then we compared the incidence of fetal students body mass,neonatal complications.Results Fetal body mass of GIGT and GDM groups was large for gestational age and fetal macrosomia,significantly higher than that of the control group,the appropriate for gestational age at birth rate was significantly lower than that of the control group,there was statistical significant difference (P < 0.01); small for gestational age infants birth rate was also higher than that of the control group (P < 0.05); GIGT and GDM groups of pregnant women neonatal hypoglycemia,hyperbilirubinemia and in birth injury incidence was significantly higher than that in the control group,there was significant difference (P < 0.01); concurrent premature,asphyxia morbidity were igher than those of the control group,there was statistical significant difference (P < 0.05).Conclusion In clinical practice it is very necessary to detect glucose metabolism with anomaly detection and diagnosis system for all pregnant women,normal glucose metabolism treatment should be standardized and monitored; neonates delivered by all pregnant women with abnormal glucose metabolism should be given timely monitoring of blood glucose,complications and timely intervention.%目的 探讨妊娠期糖耐量异常对胎儿体质量及新生儿并发症发生率的影响.方法 对2502例孕妇进行口服50 g葡萄糖筛查试验(GCT),对156例异常者再行75 g葡萄糖耐量试验(OGTT),确诊妊娠期糖尿病(GDM) 86例,妊娠糖耐量受损(GIGT) 70例,与对照组300

  20. 糖耐量异常对冠心病支架植入术后主要心脏事件的影响%Impact of abnormal glucose metabolism on major adverse cardiac event in patients after coronary artery gent implantation

    Institute of Scientific and Technical Information of China (English)

    纪军; 何胜虎

    2008-01-01

    目的 探讨糖耐量异常对冠心病支架植入术后冠心病患者主要心脏事件的影响.方法 215例冠状动脉造影资料齐全的支架术后的患者,分为合并2型糖尿病(2-DM)组(A组)、糖耐量异常组(B组)、糖代谢正常组(NDM)(C组),比较三组在住院期间和随访期间发生典型心绞痛、非致死性心肌梗死、心源性死亡和靶血管重建等主要心脏事件(MACE)的发生率.结果 A组与B组主要心脏事件发生率显著高于C组(P<0.01);A组与B组间差异无统计学意义;A组再狭窄发生率高于B组(P<0.01).结论 冠心病合并糖耐量异常患者与冠心病合并糖尿病患者一样,有较高的心脏事件发生率,故对合并糖耐量异常的冠心病患者应及早干预,积极控制血糖.%Objective To investigate impact of abnormal slucose metabolism on major adverse cardiac event in patients after coronary artery stent implantation.Methods Two hundred and fifteen patients whose data were available were enrolled in this study,and the patients were divided into 3 groups,diabetes group(group A),abnormal glucose metabolism group(group B),normal glucose tolerance group(group C).The clinica,coronary artery lesion characteristics and major adverse cardiac event(MACE)rate during in hospital and follow up periods were compared.Resuits There was a higher occurrence of MACE in group A and group B than that in group C(P<0.01).There was no significant difference between group A and group B.Conclusion The patients of coronary heart disease with abnormal slucose metabolism have higher MACE rate than abnormal slueese metabolism.

  1. Metabolic fate of extracted glucose in normal human myocardium.

    OpenAIRE

    Wisneski, J A; Gertz, E W; Neese, R A; Gruenke, L D; D. L. Morris; Craig, J. C.

    1985-01-01

    Glucose is an important substrate for myocardial metabolism. This study was designed to determine the effect of circulating metabolic substrates on myocardial glucose extraction and to determine the metabolic fate of glucose in normal human myocardium. Coronary sinus and arterial catheters were placed in 23 healthy male volunteers. [6-14C]Glucose was infused as a tracer in 10 subjects. [6-14C]Glucose and [U-13C]lactate were simultaneously infused in the other 13 subjects. Simultaneous blood s...

  2. Effect of Metformin Intervention on Blood Sugar of Patients with Breast Cancer Chemotherapy with Abnormal Glucose Metabolism%二甲双胍干预对乳腺癌化疗伴糖代谢异常患者血糖的影响

    Institute of Scientific and Technical Information of China (English)

    翟媛媛

    2016-01-01

    目的 研究二甲双胍干预对乳腺癌化疗伴糖代谢异常患者血糖的影响.方法 整群选择2012年2月—2014年8月来该院行乳腺癌化疗,伴糖代谢紊乱的60例患者作为研究对象,随机分为两组. 对照组给予AC-T化疗方案,同时给予患者饮食控制和运动治疗,观察组在对照组基础上加用二甲双胍,观察两组血糖控制情况. 结果 观察组化疗结束时和化疗结束后3个月正常血糖患者例数显著多于对照组,差异具有统计学意义(P0.05). 结论 二甲双胍对于控制乳腺癌化疗伴糖代谢紊乱患者血糖水平效果显著,且具有潜在抗肿瘤作用,值得进一步研究.%Objective To research the effect of metformin intervention on blood sugar of patients with breast cancer chemotherapy with abnormal glucose metabolism. Methods 60 cases of patients with breast cancer chemotherapy with ab-normal glucose metabolism in our hospital from February 2012 to August 2014 were selected as the research object and randomly divided into two groups, the control group received AC-T chemotherapy plan, and were treated with diet control and exercise, the observation group were given additional metformin on the basis of the control group, the blood sugar con-trol conditions of the two groups were observed. Results The case number of patients with normal blood sugar at the end of chemotherapy and in 3 months after chemotherapy in the observation group was obviously more than that in the control group, and the difference was statistically significant (P0.05). Conclusion Metformin for controlling the blood sugar levels of patients with breast cancer chemotherapy with abnormal glucose metabolism has an obvious effect and has a potential anti-tumor effect, which is further research.

  3. Effect of metabolic abnormalities on cognitive performance and clinical symptoms in schizophrenia

    Directory of Open Access Journals (Sweden)

    Wysokiński, Adam

    2013-12-01

    Full Text Available Aim. The objective of this study is to determine whether and how metabolic abnormalities are associated with clinical symptoms and cognitive performance in schizophrenia. Methods. 46 adult patients with schizophrenia taking first- or second generation antipsychotics were included in the study. The following data were collected: BMI, abdominal circumference, lipid panel and blood glucose, blood pressure and treatment of comorbidities. Clinical symptoms were assessed using PANSS, CDSS, CGI and SAS scales. Cognitive performance was assessed using CNS Vital Signs computerized battery of tests: Verbal Memory test, Visual Memory test, Finger Tapping Test, Symbol Digit Coding, Stroop Test, Shifting Attention Test, and Continuous Performance Test. Results. Dyslipidemia, raised LDL and raised blood glucose levels were the best predictors of more severe clinical symptoms (PANSS, PANSS P, PANSS G, CGI and lower neurocognitive index, worse cognitive flexibility, executive functions, complex attention composite memory, verbal memory, slower reaction time and worse performance in SAT, CPT, ST tests. Obesity was associated with worse results in VBM, VIM, FTT, SDC tests. Raised blood pressure was associated with improvements in all cognitive domains and better performance in SAT, CPT, ST tests. Discussion. There are several weak associations between severity of clinical symptoms and metabolic abnormalities. Most of these were for blood glucose levels and raised blood glucose. Lipids and glucose abnormalities are the best predictors of deteriorated cognitive performance. Contrary to previous observations, raised blood pressure was associated with better results in cognitive tests. Conclusions. These findings indicate that cognitive impairment and metabolic abnormalities may be linked in patients with schizophrenia

  4. 妊娠期孕妇糖代谢异常对外阴阴道假丝酵母菌感染及妊娠结局的影响%The influence of gestational abnormal glucose metabolism on vulvovaginal candidiasis infection and pregnan-cy outcome

    Institute of Scientific and Technical Information of China (English)

    董海玲

    2015-01-01

    Objective To investigate the effect of abnormal glucose metabolism on vulvovaginal candidiasis infection and pregnancy outcome in pregnant women.Methods One thousand and fifty-six pregnant women were col-lected who did prenatal examination and termly deliveried in the department of obstetrics and gynecology of our hospi-tal from Jun 2011 to Jun 2013.According to the glucose screening test results, they were divided into glucose normal group(n=624), GCT abnormal group(n=326)and gestational diabetes mellitus(GDM) group(n=106).The oc-currence of the vulvovaginal candidiasis(VVC) infection and pregnancy outcome of the three groups were observed during pregnancy.Results The occurrence rates of VVC of GCT abnormal group and GDM group had no significant differences(P>0.05), but they were significantly higher than those of glucose normal group(P0.05).Conclusion Abnormal glucose metabolism during pregnancy may increase occurrence risk of VVC, which affects the outcome of pregnancy and in-creases the risk of cesarean section and premature rupture of membranes and intrauterine fetal distress, thus it should be payed more attention to the changes of blood glucose level.Glycated hemoglobin level in pregnant women should be monitored.%目的:探讨妊娠期孕妇糖代谢异常对外阴阴道假丝酵母菌感染及妊娠结局的影响。方法收集行产前检查并足月分娩的初次孕产妇1056例,根据葡萄糖筛查试验( GCT )结果将孕妇分为血糖正常组624例,GCT异常组326例,妊娠期糖尿病( GDM)组106例。观察三组在妊娠期间外阴阴道假丝酵母菌病(VVC)的发生情况及妊娠结局情况。结果 GDM组、GCT异常组VVC发生率差异无统计学意义(P>0.05),但均明显高于血糖正常组(P<0.05);三组VVC复发率差异无统计学意义(P>0.05)。 GCT异常组、GDM组的胎膜早破、胎儿宫内窘迫发生率、剖宫产率、足月低体重儿率

  5. Metabolic glucose status and pituitary pathology portend therapeutic outcomes in acromegaly.

    Directory of Open Access Journals (Sweden)

    Sonia Cheng

    Full Text Available INTRODUCTION: Acromegaly is frequently associated with impaired glucose tolerance and/or diabetes. To evaluate the relationship between glucose metabolism and acromegaly disease, we evaluated 269 consecutive patients from two referral centres. METHODS: Clinical presentation, pituitary tumor size and invasiveness, and pituitary pathology were captured in a dedicated database. RESULTS: 131 women and 138 men with a mean age of 53.8 years were included. Of these, 201 (74.7% presented with a macroadenoma and 18 (6.7% with a microadenoma. Radiographic invasion was present in 91 cases (33.8%. Mean tumor diameter was 1.86 cm (0.2-4.6. Pituitary histopathologic findings revealed pure GH-producing somatotroph adenomas (SA in 147 patients, prolactin-production by mixed lactotroph (LA and SA or mammosomatotroph adenoma (MSA in 46 [22.4%], acidophil stem cell adenoma in 6 [2.9%], and other diagnoses in 6 [2.9%]. Medical treatment included octreotide in 96 [36.9%] and in combination with pegvisomant or dopamine agonists in 63 [24.2%]. Nearly 80% of patients achieved IGF-1 normalization. Importantly, patients with pure somatotroph adenomas were significantly more likely to present with abnormal glucose metabolism [48.7%] than those with mixed adenomas [9.7%] [p<0.001] independent of GH/IGF-1 levels or tumor invasiveness. Abnormal glucose metabolism and pituitary pathology also remained linked following IGF-1 normalization. Moreover patients with pure SA and abnormal glucose metabolism were significantly (p<0.001 less likely to achieve disease remission despite the same therapeutic strategies. Conversely, patients with mixed adenomas were more likely (OR: 2.766 (95% CI: 1.490-5.136 to achieve disease remission. CONCLUSIONS: Patients with pure somatotroph adenomas are more likely than those with mixed adenomas to exhibit abnormal glucose metabolism.

  6. Parameters of glucose metabolism and the aging brain

    DEFF Research Database (Denmark)

    Akintola, Abimbola A; van den Berg, Annette; Altmann-Schneider, Irmhild;

    2015-01-01

    Given the concurrent, escalating epidemic of diabetes mellitus and neurodegenerative diseases, two age-related disorders, we aimed to understand the relation between parameters of glucose metabolism and indices of pathology in the aging brain. From the Leiden Longevity Study, 132 participants (mean...... age 66 years) underwent a 2-h oral glucose tolerance test to assess glucose tolerance (fasted and area under the curve (AUC) glucose), insulin sensitivity (fasted and AUC insulin and homeostatic model assessment of insulin sensitivity (HOMA-IS)) and insulin secretion (insulinogenic index). 3-T brain...... different parameters of glucose metabolism (impairment of which is characteristic of diabetes mellitus) and brain aging....

  7. Impact of maternal metabolic abnormalities in pregnancy on human milk and subsequent infant metabolic development: methodology and design

    Directory of Open Access Journals (Sweden)

    Hamilton Jill K

    2010-10-01

    Full Text Available Abstract Background Childhood obesity is on the rise and is a major risk factor for type 2 diabetes later in life. Recent evidence indicates that abnormalities that increase risk for diabetes may be initiated early in infancy. Since the offspring of women with diabetes have an increased long-term risk for obesity and type 2 diabetes, the impact of maternal metabolic abnormalities on early nutrition and infant metabolic trajectories is of considerable interest. Human breast milk, the preferred food during infancy, contains not only nutrients but also an array of bioactive substances including metabolic hormones. Nonetheless, only a few studies have reported concentrations of metabolic hormones in human milk specifically from women with metabolic abnormalities. We aim to investigate the impact of maternal metabolic abnormalities in pregnancy on human milk hormones and subsequently on infant development over the first year of life. The objective of this report is to present the methodology and design of this study. Methods/Design The current investigation is a prospective study conducted within ongoing cohort studies of women and their offspring. Pregnant women attending outpatient obstetrics clinics in Toronto, Canada were recruited. Between April 2009 and July 2010, a total of 216 pregnant women underwent a baseline oral glucose tolerance test and provided medical and lifestyle history. Follow-up visits and telephone interviews are conducted and expected to be completed in October 2011. Upon delivery, infant birth anthropometry measurements and human breast milk samples are collected. At 3 and 12 months postpartum, mothers and infants are invited for follow-up assessments. Interim telephone interviews are conducted during the first year of offspring life to characterize infant feeding and supplementation behaviors. Discussion An improved understanding of the link between maternal metabolic abnormalities in pregnancy and early infant nutrition may

  8. Clinical Analysis of Wine age and Metabolic Syndrome and Abnormal Glucose Regulation Ties%酒龄与代谢综合征及糖调节异常的关系探讨

    Institute of Scientific and Technical Information of China (English)

    彭达平

    2014-01-01

    Objective:To explore the relationship of wine age and metabolic syndrome(MS)and glucose regulation (IGR)relationship.Method:309 males with different wine age were selected and analyzed. They were divided into three groups(A1-A3)accordance their drinking time. 103 cases of remaining non-drinking history were set up the control group. Drinking relationship with MS were analyzed through 412 cases of the research object of test results.Result:The longer the wine age men,their BMI,TGL and equivalents increased,while HDL-C was gradually reduced,the differences were statistically significant(P<0.01).Conclusion:With the probability of prolonge alcohol consumption of time,MS and other diseases is increasing. The efficient by limiting alcohol consumption can be prevented.%目的:探讨酒龄与代谢综合征(MS)及糖调节异常(IGR)的关系。方法:本次研究对象为309例男性,均有不同的酒龄。按照其饮酒的时间分三组(A1~A3)。其余无饮酒史的103例男性为对照组。通过412例研究对象的检测结果分析饮酒与MS等的关系。结果:酒龄越长的男性,其BMI、TGL以及等值均增加,而HDL-C却逐渐降低,差异均有统计学意义(P<0.01)。结论:随着饮酒时间的延长,MS等疾病的几率逐渐增加。而通过限制饮酒可以高效地对其进行预防。

  9. The effect of PCSK1 variants on waist, waist-hip ratio and glucose metabolism is modified by sex and glucose tolerance status

    DEFF Research Database (Denmark)

    Gjesing, Anette P; Vestmar, Marie A; Jørgensen, Torben;

    2011-01-01

    Background: We aimed to evaluate the effects of the G-allele of rs6232 and the C-allele of rs6235 within PCSK1 on measures of body fat and glucose homeostasis in Danish individuals and to assess interactions of genotypes with age, sex and glucose tolerance status. Data were included in meta-analy...... composition which may be modified by sex, whereas the effect of rs6235 C-allele on fasting and stimulated circulating plasma glucose and hormone levels may be influenced by glucose tolerance status.......-allele was associated nominally with a 0.6% (0.1–1%, p = 0.01) reduction in fasting glucose, it interacted with glucose tolerance status for traits related to glucose metabolism and analysis among individuals having abnormal glucose tolerance revealed a 5% (20.7–9%, p = 0.02) elevated level of acute insulin response...

  10. The Mediterranean diet adoption improves metabolic, oxidative, and inflammatory abnormalities in Algerian metabolic syndrome patients.

    Science.gov (United States)

    Bekkouche, L; Bouchenak, M; Malaisse, W J; Yahia, D Ait

    2014-04-01

    This study was aimed to explore the effects of Mediterranean diet (MD) adoption on insulin resistance, oxidative, and inflammatory status in metabolic syndrome (MS) patients. Eighty four patients with MS were randomly recruited in the medical centers of Oran, Algeria. Eighteen healthy participants were selected as a control group. Among these 84 patients, only 36 patients completed the nutritional advices for 3 months. Patients were instructed to follow a Mediterranean-style diet and received some other selected nutritional and physical activity instructions. Anthropometric measurements were performed and a questionnaire was used to assess dietary intake. Blood samples were drawn at baseline and after 3 months of nutritional intervention from all subjects. At baseline, the MS patients were obese and had altered anthropometric parameters, higher systolic and diastolic blood pressure, plasma lipids, glucose, insulin, HOMA-IR, HbA1c, urea, creatinine, uric acid, and lower albumin compared to healthy subjects. A decrease in plasma, erythrocyte, and platelet antioxidant enzymes, and a rise in lipid and protein oxidation, plasma CRP, and fibrinogen were noted in the MS patients. Moreover, they had an unbalanced dietary pattern when compared to Mediterranean recommendations. Patients following the Mediterranean-style diet had significantly reduced weight, BMI, waist circumference, waist/hip circumference ratio, decreased systolic and diastolic blood pressure, plasma glucose, insulin, HOMA-IR, HbA1c, cholesterol, triacylglycerols, CRP, urea, creatinine, creatinine clearance, lipid and protein oxidation, and higher plasma, erythrocyte, and platelet antioxidant enzymes. In conclusion, a lifestyle intervention based mainly on nutritional advices improves metabolic, oxidative, and inflammatory abnormalities of metabolic syndrome.

  11. 妊娠期糖代谢异常与尿酸、C肽、超敏C反应蛋白、糖化血红蛋白相关性%Correlation of gestational abnormal glucose metabolism and uric acid,C peptide,high sensitivity C reactive protein,glycated hemoglobin

    Institute of Scientific and Technical Information of China (English)

    周静姝; 金海甲; 刘飞; 郝凤燕

    2015-01-01

    目的:探讨C肽、超敏C反应蛋白、糖化血红蛋白、尿酸及血脂等多因素与妊娠期糖代谢异常的相关性。方法:2010年1月-2011年8月收集分娩孕妇,统计其在孕24~28周前后检测的血糖与尿酸、CRP、血脂、超敏CRP、C肽、糖化血红蛋白、体重、血压及文化背景等,其中异常23例;随机抽取40例正常者为对照。C肽采用电化学发光方法,超敏C反应蛋白采用芬兰试剂,糖化血红蛋白用TDM100糖化血红蛋白分析仪测定。采用多因素分析评价其相关性。结果:多因素联合分析比单个独立因素评价糖代谢异常相关性高。结论:多项联合检测能提前预测糖代谢异常的发生,提前采取治疗措施,预防疾病发生,得到很好的预后效果。%Objective:To explore the correlation of gestational abnormal glucose metabolism and C peptide,high sensitivity C reactive protein,glycated hemoglobin,uric acid,blood lipid and other factors.Methods:Childbirth pregnant womens were selected from January 2010 to August 2011.The blood glucose and uric acid,CRP,blood lipid,high sensitivity CRP,C peptide,glycated hemoglobin that were detected before and after pregnancy 24 to 28 weeks.Weight,blood pressure and cultural background were statistically analyzed,in which 23 cases were abnormal.A random sample of 40 normal persons was as the control.C peptide used electrochemiluminescence method,the high sensitive C reactive protein used finland reagent,the glycated hemoglobin was detected by TDM100 glycated hemoglobin analyzer instrument.The correlation was analyzed and evaluated by multi factors. Results:The multi factor combined analysis in the evaluation of abnormal glucose metabolism correlation was higher than a single independent factor.Conclusion:The multiple combined detection can predict abnormal glucose metabolism in advance.It can advance to take treatment,prevent disease,and obtain very good prognosis effect.

  12. Abnormal fibrillin metabolism in bovine Marfan syndrome.

    Science.gov (United States)

    Potter, K. A.; Hoffman, Y.; Sakai, L. Y.; Byers, P. H.; Besser, T. E.; Milewicz, D. M.

    1993-01-01

    Bovine Marfan syndrome is a disorder that closely resembles human Marfan syndrome in its clinical signs and pathological lesions. The similarities between the human and bovine diseases suggest that similar metabolic defects could be responsible. Although indirect immunofluorescent assays for fibrillin in skin biopsies did not distinguish affected cattle from control animals, cultures of skin fibroblasts of affected animals were distinguished from normal, unrelated control animals and normal half-siblings on the basis of fibrillin staining. After 72 to 96 hours in culture, stained with anti-fibrillin monoclonal antibody 201, hyperconfluent fibroblast cultures of affected cattle had less immunoreactive fibrillin than control cultures, and the staining pattern was granular rather than fibrillar. Under similar culture conditions, normal bovine aortic smooth muscle cells produced large amounts of immunoreactive fibrillin, but smooth muscle cells from a single affected cow showed markedly less fibrillin staining. In pulse-chase metabolic labeling experiments with [35S]cysteine, dermal fibroblasts from 6 affected calves, incorporated far less fibrillin into the extracellular matrix than control cells. These findings are similar to those reported in human Marfan syndrome, and they suggest that the bovine Marfan syndrome, like the human disorder, is caused by a mutation in fibrillin, leading to defective microfibrillar synthesis. Images Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 PMID:8456941

  13. Evaluation of regional metabolic abnormality and treatment effect in patients with narcolepsy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyeong; Yoon, In Young; Shin, Youn Kyung; Eo, Jae Sean; Won, Oh So; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    The aim of the present study was to evaluated regional metabolic abnormalities in untreated narcoleptic patients and the changes in regional cerebral metabolism after treatment with modafinil. Eight drug free narcoleptic patients (mean age of 17{+-}1 yr) participated in this study. Two [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) scans before and after a 2-week titrated modafinil treatment (target dose = 100{approx}400 mg/day). The PET data were analyzed by using statistical parametric mapping methods to identify the regional cerebral abnormalities compared with those of healthy young controls. In addition, treatment effect was evaluated by comparison between before and after treatment scan. In narcolepsy patients, a significant reduction of regional metabolism was demonstrated in the brain stem, bilateral hypothalamus, posterior thalamus, hippocampus, parahippocampal gyrus, and adjacent perihinal area on pretreatment scans compared with those of healthy subjects. The decrease glucose metabolism was also found in the occipital cortex and cerebellum. The patients could control daytime sleepiness after treatment. Posttreatment scan showed a significant increase in regional metabolism in the left hippocampus. This study demonstrated the metabolic abnormalities and the effect of modafinil treatment in narcoleptic patients in the sleep associated regions. This results could be helpful to understand the pathophysiology of the narcolepsy and treatment mechanism.

  14. Persistent impaired glucose metabolism in a zebrafish hyperglycemia model.

    Science.gov (United States)

    Capiotti, Katiucia Marques; Antonioli, Régis; Kist, Luiza Wilges; Bogo, Maurício Reis; Bonan, Carla Denise; Da Silva, Rosane Souza

    2014-05-01

    Diabetes mellitus (DM) affects over 10% of the world's population. Hyperglycemia is the main feature for the diagnosis of this disease. The zebrafish (Danio rerio) is an established model organism for the study of various metabolic diseases. In this paper, hyperglycemic zebrafish, when immersed in a 111 mM glucose solution for 14 days, developed increased glycation of proteins from the eyes, decreased mRNA levels of insulin receptors in the muscle, and a reversion of high blood glucose level after treatment with anti-diabetic drugs (glimepiride and metformin) even after 7 days of glucose withdrawal. Additionally, hyperglycemic zebrafish developed an impaired response to exogenous insulin, which was recovered after 7 days of glucose withdrawal. These data suggest that the exposure of adult zebrafish to high glucose concentration is able to induce persistent metabolic changes probably underlined by a hyperinsulinemic state and impaired peripheral glucose metabolism.

  15. Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2-fluoro-2-deoxy-D-glucose and PET.

    Science.gov (United States)

    Balestri, P; Lucignani, G; Fois, A; Magliani, L; Calistri, L; Grana, C; Di Bartolo, R M; Perani, D; Fazio, F

    1994-01-01

    Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This finding suggests that the abnormalities seen on MRI are not due to defective blood supply, localised oedema, or grey matter heterotopic foci as previously hypothesised. The presence of the hypometabolic areas seems to be inconsistently related to the occurrence of seizures and is not proportional to the degree of mental impairment. This study provides evidence of a widespread cerebral hypometabolism that is not related to the presence of MRI abnormalities; conversely normal metabolism was present in the areas with an abnormal MRI signal. Images PMID:7798976

  16. Local cerebral glucose metabolism during controlled hypoxemia in rats.

    Science.gov (United States)

    Pulsinelli, W A; Duffy, T E

    1979-05-11

    2-Deoxy-[14C]glucose metabolism was examined in brains of hypoxic, normotensive rats by autoradiography, which revealed alternating cortical columns of high and low metabolism. Activity in white matter was increased severalfold over that in adjacent gray matter. The columns were anatomically related to penetrating cortical arteries with areas between arteries demonstrating higher rates of metabolism. The results suggest the presence of interarterial tissue oxygen gradients that influence regional glucose metabolism. The relatively greater sensitivity of white matter metabolism to hypoxia may lead to an understanding of white matter damage in postanoxic leukoencephalopathy.

  17. Value of fructosamine measurement in pregnant women with abnormal glucose tolerance

    Institute of Scientific and Technical Information of China (English)

    LI Kui; YANG Hui-xia

    2006-01-01

    Background The concentration of serum fructosamine is correlated with plasma glucose level. The aim of this study was to determine whether the level of serum fructosamine can be diagnostic for abnormal glucose tolerance in pregnant women.Methods Serum samples were collected from 161 pregnant women between November 2004 and April 2005.The women were divided into three groups according to the gestational age (16-20 weeks group, 56 patients; 28-34 weeks group, 72; and 37-41 weeks group, 33). Each group was subdivided into normal and abnormal glucose tolerance subgroups. The levels of serum fructosamine were measured. Differences among the groups were assessed by ANOVA and Student-Newman-Keuls test. Correlations between the level of fructosamine and other variables including the results of glucose challenge test (GCT), oral glucose tolerance test (OGTT), and glycosylated hemoglobin (HbA1c) test, and infant's birth weight were analyzed by Pearson correlation.Results The level of serum fructosamine decreased with gestational age [(223.25 ±48.90) μmol/L, (98.44±29.57)μmol/L, and (53.99±29.94) μmol/L, respectively. P<0.05]. It was higher in women with abnormal glucose tolerance than that in women with normal glucose tolerance, however, the difference reached statistical significance only in the 28-34 weeks group (P<0.05). In this group, the level of serum fructosamine correlated positively with the GCT result (r=0.28, P<0.05). No correlation was found between fructosamine level and OGTT result, HbA1c level, or neonatal weight.Conclusions Fructosamine can be used to monitor the glucose level of pregnant women with abnormal glucose tolerance, and to identify the patients at high risk of abnormal glucose tolerance, but can not be used to predict gestational diabetes mellitus (GDM) in early stage of pregnancy.

  18. Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

    Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

  19. Aerobic glucose metabolism of Saccharomyces kluyveri: Growth, metabolite production, and quantification of metabolic fluxes

    DEFF Research Database (Denmark)

    Møller, Kasper; Christensen, B.; Förster, Jochen

    2002-01-01

    .29 +/- 0.01 g/g). The glucose metabolism of S. kluyveri was further characterized by the new and powerful techniques of metabolic network analysis. Flux distributions in the central carbon metabolism were estimated for respiro-fermentative growth in aerobic batch cultivation on glucose and respiratory...... at a constant specific rate of 0.12 g ethyl acetate per g dry weight per hour. The aerobic glucose metabolism in S. kluyveri was found to be less fermentative than in S. cerevisiae, as illustrated by the comparably low yield of ethanol on glucose (0.08 +/- 0.02 g/g), and high yield of biomass on glucose (0...... growth in aerobic glucose-limited continuous cultivation. It was found that in S. kluyveri the flux into the pentose phosphate pathway was 18.8 mmole per 100 mmole glucose consumed during respiratory growth in aerobic glucose-limited continuous cultivation. Such a low flux into the pentose phosphate...

  20. Resveratrol Ameliorates the Depressive-Like Behaviors and Metabolic Abnormalities Induced by Chronic Corticosterone Injection

    Directory of Open Access Journals (Sweden)

    Yu-Cheng Li

    2016-10-01

    Full Text Available Chronic glucocorticoid exposure is known to cause depression and metabolic disorders. It is critical to improve abnormal metabolic status as well as depressive-like behaviors in patients with long-term glucocorticoid therapy. This study aimed to investigate the effects of resveratrol on the depressive-like behaviors and metabolic abnormalities induced by chronic corticosterone injection. Male ICR mice were administrated corticosterone (40 mg/kg by subcutaneous injection for three weeks. Resveratrol (50 and 100 mg/kg, fluoxetine (20 mg/kg and pioglitazone (10 mg/kg were given by oral gavage 30 min prior to corticosterone administration. The behavioral tests showed that resveratrol significantly reversed the depressive-like behaviors induced by corticosterone, including the reduced sucrose preference and increased immobility time in the forced swimming test. Moreover, resveratrol also increased the secretion of insulin, reduced serum level of glucose and improved blood lipid profiles in corticosterone-treated mice without affecting normal mice. However, fluoxetine only reverse depressive-like behaviors, and pioglitazone only prevent the dyslipidemia induced by corticosterone. Furthermore, resveratrol and pioglitazone decreased serum level of glucagon and corticosterone. The present results indicated that resveratrol can ameliorate depressive-like behaviors and metabolic abnormalities induced by corticosterone, which suggested that the multiple effects of resveratrol could be beneficial for patients with depression and/or metabolic syndrome associated with long-term glucocorticoid therapy.

  1. Glucose Metabolism Disorders, HIV and Antiretroviral Therapy among Tanzanian Adults.

    Directory of Open Access Journals (Sweden)

    Emmanuel Maganga

    Full Text Available Millions of HIV-infected Africans are living longer due to long-term antiretroviral therapy (ART, yet little is known about glucose metabolism disorders in this group. We aimed to compare the prevalence of glucose metabolism disorders among HIV-infected adults on long-term ART to ART-naïve adults and HIV-negative controls, hypothesizing that the odds of glucose metabolism disorders would be 2-fold greater even after adjusting for possible confounders.In this cross-sectional study conducted between October 2012 and April 2013, consecutive adults (>18 years attending an HIV clinic in Tanzania were enrolled in 3 groups: 153 HIV-negative controls, 151 HIV-infected, ART-naïve, and 150 HIV-infected on ART for ≥ 2 years. The primary outcome was the prevalence of glucose metabolism disorders as determined by oral glucose tolerance testing. We compared glucose metabolism disorder prevalence between each HIV group vs. the control group by Fisher's exact test and used multivariable logistic regression to determine factors associated with glucose metabolism disorders.HIV-infected adults on ART had a higher prevalence of glucose metabolism disorders (49/150 (32.7% vs.11/153 (7.2%, p<0.001 and frank diabetes mellitus (27/150 (18.0% vs. 8/153 (5.2%, p = 0.001 than HIV-negative adults, which remained highly significant even after adjusting for age, gender, adiposity and socioeconomic status (OR = 5.72 (2.78-11.77, p<0.001. Glucose metabolism disorders were significantly associated with higher CD4+ T-cell counts. Awareness of diabetes mellitus was <25%.HIV-infected adults on long-term ART had 5-fold greater odds of glucose metabolism disorders than HIV-negative controls but were rarely aware of their diagnosis. Intensive glucose metabolism disorder screening and education are needed in HIV clinics in sub-Saharan Africa. Further research should determine how glucose metabolism disorders might be related to immune reconstitution.

  2. Regional glucose metabolism using PETT in normal and psychiatric populations

    Energy Technology Data Exchange (ETDEWEB)

    Brodie, J.D.; Wolf, A.P.; Volkow, N.

    1982-01-01

    The metabolism of /sup 18/F-2-deoxy-2-fluoro-D-glucose (/sup 18/FDG) in 150 subjects including normals, schizophrenics, senile dementias, and primary affective disorders was studied. Some of the data analyzed to date are discussed.

  3. Visfatin, glucose metabolism and vascular disease: a review of evidence

    Directory of Open Access Journals (Sweden)

    Saddi-Rosa Pedro

    2010-03-01

    Full Text Available Abstract The adipose tissue is an endocrine organ producing substances called adipocytokines that have different effects on lipid metabolism, metabolic syndrome, and cardiovascular risk. Visfatin was recently described as an adipocytokine with potentially important effects on glucose metabolism and atherosclerosis. Visfatin has been linked to several inflammatory conditions, beta cell function, and cardiovascular disease. The growing number of publications on the subject shall bring further evidence about this adipocytokine. Its findings may contribute in the identification of higher risk individuals for diabetes and cardiovascular disease with a better comprehension about the complex intercorrelation between adiposity, glucose metabolism and vascular disease.

  4. Intra- and intercellular mechanisms regulating glucose metabolism in the liver.

    NARCIS (Netherlands)

    E. Casteleijn (Eric)

    1988-01-01

    textabstractThe regulation of glucose metabolism in the liver by intraand intercellular mechanisms was studied. Fructose-1,6-bisphosphatase, an enzyme involved in de novo synthesis of glucose was found to be stimulated by glucagon in isolated parenchym~l liver cells. Glucagon increased the Vmax of f

  5. Adult glucose metabolism in extremely birthweight-discordant monozygotic twins

    DEFF Research Database (Denmark)

    Frost, M; Petersen, I; Brixen, K

    2012-01-01

    Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment.......Low birthweight (BW) is associated with increased risk of type 2 diabetes. We compared glucose metabolism in adult BW-discordant monozygotic (MZ) twins, thereby controlling for genetic factors and rearing environment....

  6. Glucose metabolism in injured tissue: A longitudinal study

    Energy Technology Data Exchange (ETDEWEB)

    Daley, J.M.; Shearer, J.D.; Mastrofrancesco, B.; Caldwell, M.D. (Brown Univ., Providence, RI (USA))

    1990-02-01

    Injured tissue is characterized by increased glucose uptake and increased lactate production as compared to normal tissue. These metabolic changes have been attributed to the presence of inflammatory cells in injured tissues. To correlate these metabolic changes with changes in the inflammatory cell population at various times after injury, we studied the lambda-carrageenan hindlimb wound model in anesthetized rats. Perfusion studies demonstrated that at 3 and 5 days after injury glucose uptake was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. At 3, 5, and 10 days after injury, lactate production from glucose was increased in injured hindlimbs, compared with hindlimbs from pair-fed control animals. These metabolic changes were not related to differences in body weight or food intake. There was no difference in glucose oxidation or in oxygen consumption in injured hindlimbs, compared with hindlimbs from pair-fed control animals. The increased glucose uptake and increased lactate production from glucose was coincident with the presence of inflammatory cells--predominantly macrophages--at the site of injury. It is suggested that the glucose metabolism in injured tissue reflects the metabolism of the inflammatory cells at the site of injury.

  7. Soy and cardio-metabolic abnormalities: an update

    Directory of Open Access Journals (Sweden)

    Leila Azadbakht

    2008-04-01

    Full Text Available

    • Soy protein contains beneficial components like complex carbohydrates, unsaturated fatty acids, vegetable protein, soluble fiber, oligosaccharides, vitamins, minerals, inositol-derived substances and phytoestrogens, particularly the isoflavones  genistein, diadzein, and glycitein, which might affect different cardio-metabolic abnormalities. Soy consumption has been reported to beneficially affect features of the metabolic syndrome in animal models and also in humans to some extent. There are inconsistent reports regarding the hypothesis of the effectiveness of soy protein on obesity. While some studies have shown that soy consumption can improve the features of the metabolic syndrome without affecting body weight, others showed that soy consumption has beneficial role in weight management and might improve the metabolic syndrome by affecting body weight control. Several studies have consistently reported the effects of soy on cardiovascular risks. Beneficial role of soy intake on diabetes is another aspect of soy inclusion in the diet. The present study discusses the effects of soy consumption on different cardio-metabolic abnormalities and provides information regarding the possible mechanisms by which soy protein might exert its beneficial roles.
    • KEY WORDS: Soy, cardiovascular disease, diabetes, obesity, metabolic syndrome.

  8. Glucose and galactose metabolism in Gluconabacter liquefaciens

    NARCIS (Netherlands)

    Stouthamer, A.H.

    1961-01-01

    Glucose-grown cells of Gluconobacter liquefaciens oxidize glucose, gluconate and 2-ketogluconate practically completely to 2,5-diketogluconate by particulate enzymes, localized in the protoplasmic membrane. The bulk of the 2,5-diketgluconate (and 5-ketogluconate) enters the cytoplasm and is metaboli

  9. Effects of MDMA on blood glucose levels and brain glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M. [Hospital General Universitario Gregorio Maranon, Laboratorio de Imagen, Medicina Experimental, Madrid (Spain); Arango, C. [Hospital General Gregorio Maranon, Departamento de Psiquiatria, Madrid (Spain); Ricaurte, G. [Johns Hopkins University School of Medicine, Department of Neurology, Baltimore, MD (United States)

    2007-06-15

    This study was designed to assess changes in glucose metabolism in rats administered single or repeated doses of MDMA. Two different experiments were performed: (1) A single-dose study with four groups receiving 20 mg/kg, 40 mg/kg, saline or heat, and (2) a repeated-dose study with two groups receiving three doses, at intervals of 2 h, of 5 mg/kg or saline. Rats were imaged using a dedicated small-animal PET scanner 1 h after single-dose administration or 7 days after repeated doses. Glucose metabolism was measured in 12 cerebral regions of interest. Rectal temperature and blood glucose were monitored. Peak body temperature was reached 1 h after MDMA administration. Blood glucose levels decreased significantly after MDMA administration. In the single-dose experiment, brain glucose metabolism showed hyperactivation in cerebellum and hypo-activation in the hippocampus, amygdala and auditory cortex. In the repeated-dose experiment, brain glucose metabolism did not show any significant change at day 7. These results are the first to indicate that MDMA has the potential to produce significant hypoglycaemia. In addition, they show that MDMA alters glucose metabolism in components of the motor, limbic and somatosensory systems acutely but not on a long-term basis. (orig.)

  10. Effects of central gastrin-releasing peptide on glucose metabolism

    NARCIS (Netherlands)

    Jha, Pawan Kumar; Foppen, Ewout; Challet, Etienne; Kalsbeek, A.

    2015-01-01

    Gastrin-releasing peptide (GRP) mediated signals in the central nervous system (CNS) influence many functions associated with energy metabolism. The purpose of the present study was to investigate the central effect of GRP on glucose metabolism in the male rat. Intracerebroventricular (icv) administ

  11. Utilization of dietary glucose in the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Alemany Marià

    2011-10-01

    Full Text Available Abstract This review is focused on the fate of dietary glucose under conditions of chronically high energy (largely fat intake, evolving into the metabolic syndrome. We are adapted to carbohydrate-rich diets similar to those of our ancestors. Glucose is the main energy staple, but fats are our main energy reserves. Starvation drastically reduces glucose availability, forcing the body to shift to fatty acids as main energy substrate, sparing glucose and amino acids. We are not prepared for excess dietary energy, our main defenses being decreased food intake and increased energy expenditure, largely enhanced metabolic activity and thermogenesis. High lipid availability is a powerful factor decreasing glucose and amino acid oxidation. Present-day diets are often hyperenergetic, high on lipids, with abundant protein and limited amounts of starchy carbohydrates. Dietary lipids favor their metabolic processing, saving glucose, which additionally spares amino acids. The glucose excess elicits hyperinsulinemia, which may derive, in the end, into insulin resistance. The available systems of energy disposal could not cope with the excess of substrates, since they are geared for saving not for spendthrift, which results in an unbearable overload of the storage mechanisms. Adipose tissue is the last energy sink, it has to store the energy that cannot be used otherwise. However, adipose tissue growth also has limits, and the excess of energy induces inflammation, helped by the ineffective intervention of the immune system. However, even under this acute situation, the excess of glucose remains, favoring its final conversion to fat. The sum of inflammatory signals and deranged substrate handling induce most of the metabolic syndrome traits: insulin resistance, obesity, diabetes, liver steatosis, hyperlipidemia and their compounded combined effects. Thus, a maintained excess of energy in the diet may result in difficulties in the disposal of glucose, eliciting

  12. Development of evaluation tool for the risk level of abnormal glucose metabolism morbidity in middle-aged and elder populations%中老年人群糖代谢异常患病危险度评估工具的开发研究

    Institute of Scientific and Technical Information of China (English)

    黄晓波; 黄斌; 魏东; 曾伟; 欧阳凌云; 刘雅; 栾荣生; 张廷杰; 徐俊波; 赵思勤; 李秀钧

    2010-01-01

    目的 研究开发适合中老年人群的糖代谢异常患病危险度评估工具.方法 于2008年4至11月采用分层整群抽样的方法,在成都城乡地区40~79岁中老年人口中开展问卷调查,并进行血压、空腹血糖、葡萄糖75 g餐后血糖、血脂、血尿酸、身高、体质量、腰围等检测,共获取有效调查资料5205份.进行判别分析及多因素Logistic回归分析,建立量化评分体系,ROC分析筛选量化评分体系的界点,336例体检人群验证简易评分模型判别效能.结果 判别分析男女模型准确度分别为79.04%和81.35%.年龄、工作体力强度、体育锻炼、家族史、兄弟姐妹糖尿病史、体质指数、腹型肥胖和高血压病史8个指标构成男性简易评分模型;年龄、工作体力强度、体育锻炼、家族史、兄弟姐妹糖尿病史、体质指数、腹型肥胖、高血压病史、分娩次数和妊娠糖尿病史构成女性简易评分模型.ROC曲线下面积男性模型为0.702,女性模型为0.728.在其他人群应用中男性模型灵敏度和特异度分别为86.86%和65.12%,女性模型灵敏度和特异度分别为88.89%和72.97%.结论 初步开发的中老年人群糖代谢异常患病危险度评估工具简便可行,有一定实用性,可应用于中老年人群糖代谢异常的筛查.%Objective To develop the evaluation tool for the risk level of abnormal glucose metabolism morbidity in the middle-aged and elder populations. Methods By the stratified cluster sampling method, a survey was conducted in middle-aged and elder populations aged 40 -70 years old in urban and rural areas of Chengdu during April-November 2008. The parameters included blood pressure, fasting blood glucose, blood glucose after oral administration of 75 g glucose, blood lipid, blood uric acid, height, body weight and waistline, etc. A total of 5205 valid copies of questionnaires were obtained. A discriminant analysis and a multifactorial logistic regression

  13. A link between sleep loss, glucose metabolism and adipokines

    Directory of Open Access Journals (Sweden)

    H.G. Padilha

    2011-10-01

    Full Text Available The present review evaluates the role of sleep and its alteration in triggering problems of glucose metabolism and the possible involvement of adipokines in this process. A reduction in the amount of time spent sleeping has become an endemic condition in modern society, and a search of the current literature has found important associations between sleep loss and alterations of nutritional and metabolic contexts. Studies suggest that sleep loss is associated with problems in glucose metabolism and a higher risk for the development of insulin resistance and type 2 diabetes mellitus. The mechanism involved may be associated with the decreased efficacy of regulation of the hypothalamus-pituitary-adrenal axis by negative feedback mechanisms in sleep-deprivation conditions. In addition, changes in the circadian pattern of growth hormone (GH secretion might also contribute to the alterations in glucose regulation observed during sleep loss. On the other hand, sleep deprivation stress affects adipokines - increasing tumor necrosis factor-α (TNF-α and interleukin-6 (IL-6 and decreasing leptin and adiponectin -, thus establishing a possible association between sleep-debt, adipokines and glucose metabolism. Thus, a modified release of adipokines resulting from sleep deprivation could lead to a chronic sub-inflammatory state that could play a central role in the development of insulin resistance and type 2 diabetes mellitus. Further studies are necessary to investigate the role of sleep loss in adipokine release and its relationship with glucose metabolism.

  14. Glucose metabolism in cultured trophoblasts from human placenta

    Energy Technology Data Exchange (ETDEWEB)

    Moe, A.J.; Farmer, D.R.; Nelson, D.M.; Smith, C.H. (Washington Univ., St. Louis, MO (United States))

    1990-02-26

    The development of appropriate placental trophoblast isolation and culture techniques enables the study of pathways of glucose utilization by this important cell layer in vitro. Trophoblasts from normal term placentas were isolated and cultured 24 hours and 72 hours in uncoated polystyrene culture tubes or tubes previously coated with a fibrin matrix. Trophoblasts cultured on fibrin are morphologically distinct from those cultured on plastic or other matrices and generally resemble in vivo syncytium. Cells were incubated up to 3 hours with {sup 14}C-labeled glucose and reactions were stopped by addition of perchloric acid. {sup 14}CO{sub 2} production by trophoblasts increased linearly with time however the largest accumulation of label was in organic acids. Trophoblasts cultured in absence of fibrin utilized more glucose and accumulated more {sup 14}C in metabolic products compared to cells cultured on fibrin. Glucose oxidation to CO{sub 2} by the phosphogluconate (PG) pathway was estimated from specific yields of {sup 14}CO{sub 2} from (1-{sup 14}C)-D-glucose and (6-{sup 14}C)-D-glucose. Approximately 6% of glucose oxidation was by the PG pathway when cells were cultured on fibrin compared to approximately 1% by cells cultured in the absence of fibrin. The presence of a fibrin growth matrix appears to modulate the metabolism of glucose by trophoblast from human placenta in vitro.

  15. Enhanced muscle glucose metabolism after exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Garetto, L P; Goodman, M N;

    1984-01-01

    Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase in the pr...

  16. Calorie Restriction Prevents Metabolic Aging Caused by Abnormal SIRT1 Function in Adipose Tissues.

    Science.gov (United States)

    Xu, Cheng; Cai, Yu; Fan, Pengcheng; Bai, Bo; Chen, Jie; Deng, Han-Bing; Che, Chi-Ming; Xu, Aimin; Vanhoutte, Paul M; Wang, Yu

    2015-05-01

    Adipose tissue is a pivotal organ determining longevity, due largely to its role in maintaining whole-body energy homeostasis and insulin sensitivity. SIRT1 is a NAD-dependent protein deacetylase possessing antiaging activities in a wide range of organisms. The current study demonstrates that mice with adipose tissue-selective overexpression of hSIRT1(H363Y), a dominant-negative mutant that disrupts endogenous SIRT1 activity, show accelerated development of metabolic aging. These mice, referred to as Adipo-H363Y, exhibit hyperglycemia, dyslipidemia, ectopic lipid deposition, insulin resistance, and glucose intolerance at a much younger age than their wild-type littermates. The metabolic defects of Adipo-H363Y are associated with abnormal epigenetic modifications and chromatin remodeling in their adipose tissues, as a result of excess accumulation of biotin, which inhibits endogenous SIRT1 activity, leading to increased inflammation, cellularity, and collagen deposition. The enzyme acetyl-CoA carboxylase 2 plays an important role in biotin accumulation within adipose tissues of Adipo-H363Y. Calorie restriction prevents biotin accumulation, abolishes abnormal histone biotinylation, and completely restores the metabolic and adipose functions of Adipo-H363Y. The effects are mimicked by short-term restriction of biotin intake, an approach potentially translatable to humans for maintaining the epigenetic and chromatin remodeling capacity of adipose tissues and preventing aging-associated metabolic disorders.

  17. Gastric emptying, glucose metabolism and gut hormones

    DEFF Research Database (Denmark)

    Vermeulen, Mechteld A R; Richir, Milan C; Garretsen, Martijn K

    2011-01-01

    To study the gastric-emptying rate and gut hormonal response of two carbohydrate-rich beverages. A specifically designed carbohydrate-rich beverage is currently used to support the surgical patient metabolically. Fruit-based beverages may also promote recovery, due to natural antioxidant...... and carbohydrate content. However, gastric emptying of fluids is influenced by its nutrient composition; hence, safety of preoperative carbohydrate loading should be confirmed. Because gut hormones link carbohydrate metabolism and gastric emptying, hormonal responses were studied....

  18. Neurodynamics of abnormalities in cerebral metabolism and structure in schizophrenia.

    Science.gov (United States)

    Waddington, J L

    1993-01-01

    Much evidence points to the importance of intrauterine events in the etiology of schizophrenia and suggests a complex interplay between dysfunctional and intact neurons in the pathophysiology of the disorder. This article contrasts what is known of the topographies of metabolic and structural brain abnormalities in schizophrenia at differing stages of the illness. From these contrasts, a schema is elaborated by which subtle neurodevelopmental perturbation in early to middle gestation might give rise to functional and structural abnormalities that ultimately release the diagnostic symptoms of schizophrenia. An interaction between those mechanisms mediating the expression of psychosis and the initially subtle stages of normal aging is posited to act on the substrate of a brain that is already developmentally compromised. Such a process might masquerade as "progression" in the absence of any active disease directly attributable to the original etiological event.

  19. HDL and glucose metabolism: current evidence and therapeutic potential.

    Science.gov (United States)

    Siebel, Andrew L; Heywood, Sarah Elizabeth; Kingwell, Bronwyn A

    2015-01-01

    High-density lipoprotein (HDL) and its principal apolipoprotein A-I (ApoA-I) have now been convincingly shown to influence glucose metabolism through multiple mechanisms. The key clinically relevant observations are that both acute HDL elevation via short-term reconstituted HDL (rHDL) infusion and chronically raising HDL via a cholesteryl ester transfer protein (CETP) inhibitor reduce blood glucose in individuals with type 2 diabetes mellitus (T2DM). HDL may mediate effects on glucose metabolism through actions in multiple organs (e.g., pancreas, skeletal muscle, heart, adipose, liver, brain) by three distinct mechanisms: (i) Insulin secretion from pancreatic beta cells, (ii) Insulin-independent glucose uptake, (iii) Insulin sensitivity. The molecular mechanisms appear to involve both direct HDL signaling actions as well as effects secondary to lipid removal from cells. The implications of glucoregulatory mechanisms linked to HDL extend from glycemic control to potential anti-ischemic actions via increased tissue glucose uptake and utilization. Such effects not only have implications for the prevention and management of diabetes, but also for ischemic vascular diseases including angina pectoris, intermittent claudication, cerebral ischemia and even some forms of dementia. This review will discuss the growing evidence for a role of HDL in glucose metabolism and outline related potential for HDL therapies.

  20. Acute effects of ghrelin administration on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, Esben Thyssen; Djurhuus, Christian Born; Gjedsted, Jakob;

    2007-01-01

    CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single-blind, p......CONTEXT: Ghrelin infusion increases plasma glucose and nonesterified fatty acids, but it is uncertain whether this is secondary to the concomitant release of GH. OBJECTIVE: Our objective was to study direct effects of ghrelin on substrate metabolism. DESIGN: This was a randomized, single...

  1. Antilipolytic drug boosts glucose metabolism in prostate cancer

    DEFF Research Database (Denmark)

    Andersen, Kim Francis; Divilov, Vadim; Koziorowski, Jacek;

    2013-01-01

    The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts.......The antilipolytic drug Acipimox reduces free fatty acid (FFA) levels in the blood stream. We examined the effect of reduced FFAs on glucose metabolism in androgen-dependent (CWR22Rv1) and androgen-independent (PC3) prostate cancer (PCa) xenografts....

  2. 糖代谢异常对原发性高血压患者动脉粥样硬化及血压的影响%Roles of impaired glucose metabolism in the pathologic process of atherosclerosis and abnormal fluctuation of blood pressure in essential hypertension patients

    Institute of Scientific and Technical Information of China (English)

    王钢

    2015-01-01

    目的探讨糖代谢异常(IGM)在原发性高血压(EH)患者动脉粥样硬化(AS)病变及动态血压异常中的作用。方法选取46例单纯 EH 及36例合并2型糖尿病(T2DM)的 EH 患者,对比分析两组患者的血糖、血脂、血尿酸、纤维蛋白原等代谢参数及颈动脉 AS 病变与24 h 动态血压参数的差异,然后对合并 T2DM 的 EH 患者颈动脉内膜中层厚度(CIMT)与血糖代谢参数,以及 CIMT 与动态血压参数之间的相关性进行分析。结果合并 T2DM 的 EH 患者体质量指数(BMI)、空腹血糖(FBG)、餐后2 h 血糖(2 h PBG)、糖化血红蛋白(HbA1 c)、三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇脂(LDL-C)、载脂蛋白 B(apo-B)、尿酸、纤维蛋白原浓度等代谢参数均显著高于单纯 EH 患者(P 0.05)。 Pearson 相关分析显示,在合并 T2DM 的 EH 患者中,其 CIMT 与 FPG (r =0.418, P =0.011)、HbA1 c(r =0.719,P 0.05);而动态血压参数中24 h-mSBP(r =0.414,P =0.012)、dmSBP(r =0.422,P =0.01)、nmSBP(r =0.372,P =0.026)及24 h-mPP(r =0.639,P 0.05)。结论糖代谢异常可与其他心血管疾病(CVD)危险因素协同作用,加重 EH 患者 AS 病变,进而导致血压波动异常。因此,改善这些 EH 患者的糖代谢状态可降低其心脑血管疾病并发症的危险。%Objective To explore the roles of impaired glucose metabolism (IGM) in the pathologic process of atherosclerosis (AS) and abnormal fluctuation of blood pressure in the essential hypertension (EH) patients. Methods Patients with simple EH (n = 46) and with EH combined with type 2 diabetes mellitus (T2DM) (n =36) were enrolled in the study. We conducted comparisons on the meta-bolic parameters [such as blood glucose, blood lipids, body mass index (BMI), serum uric acid (UA) and fibrinogen (Fib), along with detection of atherosclerotic plaques as well as ambulatory blood pressure (ABP)] between the two groups of patients, and then ana-lyzed the correlation in the patients

  3. Glucose regulates lipid metabolism in fasting king penguins.

    Science.gov (United States)

    Bernard, Servane F; Orvoine, Jord; Groscolas, René

    2003-08-01

    This study aims to determine whether glucose intervenes in the regulation of lipid metabolism in long-term fasting birds, using the king penguin as an animal model. Changes in the plasma concentration of various metabolites and hormones, and in lipolytic fluxes as determined by continuous infusion of [2-3H]glycerol and [1-14C]palmitate, were examined in vivo before, during, and after a 2-h glucose infusion under field conditions. All the birds were in the phase II fasting status (large fat stores, protein sparing) but differed by their metabolic and hormonal statuses, being either nonstressed (NSB; n = 5) or stressed (SB; n = 5). In both groups, glucose infusion at 5 mg.kg-1.min-1 induced a twofold increase in glycemia. In NSB, glucose had no effect on lipolysis (maintenance of plasma concentrations and rates of appearance of glycerol and nonesterified fatty acids) and no effect on the plasma concentrations of triacylglycerols (TAG), glucagon, insulin, or corticosterone. However, it limited fatty acid (FA) oxidation, as indicated by a 25% decrease in the plasma level of beta-hydroxybutyrate (beta-OHB). In SB, glucose infusion induced an approximately 2.5-fold decrease in lipolytic fluxes and a large decrease in FA oxidation, as reflected by a 64% decrease in the plasma concentration of beta-OHB. There were also a 35% decrease in plasma TAG, a 6.5- and 2.8-fold decrease in plasma glucagon and corticosterone, respectively, and a threefold increase in insulinemia. These data show that in fasting king penguins, glucose regulates lipid metabolism (inhibition of lipolysis and/or of FA oxidation) and affects hormonal status differently in stressed vs. nonstressed individuals. The results also suggest that in birds, as in humans, the availability of glucose, not of FA, is an important determinant of the substrate mix (glucose vs. FA) that is oxidized for energy production.

  4. DLK1 regulates whole body glucose metabolism

    DEFF Research Database (Denmark)

    Abdallah, Basem; Ditzel, Nicholas; Laborda, Jorge

    2015-01-01

    The endocrine role of the skeleton in regulating energy metabolism is supported by a feed forward loop between circulating osteoblasts (OBs)-derived undercaboxylated osteocalcin (Glu-OCN) and pancreatic β-cell-insulin; in turn insulin favors osteocalcin bioactivity. These data suggest the existence...... cells acts as a negative feedback mechanism to counteract the stimulatory effects of insulin on osteoblast production of Glu-OCN, a potential mechanism preventing OCN-induced hypoglycemia....

  5. Cerebral glucose metabolism in patients with spasmodic torticollis

    NARCIS (Netherlands)

    MagyarLehmann, S; Antonini, A; Roelcke, U; Maguire, RP; Missimer, J; Leenders, KL

    1997-01-01

    The pathophysiology of spasmodic torticollis is not clear. Basal ganglia dysfunction has been suggested to underlie this clinical syndrome. We studied resting cerebral glucose metabolism in 10 spasmodic torticollis patients and 10 healthy controls by using positron-emission tomography and [F-18]2-fl

  6. Glucose Metabolism via the Entner-Doudoroff Pathway in Campylobacter

    DEFF Research Database (Denmark)

    Vegge, Christina S; Jansen van Rensburg, Melissa J; Rasmussen, Janus J;

    2016-01-01

    Isolates of the zoonotic pathogen Campylobacter are generally considered to be unable to metabolize glucose due to lack of key glycolytic enzymes. However, the Entner-Doudoroff (ED) pathway has been identified in Campylobacter jejuni subsp. doylei and a few C. coli isolates. A systematic search f...

  7. ACE Reduces Metabolic Abnormalities in a High-Fat Diet Mouse Model

    Directory of Open Access Journals (Sweden)

    Seong-Jong Lee

    2015-01-01

    Full Text Available The medicinal plants Artemisia iwayomogi (A. iwayomogi and Curcuma longa (C. longa radix have been used to treat metabolic abnormalities in traditional Korean medicine and traditional Chinese medicine (TKM and TCM. In this study we evaluated the effect of the water extract of a mixture of A. iwayomogi and C. longa (ACE on high-fat diet-induced metabolic syndrome in a mouse model. Four groups of C57BL/6N male mice (except for the naive group were fed a high-fat diet freely for 10 weeks. Among these, three groups (except the control group were administered a high-fat diet supplemented with ACE (100 or 200 mg/kg or curcumin (50 mg/kg. Body weight, accumulation of adipose tissues in abdomen and size of adipocytes, serum lipid profiles, hepatic steatosis, and oxidative stress markers were analyzed. ACE significantly reduced the body and peritoneal adipose tissue weights, serum lipid profiles (total cholesterol and triglycerides, glucose levels, hepatic lipid accumulation, and oxidative stress markers. ACE normalized lipid synthesis-associated gene expressions (peroxisome proliferator-activated receptor gamma, PPARγ; fatty acid synthase, FAS; sterol regulatory element-binding transcription factor-1c, SREBP-1c; and peroxisome proliferator-activated receptor alpha, PPARα. The results from this study suggest that ACE has the pharmaceutical potential reducing the metabolic abnormalities in an animal model.

  8. Glucose Metabolism in Sheep Fed Grass Supplemented with Gliricidia Sepium

    Directory of Open Access Journals (Sweden)

    Y. Widiawati

    2014-12-01

    Full Text Available The limiting factor on improving ruminant production for most of the available feed in developing countries are low in quality. Therefore high fibre diet must be supplemented by high nutritivefeed such as leguminous trees that much available in those regions. Gliricidia sepium was one of very potential candidates. Glucose as a major energy source in fed animals required precursor in form of propionat and amino acids from diet. Those precursors might be supplied by these legume leaves. The aim of this research was to investigate the glucose metabolism in the sheep fed grass supplemented by Gliricidia sepium. Fifteen sheeps (18 months old were used in the experiment. Theseare were divided into three groups that fed by experimental diet of Mitchell grass (MG group, Gliricidia(GS group, and MG supplemented with GS (MGGS group. D-[U-14C]glucoseinfusate was infused continuously through the left jugular venous catheter of each animal to measure glucose metabolism in those sheeps. The measurements were done on feed utilisation and glucose metabolism. The results indicated that there was an improvement in efficiency of feed utilisation in the MGGS group as reflected by lower feed conversion ratio by the group. Plasma glucose concentration profile per unit of OM intake were similar for GS and MGGS groups, but higher than that in the MG group (P<0.01. Glucose entry rate (GER increased in MG group through GS to the MGGS group, while N retention accordingly was increased. It can be concluded that theutilization of GS by the ruminant animal could be improved by feeding it with a low quality feed at a ratio of 40:60 (GS:Low quality feed to achieve an NI:DOMI ratio of 0.03 - 0.04. This improvement would be manifested in increasing DOMI, with subsequent increase in GER or net protein deposition as might be expressed in positive N retention.

  9. Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

    Energy Technology Data Exchange (ETDEWEB)

    Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Largo P. Daneo, 3, 16132, Genoa (Italy); Polidori, M.C. [University of Cologne, Institute of Geriatrics, Cologne (Germany); Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia [University of Perugia, Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, Perugia (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS San Martino-IST, Nuclear Medicine, Department of Health Science (DISSAL), Genoa (Italy); Fiorucci, Giuliana; Dottorini, Massimo Eugenio [Nuclear Medicine, S. M. della Misericordia Hospital, Perugia (Italy)

    2014-04-15

    The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain{sup 18}F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

  10. Clustered metabolic abnormalities blunt regression of hypertensive left ventricular hypertrophy: the LIFE study

    DEFF Research Database (Denmark)

    de Simone, G; Okin, P M; Gerdts, E;

    2009-01-01

    BACKGROUND AND AIMS: Clusters of metabolic abnormalities resembling phenotypes of metabolic syndrome predicted outcome in the LIFE study, independently of single risk markers, including obesity, diabetes and baseline ECG left ventricular hypertrophy (LVH). We examined whether clusters of two...... of metabolic abnormalities resembling phenotypes of metabolic syndrome are related to greater initial ECG LVH in hypertensive patients with value of blood pressure similar to individuals without metabolic abnormalities, and are associated with less reduction of ECG LVH during antihypertensive therapy......, potentially contributing to the reported adverse prognosis of metabolic syndrome....

  11. 儿童及青少年肥胖症糖脂代谢异常早期诊断和干预的研究%Research into abnormal glucose and lipid metabolism in early diagnosis and intervention in obese children and adolescents.

    Institute of Scientific and Technical Information of China (English)

    穆亚平; 韩萍; 辛颖; 赵方; 马洪刚; 刘立旻; 李娜; 王岩; 李玢; 关丽君; 李书琴

    2011-01-01

    Objective To explore the relationship between obesity and glucose and lipid metabolism , and the damage of the related target organs such as liver and heart in order to take early intervention. Methods Totally 516 children with simple obesity made up obesity group, 100 normal-weight children as a control group. Detect the fasting plasma glucose (FPC) , triglyceride (TC) , total cholesterol (TC) , alanine aminotransferase (ALT) , fasting insulin (FINS) and other projects; calculate the insulin resistance index (HOMA-IR) and insulin value of f$-cell function (HOMA-p ) ; oral glucose tolerance test (OGTT) and insulin release test were done in obese children; perform liver and heart ultrasonogra-phy in all children. Results Obese children's systolic and diastolic blood pressure were higher than the control group (P< 0.05) .hypertension was detected in 12.0% (62/516)of obese children; the FBG, FINS, HOMA-IR and HOMA-B of obese children were higher than the control group (P < 0.05) ; the TC, TC, LDL-C were higher than the control group, while HDL-C lower than the control group, the differences being significant (P < 0.05) ; the incidence of fatty liver of the light moderate and severe groups were significantly different (P < 0.001). With the increase of the obesity degree, fatty liver was significantly increased ( X2 = 12.97, P < 0.001). External fat thickness of the pericardium increasedin 268 cases of obese group, external fat thickness of the pericardium being 3.372 ± 0.098 (mm) ;compared with the control group the difference was significant (P < 0.001). Early joint intervention was done in 97 MS pa-tients, including dieting and increasing physical activity, combined with oral metformin drugs,and the FINS and HDL-C improvement was of significant difference (P < 0.001) .Conclusion The risk of hypertension in obese children is higher than non-obese children.Abnormal glucose metabolism is more comman in obese children than in non-obese children; children with mild

  12. Evolution of Metabolic Abnormalities in Alcoholic Patients during Withdrawal

    Directory of Open Access Journals (Sweden)

    X. Vandemergel

    2015-01-01

    Full Text Available Chronic alcohol intoxication is accompanied by metabolic abnormalities. Evolution during the early withdrawal period has been poorly investigated. The aim of this study was to determine the evolution of metabolic parameters during alcohol withdrawal. Patients and Methods. Thirty-three patients admitted in our department for alcohol withdrawal were prospectively included. Results. Baseline hypophosphatemia was found in 24% of cases. FEPO4 was reduced from 14.2 ± 9% at baseline to 7.3 ± 4.2% at day 3 (Pnl, respectively. No correlation was found between the sodium and CPK levels (P=0.75 nor between the CPK level and the amount of alcohol ingested (rs = 0.084, P=0.097. Baseline urate level was elevated and returned to normal after three days. Baseline magnesium concentration was normal and stable over time. Conclusion. Chronic alcohol intoxication was accompanied by phosphaturia, rapidly reversible after alcohol withdrawal and inversely correlated with albuminemia, slight hyponatremia, low levels of 25 hydroxy vitamin D, elevated CPK level in about 30% of women, and hyperuricemia with rapid normalization.

  13. Abnormal glycosphingolipid metabolism in the nervous system of galactosialidosis.

    Science.gov (United States)

    Yoshino, H; Miyashita, K; Miyatani, N; Ariga, T; Hashimoto, Y; Tsuji, S; Oyanagi, K; Ohama, E; Ikuta, F; Suzuki, A

    1990-06-01

    In an autopsy case of galactosialidosis, GM3, GM2, GM1, and GD1a were accumulated in sympathetic and spinal ganglia and grey matter of the spinal cord. Especially, the accumulations of GM3 and GM2 amounted to 41- and 86-fold increases in sympathetic ganglia, respectively, as compared to normal controls. In addition LacCer, GA2 and GA1 were accumulated in sympathetic and spinal ganglia. The accumulations of GM3 and GD1a are considered to be the result of defective lysosomal sialidase activity and the accumulation of GM1, LacCer and GA1 is also considered to be due to decreased beta-galactosidase activity in this disorder. To better understand the possible mechanism of GM2 accumulation, we determined the activity of GM2 synthesizing enzyme (GM3:UDP-GalNAc transferase), as well as hexosaminidase activity, in sympathetic ganglia, but they did not change. Abnormal ganglioside and neutral glycosphingolipid metabolism, as well as sialyloligosaccharide and sialylglycoprotein metabolism, may be involved in the pathogenesis of this disorder.

  14. Prevalence of diabetes, metabolic syndrome and metabolic abnormalities in schizophrenia over the course of the illness: a cross-sectional study

    Directory of Open Access Journals (Sweden)

    Wampers M

    2006-06-01

    Full Text Available Abstract Background Patients with schizophrenia are at high risk of developing metabolic abnormalities. Method A prospective study focusing on metabolic disturbances in patients with schizophrenia, including an oral glucose tolerance test, is currently ongoing at our University Hospital and affiliate services. The prevalence of metabolic abnormalities at baseline was assessed in a cohort of 415 patients with schizophrenia. The sample was divided into 4 groups according to duration of illness: first-episode patients (20 years. Results Metabolic abnormalities were already present in first-episode patients, and considerably increased with increasing duration of illness. When compared to the general population matched for age and gender, much higher rates of the metabolic syndrome (MetS and diabetes were observed for patients with schizophrenia. For MetS, the increase over time was similar to that of the general population. In contrast, the difference in the prevalence of diabetes in patients with schizophrenia and the general population dramatically and linearly increased from 1.6% in the 15–25 age-band to 19.2% in the 55–65 age-band. Conclusion Thus, the current data suggest that on the one hand metabolic abnormalities are an inherent part of schizophrenic illness, as they are already present in first-episode patients. On the other hand, however, our results suggest a direct effect of the illness and/or antipsychotic medication on their occurence. The data underscore the need for screening for metabolic abnormalities in patients diagnosed with schizophrenia, already starting from the onset of the illness.

  15. Implications of Resveratrol on Glucose Uptake and Metabolism

    Directory of Open Access Journals (Sweden)

    David León

    2017-03-01

    Full Text Available Resveratrol—a polyphenol of natural origin—has been the object of massive research in the past decade because of its potential use in cancer therapy. However, resveratrol has shown an extensive range of cellular targets and effects, which hinders the use of the molecule for medical applications including cancer and type 2 diabetes. Here, we review the latest advances in understanding how resveratrol modulates glucose uptake, regulates cellular metabolism, and how this may be useful to improve current therapies. We discuss challenges and findings regarding the inhibition of glucose uptake by resveratrol and other polyphenols of similar chemical structure. We review alternatives that can be exploited to improve cancer therapies, including the use of other polyphenols, or the combination of resveratrol with other molecules and their impact on glucose homeostasis in cancer and diabetes.

  16. Activin A Levels Are Associated With Abnormal Glucose Regulation in Patients With Myocardial Infarction

    Science.gov (United States)

    Andersen, Geir Ø.; Ueland, Thor; Knudsen, Eva C.; Scholz, Hanne; Yndestad, Arne; Sahraoui, Afaf; Smith, Camilla; Lekva, Tove; Otterdal, Kari; Halvorsen, Bente; Seljeflot, Ingebjørg; Aukrust, Pål

    2011-01-01

    OBJECTIVE On the basis of the role of activin A in inflammation, atherogenesis, and glucose homeostasis, we investigated whether activin A could be related to glucometabolic abnormalities in patients with acute myocardial infarction (MI). RESEARCH DESIGN AND METHODS Activin A measurement and oral glucose tolerance tests (OGTTs) were performed in patients (n = 115) with acute MI, without previously known diabetes, and repeated after 3 months. Release of activin A and potential anti-inflammatory effects of activin A were measured in human endothelial cells. Activin A effects on insulin secretion and inflammation were tested in human pancreatic islet cells. RESULTS 1) In patients with acute MI, serum levels of activin A were significantly higher in those with abnormal glucose regulation (AGR) compared with those with normal glucose regulation. Activin A levels were associated with the presence of AGR 3 months later (adjusted odds ratio 5.1 [95% CI 1.73–15.17], P = 0.003). 2) In endothelial cells, glucose enhanced the release of activin A, whereas activin A attenuated the release of interleukin (IL)-8 and enhanced the mRNA levels of the antioxidant metallothionein. 3) In islet cells, activin A attenuated the suppressive effect of inflammatory cytokines on insulin release, counteracted the ability of these inflammatory cytokines to induce mRNA expression of IL-8, and induced the expression of transforming growth factor-β. CONCLUSIONS We found a significant association between activin A and newly detected AGR in patients with acute MI. Our in vitro findings suggest that this association represents a counteracting mechanism to protect against inflammation, hyperglycemia, and oxidative stress. PMID:21464440

  17. Gut microbiota may have influence on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian Hallundbæk; Nielsen, Morten Frost; Tvede, Michael

    2013-01-01

    New gene sequencing-based techniques and the large worldwide sequencing capacity have introduced a new era within the field of gut microbiota. Animal and human studies have shown that obesity and type 2 diabetes are associated with changes in the composition of the gut microbiota...... and that prebiotics, antibiotics or faecal transplantation can alter glucose and lipid metabolism. This paper summarizes the latest research regarding the association between gut microbiota, diabetes and obesity and some of the mechanisms by which gut bacteria may influence host metabolism....

  18. Dementia with impaired glucose metabolism in late onset metachromatic leukodystrophy

    DEFF Research Database (Denmark)

    Johannsen, P.; Ehlers, L.; Hansen, Hans Jacob

    2001-01-01

    An unusual case of very-late-onset metachromatic leukodystrophy (MLD) with dementia was studied. The patient was a 41-year-old male who presented with mild dementia and a single generalized tonic clonic seizure. Neuropsychological assessment demonstrated mild amnesia, visuospatial dysfunction and...... was observed using positron emission tomography and fluor-18-labeled fluorodesoxyglucose. The neuropsychological deficits are related to the location of deficits in glucose metabolism....

  19. Metabolic abnormalities and hypoleptinemia in α-synuclein A53T mutant mice.

    Science.gov (United States)

    Rothman, Sarah M; Griffioen, Kathleen J; Fishbein, Kenneth W; Spencer, Richard G; Makrogiannis, Sokratis; Cong, Wei-Na; Martin, Bronwen; Mattson, Mark P

    2014-05-01

    Parkinson's disease (PD) patients frequently display loss of body fat mass and increased energy expenditure, and several studies have outlined a relationship between these metabolic abnormalities and disease severity, yet energy metabolism is largely unstudied in mouse models of PD. Here we characterize metabolic and physiologic responses to a high calorie diet (HCD) in mice expressing in neurons a mutant form of human α-synuclein (A53T) that causes dominantly inherited familial forms of the disease. A53T (SNCA) and wild type (WT) littermate mice were placed on a HCD for 12 weeks and evaluated for weight gain, food intake, body fat, blood plasma leptin, hunger, glucose tolerance, and energy expenditure. Results were compared with both SNCA and WT mice on a control diet. Despite consuming similar amounts of food, WT mice gained up to 66% of their original body weight on a HCD, whereas SNCA mice gained only 17%. Further, after 12 weeks on a HCD, magnetic resonance imaging analysis revealed that WT mice had significantly greater total and visceral body fat compared with SNCA mice (p < 0.007). At the age of 24 weeks SNCA mice displayed significantly increased hunger compared with WT (p < 0.03). At the age of 36 weeks, SNCA mice displayed significant hypoleptinemia compared with WT, both on a normal diet and a HCD (p < 0.03). The HCD induced insulin insensitivity in WT, but not SNCA mice, as indicated by an oral glucose tolerance test. Finally, SNCA mice displayed greater energy expenditure compared with WT, as measured in a Comprehensive Laboratory Animal Monitoring System, after 12 weeks on a HCD. Thus, SNCA mice are resistant to HCD-induced obesity and insulin resistance and display reduced body fat, increased hunger, hypoleptinemia and increased energy expenditure. Our findings reveal a profile of metabolic dysfunction in a mouse model of PD that is similar to that of human PD patients, thus providing evidence that α-synuclein pathology is sufficient to drive such

  20. High prevalence of abnormal circadian blood pressure regulation and impaired glucose tolerance in adults with hypopituitarism.

    Science.gov (United States)

    Krzyzanowska, K; Schnack, C; Mittermayer, F; Kopp, H P; Hofer, M; Kann, T; Schernthaner, G

    2005-09-01

    Patients with hypopituitarism have an increased mortality from cardiovascular events. Reduced nocturnal blood pressure decline (non-dipping) and impaired glucose tolerance are considered as cardiovascular risk factors. To evaluate the role of these risk factors in patients with hypopituitarism we determined the 24-hour blood pressure regulation and glucose tolerance status in hypopituitary patients with and without growth hormone (GH) deficiency. Sixty-one hypopituitary subjects 5 +/- 3 years after brain surgery because of macroadenoma, 61 patients with type 2 diabetes mellitus (T2DM), and 20 healthy controls were included. Forty-four hypopituitary patients were GH deficient and 28 of these on GH treatment. Non-dipping was observed in 41 % (n = 7) of hypopituitary subjects with normal GH release, in 46 % (n = 13) of patients on GH therapy, and in 69 % (n = 11) of untreated GH deficient patients. Untreated GH deficient patients had a higher systolic night/day ratio (1.00 +/- 0.03) compared to non GH deficient (0.92 +/- 0.02; p < 0.02) and GH treated hypopituitary patients (0.93 +/- 0.01; p < 0.02). The rate of non-dipping in hypopituitarism was comparable to that in T2DM. Pathologic glucose tolerance was diagnosed in 30 % of the hypopituitary patients. The prevalence of non-dipping was independent of glucose metabolism in hypopituitary patients. All controls had normal night time blood pressure fall and glucose metabolism. The high prevalence of nocturnal non-dipping and glucose intolerance detected in this cohort might contribute to the increased cardiovascular risk of hypopituitary patients.

  1. 二甲双胍和吡格列酮对初诊糖代谢异常伴腹型肥胖患者血清ghrelin水平的影响%Effects of metformin and pioglitazone on plasma ghrelin in patients with newly diagnosed abnormal glucose metabolism and abdominal obesity

    Institute of Scientific and Technical Information of China (English)

    张淼; 郭毅飞; 时立新; 吴丹荣; 张松; 胡颖; 徐毅; 林巧

    2012-01-01

    Objective To investigate the effects of metformin and pioglitazone on plasma ghrelin in patients with newly diagnosed abnormal glucose metabolism and abdominal obesity.Methods From April to September 2010,39 patients with abnormal glucose metabolism (including impaired glucose tolerance and newly diagnosed type diabetes mellitus,glycated hemoglobin A1c(HbA1c) <7% ) and obesity were enrolled in the study.They were randomly assigned to metformin group(500 mg tid,n =20,15 females and 5 males,aged (51±9) years,MET group) or pioglitazone group (30 mg/d,n =19,11 females and 8 males,aged (53 ±7) years,PIO group) on the basis of diet and exercise therapy for3 months.Three males in PIO group with drawed because of itching and edema.At baseline and after 3 months,plasma glucose,serum insulin and ghrelin levels during oral glucose tolerance test( OGTT,0 min,0.5,1.0,2.0,3.0 h),body weight,body mass index(BMI),HbA1c,etc were measured.The t test or Wilcoxon rank-sum test was used for statistical analysis. Partial correlation and multiple regression analysis were performed to examine the association between serum ghrelin levels and influencing factors.Results ( 1 ) In PIO group,serum ghrelin levels after treatment were OGTT 0 min (1069 ±467)ng/L,0.5 h (898 ±407)ng/L,1.0 h (812 ±371) ng/L,2.0 h (705 ± 328) ng/L and 3.0 h ( 1059 ± 606 ) ng/L,respectively.All increased than those before treatment ( (905 ±449),(688 ±378),(614 ±358),(572 ± 334)and(720 ±403)ng/L,Z value was from -2.354 to - 3.351,respectively,all P < 0.05 ).(2) In MET group,serum ghrelin levels at OGTT 0 min,1.0,2.0,3.0 h after treatment were (731 ± 241 ),(642 ± 208 ),( 525 ± 195 ),(462 ± 146 ) and ( 611 ± 267 ) ng/L,respectively.Compared with the ghrelin levels before treatment( (731 ± 241 ),(642 ± 208 ),(525 ± 195 ),(462 ± 146) and (611 ± 267)ng/L),only the difference at 0 min,2.0,3.0 h was statistically significant (all P<0.05).Serum ghrelin levels of MET group at OGTT 0.5,1.0 and 3.0 h

  2. Metabolism Kinetics of Glucose in Anchorage-dependent Cell Cultures

    Institute of Scientific and Technical Information of China (English)

    孙祥明; 张元兴

    2001-01-01

    The kinetic model of glucose metabolism was established and successfully applied to batchcultures of rCHO and rBHK cells. It was found that a large amount of glucose was utilized for cellmaintenance, and the overwhelming majority of maintenance energy from glucose was by its anaerobicmetabolism in both rBHK and rCHO cell cultures. The overall maintenance coefficients from aerobicmetabolism were 1.9×10-13 mmol/(cell.h) for rCHO cells and 7×10-13 mmol/(cell.h) for rBHK cells. Inaddition, all Go/T and Eo/T gradually increased with the same trend as the cell growth in the culture ofboth rCHO and rBHK cells. The overall molecule yield coefficients of lactate to glucose were 1.61 for rCHO cells and 1.38 for rBHK cells. The yield coefficients of cell to glucose were 4.5×108 cells/mmol for rCHO cells and 1.9 × 108 cells/mmol for rBHK cells, respectively.

  3. Fetal deficiency of lin28 programs life-long aberrations in growth and glucose metabolism.

    Science.gov (United States)

    Shinoda, Gen; Shyh-Chang, Ng; Soysa, T Yvanka de; Zhu, Hao; Seligson, Marc T; Shah, Samar P; Abo-Sido, Nora; Yabuuchi, Akiko; Hagan, John P; Gregory, Richard I; Asara, John M; Cantley, Lewis C; Moss, Eric G; Daley, George Q

    2013-08-01

    LIN28A/B are RNA binding proteins implicated by genetic association studies in human growth and glucose metabolism. Mice with ectopic over-expression of Lin28a have shown related phenotypes. Here, we describe the first comprehensive analysis of the physiologic consequences of Lin28a and Lin28b deficiency in knockout (KO) mice. Lin28a/b-deficiency led to dwarfism starting at different ages, and compound gene deletions showed a cumulative dosage effect on organismal growth. Conditional gene deletion at specific developmental stages revealed that fetal but neither neonatal nor adult deficiency resulted in growth defects and aberrations in glucose metabolism. Tissue-specific KO mice implicated skeletal muscle-deficiency in the abnormal programming of adult growth and metabolism. The effects of Lin28b KO could be rescued by Tsc1 haplo-insufficiency in skeletal muscles. Our data implicate fetal expression of Lin28a/b in the regulation of life-long effects on metabolism and growth, and demonstrate that fetal Lin28b acts at least in part via mTORC1 signaling.

  4. Variants of insulin-signaling inhibitor genes in type 2 diabetes and related metabolic abnormalities.

    Science.gov (United States)

    de Lorenzo, Carlo; Greco, Annalisa; Fiorentino, Teresa Vanessa; Mannino, Gaia Chiara; Hribal, Marta Letizia

    2013-01-01

    Insulin resistance has a central role in the pathogenesis of several metabolic diseases, including type 2 diabetes, obesity, glucose intolerance, metabolic syndrome, atherosclerosis, and cardiovascular diseases. Insulin resistance and related traits are likely to be caused by abnormalities in the genes encoding for proteins involved in the composite network of insulin-signaling; in this review we have focused our attention on genetic variants of insulin-signaling inhibitor molecules. These proteins interfere with different steps in insulin-signaling: ENPP1/PC-1 and the phosphatases PTP1B and PTPRF/LAR inhibit the insulin receptor activation; INPPL1/SHIP-2 hydrolyzes PI3-kinase products, hampering the phosphoinositide-mediated downstream signaling; and TRIB3 binds the serine-threonine kinase Akt, reducing its phosphorylation levels. While several variants have been described over the years for all these genes, solid evidence of an association with type 2 diabetes and related diseases seems to exist only for rs1044498 of the ENPP1 gene and for rs2295490 of the TRIB3 gene. However, overall the data recapitulated in this Review article may supply useful elements to interpret the results of novel, more technically advanced genetic studies; indeed it is becoming increasingly evident that genetic information on metabolic diseases should be interpreted taking into account the complex biological pathways underlying their pathogenesis.

  5. Variants of Insulin-Signaling Inhibitor Genes in Type 2 Diabetes and Related Metabolic Abnormalities

    Directory of Open Access Journals (Sweden)

    Carlo de Lorenzo

    2013-01-01

    Full Text Available Insulin resistance has a central role in the pathogenesis of several metabolic diseases, including type 2 diabetes, obesity, glucose intolerance, metabolic syndrome, atherosclerosis, and cardiovascular diseases. Insulin resistance and related traits are likely to be caused by abnormalities in the genes encoding for proteins involved in the composite network of insulin-signaling; in this review we have focused our attention on genetic variants of insulin-signaling inhibitor molecules. These proteins interfere with different steps in insulin-signaling: ENPP1/PC-1 and the phosphatases PTP1B and PTPRF/LAR inhibit the insulin receptor activation; INPPL1/SHIP-2 hydrolyzes PI3-kinase products, hampering the phosphoinositide-mediated downstream signaling; and TRIB3 binds the serine-threonine kinase Akt, reducing its phosphorylation levels. While several variants have been described over the years for all these genes, solid evidence of an association with type 2 diabetes and related diseases seems to exist only for rs1044498 of the ENPP1 gene and for rs2295490 of the TRIB3 gene. However, overall the data recapitulated in this Review article may supply useful elements to interpret the results of novel, more technically advanced genetic studies; indeed it is becoming increasingly evident that genetic information on metabolic diseases should be interpreted taking into account the complex biological pathways underlying their pathogenesis.

  6. Glucose Metabolism in the Progression of Prostate Cancer

    Science.gov (United States)

    Cutruzzolà, Francesca; Giardina, Giorgio; Marani, Marina; Macone, Alberto; Paiardini, Alessandro; Rinaldo, Serena; Paone, Alessio

    2017-01-01

    Prostate cancer is one of the most common types of cancer in western country males but the mechanisms involved in the transformation processes have not been clearly elucidated. Alteration in cellular metabolism in cancer cells is recognized as a hallmark of malignant transformation, although it is becoming clear that the biological features of metabolic reprogramming not only differ in different cancers, but also among different cells in a type of cancer. Normal prostate epithelial cells have a peculiar and very inefficient energy metabolism as they use glucose to synthesize citrate that is secreted as part of the seminal liquid. During the transformation process, prostate cancer cells modify their energy metabolism from inefficient to highly efficient, often taking advantage of the interaction with other cell types in the tumor microenvironment that are corrupted to produce and secrete metabolic intermediates used by cancer cells in catabolic and anabolic processes. We recapitulate the metabolic transformations occurring in the prostate from the normal cell to the metastasis, highlighting the role of the microenvironment and summarizing what is known on the molecular mechanisms involved in the process. PMID:28270771

  7. Alleviation of metabolic abnormalities induced by excessive fructose administration in Wistar rats by Spirulina maxima

    Science.gov (United States)

    Jarouliya, Urmila; Anish, Zacharia J.; Kumar, Pravin; Bisen, P.S.; Prasad, G.B.K.S.

    2012-01-01

    Background & objectives: Diabetes mellitus is a metabolic disorder characterized by hyperglycaemia. Several natural products have been isolated and identified to restore the complications of diabetes. Spirulina maxima is naturally occurring fresh water cyanobacterium, enriched with proteins and essential nutrients. The aim of the study was to determine whether S. maxima could serve as a therapeutic agent to correct metabolic abnormalities induced by excessive fructose administration in Wistar rats. Methods: Oral administration of 10 per cent fructose solution to Wistar rats (n=5 in each group) for 30 days resulted in hyperglycaemia and hyperlipidaemia. Aqueous suspension of S. maxima (5 or 10%) was also administered orally once daily for 30 days. The therapeutic potential of the preparation with reference to metformin (500 mg/kg) was assessed by monitoring various biochemical parameters at 10 day intervals during the course of therapy and at the end of 30 days S. maxima administration. Results: Significant (P<0.001) reductions in blood glucose, lipid profile (triglycerides, cholesterol and LDL, VLDL) and liver function markers (SGPT and SGOT) were recorded along with elevated level of HDL-C at the end of 30 days therapy of 5 or 10 per cent S. maxima aquous extract. Co-administration of S. maxima extract (5 or 10% aqueous) with 10 per cent fructose solution offered a significant protection against fructose induced metabolic abnormalities in Wistar rats. Interpretation & Conclusions: The present findings showed that S. maxima exhibited anti-hyperglycaemic, anti-hyperlipidaemic and hepatoprotective activity in rats fed with fructose. Further studies are needed to understand the mechanisms. PMID:22561632

  8. Anorexia and Impaired Glucose Metabolism in Mice With Hypothalamic Ablation of Glut4 Neurons

    Science.gov (United States)

    Ren, Hongxia; Lu, Taylor Y.; McGraw, Timothy E.

    2015-01-01

    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin–mediated cell ablation to selectively remove basal hypothalamic Glut4 neurons and investigate the resulting phenotypes. After Glut4 neuron ablation, mice demonstrate altered hormone and nutrient signaling in the CNS. Accordingly, they exhibit negative energy balance phenotype characterized by reduced food intake and increased energy expenditure, without locomotor deficits or gross neuronal abnormalities. Glut4 neuron ablation affects orexigenic melanin-concentrating hormone neurons but has limited effect on neuropeptide Y/agouti-related protein and proopiomelanocortin neurons. The food intake phenotype can be partially normalized by GABA administration, suggesting that it arises from defective GABAergic transmission. Glut4 neuron–ablated mice show peripheral metabolic defects, including fasting hyperglycemia and glucose intolerance, decreased insulin levels, and elevated hepatic gluconeogenic genes. We conclude that Glut4 neurons integrate hormonal and nutritional cues and mediate CNS actions of insulin on energy balance and peripheral metabolism. PMID:25187366

  9. Anorexia and impaired glucose metabolism in mice with hypothalamic ablation of Glut4 neurons.

    Science.gov (United States)

    Ren, Hongxia; Lu, Taylor Y; McGraw, Timothy E; Accili, Domenico

    2015-02-01

    The central nervous system (CNS) uses glucose independent of insulin. Nonetheless, insulin receptors and insulin-responsive glucose transporters (Glut4) often colocalize in neurons (Glut4 neurons) in anatomically and functionally distinct areas of the CNS. The apparent heterogeneity of Glut4 neurons has thus far thwarted attempts to understand their function. To answer this question, we used Cre-dependent, diphtheria toxin-mediated cell ablation to selectively remove basal hypothalamic Glut4 neurons and investigate the resulting phenotypes. After Glut4 neuron ablation, mice demonstrate altered hormone and nutrient signaling in the CNS. Accordingly, they exhibit negative energy balance phenotype characterized by reduced food intake and increased energy expenditure, without locomotor deficits or gross neuronal abnormalities. Glut4 neuron ablation affects orexigenic melanin-concentrating hormone neurons but has limited effect on neuropeptide Y/agouti-related protein and proopiomelanocortin neurons. The food intake phenotype can be partially normalized by GABA administration, suggesting that it arises from defective GABAergic transmission. Glut4 neuron-ablated mice show peripheral metabolic defects, including fasting hyperglycemia and glucose intolerance, decreased insulin levels, and elevated hepatic gluconeogenic genes. We conclude that Glut4 neurons integrate hormonal and nutritional cues and mediate CNS actions of insulin on energy balance and peripheral metabolism.

  10. Metabolic Abnormalities Are Common among South American Hispanics Subjects with Normal Weight or Excess Body Weight: The CRONICAS Cohort Study.

    Directory of Open Access Journals (Sweden)

    Catherine P Benziger

    Full Text Available We aimed to characterize metabolic status by body mass index (BMI status.The CRONICAS longitudinal study was performed in an age-and-sex stratified random sample of participants aged 35 years or older in four Peruvian settings: Lima (Peru's capital, costal urban, highly urbanized, urban and rural Puno (both high-altitude, and Tumbes (costal semirural. Data from the baseline study, conducted in 2010, was used. Individuals were classified by BMI as normal weight (18.5-24.9 kg/m2, overweight (25.0-29.9 kg/m2, and obese (≥30 kg/m2, and as metabolically healthy (0-1 metabolic abnormality or metabolically unhealthy (≥2 abnormalities. Abnormalities included individual components of the metabolic syndrome, high-sensitivity C-reactive protein, and insulin resistance.A total of 3088 (age 55.6±12.6 years, 51.3% females had all measurements. Of these, 890 (28.8%, 1361 (44.1% and 837 (27.1% were normal weight, overweight and obese, respectively. Overall, 19.0% of normal weight in contrast to 54.9% of overweight and 77.7% of obese individuals had ≥3 risk factors (p<0.001. Among normal weight individuals, 43.1% were metabolically unhealthy, and age ≥65 years, female, and highest socioeconomic groups were more likely to have this pattern. In contrast, only 16.4% of overweight and 3.9% of obese individuals were metabolically healthy and, compared to Lima, the rural and urban sites in Puno were more likely to have a metabolically healthier profile.Most Peruvians with overweight and obesity have additional risk factors for cardiovascular disease, as well as a majority of those with a healthy weight. Prevention programs aimed at individuals with a normal BMI, and those who are overweight and obese, are urgently needed, such as screening for elevated fasting cholesterol and glucose.

  11. Metabolic profile of normal glucose-tolerant subjects with elevated 1-h plasma glucose values

    Science.gov (United States)

    Pramodkumar, Thyparambil Aravindakshan; Priya, Miranda; Jebarani, Saravanan; Anjana, Ranjit Mohan; Mohan, Viswanathan; Pradeepa, Rajendra

    2016-01-01

    Aim: The aim of this study was to compare the metabolic profiles of subjects with normal glucose tolerance (NGT) with and without elevated 1-h postglucose (1HrPG) values during an oral glucose tolerance test (OGTT). Methodology: The study group comprised 996 subjects without known diabetes seen at tertiary diabetes center between 2010 and 2014. NGT was defined as fasting plasma glucose <100 mg/dl (5.5 mmol/L) and 2-h plasma glucose <140 mg/dl (7.8 mmol/L) after an 82.5 g oral glucose (equivalent to 75 g of anhydrous glucose) OGTT. Anthropometric measurements and biochemical investigations were done using standardized methods. The prevalence rate of generalized and central obesity, hypertension, dyslipidemia, and metabolic syndrome (MS) was determined among the NGT subjects stratified based on their 1HrPG values as <143 mg/dl, ≥143–<155 mg/dl, and ≥155 mg/dl, after adjusting for age, sex, body mass index (BMI), waist circumference, alcohol consumption, smoking, and family history of diabetes. Results: The mean age of the 996 NGT subjects was 48 ± 12 years and 53.5% were male. The mean glycated hemoglobin for subjects with 1HrPG <143 mg/dl was 5.5%, for those with 1HrPG ≥143–<155 mg/dl, 5.6% and for those with 1HrPG ≥155 mg/dl, 5.7%. NGT subjects with 1HrPG ≥143–<155 mg/dl and ≥155 mg/dl had significantly higher BMI, waist circumference, systolic and diastolic blood pressure, triglyceride, total cholesterol/high-density lipoprotein (HDL) ratio, triglyceride/HDL ratio, leukocyte count, and gamma glutamyl aminotransferase (P < 0.05) compared to subjects with 1HrPG <143 mg/dl. The odds ratio for MS for subjects with 1HrPG ≥143 mg/dl was 1.84 times higher compared to subjects with 1HrPG <143 mg/dl taken as the reference. Conclusion: NGT subjects with elevated 1HrPG values have a worse metabolic profile than those with normal 1HrPG during an OGTT. PMID:27730069

  12. Effect of abomasal glucose infusion on splanchnic and whole-body glucose metabolism in periparturient dairy cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism.......Six periparturient Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the hepatic portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic and whole-body glucose metabolism....

  13. Correlation of glucose metabolism in brain cells and brain morphological changes with clinical typing in children with cerebral palsy

    Institute of Scientific and Technical Information of China (English)

    Qiongxiang Zhai; Huixian Qiao; Jiqing Liu

    2006-01-01

    BACKGROUND:It is widely known that fluorino-18-fluorodeoxyglucose positron emission tomography(18F-FDG PET)is commonly used to evaluate and diagnose epilepsy;however,whether it is beneficial to understand functional metabolism of bra in cells so as to reflect injured site and degree of brain cells or not should be studied further.OBJECTIVE:To evaluate the correlation between glucose metabolism and clinical typling as well as the conelation between active function of brain cells and degree of brain injury among children with cerbral palsy with 18F-FDG PET and MRI and compare the results of them.DESIGN:Case analysis.SETTING:Department of Pediatrics,People's Hospital of Guangdong Province.PARTICIPANTS:A total of 31 children with cerebral palsy were selected from Out-patient Clinic and In-patient Department of People's Hospital of Guangdong Province from July 2001 to August 2004.Based on clinical criteria of cerebral palsy,patients were classified into spasm(n=10),gradual movement(n=4),mixed type(n =13)and ataxia(n=4).There were 18 boys and 13 girls aged from 10 months to 4 years.All of them were met the diagnostic criteria of cerebral palsy and all parents of them were told the facts.Exclusion cdteria:Patients who had cerebral palsy caused by genetic metabolism disease were excluded.METHODS:①All children accepted MRI examination after hospitalization with Philips Acs NT 15T superconductling magnetic resonance scanner.②All children were fasted for 4 hours.And then,PET image of brain was collected based on T+EID type.If obvious hypermetabolism or hypometabolism region successively occurred on two layers, the image was regarded as abnormality. ③Different correlations of various abnormal greups of MRI and vadous types of cerebral palsy with PET image were compared and analyzed with Erusal-Willas rank sum test.MAIN OUTCOME MEASURES:①Results of 18F-FDG PET;②Results of MRI examination;③Correlation of variously abnormal groups of MRI and various types of cerebral

  14. Glucose metabolism in rats submitted to skeletal muscle denervation

    Directory of Open Access Journals (Sweden)

    Wilton Marlindo Santana Nunes

    2005-07-01

    Full Text Available This study analyzed the local and systemic effects of immobilization by denervation of the skeletal muscle on glucose metabolism. The rats were submitted to section of the right paw sciatic nerve. A reduction was observed in glucose uptake by the isolated soleus muscle of the denervated paw after 3 and 7 days, but not after 28 days in relation to the control animals. There was no difference after 3 and 7 days in glucose uptake by the soleus muscle of the opposite intact paw in relation to the control. There was increased glucose uptake in the same paw 28 days after denervation. The rate of glucose removal in response to exogenous insulin after 28 days of denervation was significantly higher than in control animals and those observed after 3 and 7 days of denervation. These results suggest that immobilization by denervation interfered not only in glucose metabolism in the skeletal muscle involved but also in other tissues.O estudo analisou os efeitos locais e sistêmicos da imobilização por desnervação do músculo esquelético sobre o metabolismo glicidico. Ratos foram submetidos à secção do nervo ciático da pata direita. Observou-se redução da captação de glicose pelo músculo sóleo isolado da pata desnervada após 3 e 7 mas não após 28 dias em relação a animais controle. Não houve diferença após 3 e 7 dias na captação de glicose pelo músculo sóleo da pata contralateral intacta em relação ao controle. Houve aumento da captação de glicose nesta mesma pata 28 dias após a desnervação. A taxa de remoção da glicose em resposta à insulina exógena após 28 dias de desnervação foi significantemente superior à do controle e àquelas observadas após 3 e 7 dias da desnervação. Esses resultados sugerem que a imobilização por desnervação interfere não só no metabolismo da glicose no músculo esquelético envolvido como também em outros tecidos.

  15. Insulin signalling and the regulation of glucose and lipid metabolism

    Science.gov (United States)

    Saltiel, Alan R.; Kahn, C. Ronald

    2001-12-01

    The epidemic of type 2 diabetes and impaired glucose tolerance is one of the main causes of morbidity and mortality worldwide. In both disorders, tissues such as muscle, fat and liver become less responsive or resistant to insulin. This state is also linked to other common health problems, such as obesity, polycystic ovarian disease, hyperlipidaemia, hypertension and atherosclerosis. The pathophysiology of insulin resistance involves a complex network of signalling pathways, activated by the insulin receptor, which regulates intermediary metabolism and its organization in cells. But recent studies have shown that numerous other hormones and signalling events attenuate insulin action, and are important in type 2 diabetes.

  16. Enhanced muscle glucose metabolism after exercise in the rat

    DEFF Research Database (Denmark)

    Garetto, L P; Richter, Erik; Goodman, M N

    1984-01-01

    glycogen was substantially repleted at the time (30 min postexercise) that glucose metabolism was examined. When rats were run at twice the previous rate (36 m/min), muscle glycogen was still substantially diminished 30 min after the run. At this time the previously noted increase in insulin sensitivity...... to near base-line values and only the increase in insulin sensitivity persists. It is proposed that phase I corresponds to the period of rapid glycogen repletion that immediately follows exercise and phase II to the period of supercompensation....

  17. Berberine improves glucose metabolism through induction of glycolysis.

    Science.gov (United States)

    Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping

    2008-01-01

    Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has recently been reported to activate AMPK. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after 5-wk administration. Fasting insulin and HOMA-IR were decreased by 46 and 48%, respectively, in the rats. In cell lines including 3T3-L1 adipocytes, L6 myotubes, C2C12 myotubes, and H4IIE hepatocytes, berberine was found to increase glucose consumption, 2-deoxyglucose uptake, and to a less degree 3-O-methylglucose (3-OMG) uptake independently of insulin. The insulin-induced glucose uptake was enhanced by berberine in the absence of change in IRS-1 (Ser307/312), Akt, p70 S6, and ERK phosphorylation. AMPK phosphorylation was increased by berberine at 0.5 h, and the increase remained for > or =16 h. Aerobic and anaerobic respiration were determined to understand the mechanism of berberine action. The long-lasting phosphorylation of AMPK was associated with persistent elevation in AMP/ATP ratio and reduction in oxygen consumption. An increase in glycolysis was observed with a rise in lactic acid production. Berberine exhibited no cytotoxicity, and it protected plasma membrane in L6 myotubes in the cell culture. These results suggest that berberine enhances glucose metabolism by stimulation of glycolysis, which is related to inhibition of glucose oxidation in mitochondria. Berberine-induced AMPK activation is likely a consequence of mitochondria inhibition that increases the AMP/ATP ratio.

  18. Metabolic inflexibility of white and brown adipose tissues in abnormal fatty acid partitioning of type 2 diabetes.

    Science.gov (United States)

    Grenier-Larouche, T; Labbé, S M; Noll, C; Richard, D; Carpentier, A C

    2012-12-01

    Type 2 diabetes (T2D) is characterized by a general dysregulation of postprandial energy substrate partitioning. Although classically described in regard to glucose metabolism, it is now evident that metabolic inflexibility of plasma lipid fluxes is also present in T2D. The organ that is most importantly involved in the latter metabolic defect is the white adipose tissue (WAT). Both catecholamine-induced nonesterified fatty acid mobilization and insulin-stimulated storage of meal fatty acids are impaired in many WAT depots of insulin-resistant individuals. Novel molecular imaging techniques now demonstrate that these defects are linked to increased dietary fatty acid fluxes toward lean organs and myocardial dysfunction in humans. Recent findings also demonstrate functional abnormalities of brown adipose tissues in T2D, thus suggesting that a generalized adipose tissue dysregulation of energy storage and dissipation may be at play in the development of lean tissue energy overload and lipotoxicity.

  19. Association between extraversion personality and abnormal glucose regulation in young Korean women.

    Science.gov (United States)

    Shim, Unjin; Oh, Jee-Young; Lee, Hyejin; Sung, Yeon-Ah; Kim, Han-Na; Kim, Hyung-Lae

    2014-01-01

    Depression and psychological distress are known to be associated with diabetes development as well as the disease progression including glycemic control and chronic complication, but relationship of personality with diabetes is controversial. We examined whether personality trait and the presence of abnormal glucose regulation (AGR; diabetes and pre-diabetes) are associated in young women. A total of 1,617 young women aged 19-39 years without previously diagnosed diabetes were participated voluntarily. Personality trait was assessed by self-reported questionnaire using the five-factor model (neuroticism, extraversion, openness to experience, agreeableness and conscientiousness) consisting of five-point scale ranging from 'strongly disagreeable' to 'strongly agreeable.' Glucose tolerance status was assessed by standard 75-g oral glucose tolerance test. One hundred and eleven women were newly diagnosed with AGR (6.9 %). Among five factors, only extraversion trait was significantly associated with AGR. Multiple linear regression analysis showed significant negative association between extraversion trait and 2-h post-load glucose after adjustment for age, BMI, systolic blood pressure, triglycerides, HDL cholesterol and family history of diabetes (β = -0.16, P = 0.026). Multiple logistic regression showed extraversion trait having a significant association with the presence of AGR after adjustment for the same covariates (OR 0.97, 95 % CI 0.95-0.99, P = 0.011). The frequency of AGR was significantly increased according to the decrease in extraversion score (P for trend with exact test = 0.047). In conclusion, extraversion may be an important personality trait having a beneficial effect on decreasing the risk of AGR.

  20. Dietary iron controls circadian hepatic glucose metabolism through heme synthesis.

    Science.gov (United States)

    Simcox, Judith A; Mitchell, Thomas Creighton; Gao, Yan; Just, Steven F; Cooksey, Robert; Cox, James; Ajioka, Richard; Jones, Deborah; Lee, Soh-Hyun; King, Daniel; Huang, Jingyu; McClain, Donald A

    2015-04-01

    The circadian rhythm of the liver maintains glucose homeostasis, and disruption of this rhythm is associated with type 2 diabetes. Feeding is one factor that sets the circadian clock in peripheral tissues, but relatively little is known about the role of specific dietary components in that regard. We assessed the effects of dietary iron on circadian gluconeogenesis. Dietary iron affects circadian glucose metabolism through heme-mediated regulation of the interaction of nuclear receptor subfamily 1 group d member 1 (Rev-Erbα) with its cosuppressor nuclear receptor corepressor 1 (NCOR). Loss of regulated heme synthesis was achieved by aminolevulinic acid (ALA) treatment of mice or cultured cells to bypass the rate-limiting enzyme in hepatic heme synthesis, ALA synthase 1 (ALAS1). ALA treatment abolishes differences in hepatic glucose production and in the expression of gluconeogenic enzymes seen with variation of dietary iron. The differences among diets are also lost with inhibition of heme synthesis with isonicotinylhydrazine. Dietary iron modulates levels of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α), a transcriptional activator of ALAS1, to affect hepatic heme. Treatment of mice with the antioxidant N-acetylcysteine diminishes PGC-1α variation observed among the iron diets, suggesting that iron is acting through reactive oxygen species signaling.

  1. Cerebral glucose metabolism in neurofibromatosis type 1 assessed with [18F]-2-fluoro-2-deoxy-D-glucose and PET.

    OpenAIRE

    Balestri, P; Lucignani, G; Fois, A.; Magliani, L; Calistri, L; Grana, C.; Di Bartolo, R M; Perani, D; Fazio, F.

    1994-01-01

    Cerebral PET with [18F]-2-fluoro-2-deoxy-D-glucose has been performed in four patients with neurofibromatosis type 1 (NF1) to assess the relation between cerebral metabolic activity, MRI, and the presence of neurological symptoms, including seizures, as well as mental and language retardation. Widespread hypometabolism occurred in three of the patients. The lesions on MRI, which were localised in the subcortical white matter and grey structures, had normal rates of glucose metabolism. This fi...

  2. Clustering of hypertension, abnormal glucose tolerance, hypercholesterolaemia and obesity in Malaysian adult population.

    Science.gov (United States)

    Lim, T O; Ding, L M; Zaki, M; Merican, I; Kew, S T; Maimunah, A H; Rozita, H H; Rugayah, B

    2000-06-01

    We determine the prevalence and determinants of clustering of hypertension, abnormal glucose tolerance, hypercholesterolaemia and overweight in Malaysia. A national probability sample of 17,392 individuals aged 30 years or older had usable data. 61% of adults had at least one risk factor, 27% had 2 or more risk factors. The observed frequency of 4 factors cluster was 6 times greater than that expected by chance. Indian and Malay women were at particular high risk of risk factors clustering. Individuals with a risk factor had 1.5 to 3 times higher prevalence of other risk factors. Ordinal regression analyses show that higher income, urban residence and physical inactivity were independently associated with risk factors clustering, lending support to the hypotheses that risk factors clustering is related to lifestyle changes brought about by modernisation and urbanisation. In conclusion, risk factor clustering is highly prevalent among Malaysian adults. Treatment and prevention programme must emphasise the multiple risk factor approach.

  3. Decreased cerebral glucose metabolism associated with mental deterioration in multi-infarct dementia

    Energy Technology Data Exchange (ETDEWEB)

    Meguro, K. (Tohoku Univ. School of Medicine (Japan). Dept. of Geriatric Medicine Miyama Hospital (Japan)); Doi, C. (Tohoku Univ. School of Literature (Japan). Dept. of Psychology); Yamaguchi, T.; Sasaki, H. (Tohoku Univ. School of Medicine (Japan). Dept. of Geriatric Medicine); Matsui, H.; Yamada, K. (Tohoku Univ. (Japan). Research Inst. for Tuberculosis and Cancer); Kinomura, S. (Miyama Hospital (Japan) Tohoku Univ. (Japan). Research Inst. for Tuberculosis and Cancer); Itoh, M. (Tohoku Univ. School of Medicine (Japan). Cyclotron Radioisotope Center)

    1991-08-01

    Cerebral glucose metabolism of 18 patients with multi-infarct dementia (MID) and 10 age-matched normal subjects were examined with positron emission tomography and the {sup 18}-F-fluoro-deoxy-glucose technique. MID patients had significantly lower glucose metabolsim in all the grey matter regions measured and were also characterized by more individuality in metabolic pattern. MID patients were also evaluated as to intelligence quotient (IQ). A positive correlation between IQ as shown by the Tanaka-Binet test and glucose metabolism for the entire grey matter was found. The clinical applicability of this test for predicting cerebral metabolism is discussed. (orig.).

  4. Myocardial glucose metabolism in patients with hypertrophic cardiomyopathy. Assessment by F-18-FDG PET study

    Energy Technology Data Exchange (ETDEWEB)

    Uehara, Toshiisa [Osaka Univ., Suita (Japan). Medical School; Ishida, Yoshio; Hayashida, Kohei [and others

    1998-04-01

    In an investigation of myocardial metabolic abnormalities in hypertrophic myocardium, the myocardial glucose metabolism was evaluated with F-18-fluorodeoxyglucose (FDG) positron emission tomography (PET) in 32 patients with hypertrophic cardiomyopathy, and the results were compared with those in 9 patients with hypertensive heart disease. F-18-FDG PET study was performed in the fasting and glucose-loading states. The myocardial regional %dose uptake was calculated quantitatively. The average regional %dose uptake in the fasting state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was significantly higher than that in the patients with hypertensive heart disease (0.75{+-}0.34%, 0.65{+-}0.25%, and 0.43{+-}0.22%/100 g myocardium, respectively). In contrast, the average %dose uptake in the glucose-loading state in the patients with asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy was not significantly different from that in patients with hypertensive heart disease (1.17{+-}0.49%, 0.80{+-}0.44% and 0.99{+-}0.45%, respectively). The patients with apical hypertrophy had also low %dose uptake in the fasting state (0.38{+-}0.21%) as in the hypertensive heart disease patients, so that the characteristics of asymmetric septal hypertrophy and dilated-phase hypertrophic cardiomyopathy are considered to be high FDG uptake throughout the myocardium in the fasting state. Patients with apical hypertrophy are considered to belong to other disease categories metabolically. F-18-FDG PET study is useful in the evaluation of the pathophysiologic diagnosis of patients with hypertrophic cardiomyopathy. (author)

  5. Insulin Stimulates S100B Secretion and These Proteins Antagonistically Modulate Brain Glucose Metabolism.

    Science.gov (United States)

    Wartchow, Krista Minéia; Tramontina, Ana Carolina; de Souza, Daniela F; Biasibetti, Regina; Bobermin, Larissa D; Gonçalves, Carlos-Alberto

    2016-06-01

    Brain metabolism is highly dependent on glucose, which is derived from the blood circulation and metabolized by the astrocytes and other neural cells via several pathways. Glucose uptake in the brain does not involve insulin-dependent glucose transporters; however, this hormone affects the glucose influx to the brain. Changes in cerebrospinal fluid levels of S100B (an astrocyte-derived protein) have been associated with alterations in glucose metabolism; however, there is no evidence whether insulin modulates glucose metabolism and S100B secretion. Herein, we investigated the effect of S100B on glucose metabolism, measuring D-(3)H-glucose incorporation in two preparations, C6 glioma cells and acute hippocampal slices, and we also investigated the effect of insulin on S100B secretion. Our results showed that: (a) S100B at physiological levels decreases glucose uptake, through the multiligand receptor RAGE and mitogen-activated protein kinase/ERK signaling, and (b) insulin stimulated S100B secretion via PI3K signaling. Our findings indicate the existence of insulin-S100B modulation of glucose utilization in the brain tissue, and may improve our understanding of glucose metabolism in several conditions such as ketosis, streptozotocin-induced dementia and pharmacological exposure to antipsychotics, situations that lead to changes in insulin signaling and extracellular levels of S100B.

  6. The Role of Gut–brain Axis in Regulating Glucose Metabolism After Acute Pancreatitis

    Science.gov (United States)

    Pendharkar, Sayali A; Asrani, Varsha M; Murphy, Rinki; Cutfield, Richard; Windsor, John A; Petrov, Maxim S

    2017-01-01

    Objectives: Diabetes has become an epidemic in developed and developing countries alike, with an increased demand for new efficacious treatments. A large body of pre-clinical evidence suggests that the gut–brain axis may be exploited as a potential therapeutic target for defective glucose homeostasis. This clinical study aimed to investigate a comprehensive panel of glucoregulatory peptides, released by both the gut and brain, in individuals after acute pancreatitis. Methods: Fasting levels of glucagon-like peptide-1 (GLP-1), glicentin, oxyntomodulin, peptide YY, ghrelin, cholecystokinin, vasoactive intestinal peptide (VIP), and secretin were studied. Modified Poisson and multivariable linear regression analyses were conducted. Pre-determined concentration ranges were used to categorize each peptide into quartiles. Results: A total of 83 individuals were included, of who 30 (36%) developed abnormal glucose metabolism (AGM) after acute pancreatitis. In individuals with AGM, the highest quartile of oxyntomodulin differed most significantly from the lowest quartile with a prevalence ratio (PR; 95% confidence interval) of 0.50 (0.21, 1.20; P=0.005); of glicentin with a PR of 0.26 (0.13, 0.54; Pcholecystokinin, ghrelin, and secretin were not significantly associated with AGM. Conclusions: Fasting circulating oxyntomodulin, glicentin, and VIP levels are significantly decreased in patients with defective glucose homeostasis after acute pancreatitis. Oxyntomodulin appears to be a promising therapeutic target for future clinical studies on diabetes associated with diseases of the exocrine pancreas. PMID:28055028

  7. Abnormalities in Glutamate Metabolism and Excitotoxicity in the Retinal Diseases

    Directory of Open Access Journals (Sweden)

    Makoto Ishikawa

    2013-01-01

    Full Text Available In the physiological condition, glutamate acts as an excitatory neurotransmitter in the retina. However, excessive glutamate can be toxic to retinal neurons by overstimulation of the glutamate receptors. Glutamate excess is primarily attributed to perturbation in the homeostasis of the glutamate metabolism. Major pathway of glutamate metabolism consists of glutamate uptake by glutamate transporters followed by enzymatic conversion of glutamate to nontoxic glutamine by glutamine synthetase. Glutamate metabolism requires energy supply, and the energy loss inhibits the functions of both glutamate transporters and glutamine synthetase. In this review, we describe the present knowledge concerning the retinal glutamate metabolism under the physiological and pathological conditions.

  8. Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes

    Science.gov (United States)

    Bally, Lia; Kempf, Patrick; Zueger, Thomas; Speck, Christian; Pasi, Nicola; Ciller, Carlos; Feller, Katrin; Loher, Hannah; Rosset, Robin; Wilhelm, Matthias; Boesch, Chris; Buehler, Tania; Dokumaci, Ayse S.; Tappy, Luc; Stettler, Christoph

    2017-01-01

    This paper aims to compare the metabolic effects of glucose-fructose co-ingestion (GLUFRU) with glucose alone (GLU) in exercising individuals with type 1 diabetes mellitus. Fifteen male individuals with type 1 diabetes (HbA1c 7.0% ± 0.6% (53 ± 7 mmol/mol)) underwent a 90 min iso-energetic continuous cycling session at 50% VO2max while ingesting combined glucose-fructose (GLUFRU) or glucose alone (GLU) to maintain stable glycaemia without insulin adjustment. GLUFRU and GLU were labelled with 13C-fructose and 13C-glucose, respectively. Metabolic assessments included measurements of hormones and metabolites, substrate oxidation, and stable isotopes. Exogenous carbohydrate requirements to maintain stable glycaemia were comparable between GLUFRU and GLU (p = 0.46). Fat oxidation was significantly higher (5.2 ± 0.2 vs. 2.6 ± 1.2 mg·kg−1·min−1, p 0.05 for all). Glucose and insulin levels, and total glucose appearance and disappearance were comparable between interventions. Glucose-fructose co-ingestion may have a beneficial impact on fuel metabolism in exercising individuals with type 1 diabetes without insulin adjustment, by increasing fat oxidation whilst sparing glycogen. PMID:28230765

  9. Levels of adipocytokines and vitamin D in a biracial sample of young metabolically healthy obese and metabolically abnormal obese women

    Science.gov (United States)

    Purpose: Adipocytokines and vitamin D (vitD) concentrations may contribute to cardiometabolic risk profiles in obese populations. The purpose was to determine if levels of adipocytokines and vitD differ between young metabolically healthy obese (MHO) and metabolically abnormal obese (MAO) black and ...

  10. Ghrelin function in insulin release and glucose metabolism.

    Science.gov (United States)

    Dezaki, Katsuya

    2013-01-01

    Given its wide spectrum of biological activities such as growth hormone (GH) release, feeding stimulation, adiposity and cardiovascular actions, the discovery of ghrelin opened many new perspectives within neuroendocrine, metabolic and cardiovascular research, thus suggesting its possible clinical application. Circulating ghrelin is produced predominantly in the stomach, and its receptor GH secretagogue receptor (GHS-R) is expressed in a variety of central and peripheral tissues. Ghrelin, GHS-R and ghrelin O-acyltransferase (GOAT), the enzyme that promotes the acylation of the third serine residue of ghrelin, are all expressed in pancreatic islets, and this peptide is released into pancreatic microcirculations. Ghrelin inhibits insulin release in mice, rats and humans. The signal transduction mechanisms of ghrelin receptor in islet β-cells are very unique, being distinct from those utilized for GH release. Pharmacological and genetic blockade of islet-derived ghrelin markedly augments glucose-induced insulin release in vitro. Ablation of ghrelin, GHS-R or GOAT enhances insulin release and prevents impaired glucose tolerance in high-fat, diet-induced and leptin-deficient obese models. Thus, manipulation of the insulinostatic function of the ghrelin-GHS-R system, particularly that in islets, could optimize the amount of insulin release to meet the systemic demand. Ghrelin antagonism provides a novel strategy to treat type 2 diabetes with dysregulated insulin release.

  11. The Coupling of Cerebral Metabolic Rate of Glucose and Cerebral Blood Flow In Vivo

    DEFF Research Database (Denmark)

    Hasselbalch, Steen; Paulson, Olaf Bjarne

    2012-01-01

    The energy supplied to the brain by metabolic substrate is largely utilized for maintaining synaptic transmission. In this regulation cerebral blood flow and glucose consumption is tightly coupled as well in the resting condition as during activation. Quantification of cerebral blood flow...... not used for aerobic metabolism. Although some of the excess glucose uptake can be explained by lactate production, this phenomenon can still not account for the excess glucose uptake. Thus, more complex metabolic patterns in the brain might be reflected in the excess glucose uptake during activation...

  12. Symptoms of depression in people with impaired glucose metabolism or Type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Adriaanse, M C; Dekker, J M; Heine, R. J.

    2008-01-01

    OBJECTIVE: To study the prevalence and risk factors of depressive symptoms, comparing subjects with normal glucose metabolism (NGM), impaired glucose metabolism (IGM) or Type 2 diabetes mellitus (DM2). RESEARCH DESIGN AND METHODS: Cross-sectional data from a population-based cohort study conducted...... among 550 residents (276 men and 274 women) of the Hoorn region, the Netherlands. Levels of depressive symptoms were measured using the Centre for Epidemiologic Studies Depression Scale (CES-D score > or = 16). Glucose metabolism status was determined by means of fasting and post-load glucose levels...

  13. Impaired glucose metabolism in HIV-infected pregnant women: a retrospective analysis.

    LENUS (Irish Health Repository)

    Moore, Rebecca

    2015-05-20

    Metabolic complications including diabetes mellitus have been increasingly recognised in HIV-infected individuals since the introduction of antiretroviral therapy, particularly protease inhibitors (PIs). Pregnancy is also a risk factor for impaired glucose metabolism, and previous studies have given conflicting results regarding the contribution of PIs to impaired glucose tolerance (IGT) and gestational diabetes mellitus (GDM) in pregnant HIV-infected women.

  14. Effect of oxandrolone on glucose metabolism in growth hormone-treated girls with Turner syndrome

    NARCIS (Netherlands)

    Menke, L.A.; Sas, T.C.J.; Stijnen, T.; Zandwijken, G.R.; Muinck Keizer-Schrama, S.M.P.F. de; Otten, B.J.; Wit, J.M.

    2011-01-01

    BACKGROUND: The weak androgen oxandrolone (Ox) may increase height but may also affect glucose metabolism in girls with Turner syndrome (TS). METHODS: In a randomized, placebo-controlled, double-blind study, we assessed the effect of Ox at a dosage of either 0.06 or 0.03 mg/kg/day on glucose metabol

  15. Implications of Hydrogen Sulfide in Glucose Regulation: How H2S Can Alter Glucose Homeostasis through Metabolic Hormones.

    Science.gov (United States)

    Pichette, Jennifer; Gagnon, Jeffrey

    2016-01-01

    Diabetes and its comorbidities continue to be a major health problem worldwide. Understanding the precise mechanisms that control glucose homeostasis and their dysregulation during diabetes are a major research focus. Hydrogen sulfide (H2S) has emerged as an important regulator of glucose homeostasis. This is achieved through its production and action in several metabolic and hormone producing organs including the pancreas, liver, and adipose. Of importance, H2S production and signaling in these tissues are altered during both type 1 and type 2 diabetes mellitus. This review first examines how H2S is produced both endogenously and by gastrointestinal microbes, with a particular focus on the altered production that occurs during obesity and diabetes. Next, the action of H2S on the metabolic organs with key roles in glucose homeostasis, with a particular focus on insulin, is described. Recent work has also suggested that the effects of H2S on glucose homeostasis goes beyond its role in insulin secretion. Several studies have demonstrated important roles for H2S in hepatic glucose output and adipose glucose uptake. The mechanism of H2S action on these metabolic organs is described. In the final part of this review, future directions examining the roles of H2S in other metabolic and glucoregulatory hormone secreting tissues are proposed.

  16. The Role of Dietary Cholesterol in Lipoprotein Metabolism and Related Metabolic Abnormalities: A Mini-review.

    Science.gov (United States)

    Kapourchali, Fatemeh Ramezani; Surendiran, Gangadaran; Goulet, Amy; Moghadasian, Mohammed H

    2016-10-25

    Cholesterol plays a vital role in cell biology. Dietary cholesterol or "exogenous" cholesterol accounts for approximately one-third of the pooled body cholesterol, and the remaining 70% is synthesized in the body (endogenous cholesterol). Increased dietary cholesterol intake may result in increased serum cholesterol in some individuals, while other subjects may not respond to dietary cholesterol. However, diet-increased serum cholesterol levels do not increase the low-density lipoprotein/high-density lipoprotein (LDL/HDL) cholesterol ratio, nor do they decrease the size of LDL particles or HDL cholesterol levels. Elevated levels of LDL cholesterol, reduced HDL cholesterol levels, and small, dense LDL particles are independent risk factors for coronary artery disease. Dietary cholesterol is the primary approach for treatment of conditions such as the Smith-Lemli-Opitz syndrome. Recent studies have highlighted mechanisms for absorption of dietary cholesterol. These studies have help understand how dietary and/or pharmaceutical agents inhibit cholesterol absorption and thereby reduce LDL cholesterol concentrations. In this article, various aspects of cholesterol metabolism, including dietary sources, absorption, and abnormalities in cholesterol metabolism, have been summarized and discussed.

  17. The prospective role of abnormal methyl metabolism in cadmium toxicity.

    OpenAIRE

    Poirier, Lionel A; Vlasova, Tatyana I

    2002-01-01

    Several lines of evidence point to the probable role of abnormal methylation processes in the toxicology of metals and other xenobiotics. The spectrum of toxic effects exhibited by such metals as Ni, As, and Cd, as well as by Zn deficiency, often resemble those seen in animals chronically fed methyl-deficient diets. These metal-associated pathologies include cancer, atherosclerosis, birth defects, neurological disturbances, and pancreatic lesions. In addition, each of the above agents has bee...

  18. Brain glucose metabolism in adults with ataxia-telangiectasia and their asymptomatic relatives.

    Science.gov (United States)

    Volkow, Nora D; Tomasi, Dardo; Wang, Gene-Jack; Studentsova, Yana; Margus, Brad; Crawford, Thomas O

    2014-06-01

    Ataxia-telangiectasia is a recessive genetic disorder (ATM is the mutated gene) of childhood with severe motor impairments and whereas homozygotes manifest the disorder, heterozygotes are asymptomatic. Structural brain imaging and post-mortem studies in individuals with ataxia-telangiectasia have reported cerebellar atrophy; but abnormalities of motor control characteristic of extrapyramidal dysfunction suggest impairment of broader motor networks. Here, we investigated possible dysfunction in other brain areas in individuals with ataxia-telangiectasia and tested for brain changes in asymptomatic relatives to assess if heterozygocity affects brain function. We used positron emission tomography and (18)F-fluorodeoxyglucose to measure brain glucose metabolism (quantified as µmol/100 g/min), which serves as a marker of brain function, in 10 adults with ataxia-telangiectasia, 19 non-affected adult relatives (12 siblings, seven parents) and 29 age-matched healthy controls. Statistical parametric mapping and region of interest analyses were used to compare individuals with ataxia-telangiectasia, asymptomatic relatives, and unrelated controls. We found that participants with ataxia-telangiectasia had lower metabolism in cerebellar hemispheres (14%, P brain stimulation. Our finding of decreased metabolism in vermis and hippocampus of asymptomatic relatives suggests that heterozygocity influences the function of these brain regions.

  19. Sex-Dependent Programming of Glucose and Fatty Acid Metabolism in Mouse Offspring by Maternal Protein Restriction

    NARCIS (Netherlands)

    van Straten, Esther M. E.; Bloks, Vincent W.; van Dijk, Theo H.; Baller, Julius F. W.; Huijkman, Nicolette C. A.; Kuipers, Irma; Verkade, Henkjan J.; Plosch, Torsten

    2012-01-01

    Background: Nutritional conditions during fetal life influence the risk of the development of metabolic syndrome and cardiovascular diseases in adult life (metabolic programming). Impaired glucose tolerance and dysregulated fatty acid metabolism are hallmarks of metabolic syndrome. Objective: We aim

  20. The Impact of Abnormal Glucose Tolerance and Obesity on Fetal Growth

    Directory of Open Access Journals (Sweden)

    Erin Graves

    2015-01-01

    Full Text Available Objective. Factors linked with insulin resistance were examined for their association with large-for-gestational-age (LGA infant birth weight and gestational diabetes. Study Design. Data came from a longitudinal cohort study of 2,305 subjects without overt diabetes, analyzed using multinomial logistic and linear regression. Results. High maternal BMI (OR=1.53 (1.11, 2.12, height (1.98 (1.62, 2.42, antidepressant use (1.71 (1.20, 2.44, pregnancy weight-gain exceeding 40 pounds (1.79 (1.25, 2.57, and high blood sugar (2.68, (1.53, 5.27 were all positively associated with LGA birth. Strikingly, the difference in risk from diagnosed and treated gestational diabetes compared to women with a single abnormal glucose tolerance test (but no diagnosis of gestational diabetes was significant (OR=0.65, p=0.12 versus OR=2.84, p<0.01. When weight/length ratio was used instead, different factors were found to be significant. BMI and pregnancy weight-gain were found to influence the development of gestational diabetes, through an additive interaction. Conclusions. High prepregnancy BM, height, antidepressant use, pregnancy weight-gain exceeding 40 pounds, and high blood sugar were associated with LGA birth, but not necessarily infant weight/length ratio. An additive interaction between BMI and pregnancy weight-gain influenced gestational diabetes development.

  1. Melatonin and the metabolic syndrome: a tool for effective therapy in obesity-associated abnormalities?

    Science.gov (United States)

    Nduhirabandi, F; du Toit, E F; Lochner, A

    2012-06-01

    The metabolic syndrome (MetS) is a cluster of metabolic abnormalities associated with increased risk for cardiovascular diseases. Apart from its powerful antioxidant properties, the pineal gland hormone melatonin has recently attracted the interest of various investigators as a multifunctional molecule. Melatonin has been shown to have beneficial effects in cardiovascular disorders including ischaemic heart disease and hypertension. However, its role in cardiovascular risk factors including obesity and other related metabolic abnormalities is not yet established, particularly in humans. New emerging data show that melatonin may play an important role in body weight regulation and energy metabolism. This review will address the role of melatonin in the MetS focusing on its effects in obesity, insulin resistance and leptin resistance. The overall findings suggest that melatonin should be exploited as a therapeutic tool to prevent or reverse the harmful effects of obesity and its related metabolic disorders.

  2. Metabolism of [U-13C]glucose in Human Brain Tumors In Vivo

    Science.gov (United States)

    Maher, Elizabeth A.; Marin-Valencia, Isaac; Bachoo, Robert M.; Mashimo, Tomoyuki; Raisanen, Jack; Hatanpaa, Kimmo J.; Jindal, Ashish; Jeffrey, F. Mark; Choi, Changho; Madden, Christopher; Mathews, Dana; Pascual, Juan M.; Mickey, Bruce E.; Malloy, Craig R.; DeBerardinis, Ralph J.

    2012-01-01

    Glioblastomas (GBMs) and brain metastases demonstrate avid uptake of 18fluoro-2-deoxyglucose (FDG) by positron emission tomography (PET) and display perturbations of intracellular metabolite pools by 1H magnetic resonance spectroscopy (MRS). These observations suggest that metabolic reprogramming contributes to brain tumor growth in vivo. The Warburg effect, excess metabolism of glucose to lactate in the presence of oxygen, is a hallmark of cancer cells in culture. FDG-positive tumors are assumed to metabolize glucose in a similar manner, with high rates of lactate formation compared to mitochondrial glucose oxidation, but few studies have specifically examined the metabolic fates of glucose in vivo. In particular, the capacity of human brain malignancies to oxidize glucose in the tricarboxylic acid cycle is unknown. Here we studied the metabolism of human brain tumors in situ. [U-13C]glucose was infused during surgical resection, and tumor samples were subsequently subjected to 13C NMR spectroscopy. Analysis of tumor metabolites revealed lactate production, as expected. We also determined that pyruvate dehydrogenase, turnover of the TCA cycle, anaplerosis and de novo glutamine and glycine synthesis contributed significantly to the ultimate disposition of glucose carbon. Surprisingly, less than 50% of the acetyl-CoA pool was derived from blood-borne glucose, suggesting that additional substrates contribute to tumor bioenergetics. This study illustrates a convenient approach that capitalizes on the high information content of 13C NMR spectroscopy and enables the analysis of intermediary metabolism in diverse malignancies growing in their native microenvironment. PMID:22419606

  3. Brain pyruvate recycling and peripheral metabolism: an NMR analysis ex vivo of acetate and glucose metabolism in the rat.

    Science.gov (United States)

    Serres, Sébastien; Bezancon, Eric; Franconi, Jean-Michel; Merle, Michel

    2007-06-01

    The occurrence of pyruvate recycling in the rat brain was studied in either pentobarbital anesthetized animals or awake animals receiving a light analgesic dose of morphine, which were infused with either [1-13C]glucose + acetate or glucose + [2-13C]acetate for various periods of time. Metabolite enrichments in the brain, blood and the liver were determined from NMR analyses of tissue extracts. They indicated that: (i) Pyruvate recycling was revealed in the brain of both the anesthetized and awake animals, as well as from lactate and alanine enrichments as from glutamate isotopomer composition, but only after infusion of glucose + [2-13C]acetate. (ii) Brain glucose was labelled from [2-13C]acetate at the same level in anaesthetized and awake rats (approximately 4%). Comparing its enrichment with that of blood and liver glucose indicated that brain glucose labelling resulted from hepatic gluconeogenesis. (iii) Analysing glucose 13C-13C coupling in the brain, blood and the liver confirmed that brain glucose could be labelled in the liver through the activities of both pyruvate recycling and gluconeogenesis. (iv) The rate of appearance and the amount of brain glutamate C4-C5 coupling, a marker of pyruvate recycling when starting from [2-13C]acetate, were lower than those of brain glucose labelling from hepatic metabolism. (v) The evaluation of the contributions of glucose and acetate to glutamate metabolism revealed that more than 60% of brain glutamate was synthesized from glucose whereas only 7% was from acetate and that glutamate C4-C5 coupling was mainly due to the metabolism of glucose labelled through hepatic gluconeogenesis. All these results indicate that, under the present conditions, the pyruvate recycling observed through the labelling of brain metabolites mainly originates from peripheral metabolism.

  4. Differential Incorporation of Glucose into Biomass during Warburg Metabolism

    OpenAIRE

    Chen, Ying-Jr; Huang, Xiaojing; Mahieu, Nathaniel G.; Cho, Kevin; Schaefer, Jacob; Patti, Gary J.

    2014-01-01

    It is well established that most cancer cells take up an increased amount of glucose relative to that taken up by normal differentiated cells. The majority of this glucose carbon is secreted from the cell as lactate. The fate of the remaining glucose carbon, however, has not been well-characterized. Here we apply a novel combination of metabolomic technologies to track uniformly labeled glucose in HeLa cancer cells. We provide a list of specific intracellular metabolites that become enriched ...

  5. Thalamic, brainstem, and cerebellar glucose metabolism in the hemiplegic monkey

    Energy Technology Data Exchange (ETDEWEB)

    Shimoyama, I.; Dauth, G.W.; Gilman, S.; Frey, K.A.; Penney, J.B. Jr.

    1988-12-01

    Unilateral ablation of cerebral cortical areas 4 and 6 of Brodmann in the macaque monkey results in a contralateral hemiplegia that resolves partially with time. During the phase of dense hemiplegia, local cerebral metabolic rate for glucose (1CMRG1c) is decreased significantly in most of the thalamic nuclei ipsilateral to the ablation, and there are slight contralateral decreases. The lCMRGlc is reduced bilaterally in most of the brainstem nuclei and bilaterally in the deep cerebellar nuclei, but only in the contralateral cerebellar cortex. During the phase of partial motor recovery, lCMRGlc is incompletely restored in many of the thalamic nuclei ipsilateral to the ablation and completely restored in the contralateral nuclei. In the brainstem and deep cerebellar nuclei, poor to moderate recovery occurs bilaterally. Moderate recovery occurs in the contralateral cerebellar cortex. The findings demonstrate that a unilateral cerebral cortical lesion strongly affects lCMRGlc in the thalamus ipsilaterally and in the cerebellar cortex contralaterally, but in the brainstem bilaterally. Partial recovery of lCMRGlc accompanies the progressive motor recovery. The structures affected include those with direct, and also those with indirect, connections to the areas ablated.

  6. Relationship between regional brain glucose metabolism and temperament factor of personality

    Energy Technology Data Exchange (ETDEWEB)

    Cho, Sang Soo; Lee, Eun Ju; Yoon, Eun Jin; Kim, Yu Kyeong; Lee, Won Woo; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2005-07-01

    Temperament factor of personality has been considered to have correlation with activity in a specific central monoaminergic system. In an attempt to explore neuronal substrate of biogenetic personality traits, we examined the relationship between regional brain glucose metabolism and temperament factor of personality. Twenty right-handed healthy subjects (age, 24{+-}4 yr: 10 females and 10 males) were studied with FDG PET. Their temperaments were assessed using the Temperament and Character Inventory (TCI), which consisted of four temperament factors (harm avoidance (HA), novelty seeking (NS), reward dependence (RD), persistency) and three personality factors. The relationship between regional glucose metabolism and each temperament score was tested using SPM99 (P < 0.005, uncorrected). NS score was negatively correlated with glucose metabolism in the frontal areas, insula, and superior temporal gyrus mainly in the right hemisphere. Positive correlation between NS score and glucose metabolism was observed in the left superior temporal gyrus. HA score showed negative correlation with glucose metabolism in the middle and orbitofrontal gyri as well as in the parahippocampal gyrus. RD score was positively correlated with glucose metabolism in the left middle frontal gyrus and negative correlated in the posterior cingulate gyrus and caudate nucleus. We identified the relationship between regional brain glucose metabolism and temperamental personality trait. Each temperament factor had a relation with functions of specific brain areas. These results help understand biological background of personality and specific feedback circuits associated with each temperament factor.

  7. Metabolic Effects of Glucose-Fructose Co-Ingestion Compared to Glucose Alone during Exercise in Type 1 Diabetes

    Directory of Open Access Journals (Sweden)

    Lia Bally

    2017-02-01

    Full Text Available This paper aims to compare the metabolic effects of glucose-fructose co-ingestion (GLUFRU with glucose alone (GLU in exercising individuals with type 1 diabetes mellitus. Fifteen male individuals with type 1 diabetes (HbA1c 7.0% ± 0.6% (53 ± 7 mmol/mol underwent a 90 min iso-energetic continuous cycling session at 50% VO2max while ingesting combined glucose-fructose (GLUFRU or glucose alone (GLU to maintain stable glycaemia without insulin adjustment. GLUFRU and GLU were labelled with 13C-fructose and 13C-glucose, respectively. Metabolic assessments included measurements of hormones and metabolites, substrate oxidation, and stable isotopes. Exogenous carbohydrate requirements to maintain stable glycaemia were comparable between GLUFRU and GLU (p = 0.46. Fat oxidation was significantly higher (5.2 ± 0.2 vs. 2.6 ± 1.2 mg·kg−1·min−1, p < 0.001 and carbohydrate oxidation lower (18.1 ± 0.8 vs. 24.5 ± 0.8 mg·kg−1·min−1 p < 0.001 in GLUFRU compared to GLU, with decreased muscle glycogen oxidation in GLUFRU (10.2 ± 0.9 vs. 17.5 ± 1.0 mg·kg−1·min−1, p < 0.001. Lactate levels were higher (2.2 ± 0.2 vs. 1.8 ± 0.1 mmol/L, p = 0.012 in GLUFRU, with comparable counter-regulatory hormones between GLUFRU and GLU (p > 0.05 for all. Glucose and insulin levels, and total glucose appearance and disappearance were comparable between interventions. Glucose-fructose co-ingestion may have a beneficial impact on fuel metabolism in exercising individuals with type 1 diabetes without insulin adjustment, by increasing fat oxidation whilst sparing glycogen.

  8. Association between dopamine D4 receptor polymorphism and age related changes in brain glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Nora D Volkow

    Full Text Available Aging is associated with reductions in brain glucose metabolism in some cortical and subcortical regions, but the rate of decrease varies significantly between individuals, likely reflecting genetic and environmental factors and their interactions. Here we test the hypothesis that the variant of the dopamine receptor D4 (DRD4 gene (VNTR in exon 3, which has been associated with novelty seeking and sensitivity to environmental stimuli (negative and positive including the beneficial effects of physical activity on longevity, influence the effects of aging on the human brain. We used positron emission tomography (PET and [(18F]fluoro-D-glucose ((18FDG to measure brain glucose metabolism (marker of brain function under baseline conditions (no stimulation in 82 healthy individuals (age range 22-55 years. We determined their DRD4 genotype and found an interaction with age: individuals who did not carry the 7-repeat allele (7R-, n = 53 had a significant (p<0.0001 negative association between age and relative glucose metabolism (normalized to whole brain glucose metabolism in frontal (r = -0.52, temporal (r = -0.51 and striatal regions (r = -0.47, p<0.001; such that older individuals had lower metabolism than younger ones. In contrast, for carriers of the 7R allele (7R+ n = 29, these correlations with age were not significant and they only showed a positive association with cerebellar glucose metabolism (r = +0.55; p = 0.002. Regression slopes of regional brain glucose metabolism with age differed significantly between the 7R+ and 7R- groups in cerebellum, inferior temporal cortex and striatum. These results provide evidence that the DRD4 genotype might modulate the associations between regional brain glucose metabolism and age and that the carriers of the 7R allele appear to be less sensitive to the effects of age on brain glucose metabolism.

  9. Abnormal release of incretins and cortisol after oral glucose in subjects with insulin-resistant myotonic dystrophy

    DEFF Research Database (Denmark)

    Johansson, Asa; Olsson, Tommy; Cederquist, Kristina;

    2002-01-01

    OBJECTIVE: Although the incretins, gastric inhibitory polypeptide (GIP) and glucagon-like peptide-1 (GLP-1), as well as glucagon and cortisol, are known to influence islet function, the role of these hormones in conditions of insulin resistance and development of type 2 diabetes is unknown...... response. Furthermore, cortisol and ACTH levels increased paradoxically in patients after glucose; this was more pronounced in patients with long CTG repeat expansions. CONCLUSIONS: This study showed that the GLP-1 and ACTH/cortisol responses to oral glucose are abnormal in insulin-resistant DM1 patients...

  10. Hemispherical dominance of glucose metabolic rate in the brain of the 'normal' ageing population

    NARCIS (Netherlands)

    Cutts, DA; Maguire, RP; Leenders, KL; Spyrou, NM

    2004-01-01

    In the 'normal' ageing brain a decrease in the cerebral metabolic rate has been determined across many brain regions. This study determines whether age differences would affect metabolic rates in regions and different hemispheres of the brain. The regional metabolic rate of glucose (rCMRGlu) was exa

  11. High-Density Lipoprotein Modulates Glucose Metabolism in Patients With Type 2 Diabetes Mellitus

    NARCIS (Netherlands)

    Drew, Brian G.; Duffy, Stephen J.; Formosa, Melissa F.; Natoli, Alaina K.; Henstridge, Darren C.; Penfold, Sally A.; Thomas, Walter G.; Mukhamedova, Nigora; de Courten, Barbora; Forbes, Josephine M.; Yap, Felicia Y.; Kaye, David M.; van Hall, Gerrit; Febbraio, Mark A.; Kemp, Bruce E.; Sviridov, Dmitri; Steinberg, Gregory R.; Kingwell, Bronwyn A.

    2009-01-01

    Background-Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP-activat

  12. Determining the optimal cutoff points for waist circumference and body mass index for identification of metabolic abnormalities and metabolic syndrome in urban Thai population.

    Science.gov (United States)

    Worachartcheewan, Apilak; Dansethakul, Prabhop; Nantasenamat, Chanin; Pidetcha, Phannee; Prachayasittikul, Virapong

    2012-11-01

    This study describes the prevalence and optimal waist circumference (WC) and body mass index (BMI) cutoff point for metabolic abnormalities and metabolic syndrome (MS) from urban Thai population. The optimal BMI/WC cutoff has been used for identifying and evaluating metabolic abnormalities for screening individuals having risk factor of MS.

  13. A randomized trial comparing the effect of weight loss and exercise training on insulin sensitivity and glucose metabolism in coronary artery disease

    DEFF Research Database (Denmark)

    Pedersen, Lene Rørholm; Olsen, Rasmus Huan; Jürs, Anders

    2015-01-01

    AIM: The majority of patients with coronary artery disease (CAD) exhibit abnormal glucose metabolism, which is associated with mortality even at non-diabetic glucose levels. This trial aims to compare the effects of a considerable weight loss and exercise with limited weight loss on glucose...... followed by 2-4 weeks' weight maintenance diet. Glucose tolerance, insulin action, β-cell function and suppression of lipolysis were assessed using a 3-h oral glucose tolerance test. ISI-composite and ISI-HOMA (=1/HOMA-IR) were calculated as surrogate measures of whole-body and hepatic insulin sensitivity......, respectively. Magnetic resonance imaging estimated abdominal adipose tissue. Twenty-six (74%) AIT and 29 (83%) LED participants completed intervention per protocol. LED increased ISI-composite by 55% and ISI-HOMA by 70% (p0.7) revealing a significant...

  14. Role of SUMO-specific protease 2 in reprogramming cellular glucose metabolism.

    Directory of Open Access Journals (Sweden)

    Shuang Tang

    Full Text Available Most cancer cells exhibit a shift in glucose metabolic strategy, displaying increased glycolysis even with adequate oxygen supply. SUMO-specific proteases (SENPs de-SUMOylate substrates including HIF1α and p53,two key regulators in cancer glucose metabolism, to regulate their activity, stability and subcellular localization. However, the role of SENPs in tumor glucose metabolism remains unclear. Here we report that SUMO-specific protease 2 (SENP2 negatively regulates aerobic glycolysis in MCF7 and MEF cells. Over-expression of SENP2 reduces the glucose uptake and lactate production, increasing the cellular ATP levels in MCF7 cells, while SENP2 knockout MEF cells show increased glucose uptake and lactate production along with the decreased ATP levels. Consistently, the MCF7 cells over-expressing SENP2 exhibit decreased expression levels of key glycolytic enzymes and an increased rate of glucose oxidation compared with control MCF7 cells, indicating inhibited glycolysis but enhanced oxidative mitochondrial respiration. Moreover, SENP2 over-expressing MCF7 cells demonstrated a reduced amount of phosphorylated AKT, whereas SENP2 knockout MEFs exhibit increased levels of phosphorylated AKT. Furthermore, inhibiting AKT phosphorylation by LY294002 rescued the phenotype induced by SENP2 deficiency in MEFs. In conclusion, SENP2 represses glycolysis and shifts glucose metabolic strategy, in part through inhibition of AKT phosphorylation. Our study reveals a novel function of SENP2 in regulating glucose metabolism.

  15. Glucose metabolism in isolated rat adipocytes: estimate of total recovery by the product summation method.

    Science.gov (United States)

    Groff, J L; Stugard, C E; Mays, C J; Koopmans, H S; DiGirolamo, M

    1992-03-01

    To determine the completeness of glucose recovery into its metabolic products, adipocyte glucose utilization was compared by two different methods in a basal and in an insulin-stimulated metabolic state. One of the methods (product summation) is based on the recovery of (( U-14C ))-labeled glucose in carbon dioxide and triglyceride, together with the assay of lactate and pyruvate released into the medium from the incubated cells. The second method is a modification of a procedure by which the quantity of tritiated water that is released by metabolism from +AD5-3H+BD-labeled glucose is determined. It was found that the results of the two methods were in very close agreement. Neither method measures glucose conversion to glycogen. However, glycogenic activity is very low in adipocytes and represents only a small percentage of utilized glucose. Therefore, the finding of comparable results between the two methods suggests that the summation of the metabolic products carbon dioxide, triglyceride, lactate, and pyruvate does account for nearly all of the glucose utilized. This has important implications for the understanding of the considerable variations in rate and patterns of glucose metabolism by the fat cells under a variety of experimental conditions.

  16. Interleukin-6 directly increases glucose metabolism in resting human skeletal muscle

    DEFF Research Database (Denmark)

    Glund, Stephan; Deshmukh, Atul; Long, Yun Chau

    2007-01-01

    suggested to promote insulin-mediated glucose utilization. In this study, we determined the direct effects of IL-6 on glucose transport and signal transduction in human skeletal muscle. Skeletal muscle strips were prepared from vastus lateralis biopsies obtained from 22 healthy men. Muscle strips were...... incubated with or without IL-6 (120 ng/ml). We found that IL-6 increased glucose transport in human skeletal muscle 1.3-fold (P ... exposure increases glucose metabolism in resting human skeletal muscle. Insulin-stimulated glucose transport and insulin signaling were unchanged after IL-6 exposure....

  17. The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Ewa Jablonska

    2016-12-01

    Full Text Available The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast. Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects.

  18. The Effect of Selenium Supplementation on Glucose Homeostasis and the Expression of Genes Related to Glucose Metabolism

    Science.gov (United States)

    Jablonska, Ewa; Reszka, Edyta; Gromadzinska, Jolanta; Wieczorek, Edyta; Krol, Magdalena B.; Raimondi, Sara; Socha, Katarzyna; Borawska, Maria H.; Wasowicz, Wojciech

    2016-01-01

    The aim of the study was to evaluate the effect of selenium supplementation on the expression of genes associated with glucose metabolism in humans, in order to explain the unclear relationship between selenium and the risk of diabetes. For gene expression analysis we used archival samples of cDNA from 76 non-diabetic subjects supplemented with selenium in the previous study. The supplementation period was six weeks and the daily dose of selenium was 200 µg (as selenium yeast). Blood for mRNA isolation was collected at four time points: before supplementation, after two and four weeks of supplementation, and after four weeks of washout. The analysis included 15 genes encoding selected proteins involved in insulin signaling and glucose metabolism. In addition, HbA1c and fasting plasma glucose were measured at three and four time points, respectively. Selenium supplementation was associated with a significantly decreased level of HbA1c but not fasting plasma glucose (FPG) and significant down-regulation of seven genes: INSR, ADIPOR1, LDHA, PDHA, PDHB, MYC, and HIF1AN. These results suggest that selenium may affect glycemic control at different levels of regulation, linked to insulin signaling, glycolysis, and pyruvate metabolism. Further research is needed to investigate mechanisms of such transcriptional regulation and its potential implication in direct metabolic effects. PMID:27983572

  19. Lack of significant metabolic abnormalities in mice with liver-specific disruption of 11β-hydroxysteroid dehydrogenase type 1.

    LENUS (Irish Health Repository)

    Lavery, Gareth G

    2012-07-01

    Glucocorticoids (GC) are implicated in the development of metabolic syndrome, and patients with GC excess share many clinical features, such as central obesity and glucose intolerance. In patients with obesity or type 2 diabetes, systemic GC concentrations seem to be invariably normal. Tissue GC concentrations determined by the hypothalamic-pituitary-adrenal (HPA) axis and local cortisol (corticosterone in mice) regeneration from cortisone (11-dehydrocorticosterone in mice) by the 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) enzyme, principally expressed in the liver. Transgenic mice have demonstrated the importance of 11β-HSD1 in mediating aspects of the metabolic syndrome, as well as HPA axis control. In order to address the primacy of hepatic 11β-HSD1 in regulating metabolism and the HPA axis, we have generated liver-specific 11β-HSD1 knockout (LKO) mice, assessed biomarkers of GC metabolism, and examined responses to high-fat feeding. LKO mice were able to regenerate cortisol from cortisone to 40% of control and had no discernible difference in a urinary metabolite marker of 11β-HSD1 activity. Although circulating corticosterone was unaltered, adrenal size was increased, indicative of chronic HPA stimulation. There was a mild improvement in glucose tolerance but with insulin sensitivity largely unaffected. Adiposity and body weight were unaffected as were aspects of hepatic lipid homeostasis, triglyceride accumulation, and serum lipids. Additionally, no changes in the expression of genes involved in glucose or lipid homeostasis were observed. Liver-specific deletion of 11β-HSD1 reduces corticosterone regeneration and may be important for setting aspects of HPA axis tone, without impacting upon urinary steroid metabolite profile. These discordant data have significant implications for the use of these biomarkers of 11β-HSD1 activity in clinical studies. The paucity of metabolic abnormalities in LKO points to important compensatory effects by HPA

  20. Associations between γ-glutamyl transferase, metabolic abnormalities and inflammation in healthy subjects from a population-based cohort: A possible implication for oxidative stress

    Institute of Scientific and Technical Information of China (English)

    Simona Bo; Roberto Gambino; Marilena Durazzo; Sabrina Guidi; Elisa Tiozzo; Federica Ghione; Luigi Gentile; Maurizio Cassader; Gian Franco Pagano

    2005-01-01

    AIM: To examine the relationships between γ -glutamyltransferase (GGT), alanine-aminotransferase (ALT),aspartate-aminotransferase (AST) and various metabolic parameters, C-reactive protein (CRP) and an oxidative stress marker (nitrotyrosine, NT) in subjects without any metabolic abnormalities from a population-based sample.METHODS: Two hundred and five subjects with normal body mass index (BMI), glucose tolerance, and without any metabolic abnormality were studied out of 1339subjects, without known liver diseases, alcohol abuse or use of hepatotoxic drugs, who are representative of the 45-64 aged population of Asti (north-western Italy).RESULTS: In all patients metabolic parameters and hs-CRP levels linearly increase from the lowest to the highest ALT and GGT tertiles, while in subjects without metabolic abnormalities, there is a significant association between fasting glucose, uric acid, waist circumference,hs-CRP, triglyceride values, and GGT levels. In these subjects, male sex, higher hs-CRP and glucose levels are associated with GGT levels in a multiple regression model, after adjustments for multiple confounders.In the same model, median NT levels are significantly associated with the increasing GGT tertile (β = 1.06;95%CI 0.67-1.45), but not with the AST and ALT tertiles.In a multiple regression model, after adjusting for age,sex, BMI, waist, smoking, and alcohol consumption, both NT (β = 0.05; 95%CI 0.02-0.08) and hs-CRP levels (β =0.09; 95%CI 0.03-0.15) are significantly associated with fasting glycemia.CONCLUSION: GGT, an easy, universally standardized and available measurement, could represent an early marker of sub-clinical inflammation and oxidative stress in otherwise healthy individuals. Prospective studies are needed to establish if GGT could predict future diabetes in these subjects.

  1. Mice deficient in GEM GTPase show abnormal glucose homeostasis due to defects in beta-cell calcium handling.

    Directory of Open Access Journals (Sweden)

    Jenny E Gunton

    Full Text Available AIMS AND HYPOTHESIS: Glucose-stimulated insulin secretion from beta-cells is a tightly regulated process that requires calcium flux to trigger exocytosis of insulin-containing vesicles. Regulation of calcium handling in beta-cells remains incompletely understood. Gem, a member of the RGK (Rad/Gem/Kir family regulates calcium channel handling in other cell types, and Gem over-expression inhibits insulin release in insulin-secreting Min6 cells. The aim of this study was to explore the role of Gem in insulin secretion. We hypothesised that Gem may regulate insulin secretion and thus affect glucose tolerance in vivo. METHODS: Gem-deficient mice were generated and their metabolic phenotype characterised by in vivo testing of glucose tolerance, insulin tolerance and insulin secretion. Calcium flux was measured in isolated islets. RESULTS: Gem-deficient mice were glucose intolerant and had impaired glucose stimulated insulin secretion. Furthermore, the islets of Gem-deficient mice exhibited decreased free calcium responses to glucose and the calcium oscillations seen upon glucose stimulation were smaller in amplitude and had a reduced frequency. CONCLUSIONS: These results suggest that Gem plays an important role in normal beta-cell function by regulation of calcium signalling.

  2. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan;

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... was seen in the dizygotic twins. The effect of the polymorphisms on lipid and glucose parameters could be mediated through linkage to genes with known effect on glucose metabolism or through free fatty acids exerting their effect on glucose metabolism.......RI RFLP) were established using polymerase chain reaction and restriction enzyme digests. The effect of genotypes on lipid levels and on glucose, insulin, and HOMA (i.e., calculated parameters of beta-cell function and insulin resistance) was assessed by multivariate analyses of variance correcting...

  3. Alleviation of glucose repression of maltose metabolism by MIG1 disruption in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Klein, Christopher; Olsson, Lisbeth; Rønnow, B.

    1996-01-01

    The MIG1 gene was disrupted in a haploid laboratory strain (B224) and in an industrial polyploid strain (DGI 342) of Saccharomyces cerevisiae. The alleviation of glucose repression of the expression of MAL genes and alleviation of glucose control of maltose metabolism were investigated in batch...... cultivations on glucose-maltose mixtures. In the MIG1-disrupted haploid strain, glucose repression was partly alleviated; i.e., maltose metabolism was initiated at higher glucose concentrations than in the corresponding wild-type strain. In contrast, the polyploid Delta mig1 strain exhibited an even more...... of glucose repression of the SUC genes. The disruption of MIG1 was shown to bring about pleiotropic effects, manifested in changes in the pattern of secreted metabolites and in the specific growth rate....

  4. The Rab-GTPase-activating protein TBC1D1 regulates skeletal muscle glucose metabolism

    DEFF Research Database (Denmark)

    Szekeres, Ferenc; Chadt, Alexandra; Tom, Robby Z

    2012-01-01

    The Rab-GTPase-activating protein TBC1D1 has emerged as a novel candidate involved in metabolic regulation. Our aim was to determine whether TBC1D1 is involved in insulin as well as energy-sensing signals controlling skeletal muscle metabolism. TBC1D1-deficient congenic B6.SJL-Nob1.10 (Nob1.10(SJL...... be explained partly by a 50% reduction in GLUT4 protein, since proximal signaling at the level of Akt, AMPK, and acetyl-CoA carboxylase (ACC) was unaltered. Paradoxically, in vivo insulin-stimulated 2-deoxyglucose uptake was increased in EDL and tibialis anterior muscle from TBC1D1-deficient mice......)) and wild-type littermates were studied. Glucose and insulin tolerance, glucose utilization, hepatic glucose production, and tissue-specific insulin-mediated glucose uptake were determined. The effect of insulin, AICAR, or contraction on glucose transport was studied in isolated skeletal muscle. Glucose...

  5. Clinical observation of glucose metabolism disorders in elderly patients with obstructive sleep apnea disorder

    Institute of Scientific and Technical Information of China (English)

    张蔷

    2013-01-01

    Objective To explore the correlation between obstructive sleep apnea hypoventilation syndrome (OSAHS) and glucose metabolism disorders in patients without diabetes mellitus.Methods A total of 88 patients with OSAHS but without diabetes mellitus from 2009 to 2011 in

  6. Roles of Chlorogenic Acid on Regulating Glucose and Lipids Metabolism: A Review

    Directory of Open Access Journals (Sweden)

    Shengxi Meng

    2013-01-01

    Full Text Available Intracellular glucose and lipid metabolic homeostasis is vital for maintaining basic life activities of a cell or an organism. Glucose and lipid metabolic disorders are closely related with the occurrence and progression of diabetes, obesity, hepatic steatosis, cardiovascular disease, and cancer. Chlorogenic acid (CGA, one of the most abundant polyphenol compounds in the human diet, is a group of phenolic secondary metabolites produced by certain plant species and is an important component of coffee. Accumulating evidence has demonstrated that CGA exerts many biological properties, including antibacterial, antioxidant, and anticarcinogenic activities. Recently, the roles and applications of CGA, particularly in relation to glucose and lipid metabolism, have been highlighted. This review addresses current studies investigating the roles of CGA in glucose and lipid metabolism.

  7. Assessment of regional glucose metabolism in aging brain and dementia with positron-emission tomography

    Energy Technology Data Exchange (ETDEWEB)

    Reivich, M.; Alavi, A.; Ferris, S.; Christman, D.; Fowler, J.; MacGregor, R.; Farkas, T.; Greenberg, J.; Dann, R.; Wolf, A.

    1981-01-01

    This paper explores the alterations in regional glucose metabolism that occur in elderly subjects and those with senile dementia compared to normal young volunteers. Results showed a tendency for the frontal regions to have a lower metabolic rate in patients with dementia although this did not reach the level of significance when compared to the elderly control subjects. The changes in glucose metabolism were symmetrical in both the left and right hemispheres. There was a lack of correlation between the mean cortical metabolic rates for glucose and the global mental function in the patients with senile dementia. This is at variance with most of the regional cerebral blood flow data that has been collected. This may be partly related to the use of substrates other than glucose by the brain in elderly and demented subjects. (PSB)

  8. Metabolic Fate of Fructose Ingested with and without Glucose in a Mixed Meal

    OpenAIRE

    Fanny Theytaz; Sara de Giorgi; Leanne Hodson; Nathalie Stefanoni; Valentine Rey; Philippe Schneiter; Vittorio Giusti; Luc Tappy

    2014-01-01

    Ingestion of pure fructose stimulates de novo lipogenesis and gluconeogenesis. This may however not be relevant to typical nutritional situations, where fructose is invariably ingested with glucose. We therefore assessed the metabolic fate of fructose incorporated in a mixed meal without or with glucose in eight healthy volunteers. Each participant was studied over six hours after the ingestion of liquid meals containing either 13C-labelled fructose, unlabeled glucose, lipids and protein (Fr...

  9. Complex Patterns of Metabolic and Ca2+ Entrainment in Pancreatic Islets by Oscillatory Glucose

    OpenAIRE

    Pedersen, Morten Gram; Mosekilde, Erik; Polonsky, Kenneth S.; Luciani, Dan S.

    2013-01-01

    Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca2+ in pancreatic islets. Periodic variations in glucose can entrain islet Ca2+ and insulin secretion, possibly promoting interislet synchronization. Here, we used fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) i...

  10. Direct neuronal glucose uptake Heralds activity-dependent increases in cerebral metabolism

    DEFF Research Database (Denmark)

    Lundgaard, Iben; Li, Baoman; Xie, Lulu

    2015-01-01

    Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two...

  11. Metabolomic profiling identifies potential pathways involved in the interaction of iron homeostasis with glucose metabolism

    Directory of Open Access Journals (Sweden)

    Lars Stechemesser

    2017-01-01

    Conclusions: Our data suggest that high serum ferritin concentrations are linked to impaired glucose homeostasis in subjects with the MetS. Iron excess is associated to distinct changes in the serum concentrations of phosphatidylcholine subsets. A pathway involving sarcosine and citrulline also may be involved in iron-induced impairment of glucose metabolism.

  12. Impact of 3-year lifestyle intervention on postprandial glucose metabolism : the SLIM study

    NARCIS (Netherlands)

    Roumen, C.; Corpeleijn, E.; Feskens, E. J. M.; Mensink, M.; Saris, W. H. M.; Blaak, E. E.

    2008-01-01

    Objective To determine the effect of a 3-year diet and exercise lifestyle intervention, based on general public health recommendations, on glucose tolerance, insulin resistance and metabolic cardiovascular risk factors in Dutch subjects with impaired glucose tolerance (IGT). Methods The study was a

  13. Physical activity energy expenditure vs cardiorespiratory fitness level in impaired glucose metabolism

    DEFF Research Database (Denmark)

    Lidegaard, Lærke P; Hansen, Anne-Louise Smidt; Johansen, Nanna B

    2015-01-01

    AIM/HYPOTHESIS: Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test...

  14. Regulation of glucose and glycogen metabolism during and after exercise

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Richter, Erik

    2012-01-01

    Utilization of carbohydrate in the form of intramuscular glycogen stores and glucose delivered from plasma becomes an increasingly important energy substrate to the working muscle with increasing exercise intensity. This review gives an update on the molecular signals by which glucose transport...... in the post-exercise period which can result in an overshoot of intramuscular glycogen resynthesis post exercise (glycogen supercompensation)....

  15. Metabolic ketoacidosis with normal blood glucose: A rare complication of sodium–glucose cotransporter 2 inhibitors

    OpenAIRE

    Saad Ullah; Noman Khan; Hassan Zeb; Hassan Tahir

    2016-01-01

    Ketoacidosis is a significant and often a life-threatening complication of diabetes mellitus seen mostly in type 1 diabetes mellitus as well as occasionally in type 2 diabetes mellitus. Diabetic ketoacidosis usually manifests with high blood glucose more than 250 mg/dL, but euglycemic diabetic ketoacidosis is defined as ketoacidosis associated with blood glucose level less than 250 mg/dL. Normal blood glucose in such patients results in significant delay in diagnosis and management of diabeti...

  16. Abnormal Transmethylation/Transsulfuration Metabolism and DNA Hypomethylation among Parents of Children with Autism

    Science.gov (United States)

    James, S. Jill; Melnyk, Stepan; Jernigan, Stefanie; Hubanks, Amanda; Rose, Shannon; Gaylor, David W.

    2008-01-01

    An integrated metabolic profile reflects the combined influence of genetic, epigenetic, and environmental factors that affect the candidate pathway of interest. Recent evidence suggests that some autistic children may have reduced detoxification capacity and may be under chronic oxidative stress. Based on reports of abnormal methionine and…

  17. Muscle glucose metabolism following exercise in the rat

    DEFF Research Database (Denmark)

    Richter, Erik; Garetto, L P; Goodman, M N

    1982-01-01

    Muscle glycogen stores are depleted during exercise and are rapidly repleted during the recovery period. To investigate the mechanism for this phenomenon, untrained male rats were run for 45 min on a motor-driven treadmill and the ability of their muscles to utilize glucose was then assessed during...... in glucose utilization enhanced by prior exercise appeared to be glucose transport across the cell membrane, as in neither control nor exercised rats did free glucose accumulate in the muscle cell. Following exercise, the ability of insulin to stimulate the release of lactate into the perfusate was unaltered......; however its ability to stimulate the incorporation of [(14)C]glucose into glycogen in certain muscles was enhanced. Thus at a concentration of 75 muU/ml insulin stimulated glycogen synthesis eightfold more in the fast-twitch red fibers of the red gastrocnemius than it did in the same muscle...

  18. Pregnancy and undernutrition alter glucose metabolic responses to insulin in sheep.

    Science.gov (United States)

    Petterson, J A; Dunshea, F R; Ehrhardt, R A; Bell, A W

    1993-07-01

    Nonpregnant and late-pregnant ditocous ewes were fed either to maintain zero energy balance in maternal tissues (fed) or at 50% of this level (underfed) for several weeks. Whole-body kinetics of glucose metabolism were measured under basal conditions, and the hyperinsulinemic, euglycemic clamp technique was used to define insulin-dose response profiles for several indices of whole-body glucose utilization, and for endogenous glucose production. Pregnancy increased and undernutrition decreased basal glucose entry rate (GER), glucose metabolic clearance rate (GMCR) and insulin-independent glucose utilization (IIGU). The consistent increment in IIGU of pregnant over nonpregnant ewes was comparable to previous estimates of uterine glucose uptake. Pregnancy resulted in higher plasma concentration for 50% maximal responses (ED50) to insulin of GER, GMCR, steady-state glucose infusion rate (SSGIR) to maintain euglycemia and insulin-dependent glucose utilization (IDGU). These changes were especially large in underfed pregnant ewes. Effects on the maximal response to insulin of these variables (Rmax) were relatively small (GMCR, IDGU) or nonsignificant (GER, SSGIR). Maximum insulin-induced suppression of endogenous glucose production was significantly lower due to undernutrition; neither Rmax nor ED50 for this response was affected by pregnancy. Insulin resistance in late-pregnant ewes is primarily due to decreased insulin sensitivity in (presumably) peripheral tissues, implying an alteration of receptor function or of early postreceptor signal transduction.

  19. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition

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    Zhu Zhu

    2016-01-01

    Full Text Available Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice by altering exposure to light. C57 BL/6J mice (C57 mice and ApoE-KO mice (ApoE-KO mice exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1 levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  20. Altered Clock and Lipid Metabolism-Related Genes in Atherosclerotic Mice Kept with Abnormal Lighting Condition.

    Science.gov (United States)

    Zhu, Zhu; Hua, Bingxuan; Shang, Zhanxian; Yuan, Gongsheng; Xu, Lirong; Li, Ermin; Li, Xiaobo; Sun, Ning; Yan, Zuoqin; Qian, Ruizhe; Lu, Chao

    2016-01-01

    Background. The risk of atherosclerosis is elevated in abnormal lipid metabolism and circadian rhythm disorder. We investigated whether abnormal lighting condition would have influenced the circadian expression of clock genes and clock-controlled lipid metabolism-related genes in ApoE-KO mice. Methods. A mouse model of atherosclerosis with circadian clock genes expression disorder was established using ApoE-KO mice (ApoE-KO LD/DL mice) by altering exposure to light. C57 BL/6J mice (C57 mice) and ApoE-KO mice (ApoE-KO mice) exposed to normal day and night and normal diet served as control mice. According to zeitgeber time samples were acquired, to test atheromatous plaque formation, serum lipids levels and rhythmicity, clock genes, and lipid metabolism-related genes along with Sirtuin 1 (Sirt1) levels and rhythmicity. Results. Atherosclerosis plaques were formed in the aortic arch of ApoE-KO LD/DL mice. The serum lipids levels and oscillations in ApoE-KO LD/DL mice were altered, along with the levels and diurnal oscillations of circadian genes, lipid metabolism-associated genes, and Sirt1 compared with the control mice. Conclusions. Abnormal exposure to light aggravated plaque formation and exacerbated disorders of serum lipids and clock genes, lipid metabolism genes and Sirt1 levels, and circadian oscillation.

  1. Voxel-based statistical analysis of regional cerebral glucose metabolism in children with attention-deficit hyperactivity disorder

    Institute of Scientific and Technical Information of China (English)

    Ji-Hoon Kim; Young-In Chung; Jung Sub Lee; In-Joo Kim; Yong-Ki Kim; Seong-Jang Kim

    2011-01-01

    The technique of region of interest-based positron emission tomography is limited by its poor reliability and relatively few examined brain regions. In the present study, we compared brain metabolism assessed using fluorine-18-fluorodeoxyglucose positron emission tomography between 14 attention-deficit hyperactivity disorder (ADHD) patients and 15 normal controls with scoliosis at resting state by statistical parametric mapping. Glucose metabolism was decreased in the left parahippocampal gyrus, left hippocampus, left anterior cingulate gyrus, right anterior and posterior lobes of the cerebellum, left superior temporal gyrus, left insula, left medial and middle frontal gyri, right medial frontal gyrus, and left basal ganglia (putamen, amygdala, and caudate nucleus) in children with ADHD. These data suggest that children with ADHD exhibit hypometabolism in various brain regions compared to controls, indicating that ADHD symptoms are unlikely the result of abnormalities in specific areas.

  2. Transcriptome profiling of brown adipose tissue during cold exposure reveals extensive regulation of glucose metabolism

    DEFF Research Database (Denmark)

    Hao, Qin; Yadav, Rachita; Basse, Astrid L.

    2015-01-01

    exposure, we propose a model for the intermediary glucose metabolism in activated BAT: 1) fluxes through glycolysis and the pentose phosphate pathway are induced, the latter providing reducing equivalents for de novo fatty acid synthesis; 2) glycerol synthesis from glucose is increased, facilitating...... metabolism, and the pentose phosphate pathway was observed in BAT from cold-exposed animals. In addition, glycerol-3-phosphate dehydrogenase 1 expression was induced in BAT from cold-challenged mice, suggesting increased synthesis of glycerol from glucose. Similarly, expression of lactate dehydrogenases...

  3. The direct effect of incretin hormones on glucose and glycerol metabolism and hemodynamics

    DEFF Research Database (Denmark)

    Karstoft, Kristian; Mortensen, Stefan; Knudsen, Sine H;

    2015-01-01

    The objective of this study was to assess the insulin-independent effects of incretin hormones on glucose and glycerol metabolism and hemodynamics under eu- and hyperglycemic conditions. Young, healthy males (n=10) underwent three trials in a randomized, controlled, cross-over study. Each trial...... consisted of a 2-stage (eu- and hyperglycemia) pancreatic clamp (using somatostatin to prevent endogenous insulin secretion). Glucose and lipid metabolism were measured via infusion of stable glucose and glycerol isotopic tracers. Hemodynamic variables (femoral, brachial and common carotid artery blood flow...... a higher femoral blood flow during hyperglycemia in GIP (vs. CON and GLP-1, Pmetabolism or hemodynamics during euglycemia. On contrary, during...

  4. Comparison of glucose and lipid metabolic gene expressions between fat and lean lines of rainbow trout after a glucose load.

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    Junyan Jin

    Full Text Available Two experimental rainbow trout lines developed through divergent selection for low (Lean 'L' line or high (Fat 'F' line muscle fat content were used as models to study the genetic determinism of fat depots. Previous nutritional studies suggested that the F line had a better capability to use glucose than the L line during feeding trials. Based on that, we put forward the hypothesis that F line has a greater metabolic ability to clear a glucose load effectively, compared to L line. In order to test this hypothesis, 250 mg/kg glucose was intraperitoneally injected to the two rainbow trout lines fasted for 48 h. Hyperglycemia was observed after glucose treatment in both lines without affecting the phosphorylation of AMPK (cellular energy sensor and Akt-TOR (insulin signaling components. Liver glucokinase and glucose-6-phosphate dehydrogenase expression levels were increased by glucose, whereas mRNA levels of β-oxidation enzymes (CPT1a, CPT1b, HOAD and ACO were down-regulated in the white skeletal muscle of both lines. Regarding the genotype effect, concordant with normoglycemia at 12 h after glucose treatment, higher muscle glycogen was found in F line compared to L line which exhibited hyperglycemia. Moreover, mRNA levels of hepatic glycolytic enzymes (GK, 6PFK and PK, gluconeogenic enzyme PEPCK and muscle fatty acid oxidation enzymes (CPT1a, CPT1b and HOAD were concurrently higher in the F line. Overall, these findings suggest that F line may have a better ability to maintain glucose homeostasis than L line.

  5. Metabolic ketoacidosis with normal blood glucose: A rare complication of sodium–glucose cotransporter 2 inhibitors

    Science.gov (United States)

    Ullah, Saad; Khan, Noman; Zeb, Hassan; Tahir, Hassan

    2016-01-01

    Ketoacidosis is a significant and often a life-threatening complication of diabetes mellitus seen mostly in type 1 diabetes mellitus as well as occasionally in type 2 diabetes mellitus. Diabetic ketoacidosis usually manifests with high blood glucose more than 250 mg/dL, but euglycemic diabetic ketoacidosis is defined as ketoacidosis associated with blood glucose level less than 250 mg/dL. Normal blood glucose in such patients results in significant delay in diagnosis and management of diabetic ketoacidosis, thus increasing mortality and morbidity. We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient. PMID:27928503

  6. Metabolic ketoacidosis with normal blood glucose: A rare complication of sodium–glucose cotransporter 2 inhibitors

    Directory of Open Access Journals (Sweden)

    Saad Ullah

    2016-11-01

    Full Text Available Ketoacidosis is a significant and often a life-threatening complication of diabetes mellitus seen mostly in type 1 diabetes mellitus as well as occasionally in type 2 diabetes mellitus. Diabetic ketoacidosis usually manifests with high blood glucose more than 250 mg/dL, but euglycemic diabetic ketoacidosis is defined as ketoacidosis associated with blood glucose level less than 250 mg/dL. Normal blood glucose in such patients results in significant delay in diagnosis and management of diabetic ketoacidosis, thus increasing mortality and morbidity. We present a case of euglycemic diabetic ketoacidosis secondary to canagliflozin in a type 2 diabetic patient.

  7. Dietary intake, food pattern, and abnormal blood glucose status of middle-aged adults: a cross-sectional community-based study in Myanmar

    Directory of Open Access Journals (Sweden)

    Hlaing Hlaing Hlaing

    2016-05-01

    Full Text Available Background: Lifestyle changes, particularly dietary intake, had resulted in increasing trends of type-2 diabetes mellitus worldwide. However, dietary intake is diverse across country contexts. This study aimed to compare the dietary intake, food patterns, and blood glucose among middle-aged adults living in urban and suburban areas in Mandalay city, Myanmar, and explore their relationships. Methods: A cross-sectional community-based study was conducted during June–November 2014. Adults aged 35–64 were randomly selected and requested to record all food they ate in a 4-day diary. Fasting and 2-hour postprandial blood glucose values were measured over two consecutive days. Dietary intakes were calculated in terms of energy, macronutrients, glycemic index, and glycemic load, and food patterns were identified by factor analysis. The relationships between food pattern, dietary intake, and blood glucose were assessed. Results: Of 440 participants, dietary intake between urban and suburban residents was significantly different. Six food patterns were identified. There was no difference in fasting and 2-hour postprandial blood glucose between urban and suburban residents, but a strong correlation between fasting blood glucose and 2-hour postprandial blood glucose was found (correlation coefficient=0.8. Identification of abnormal blood glucose status using original fasting and converted 2-hour postprandial values showed substantial agreement (prevalence-adjusted bias-adjusted Kappa= 0.8. Relationships between food patterns and blood glucose or abnormal blood glucose status were not found. Conclusion: Food patterns were associated with dietary intake, not with abnormal blood glucose status. Two-hour postprandial blood glucose was highly correlated with fasting blood glucose and may be used for identifying abnormal blood glucose status.

  8. Effects of an oral insulin nanoparticle administration on hepatic glucose metabolism assessed by 13C and 2H isotopomer analysis

    NARCIS (Netherlands)

    Reis, C.P.; Neufeld, R.; Veiga, F.; Figueiredo, I.V.; Jones, J.; Soares, A.F.; Nunes, P.M.; Damg\\'e, C.; Carvalho, R.A.

    2012-01-01

    The purpose of this study was to evaluate hepatic glucose metabolism of diabetic induced rats after a daily oral load of insulin nanoparticles over 2 weeks. After the 2-week treatment, an oral glucose tolerance test was performed with [U-‘‘C] glucose and ‘H2O. Plasma glucose ‘H and ‘‘C enrichments w

  9. Effects of pituitary hormone deficiency on growth and glucose metabolism of the sheep fetus.

    Science.gov (United States)

    Fowden, A L; Forhead, A J

    2007-10-01

    Pituitary hormones are essential for normal growth and metabolic responsiveness after birth, but their role before birth remains unclear. This study examined the effects of hypophysectomizing fetal sheep on their growth and glucose metabolism during the late normal and extended periods of gestation, and on their metabolic response to maternal fasting for 48 h near term. Fetal hypophysectomy reduced crown rump length (CRL), limb lengths, and body weight but increased ponderal index relative to controls near normal term. It also lowered the daily rate of crown rump length increment uniformly from 35 d before, to 20 d after normal term. Hypophysectomized (HX) fetuses had normal weight-specific rates of umbilical uptake, utilization, and oxidation of glucose but lower rates of umbilical oxygen uptake than controls near term. All these metabolic rates were significantly less in HX fetuses during the extended period of gestation than in HX and intact fetuses near normal term. In contrast to controls, glucogenesis was negligible in HX fetuses during maternal fasting. Consequently, the rate of glucose utilization decreased significantly in fasted HX but not intact fetuses. Conversely, the rate of CO(2) production from glucose carbon decreased in fasted intact but not HX fetuses. Fetal hypophysectomy also prevented the fasting-induced increases in plasma cortisol and norepinephrine concentrations seen in controls. These findings demonstrate that the pituitary hormones are important in regulating the growth rate and adaptive responses of glucose metabolism to undernutrition in fetal sheep. They also suggest that fetal metabolism is altered when gestational length is extended.

  10. Glucose metabolism in mammalian cell culture: new insights for tweaking vintage pathways.

    Science.gov (United States)

    Mulukutla, Bhanu Chandra; Khan, Salmaan; Lange, Alex; Hu, Wei-Shou

    2010-09-01

    Cultured mammalian cells are major vehicles for producing therapeutic proteins, and energy metabolism in those cells profoundly affects process productivity. The characteristic high glucose consumption and lactate production of industrial cell lines as well as their adverse effects on productivity have been the target of both cell line and process improvement for several decades. Recent research advances have shed new light on regulation of glucose metabolism and its links to cell proliferation. This review highlights our current understanding in this area of crucial importance in bioprocessing and further discusses strategies for harnessing new findings toward process enhancement through the manipulation of cellular energy metabolism.

  11. Visual and SPM analysis of regional cerebral glucose metabolism in adult patients with neurofibromatosis

    Energy Technology Data Exchange (ETDEWEB)

    Yoon, Joon Kee; An, Young Sil; Hong, Seon Pyo; Joh, Chul Woo; Yoon, Seok Nam [Ajou University, School of Medicine, Suwon (Korea, Republic of)

    2005-07-01

    We evaluated the regional cerebral glucose metabolism in adult patients with neurofibromatosis (NF) using visual and SPM analysis, and compared with MRI findings. A total of 11 adult patients with NF type I were prospectively included in the study. All patients underwent F-18 FDG PET and brain MRI within 2 month of each other. All hypometabolic areas on PET were determined visually by 2 nuclear medicine physician and compared with MRI findings. SPM analysis was done using 42 normal controls with p = 0.005. Seven of 11 PET images showed 10 hypometabolic areas and 4 of 11 MRIs showed 6 areas of signal change brain parenchyma. Hypometabolic areas were bilateral thalamus (n=5), left temporal cortex (n=4) and dentate nucleus (n=1). In only 2 lesions (thalamus and dentate nucleus), hypometabolic foci were consistently related to signal change on MRI. SPM analysis revealed significantly decreased area in bilateral thalamus and left temporal cortex. F-18 FDG PET revealed significant hypometabolism in bilateral thalamus and left temporal cortex in adult patients with NF, and it might be helpful in understanding developmental abnormality of NF.

  12. Cerebral glucose metabolism in Wernicke's, Broca's, and conduction aphasia

    Energy Technology Data Exchange (ETDEWEB)

    Metter, E.J.; Kempler, D.; Jackson, C.; Hanson, W.R.; Mazziotta, J.C.; Phelps, M.E.

    1989-01-01

    Cerebral glucose metabolism was evaluated in patients with either Wernicke's (N = 7), Broca's (N = 11), or conduction (N = 10) aphasia using /sup 18/F-2-fluoro-2-deoxy-D-glucose with positron emission tomography. The three aphasic syndromes differed in the degree of left-to-right frontal metabolic asymmetry, with Broca's aphasia showing severe asymmetry and Wernicke's aphasia mild-to-moderate metabolic asymmetry, while patients with conduction aphasia were metabolically symmetric. On the other hand, the three syndromes showed the same degree of metabolic decline in the left temporal region. The parietal region appeared to separate conduction aphasia from both Broca's and Wernicke's aphasias. Common aphasic features in the three syndromes appear to be due to common changes in the temporal region, while unique features were associated with frontal and parietal metabolic differences.

  13. Demographic and metabolic characteristics of individuals with progressive glucose tolerance

    Directory of Open Access Journals (Sweden)

    A.L. Mendes

    2009-03-01

    Full Text Available We evaluated changes in glucose tolerance of 17 progressors and 62 non-progressors for 9 years to improve our understanding of the pathogenesis of type 2 diabetes mellitus. Changes in anthropometric measurements and responses to an oral glucose tolerance test (OGTT were analyzed. We identified 14 pairs of individuals, one from each group, who were initially normal glucose tolerant and were matched for gender, age, weight, and girth. We compared initial plasma glucose and insulin curves (from OGTT, insulin secretion (first and second phases and insulin sensitivity indices (from hyperglycemic clamp assay for both groups. In the normal glucose tolerant phase, progressors presented: 1 a higher OGTT blood glucose response with hyperglycemia in the second hour and a similar insulin response vs non-progressors; 2 a reduced first-phase insulin secretion (2.0 ± 0.3 vs 2.3 ± 0.3 pmol/L; P < 0.02 with a similar insulin sensitivity index and a lower disposition index (3.9 ± 0.2 vs 4.1 ± 0.2 µmol·kg-1·min-1 ; P < 0.05 vs non-progressors. After 9 years, both groups presented similar increases in weight and fasting blood glucose levels and progressors had an increased glycemic response at 120 min (P < 0.05 and reduced early insulin response to OGTT (progressors, 1st: 2.10 ± 0.34 vs 2nd: 1.87 ± 0.25 pmol/mmol; non-progressors, 1st: 2.15 ± 0.28 vs 2nd: 2.03 ± 0.39 pmol/mmol; P < 0.05. Theses data suggest that β-cell dysfunction might be a risk factor for type 2 diabetes mellitus.

  14. Program for PET image alignment: Effects on calculated differences in cerebral metabolic rates for glucose

    Energy Technology Data Exchange (ETDEWEB)

    Phillips, R.L.; London, E.D.; Links, J.M.; Cascella, N.G. (NIDA Addiction Research Center, Baltimore, MD (USA))

    1990-12-01

    A program was developed to align positron emission tomography images from multiple studies on the same subject. The program allowed alignment of two images with a fineness of one-tenth the width of a pixel. The indications and effects of misalignment were assessed in eight subjects from a placebo-controlled double-blind crossover study on the effects of cocaine on regional cerebral metabolic rates for glucose. Visual examination of a difference image provided a sensitive and accurate tool for assessing image alignment. Image alignment within 2.8 mm was essential to reduce variability of measured cerebral metabolic rates for glucose. Misalignment by this amount introduced errors on the order of 20% in the computed metabolic rate for glucose. These errors propagate to the difference between metabolic rates for a subject measured in basal versus perturbed states.

  15. Evidence for metabolic abnormalities in the muscles of patients with fibromyalgia.

    Science.gov (United States)

    Park, J H; Niermann, K J; Olsen, N

    2000-04-01

    Widespread muscle pain, fatigue, and weakness are defining characteristics of patients with fibromyalgia (FM). The aim of this review is to summarize recent investigations of muscle abnormalities in FM, which can be classified as structural, metabolic, or functional in nature. Histologic muscle abnormalities of membranes, mitochondria, and fiber type have been well described at both the light microscopic and ultrastructural levels. These structural abnormalities often correlate with biochemical abnormalities, defective energy production, and the resultant dysfunction of FM muscles. The observed abnormalities in FM muscles are consistent with neurologic findings and disturbances in the hypothalamic-pituitary-adrenal axis. Functional changes in FM muscles are assessed most directly by strength and endurance measurements, but pain and psychologic factors may interfere with accurate assessments. To compensate for diminished effort, the decreased efficiency of the work performance by patients with FM can be verified from P-31 magnetic resonance spectroscopy (MRS) data by calculation of the work/energy-cost ratio for various tasks. In the disease course, muscle abnormalities may be elicited by intrinsic changes within the muscle tissue itself and/or extrinsic neurologic and endocrine factors. The accurate assignment of intrinsic or extrinsic factors has been substantially clarified by a recent surge of experimental findings. Irrespective of the multifaceted causes of muscle dysfunction and pain, an in-depth understanding of the muscle defects may provide ideas for characterization of the underlying pathogenesis and development of new therapeutic approaches for fibromyalgia syndrome.

  16. Sleep apnea predicts distinct alterations in glucose homeostasis and biomarkers in obese adults with normal and impaired glucose metabolism

    Directory of Open Access Journals (Sweden)

    Hill Nathan R

    2010-12-01

    Full Text Available Abstract Background Notwithstanding previous studies supporting independent associations between obstructive sleep apnea (OSA and prevalence of diabetes, the underlying pathogenesis of impaired glucose regulation in OSA remains unclear. We explored mechanisms linking OSA with prediabetes/diabetes and associated biomarker profiles. We hypothesized that OSA is associated with distinct alterations in glucose homeostasis and biomarker profiles in subjects with normal (NGM and impaired glucose metabolism (IGM. Methods Forty-five severely obese adults (36 women without certain comorbidities/medications underwent anthropometric measurements, polysomnography, and blood tests. We measured fasting serum glucose, insulin, selected cytokines, and calculated homeostasis model assessment estimates of insulin sensitivity (HOMA-IS and pancreatic beta-cell function (HOMA-B. Results Both increases in apnea-hypopnea index (AHI and the presence of prediabetes/diabetes were associated with reductions in HOMA-IS in the entire cohort even after adjustment for sex, race, age, and BMI (P = 0.003. In subjects with NGM (n = 30, OSA severity was associated with significantly increased HOMA-B (a trend towards decreased HOMA-IS independent of sex and adiposity. OSA-related oxyhemoglobin desaturations correlated with TNF-α (r=-0.76; P = 0.001 in women with NGM and with IL-6 (rho=-0.55; P = 0.035 in women with IGM (n = 15 matched individually for age, adiposity, and AHI. Conclusions OSA is independently associated with altered glucose homeostasis and increased basal beta-cell function in severely obese adults with NGM. The findings suggest that moderate to severe OSA imposes an excessive functional demand on pancreatic beta-cells, which may lead to their exhaustion and impaired secretory capacity over time. The two distinct biomarker profiles linking sleep apnea with NGM and IGM via TNF-α and IL-6 have been discerned in our study to suggest that sleep apnea and particularly

  17. Effects of growth hormone on glucose and fat metabolism in human subjects

    DEFF Research Database (Denmark)

    Jørgensen, Jens O L; Møller, Louise; Krag, Morten Brøgger;

    2007-01-01

    This article focuses on in vivo data from tests performed in normal subjects and in patients who had abnormal growth hormone (GH) status. Experimental data in human subjects demonstrate that GH acutely inhibits glucose disposal in skeletal muscle. At the same time GH stimulates the turnover...

  18. Simultaneous utilization of glucose and gluconate in Penicillium chrysogenum during overflow metabolism.

    Science.gov (United States)

    Schmitz, Katja; Peter, Vivien; Meinert, Sabine; Kornfeld, Georg; Hardiman, Timo; Wiechert, Wolfgang; Noack, Stephan

    2013-12-01

    The filamentous fungus Penicillium chrysogenum is one of the most important production organism for β-lactam antibiotics, especially penicillin. A specific feature of P. chrysogenum is the formation of gluconate as the primary overflow metabolite under non-limiting growth on glucose. Gluconate can be formed extracellularly by the enzyme glucose oxidase (GOD) that shows high activities under glucose excess conditions. Currently, it is assumed that under these conditions glucose is the preferred carbon substrate for P. chrysogenum and gluconate consumption first starts after glucose becomes limiting. Here, we specifically address this hypothesis by combining batch cultivation experiments on defined glucose media, time-dependent GOD activity measurements, and (13)C-tracer studies. Our data prove that both substrates are metabolized simultaneously independent from the actual glucose concentration and therefore suggest that no distinct mechanism of carbon catabolite repression exists for gluconate in P. chrysogenum. Moreover, gluconate consumption does not interfere with penicillin V production by repression of the penicillin genes. Finally, by following a model-driven approach the specific uptake rates for glucose and gluconate were quantified and found to be significantly higher for gluconate. In summary, our results show that P. chrysogenum metabolizes gluconate directly and at high rates making it an interesting alternative carbon source for production purposes.

  19. Neuroendocrinology: Electromagnetogenetic Control over Feeding and Glucose Metabolism.

    Science.gov (United States)

    Ruud, Johan; Brüning, Jens C

    2016-06-06

    Cutting-edge experiments show a new means to control the activity of specifically genetically targeted neurons in the hypothalamus using electromagnetic force. At the flip of a switch, the system bidirectionally regulates feeding behavior and glucose homeostasis, demonstrating wireless control over deep brain regions and their strong influence over energy balance.

  20. The Alzheimer's Disease-Related Glucose Metabolic Brain Pattern

    NARCIS (Netherlands)

    Teune, Laura K.; Strijkert, Fijanne; Renken, Remco J.; Izaks, Gerbrand J.; de Vries, Jeroen J.; Segbers, Marcel; Roerdink, Jos B. T. M.; Dierckx, Rudi A. J. O.; Leenders, Klaus L.

    2014-01-01

    Purpose: [F-18] fluorodeoxyglucose (FDG) PET imaging of the brain can be used to assist in the differential diagnosis of dementia. Group differences in glucose uptake between patients with dementia and controls are well-known. However, a multivariate analysis technique called scaled subprofile model

  1. Prevalence of glucose tolerance test abnormalities in women with polycystic ovarian syndrome

    Directory of Open Access Journals (Sweden)

    Leila J. Gracelyn

    2015-12-01

    Conclusions: High prevalence of IGT and Non-Insulin Dependent Diabetes Mellitus (NIDDM in women with PCOS was observed than expected. They have accelerated conversion from IGT to NIDDM. IGT is often asymptomatic and is a known risk factor for type 2 DM and cardiovascular disease. OGTT with 75 gms of glucose is the best screening method for glucose intolerance and a good measure to diagnose type 2 DM in PCOS women. [Int J Reprod Contracept Obstet Gynecol 2015; 4(6.000: 1739-1745

  2. Correction of metabolic abnormalities in a rodent model of obesity, metabolic syndrome, and type 2 diabetes mellitus by inhibitors of hepatic protein kinase C-ι.

    Science.gov (United States)

    Sajan, Mini P; Nimal, Sonali; Mastorides, Stephen; Acevedo-Duncan, Mildred; Kahn, C Ronald; Fields, Alan P; Braun, Ursula; Leitges, Michael; Farese, Robert V

    2012-04-01

    Excessive activity of hepatic atypical protein kinase (aPKC) is proposed to play a critical role in mediating lipid and carbohydrate abnormalities in obesity, the metabolic syndrome, and type 2 diabetes mellitus. In previous studies of rodent models of obesity and type 2 diabetes mellitus, adenoviral-mediated expression of kinase-inactive aPKC rapidly reversed or markedly improved most if not all metabolic abnormalities. Here, we examined effects of 2 newly developed small-molecule PKC-ι/λ inhibitors. We used the mouse model of heterozygous muscle-specific knockout of PKC-λ, in which partial deficiency of muscle PKC-λ impairs glucose transport in muscle and thereby causes glucose intolerance and hyperinsulinemia, which, via hepatic aPKC activation, leads to abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. One inhibitor, 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)], binds to the substrate-binding site of PKC-λ/ι, but not other PKCs. The other inhibitor, aurothiomalate, binds to cysteine residues in the PB1-binding domains of aPKC-λ/ι/ζ and inhibits scaffolding. Treatment with either inhibitor for 7 days inhibited aPKC, but not Akt, in liver and concomitantly improved insulin signaling to Akt and aPKC in muscle and adipocytes. Moreover, both inhibitors diminished excessive expression of hepatic, aPKC-dependent lipogenic, proinflammatory, and gluconeogenic factors; and this was accompanied by reversal or marked improvements in hyperglycemia, hyperinsulinemia, abdominal obesity, hepatosteatosis, hypertriglyceridemia, and hypercholesterolemia. Our findings highlight the pathogenetic importance of insulin signaling to hepatic PKC-ι in obesity, the metabolic syndrome, and type 2 diabetes mellitus and suggest that 1H-imidazole-4-carboxamide, 5-amino-1-[2,3-dihydroxy-4-[(phosphonooxy)methyl]cyclopentyl-[1R-(1a,2b,3b,4a)] and aurothiomalate or similar agents that

  3. Glucose metabolism in the antibiotic producing actinomycete Nonomuraea sp ATCC 39727

    DEFF Research Database (Denmark)

    Gunnarsson, Nina; Bruheim, Per; Nielsen, Jens

    2004-01-01

    primary carbon metabolism in further detail, Nonomuraea was cultivated with [1-C-13] glucose as the only carbon source and the C-13-labeling patterns of proteinogenic amino acids were determined by GC-MS analysis. Through this method, the fluxes in the central carbon metabolism during balanced growth were......The actinomycete Nonomuraea sp. ATCC 39727, producer of the glycopeptide A40926 that is used as precursor for the novel antibiotic dalbavancin, has an unusual carbon metabolism. Glucose is primarily metabolized via the Entner-Doudoroff (ED) pathway, although the energetically more favorable Embden...... - Meyerhof - Parnas (EMP) pathway is present in this organism. Moreover, Nonomuraea utilizes a PPi-dependent phosphofructokinase, an enzyme that has been connected with anaerobic metabolism in eukaryotes and higher plants, but recently has been recognized in several actinomycetes. In order to study its...

  4. Sex-related differences in peripheral glucose metabolism in normal subjects.

    Science.gov (United States)

    Paula, F J; Pimenta, W P; Saad, M J; Paccola, G M; Piccinato, C E; Foss, M C

    1990-01-01

    The metabolic response of muscle tissue to glucose ingestion was studied in 10 normal men (M) and women (F) by using the forearm balance technique and indirect calorimetry simultaneously. During the 3 hours after a 75 g--oral glucose load, glucose uptake per unit muscle mass was significantly higher in women than in men, F = 187.3 +/- 26.9 vs M = 116.7 +/- 9.5 mg/100 g forearm muscle (P less than 0.05). A significant difference in muscle glucose fate was also observed since the amount of glucose utilized through a nonoxidative pathway was significantly higher in women, F = 84.5 +/- 2.6% (161.8 +/- 27.3 mg/100 g forearm muscle) vs M = 75.3 +/- 2.2% (87.2 +/- 8.6 mg/100 g forearm muscle) (P less than 0.05), whereas the amount of glucose oxidized in relation to glucose uptake was significantly higher in men, M = 24.7 +/- 2.2% (28.2 +/- 3.2 mg/100 g forearm muscle) vs F = 15.5 +/- 2.6% (27.8 +/- 5.4 mg/100 g forearm muscle) (P less than 0.05). No significant differences in insulin response to glucose ingestion were detected between groups. The women showed greater suppression of serum free fatty acids (FFA) levels in relation to basal levels than men. We conclude that: 1) after ingesting 75 g glucose, normal women showed greater glucose uptake per unit muscle mass than normal men, 2) for 3 hours after the ingestion of 75 g glucose, the predominant tendency toward utilizing glucose by a nonoxidative pathway is more marked in normal women than in normal men, and 3) the higher glucose uptake per unit muscle mass in the female group in the presence of an insulin response not significantly different from that of the male group suggests that muscle insulin sensitivity is greater in normal women.

  5. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain;

    2015-01-01

    The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... with measurements of postprandial glucose tolerance and postprandial release of insulin and gut hormones were performed before, immediately after and 6 weeks after a 4-day, broad-spectrum, per oral antibiotic cocktail (vancomycin 500 mg, gentamycin 40 mg and meropenem 500 mg once-daily) in a group of 12 lean...... and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose...

  6. High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

    Directory of Open Access Journals (Sweden)

    Xiaofei Cheng

    2016-01-01

    Full Text Available Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM. Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9, matrix metalloproteinase 3 (MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1, was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

  7. Rhinacanthus nasutus leaf improves metabolic abnormalities in high-fat diet-induced obese mice

    Institute of Scientific and Technical Information of China (English)

    Supaporn Wannasiri; Pritsana Piyabhan; Jarinyaporn Naowaboot

    2016-01-01

    Objective:To investigate the effect of Rhinacanthus nasutus(R.nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice.Methods:Obesity was induced in the male ICR mice by feeding them a high-fat diet(60 kcal%fat) for 12 weeks.After the first six weeks of the diet,the obese mice were administered with the water extract of R.nasutus leaves at 250 and 500 mg/kg per day for the next six weeks.Subsequently,the blood glucose,lipid profiles,insulin,leptin,and adiponectin levels were measured.The liver and adipose tissues were excised for histopathological examination and protein expression study.Results:After six weeks of the treatment,R.nasutus extract(at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level,improve the insulin sensitivity,decrease the serum leptin,and increase the serum adiponectin levels.The obese mice treated with R.nasutus were found to have a reduction in the increased lipid concentrations in their serum and liver tissues.Moreover,treatment with R.nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues.Interestingly,the administration with R.nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha,fat cell adiponectin,and glucose transporter 4 proteins.Conclusions:To the best of our knowledge,the present study is the first report on the impact of R.nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.

  8. Rhinacanthus nasutus leaf improves metabolic abnormalities in high-fat diet-induced obese mice

    Institute of Scientific and Technical Information of China (English)

    Supaporn Wannasiri; Pritsana Piyabhan; Jarinyaporn Naowaboot

    2016-01-01

    Objective: To investigate the effect of Rhinacanthus nasutus (R. nasutus) leaf extract on impaired glucose and lipid metabolism in obese ICR mice. Methods: Obesity was induced in the male ICR mice by feeding them a high-fat diet (60 kcal% fat) for 12 weeks. After the first six weeks of the diet, the obese mice were administered with the water extract of R. nasutus leaves at 250 and 500 mg/kg per day for the next six weeks. Subsequently, the blood glucose, lipid profiles, insulin, leptin, and adiponectin levels were measured. The liver and adipose tissues were excised for his-topathological examination and protein expression study. Results: After six weeks of the treatment, R. nasutus extract (at 250 and 500 mg/kg per day) was found to reduce the elevated blood glucose level, improve the insulin sensitivity, decrease the serum leptin, and increase the serum adiponectin levels. The obese mice treated with R. nasutus were found to have a reduction in the increased lipid concen-trations in their serum and liver tissues. Moreover, treatment with R. nasutus reduced the fat accumulation in the liver and the large adipocyte size in the fat tissues. Interestingly, the administration with R. nasutus extract was marked by an increase in the hepatic peroxisome proliferators-activated receptor alpha, fat cell adiponectin, and glucose transporter 4 proteins. Conclusions: To the best of our knowledge, the present study is the first report on the impact of R. nasutus extract in improving the impaired glucose and lipid metabolism in high-fat diet-induced obesity in mice via stimulating the insulin sensitivity in the liver and adipose tissues.

  9. Preliminary Study of Brain Glucose Metabolism Changes in Patients with Lung Cancer of Different Histological Types

    Institute of Scientific and Technical Information of China (English)

    Wei-Ling Li; Chang Fu; Ang Xuan; Da-Peng Shi; Yong-Ju Gao; Jie Zhang; Jun-Ling Xu

    2015-01-01

    Background:Cerebral glucose metabolism changes are always observed in patients suffering from malignant tumors.This preliminary study aimed to investigate the brain glucose metabolism changes in patients with lung cancer of different histological types.Methods:One hundred and twenty patients with primary untreated lung cancer,who visited People's Hospital of Zhengzhou University from February 2012 to July 2013,were divided into three groups based on histological types confirmed by biopsy or surgical pathology,which included adenocarcinoma (52 cases),squamous cell carcinoma (43 cases),and small-cell carcinoma (25 cases).The whole body 18F-fluorodeoxyglucose (1 8F-FDG) positron emission tomography (PET)/computed tomography (CT) of these cases was retrospectively studied.The brain PET data of three groups were analyzed individually using statistical parametric maps (SPM) software,with 50 age-matched and gender-matched healthy controls for comparison.Results:The brain resting glucose metabolism in all three lung cancer groups showed regional cerebral metabolic reduction.The hypo-metabolic cerebral regions were mainly distributed at the left superior and middle frontal,bilateral superior and middle temporal and inferior and middle temporal gyrus.Besides,the hypo-metabolic regions were also found in the right inferior parietal lobule and hippocampus in the small-cell carcinoma group.The area of the total hypo-metabolic cerebral regions in the small-cell carcinoma group (total voxel value 3255) was larger than those in the adenocarcinoma group (total voxel value 1217) and squamous cell carcinoma group (total voxel value 1292).Conclusions:The brain resting glucose metabolism in patients with lung cancer shows regional cerebral metabolic reduction and the brain hypo-metabolic changes are related to the histological types of lung cancer.

  10. Glucose metabolism in small subcortical structures in Parkinson's disease

    DEFF Research Database (Denmark)

    Borghammer, Per; Hansen, Søren B; Eggers, Carsten;

    2012-01-01

    Evidence from experimental animal models of Parkinson's disease (PD) suggests a characteristic pattern of metabolic perturbation in discrete, very small basal ganglia structures. These structures are generally too small to allow valid investigation by conventional positron emission tomography (PET...

  11. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

    OpenAIRE

    Vijayalakshmi Varma; Boros, László G; Nolen, Greg T.; Ching-Wei Chang; Martin Wabitsch; Beger, Richard D.; Jim Kaput

    2015-01-01

    Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS) preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate asso...

  12. Changes in metabolism during a fasting period and a subsequent vegetarian diet with particular reference to glucose metabolism.

    Science.gov (United States)

    Lithell, H; Vessby, B; Hellsing, K; Ljunghall, K; Höglund, N J; Werner, I; Bruce, A

    1983-01-01

    During an investigation on the effect of fasting and a vegetarian diet on the symptoms and signs in chronic cutaneous and arthritic diseases studies were made of glucose metabolism, liver function and the plasma concentration and urine excretion of some minerals. The study was performed on 27 patients who stayed as in-patients on a metabolic ward for five weeks. After the fasting period the blood glucose and serum insulin concentrations were lower (p less than 0.01) than before the fast. At the end of the period on the vegetarian (vegan) diet (three weeks) the insulin/glucose ratio was lower than at the start of the fast. Serum enzyme concentrations reflecting liver function increased during the fast, but normalized during the vegan diet. The intake of vitamin B12 and of selenium due to the vegan diets was very low, which may give reason for some concern during long-term use of this type of vegetarian diet.

  13. Expressions of inflammatory cytokines and fat factors in placentas of patients with gestational diabetes mellitus and their relationship with glucose and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Juan Du; Yi-Lin Zhu; Xue-Mei Gao

    2016-01-01

    Objective:To study the expressions of inflammatory cytokines and fat factors in the placentas of patients with gestational diabetes mellitus and their relationship with glucose and lipid metabolism.Methods:Maternal women who delivered in obstetric department of our hospital from May 2012 to August 2015 were studied, including 45 cases of gestational diabetes mellitus patients and 45 cases of healthy women who were enrolled in the GDM group and the control group respectively. Placentas were collected to detect inflammatory factor and fatty factor contents as well as glucose and lipid metabolism indicators, and serum was collected to detect blood glucose indexes.Results:Inflammatory factors NF-kB, TNF-α, IL-1β, IL-6, IL-8, leptin, visfatin, RBP-4, Chemerin and Nesfatin-1 contents in GDM placental tissues were significantly higher than those in control group while adiponectin content was significantly lower than that in control group. FBG, FINS and HOMA-IRG of GDM patients were higher than those of the control group while HOMA-β was lower than that of control group. IRS-1, ISR-2, FATP-4, El, LPL, FABP-1, FABP-3, FABP-4 and FABP-5 contents in GDM patients’ placentas were significantly lower than those in control group. Glycolipid metabolism indexes were correlated with inflammatory factor and fat factor contents.Conclusions: Inflammatory cytokines and fat factors were abnormally highly expressed in the placentas of gestational diabetes mellitus patients, and were correlated with the indexes of glucose and lipid metabolism.

  14. High glucose repatterns human podocyte energy metabolism during differentiation and diabetic nephropathy

    Science.gov (United States)

    Imasawa, Toshiyuki; Obre, Emilie; Bellance, Nadège; Lavie, Julie; Imasawa, Tomoko; Rigothier, Claire; Delmas, Yahsou; Combe, Christian; Lacombe, Didier; Benard, Giovanni; Claverol, Stéphane; Bonneu, Marc; Rossignol, Rodrigue

    2017-01-01

    Podocytes play a key role in diabetic nephropathy pathogenesis, but alteration of their metabolism remains unknown in human kidney. By using a conditionally differentiating human podocyte cell line, we addressed the functional and molecular changes in podocyte energetics during in vitro development or under high glucose conditions. In 5 mM glucose medium, we observed a stepwise activation of oxidative metabolism during cell differentiation that was characterized by peroxisome proliferator-activated receptor-γ coactivator 1α (PGC-1α)–dependent stimulation of mitochondrial biogenesis and function, with concomitant reduction of the glycolytic enzyme content. Conversely, when podocytes were cultured in high glucose (20 mM), stepwise oxidative phosphorylation biogenesis was aborted, and a glycolytic switch occurred, with consecutive lactic acidosis. Expression of the master regulators of oxidative metabolism transcription factor A mitochondrial, PGC-1α, AMPK, and serine–threonine liver kinase B1 was altered by high glucose, as well as their downstream signaling networks. Focused transcriptomics revealed that myocyte-specific enhancer factor 2C (MEF2C) and myogenic factor 5 (MYF5) expression was inhibited by high glucose levels, and endoribonuclease-prepared small interfering RNA–mediated combined inhibition of those transcription factors phenocopied the glycolytic shift that was observed in high glucose conditions. Accordingly, a reduced expression of MEF2C, MYF5, and PGC-1α was found in kidney tissue sections that were obtained from patients with diabetic nephropathy. These findings obtained in human samples demonstrate that MEF2C-MYF5–dependent bioenergetic dedifferentiation occurs in podocytes that are confronted with a high-glucose milieu.—Imasawa, T., Obre, E., Bellance, N., Lavie, J., Imasawa, T., Rigothier, C., Delmas, Y., Combe, C., Lacombe, D., Benard, G., Claverol, S., Bonneu, M., Rossignol, R. High glucose repatterns human podocyte energy

  15. Complex Patterns of Metabolic and Ca2+ Entrainment in Pancreatic Islets by Oscillatory Glucose

    DEFF Research Database (Denmark)

    Pedersen, Morten Gram; Mosekilde, Erik; Polonsky, Kenneth S.

    2013-01-01

    fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) in islet Ca2+ , NAD(P)H, and mitochondrial membrane potential. To our knowledge, this is the first......Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca2+in pancreatic islets. Periodic variations in glucose can entrain islet Ca2+ and insulin secretion, possibly promoting interislet synchronization. Here, we used...... demonstration of metabolic entrainment in islets, and we found that entrainment of metabolic oscillations requires voltage-gated Ca2+ influx. We identified diverse patterns of 1:2 entrainment and showed that islet synchronization during entrainment involves adjustments of both oscillatory phase and period. All...

  16. A PET study of cerebellar metabolism in normal and abnormal states

    Energy Technology Data Exchange (ETDEWEB)

    Kushner, M.; Alavi, A.; Chawluk, J.; Silver, F.; Dann, R.; Rosen, M.; Reivich, M.

    1985-05-01

    The authors studied cerebellar metabolism under varying conditions of sensory stimulation. Cerebellar glucose consumption was measured by positron emission scanning and 18F-fluorodeoxyglucose in 64 subjects. Cerebellar metabolism relative to the whole brain (CM), and the asymmetry of metabolism between the cerebellar hemispheres (CA) was determined. The lowest CM occurred with maximal sensory deprivation, eyes and ears closed, (CM=96%, n=6). CM increased nonsignificantly with visual stimulation (CM=99%,n=17) and was highest for auditory stimulation (CM=104%,n=10,p<.05). CA was unaffected by sensory input. Under ambient conditions the CM values were 101%, 113% and 135% respectively for young controls (n=9, age=22), old controls (n=8, age=61) and Alzheimer patients (SDAT, n=14, age=69). This difference was significant for SDAT vs young and old controls and was nearly significant for young vs old controls.

  17. Akt Requires Glucose Metabolism to Suppress Puma Expression and Prevent Apoptosis of Leukemic T Cells*

    Science.gov (United States)

    Coloff, Jonathan L.; Mason, Emily F.; Altman, Brian J.; Gerriets, Valerie A.; Liu, Tingyu; Nichols, Amanda N.; Zhao, Yuxing; Wofford, Jessica A.; Jacobs, Sarah R.; Ilkayeva, Olga; Garrison, Sean P.; Zambetti, Gerard P.; Rathmell, Jeffrey C.

    2011-01-01

    The PI3K/Akt pathway is activated in stimulated cells and in many cancers to promote glucose metabolism and prevent cell death. Although inhibition of Akt-mediated cell survival may provide a means to eliminate cancer cells, this survival pathway remains incompletely understood. In particular, unlike anti-apoptotic Bcl-2 family proteins that prevent apoptosis independent of glucose, Akt requires glucose metabolism to inhibit cell death. This glucose dependence may occur in part through metabolic regulation of pro-apoptotic Bcl-2 family proteins. Here, we show that activated Akt relies on glycolysis to inhibit induction of Puma, which was uniquely sensitive to metabolic status among pro-apoptotic Bcl-2 family members and was rapidly up-regulated in glucose-deficient conditions. Importantly, preventing Puma expression was critical for Akt-mediated cell survival, as Puma deficiency protected cells from glucose deprivation and Akt could not readily block Puma-mediated apoptosis. In contrast, the pro-apoptotic Bcl-2 family protein Bim was induced normally even when constitutively active Akt was expressed, yet Akt could provide protection from Bim cytotoxicity. Up-regulation of Puma appeared mediated by decreased availability of mitochondrial metabolites rather than glycolysis itself, as alternative mitochondrial fuels could suppress Puma induction and apoptosis upon glucose deprivation. Metabolic regulation of Puma was mediated through combined p53-dependent transcriptional induction and control of Puma protein stability, with Puma degraded in nutrient-replete conditions and long lived in nutrient deficiency. Together, these data identify a key role for Bcl-2 family proteins in Akt-mediated cell survival that may be critical in normal immunity and in cancer through Akt-dependent stimulation of glycolysis to suppress Puma expression. PMID:21159778

  18. Metabolic determinants of cancer cell sensitivity to glucose limitation and biguanides

    Science.gov (United States)

    Birsoy, Kıvanç; Possemato, Richard; Lorbeer, Franziska K.; Bayraktar, Erol C.; Thiru, Prathapan; Yucel, Burcu; Wang, Tim; Chen, Walter W.; Clish, Clary B.; Sabatini, David M.

    2014-04-01

    As the concentrations of highly consumed nutrients, particularly glucose, are generally lower in tumours than in normal tissues, cancer cells must adapt their metabolism to the tumour microenvironment. A better understanding of these adaptations might reveal cancer cell liabilities that can be exploited for therapeutic benefit. Here we developed a continuous-flow culture apparatus (Nutrostat) for maintaining proliferating cells in low-nutrient media for long periods of time, and used it to undertake competitive proliferation assays on a pooled collection of barcoded cancer cell lines cultured in low-glucose conditions. Sensitivity to low glucose varies amongst cell lines, and an RNA interference (RNAi) screen pinpointed mitochondrial oxidative phosphorylation (OXPHOS) as the major pathway required for optimal proliferation in low glucose. We found that cell lines most sensitive to low glucose are defective in the OXPHOS upregulation that is normally caused by glucose limitation as a result of either mitochondrial DNA (mtDNA) mutations in complex I genes or impaired glucose utilization. These defects predict sensitivity to biguanides, antidiabetic drugs that inhibit OXPHOS, when cancer cells are grown in low glucose or as tumour xenografts. Notably, the biguanide sensitivity of cancer cells with mtDNA mutations was reversed by ectopic expression of yeast NDI1, a ubiquinone oxidoreductase that allows bypass of complex I function. Thus, we conclude that mtDNA mutations and impaired glucose utilization are potential biomarkers for identifying tumours with increased sensitivity to OXPHOS inhibitors.

  19. Berberine Improves Glucose Metabolism through Induction of Glycolysis

    OpenAIRE

    Yin, Jun; Gao, Zhanguo; Liu, Dong; Liu, Zhijun; Ye, Jianping

    2007-01-01

    Berberine, a botanical alkaloid used to control blood glucose in type 2 diabetes in China, has been reported to activate AMPK recently. However, it is not clear how AMPK is activated by berberine. In this study, activity and action mechanism of berberine were investigated in vivo and in vitro. In dietary obese rats, berberine increased insulin sensitivity after five week administration. Fasting insulin and HOMA-IR were decreased by 46% and 48% in the rats, respectively. In cell lines includin...

  20. Ketones and brain development: Implications for correcting deteriorating brain glucose metabolism during aging

    Directory of Open Access Journals (Sweden)

    Nugent Scott

    2016-01-01

    Full Text Available Brain energy metabolism in Alzheimer’s disease (AD is characterized mainly by temporo-parietal glucose hypometabolism. This pattern has been widely viewed as a consequence of the disease, i.e. deteriorating neuronal function leading to lower demand for glucose. This review will address deteriorating glucose metabolism as a problem specific to glucose and one that precedes AD. Hence, ketones and medium chain fatty acids (MCFA could be an alternative source of energy for the aging brain that could compensate for low brain glucose uptake. MCFA in the form of dietary medium chain triglycerides (MCT have a long history in clinical nutrition and are widely regarded as safe by government regulatory agencies. The importance of ketones in meeting the high energy and anabolic requirements of the infant brain suggest they may be able to contribute in the same way in the aging brain. Clinical studies suggest that ketogenesis from MCT may be able to bypass the increasing risk of insufficient glucose uptake or metabolism in the aging brain sufficiently to have positive effects on cognition.

  1. Glucose metabolism during fasting is altered in experimental porphobilinogen deaminase deficiency.

    Science.gov (United States)

    Collantes, María; Serrano-Mendioroz, Irantzu; Benito, Marina; Molinet-Dronda, Francisco; Delgado, Mercedes; Vinaixa, María; Sampedro, Ana; Enríquez de Salamanca, Rafael; Prieto, Elena; Pozo, Miguel A; Peñuelas, Iván; Corrales, Fernando J; Barajas, Miguel; Fontanellas, Antonio

    2016-04-01

    Porphobilinogen deaminase (PBGD) haploinsufficiency (acute intermittent porphyria, AIP) is characterized by neurovisceral attacks when hepatic heme synthesis is activated by endogenous or environmental factors including fasting. While the molecular mechanisms underlying the nutritional regulation of hepatic heme synthesis have been described, glucose homeostasis during fasting is poorly understood in porphyria. Our study aimed to analyse glucose homeostasis and hepatic carbohydrate metabolism during fasting in PBGD-deficient mice. To determine the contribution of hepatic PBGD deficiency to carbohydrate metabolism, AIP mice injected with a PBGD-liver gene delivery vector were included. After a 14 h fasting period, serum and liver metabolomics analyses showed that wild-type mice stimulated hepatic glycogen degradation to maintain glucose homeostasis while AIP livers activated gluconeogenesis and ketogenesis due to their inability to use stored glycogen. The serum of fasted AIP mice showed increased concentrations of insulin and reduced glucagon levels. Specific over-expression of the PBGD protein in the liver tended to normalize circulating insulin and glucagon levels, stimulated hepatic glycogen catabolism and blocked ketone body production. Reduced glucose uptake was observed in the primary somatosensorial brain cortex of fasted AIP mice, which could be reversed by PBGD-liver gene delivery. In conclusion, AIP mice showed a different response to fasting as measured by altered carbohydrate metabolism in the liver and modified glucose consumption in the brain cortex. Glucose homeostasis in fasted AIP mice was efficiently normalized after restoration of PBGD gene expression in the liver.

  2. Perinatal exposure to perfluorooctane sulfonate affects glucose metabolism in adult offspring.

    Directory of Open Access Journals (Sweden)

    Hin T Wan

    Full Text Available Perfluoroalkyl acids (PFAAs are globally present in the environment and are widely distributed in human populations and wildlife. The chemicals are ubiquitous in human body fluids and have a long serum elimination half-life. The notorious member of PFAAs, perfluorooctane sulfonate (PFOS is prioritized as a global concerning chemical at the Stockholm Convention in 2009, due to its harmful effects in mammals and aquatic organisms. PFOS is known to affect lipid metabolism in adults and was found to be able to cross human placenta. However the effects of in utero exposure to the susceptibility of metabolic disorders in offspring have not yet been elucidated. In this study, pregnant CD-1 mice (F0 were fed with 0, 0.3 or 3 mg PFOS/kg body weight/day in corn oil by oral gavage daily throughout gestational and lactation periods. We investigated the immediate effects of perinatal exposure to PFOS on glucose metabolism in both maternal and offspring after weaning (PND 21. To determine if the perinatal exposure predisposes the risk for metabolic disorder to the offspring, weaned animals without further PFOS exposure, were fed with either standard or high-fat diet until PND 63. Fasting glucose and insulin levels were measured while HOMA-IR index and glucose AUCs were reported. Our data illustrated the first time the effects of the environmental equivalent dose of PFOS exposure on the disturbance of glucose metabolism in F1 pups and F1 adults at PND 21 and 63, respectively. Although the biological effects of PFOS on the elevated levels of fasting serum glucose and insulin levels were observed in both pups and adults of F1, the phenotypes of insulin resistance and glucose intolerance were only evident in the F1 adults. The effects were exacerbated under HFD, highlighting the synergistic action at postnatal growth on the development of metabolic disorders.

  3. Effects of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in bovine mammary epithelial cells.

    Directory of Open Access Journals (Sweden)

    Hongyun Liu

    Full Text Available As the main precursor for lactose synthesis, large amounts of glucose are required by lactating dairy cows. Milk yield greatly depends on mammary lactose synthesis due to its osmoregulatory property for mammary uptake of water. Thus, glucose availability to the mammary gland could be a potential regulator of milk production. In the present study, the effect of glucose availability on expression of the key genes involved in synthesis of milk fat, lactose and glucose metabolism in vitro was investigated. Bovine mammary epithelial cells (BMEC were treated for 12 h with various concentrations of glucose (2.5, 5, 10 or 20 mmol/L. The higher concentrations of glucose (10-20 mmol/L did not affect the mRNA expression of acetyl-CoA carboxylase, diacyl glycerol acyl transferase, glycerol-3 phosphate acyl transferase and α-lactalbumin, whereas fatty acid synthase, sterol regulatory element binding protein-1 and beta-1, 4-galactosyl transferase mRNA expression increased at 10 mmol/L and then decreased at 20 mmol/L. The content of lactose synthase increased with increasing concentration of glucose, with addition of highest value at 20 mmol/L of glucose. Moreover, the increased glucose concentration stimulated the activities of pyruvate kinase and glucose-6-phosphate dehydrogenase, and elevated the energy status of the BMEC. Therefore, it was deduced that after increasing glucose availability, the extra absorbed glucose was partitioned to entering the synthesis of milk fat and lactose by the regulation of the mRNA expression of key genes, promoting glucose metabolism by glycolysis and pentose phosphate pathway as well as energy status. These results indicated that the sufficient availability of glucose in BMEC may promote glucose metabolism, and affect the synthesis of milk composition.

  4. Disturbed postprandial glucose metabolism and gut hormone responses in non-diabetic patients with psoriasis

    DEFF Research Database (Denmark)

    Gyldenløve, M; Vilsbøll, T; Holst, Jens Juul

    2016-01-01

    Patients with psoriasis have increased risk of developing type 2 diabetes.(1-4) Though the aetiology is not fully understood, overrepresentation of traditional diabetes risk factors, shared genetics, and chronic inflammation likely explain some of the increased susceptibility. Glucose metabolism...... in patients with psoriasis has only been sparsely investigated. Previous studies are based on fasting blood samples analysed for glucose and insulin or various forms of glucose and/or insulin challenges.(5-11) The results are generally difficult to compare due to methodological differences and limitations...

  5. Germ band retraction as a landmark in glucose metabolism during Aedes aegypti embryogenesis

    Directory of Open Access Journals (Sweden)

    Logullo Carlos

    2010-02-01

    Full Text Available Abstract Background The mosquito A. aegypti is vector of dengue and other viruses. New methods of vector control are needed and can be achieved by a better understanding of the life cycle of this insect. Embryogenesis is a part of A. aegypty life cycle that is poorly understood. In insects in general and in mosquitoes in particular energetic metabolism is well studied during oogenesis, when the oocyte exhibits fast growth, accumulating carbohydrates, lipids and proteins that will meet the regulatory and metabolic needs of the developing embryo. On the other hand, events related with energetic metabolism during A. aegypti embryogenesis are unknown. Results Glucose metabolism was investigated throughout Aedes aegypti (Diptera embryonic development. Both cellular blastoderm formation (CBf, 5 h after egg laying - HAE and germ band retraction (GBr, 24 HAE may be considered landmarks regarding glucose 6-phosphate (G6P destination. We observed high levels of glucose 6-phosphate dehydrogenase (G6PDH activity at the very beginning of embryogenesis, which nevertheless decreased up to 5 HAE. This activity is correlated with the need for nucleotide precursors generated by the pentose phosphate pathway (PPP, of which G6PDH is the key enzyme. We suggest the synchronism of egg metabolism with carbohydrate distribution based on the decreasing levels of phosphoenolpyruvate carboxykinase (PEPCK activity and on the elevation observed in protein content up to 24 HAE. Concomitantly, increasing levels of hexokinase (HK and pyruvate kinase (PK activity were observed, and PEPCK reached a peak around 48 HAE. Glycogen synthase kinase (GSK3 activity was also monitored and shown to be inversely correlated with glycogen distribution during embryogenesis. Conclusions The results herein support the hypothesis that glucose metabolic fate changes according to developmental embryonic stages. Germ band retraction is a moment that was characterized as a landmark in glucose

  6. Comparing brain amyloid deposition, glucose metabolism, and atrophy in mild cognitive impairment with and without a family history of dementia.

    Science.gov (United States)

    Mosconi, Lisa; Andrews, Randolph D; Matthews, Dawn C

    2013-01-01

    This study compares the degree of brain amyloid-β (Aβ) deposition, glucose metabolism, and grey matter volume (GMV) reductions in mild cognitive impairment (MCI) patients overall and as a function of their parental history of dementia. Ten MCI with maternal history (MH), 8 with paternal history (PH), and 24 with negative family history (NH) received 11C-PiB and 18F-FDG PET and T1-MRI as part of the Alzheimer's Disease Neuroimaging Initiative. Statistical parametric mapping, voxel based morphometry, and Z-score mapping were used to compare biomarkers across MCI groups, and relative to 12 normal controls. MCI had higher PiB retention, hypometabolism, and GMV reductions in Alzheimer-vulnerable regions compared to controls. Biomarker abnormalities were more pronounced in MCI with MH than those with PH and NH. After partial volume correction of PET, Aβ load exceeded hypometabolism and atrophy with regard to the number of regions affected and magnitude of impairment in those regions. Hypometabolism exceeded atrophy in all MCI groups and exceeded Aβ load in medial temporal and posterior cingulate regions of MCI MH. While all three biomarkers were abnormal in MCI compared to controls, Aβ deposition was the most prominent abnormality, with MCI MH having the greatest degree of co-occurring hypometabolism.

  7. Alterations in local cerebral glucose metabolism and endogenous thyrotropin-releasing hormone levels in rolling mouse Nagoya and effect of thyrotropin-releasing hormone tartrate.

    Science.gov (United States)

    Nakayama, T; Nagai, Y

    1996-11-01

    To identify the brain region(s) responsible for the expression of ataxic gaits in an ataxic mutant mouse model, Rolling mouse Nagoya (RMN), changes in local cerebral glucose metabolism in various brain regions and the effect of thyrotropin-releasing hormone tartrate (TRH-T), together with alterations in endogenous thyrotropin-releasing hormone (TRH) levels in the brains of RMN, were investigated. Ataxic mice [RMN (rol/rol)] showed significant decreases in glucose metabolism in regions of the diencephalon: thalamic dorsomedial nucleus, lateral geniculate body and superior colliculus; brain stem: substantia nigra, raphe nucleus and vestibular nucleus; and cerebellar nucleus as compared with normal controls [RMN (+/+)]. When RMN (rol/rol) was treated with TRH-T (10 mg/kg, equivalent to 7 mg/kg free TRH), glucose metabolism was significantly increased in these regions. These results suggest that these regions may be responsible for ataxia. We also found that TRH levels in the cerebellum and brain stem of RMN (rol/rol) were significantly higher than those of RMN (+/+). These results suggest that ataxic symptoms in RMN (rol/rol) may relate to the abnormal metabolism of TRH and energy metabolism in the cerebellum and/or brain stem and that exogenously given TRH normalizes them.

  8. Metabolic network analysis of Bacillus clausii on minimal and semirich medium using C-13-Labeled glucose

    DEFF Research Database (Denmark)

    Christiansen, Torben; Christensen, Bjarke; Nielsen, Jens

    2002-01-01

    from the medium and partly synthesized from glucose. The metabolic network analysis was extended to include analysis of growth on the semirich medium containing amino acids, and the metabolic flux distribution on this medium was estimated and compared with growth on minimal medium....... to increase with increasing specific growth rate but at a much lower level than previously reported for Bacillus subtilis. Two futile cycles in the pyruvate metabolism were included in the metabolic network. A substantial flux in the futile cycle involving malic enzyme was estimated, whereas only a very small......Using C-13-labeled glucose fed to the facultative alkalophilic Bacillus clausii producing the alkaline serine protease Savinase, the intracellular fluxes were quantified in continuous cultivation and in batch cultivation on a minimal medium. The flux through the pentose phosphate pathway was found...

  9. The effect of vagal nerve blockade using electrical impulses on glucose metabolism in nondiabetic subjects

    Directory of Open Access Journals (Sweden)

    Sathananthan M

    2014-07-01

    Full Text Available Matheni Sathananthan,1 Sayeed Ikramuddin,2 James M Swain,3,6 Meera Shah,1 Francesca Piccinini,4 Chiara Dalla Man,4 Claudio Cobelli,4 Robert A Rizza,1 Michael Camilleri,5 Adrian Vella1 1Division of Endocrinology, Diabetes and Metabolism, Mayo Clinic College of Medicine, Rochester, MN, USA; 2Division of General Surgery, University of Minnesota, Minneapolis, MN, USA; 3Division of General Surgery, Mayo Clinic College of Medicine, Rochester, MN, USA; 4Department of Information Engineering, University of Padua, Padua, Italy; 5Division of Gastroenterology and Hepatology, Mayo Clinic College of Medicine, Rochester, MN, USA; 6Scottsdale Healthcare Bariatric Center, Scottsdale, AZ, USA Purpose: Vagal interruption causes weight loss in humans and decreases endogenous glucose production in animals. However, it is unknown if this is due to a direct effect on glucose metabolism. We sought to determine if vagal blockade using electrical impulses alters glucose metabolism in humans. Patients and methods: We utilized a randomized, cross-over study design where participants were studied after 2 weeks of activation or inactivation of vagal nerve blockade (VNB. Seven obese subjects with impaired fasting glucose previously enrolled in a long-term study to examine the effect of VNB on weight took part. We used a standardized triple-tracer mixed meal to enable measurement of the rate of meal appearance, endogenous glucose production, and glucose disappearance. The 550 kcal meal was also labeled with 111In-diethylene triamine pentaacetic acid (DTPA to measure gastrointestinal transit. Insulin action and ß-cell responsivity indices were estimated using the minimal model. Results: Integrated glucose, insulin, and glucagon concentrations did not differ between study days. This was also reflected in a lack of effect on β-cell responsivity and insulin action. Furthermore, fasting and postprandial endogenous glucose production, integrated meal appearance, and glucose

  10. The Lin28/let-7 Axis Regulates Glucose Metabolism

    NARCIS (Netherlands)

    Zhu, Hao; Shyh-Chang, Ng; Segre, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G.; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

    2011-01-01

    The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by inhibiting let-7 biogenesis. We have uncovered unexpected roles for the Lin28/let-7 pathway in regulating-metabolism. When overexpressed in mice, both Lin28

  11. The characteristics of cortical glucose metabolism in amblyopia

    Energy Technology Data Exchange (ETDEWEB)

    Ahn, Ji Young [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of); Lee, Dong Soo; Chung, June Key; Shin, Seung Ai; Lee, Myung Chul [College of Medicine, Ewha Womans Univ., Seoul (Korea, Republic of)

    2000-07-01

    Cortical metabolism of amblyopia patients was investigated with F-18-FDG PET and Statistical Parametric Mapping (SPM) and quantificiation based on volume of interest (VOI) by statistical probabilistic anatomical map (SPAM). In 9 amblyopic patients (12{+-}7 years ) and 20 normal subjects (23{+-}2 years), F-18-FDG PET scans were peformed in amblyopic patients after amblyopic eye or sound eye was patch-closed during PET studies. SPM was done with SPM96. By multiplying SPAM to FDG images, counts of 98 VOI's were calculated and compared with 3 S. D. range of those of normal subjects. On SPM, cortical metabolism decreased (p<0.05) in occipital lobe (Ba 17, 18, 19), superior partietal lobe (Ba 7), and inferior temporal lobe (BA 37, 20). FDG uptake of gyri of occuipital lobe was decreased in 2 and increased in 2, and was normal in the other 5. FDG uptake of gyri of parietal, frontal, and temporal lobes were decreased in FDG uptake on these VOIs. We conclude that cortical metabolism in occipital lobe and extraoccipital lobes was variable but was consistent regardless of visual input during PET studies in amblyopic patients. SPM and quantification of functional images using SPAM could reveal subtle differences or changes according to visual input. The significance of metabolic changes of extraoccipital lobes should be studies further.

  12. Sexual Dimorphism in Glucose and Lipid Metabolism during Fasting, Hypoglycemia, and Exercise

    OpenAIRE

    Hedrington, Maka S.; Davis, Stephen N.

    2015-01-01

    Sexually dimorphic physiologic responses occur during fasting, hypoglycemia, and exercise. The areas covered in this mini review include studies that have used isotopic tracer methods and/or euglycemic clamp studies to investigate substrate metabolism during the above common physiologic stress. Women have greater reliance on lipid metabolism during fasting, hypoglycemia, and exercise while men exhibit preference of carbohydrate utilization. Plasma glucose concentrations were shown to be lower...

  13. TAp63 is a master transcriptional regulator of lipid and glucose metabolism

    OpenAIRE

    Su, Xiaohua; Gi, Young Jin; Chakravarti, Deepavali; Chan, Io Long; Zhang, Aijun; Xia, Xuefeng; Tsai, Kenneth Y.; Flores, Elsa R.

    2012-01-01

    TAp63 prevents premature aging suggesting a link to genes that regulate longevity. Further characterization of TAp63−/− mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance, similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulati...

  14. Possible associations between antioxidant enzyme polymorphisms and metabolic abnormalities in patients with schizophrenia

    Directory of Open Access Journals (Sweden)

    Saruwatari J

    2013-11-01

    Full Text Available Junji Saruwatari,1,* Norio Yasui-Furukori,2,* Ryoko Kamihashi,1 Yuki Yoshimori,1 Kentaro Oniki,1 Shoko Tsuchimine,2 Madoka Noai,1 Yasushi Sato,3 Taku Nakagami,4 Norio Sugawara,2 Manabu Saito,2 Akira Fujii,2 Ayami Kajiwara,1 Shuichi Mihara,5 Yasuhiro Ogata,6 Sunao Kaneko,2 Kazuko Nakagawa1,71Division of Pharmacology and Therapeutics, Graduate School of Pharmaceutical Sciences, Kumamoto University, Kumamoto, 2Department of Neuropsychiatry, Hirosaki University School of Medicine, Hirosaki, 3Department of Psychiatry, Hirosaki Aiseikai Hospital, Hirosaki, 4Department of Psychiatry, Odate Municipal General Hospital, Odate, 5Mihara Life Care Clinic, Kumamoto, 6Japanese Red Cross Kumamoto Health Care Center, Kumamoto, 7Center for Clinical Pharmaceutical Sciences, Kumamoto University, Kumamoto, Japan*These authors contributed equally to this paperBackground: This study investigated the possible association between common and potentially functional polymorphisms of antioxidant enzymes and metabolic abnormalities in patients with schizophrenia.Methods: The possible associations of the glutathione S-transferase (GST M1 null and GSTT1 null genotypes, and the superoxide dismutase 2 (SOD2 Val16Ala polymorphism with the risks of being overweight and having metabolic syndrome were examined using a logistic regression analysis in 154 schizophrenic Japanese patients and 203 controls.Results: Among smokers with schizophrenia, the risks of being overweight and having decreased high-density lipoprotein cholesterol were significantly higher in those with the GSTM1 null genotype than in those with the present genotype (odds ratio 3.20 and 3.15, P=0.03 and P=0.04, respectively, while among nonsmokers with schizophrenia, the risk of an abnormal waist circumference was lower in those with the GSTM1 null genotype (odds ratio 0.34, P=0.04. The risk of a decreased high-density lipoprotein cholesterol level was significantly higher in patients with the combined GSTM1 null and

  15. Correlation of brain cell glucose metabolism and patient's condition in children with epileptic encephalopathy An assessment using fluorine-18-fluoro-2-deoxy-D-glucose positron emission computed tomography

    Institute of Scientific and Technical Information of China (English)

    Qiongxiang Zhai; Yuxiong Guo; Yuxin Zhang; Zhihong Chen; Jian Ding; Juan Gui; Ying Hao

    2011-01-01

    We examined a total of 16 children with epileptic encephalopathy using fluorine-18-fluoro-2-deoxy-D-glucose (18F-FDG) positron emission computed tomography (PET), magnetic resonance imaging (MRI) and electroencephalography.Children with infantile spasms showed significant mental retardation, severely abnormal electroencephalogram recordings, and bilateral diffuse cerebral cortex hypometabolism with 18F-FDG PET imaging.MRI in these cases showed brain atrophy, multi-micropolygyria, macrogyria, and porencephalia.In cases with Lennox-Gastaut syndrome, 18F-FDG PET showed bilateral diffuse glucose hypometabolism, while MRI showed cortical atrophy, heterotopic gray matter and tuberous sclerosis.MRI in cases with myoclonic encephalopathy demonstrated bilateral frontal and temporal cortical and white matter atrophy and 18F-FDG PET imaging showed bilateral frontal lobe atrophy with reduced bilateral frontal cortex, occipital cortex, temporal cortex and cerebellar glucose uptake.In children who could not be clearly classified, MRI demonstrated cerebral cortical atrophy and 18F-FDG PET exhibited multifocal glucose hypometabolism.Overall, this study demonstrated that the degree of brain metabolic abnormality was consistent with clinical seizure severity.In addition, 18F-FDG PET imaging after treatment was consistent with clinical outcomes.These findings indicate that 18F-FDG PET can be used to assess the severity of brain injury and prognosis in children with epileptic encephalopathy.

  16. Pattern of cerebral glucose metabolism on F-18 FDG brain PET during vomiting and symptom free periods in cyclic vomiting syndrome

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Yu Kyeong; Lee, Dong Soo; Kang, Eun Joo; Seo, Jeong Kee; Yeo, Jeong Seok; Chung, June Key; Lee, Myung Chul [College of Medicine, Seoul National Univ., Seoul (Korea, Republic of)

    2001-06-01

    Cyclic Vomiting Syndrome (CVS) is characterized by recurrent, periodic, self-limiting vomiting. However, its pathogenesis is not yet established. We investigated the changes of the cerebral glucose metabolism using F-18 FDG during the vomiting attack and symptom free period in two children with CVS. FDG PET study showed the markedly increased metabolism in both temporal lobes and also in the medulla and cerebellum during the vomiting period. Also, FDG PET showed the decreased metabolism in the parieto-occipital and occipital areas during the in vomiting period. The area with decreased metabolism seemed to be related with the region showing abnormalities in EEG and perfusion SPECT studies. We expect that what we observed would be a helpful finding in clarifying the pathogenesis of the CVS.

  17. The Severity of Fatty Liver Disease Relating to Metabolic Abnormalities Independently Predicts Coronary Calcification

    Directory of Open Access Journals (Sweden)

    Ying-Hsiang Lee

    2011-01-01

    Full Text Available Background. Nonalcoholic fatty liver disease (NAFLD is one of the metabolic disorders presented in liver. The relationship between severity of NAFLD and coronary atherosclerotic burden remains largely unknown. Methods and Materials. We analyzed subjects undergoing coronary calcium score evaluation by computed tomography (MDCT and fatty liver assessment using abdominal ultrasonography. Framingham risk score (FRS and metabolic risk score (MRS were obtained in all subjects. A graded, semiquantitative score was established to quantify the severity of NAFLD. Multivariate logistic regression analysis was used to depict the association between NAFLD and calcium score. Results. Of all, 342 participants (female: 22.5%, mean age: 48.7±7.0 years met the sufficient information rendering detailed analysis. The severity of NAFLD was positively associated with MRS (X2=6.12, trend P<0.001 and FRS (X2=5.88, trend P<0.001. After multivariable adjustment for clinical variables and life styles, the existence of moderate to severe NAFLD was independently associated with abnormal calcium score (P<0.05. Conclusion. The severity of NAFLD correlated well with metabolic abnormality and was independently predict coronary calcification beyond clinical factors. Our data suggests that NAFLD based on ultrasonogram could positively reflect the burden of coronary calcification.

  18. Glucose metabolism and astrocyte-neuron interactions in the neonatal brain.

    Science.gov (United States)

    Brekke, Eva; Morken, Tora Sund; Sonnewald, Ursula

    2015-03-01

    Glucose is essentially the sole fuel for the adult brain and the mapping of its metabolism has been extensive in the adult but not in the neonatal brain, which is believed to rely mainly on ketone bodies for energy supply. However, glucose is absolutely indispensable for normal development and recent studies have shed light on glycolysis, the pentose phosphate pathway and metabolic interactions between astrocytes and neurons in the 7-day-old rat brain. Appropriately (13)C labeled glucose was used to distinguish between glycolysis and the pentose phosphate pathway during development. Experiments using (13)C labeled acetate provided insight into the GABA-glutamate-glutamine cycle between astrocytes and neurons. It could be shown that in the neonatal brain the part of this cycle that transfers glutamine from astrocytes to neurons is operating efficiently while, in contrast, little glutamate is shuttled from neurons to astrocytes. This lack of glutamate for glutamine synthesis is compensated for by anaplerosis via increased pyruvate carboxylation relative to that in the adult brain. Furthermore, compared to adults, relatively more glucose is prioritized to the pentose phosphate pathway than glycolysis and pyruvate dehydrogenase activity. The reported developmental differences in glucose metabolism and neurotransmitter synthesis may determine the ability of the brain at various ages to resist excitotoxic insults such as hypoxia-ischemia.

  19. Muscle insulin sensitivity and glucose metabolism are controlled by the intrinsic muscle clock★

    Science.gov (United States)

    Dyar, Kenneth A.; Ciciliot, Stefano; Wright, Lauren E.; Biensø, Rasmus S.; Tagliazucchi, Guidantonio M.; Patel, Vishal R.; Forcato, Mattia; Paz, Marcia I.P.; Gudiksen, Anders; Solagna, Francesca; Albiero, Mattia; Moretti, Irene; Eckel-Mahan, Kristin L.; Baldi, Pierre; Sassone-Corsi, Paolo; Rizzuto, Rosario; Bicciato, Silvio; Pilegaard, Henriette; Blaauw, Bert; Schiaffino, Stefano

    2013-01-01

    Circadian rhythms control metabolism and energy homeostasis, but the role of the skeletal muscle clock has never been explored. We generated conditional and inducible mouse lines with muscle-specific ablation of the core clock gene Bmal1. Skeletal muscles from these mice showed impaired insulin-stimulated glucose uptake with reduced protein levels of GLUT4, the insulin-dependent glucose transporter, and TBC1D1, a Rab-GTPase involved in GLUT4 translocation. Pyruvate dehydrogenase (PDH) activity was also reduced due to altered expression of circadian genes Pdk4 and Pdp1, coding for PDH kinase and phosphatase, respectively. PDH inhibition leads to reduced glucose oxidation and diversion of glycolytic intermediates to alternative metabolic pathways, as revealed by metabolome analysis. The impaired glucose metabolism induced by muscle-specific Bmal1 knockout suggests that a major physiological role of the muscle clock is to prepare for the transition from the rest/fasting phase to the active/feeding phase, when glucose becomes the predominant fuel for skeletal muscle. PMID:24567902

  20. Branched-chain amino acid metabolism in rat muscle: abnormal regulation in acidosis

    Energy Technology Data Exchange (ETDEWEB)

    May, R.C.; Hara, Y.; Kelly, R.A.; Block, K.P.; Buse, M.G.; Mitch, W.E.

    1987-06-01

    Branched-chain amino acid (BCAA) metabolism is frequently abnormal in pathological conditions accompanied by chronic metabolic acidosis. To study how metabolic acidosis affects BCAA metabolism in muscle, rats were gavage fed a 14% protein diet with or without 4 mmol NH/sub 4/Cl x 100 g body wt/sup -1/ x day/sup -1/. Epitrochlearis muscles were incubated with L-(1-/sup 14/C)-valine and L-(1-/sup 14/C)leucine, and rates of decarboxylation, net transamination, and incorporation into muscle protein were measured. Plasma and muscle BCAA levels were lower in acidotic rats. Rates of valine and leucine decarboxylation and net transamination were higher in muscles from acidotic rats; these differences were associated with a 79% increase in the total activity of branched-chain ..cap alpha..-keto acid dehydrogenase and a 146% increase in the activated form of the enzyme. They conclude that acidosis affects the regulation of BCAA metabolism by enhancing flux through the transaminase and by directly stimulating oxidative catabolism through activation of branched-chain ..cap alpha..-keto acid dehydrogenase.

  1. Neonatal seizures: the overlap between diagnosis of metabolic disorders and structural abnormalities. Case report

    Directory of Open Access Journals (Sweden)

    Freitas Alessandra

    2003-01-01

    Full Text Available Inborn metabolic errors (IME and cortical developmental malformations are uncommon etiologies of neonatal seizures, however they may represent treatable causes of refractory epilepsy and for this reason must be considered as possible etiological factors. This case report aims to demonstrate the importance of neuroimaging studies in one patient with neonatal seizures, even when there are clues pointing to a metabolic disorder. CASE REPORT: A previously healthy 14 day-old child started presenting reiterated focal motor seizures (FMS which evolved to status epilepticus. Exams showed high serum levels of ammonia and no other abnormalities. A metabolic investigation was conducted with normal results. During follow-up, the patient presented developmental delay and left side hemiparesia. Seizures remained controlled with anti-epileptic drugs for four months, followed by relapse with repetitive FMS on the left side. Temporary improvement was obtained with anti-epileptic drug adjustment. At the age of 6 months, during a new episode of status epilepticus, high ammonia levels were detected. Other metabolic exams remained normal. The child was referred to a video-electroencephalographic monitoring and continuous epileptiform discharges were recorded over the right parasagittal and midline regions, with predominance over the posterior quadrant. A new neuroimaging study was performed and displayed a malformation of cortical development. Our case illustrates that because newborns are prone to present metabolic disarrangement, an unbalance such as hyperammonemia may be a consequence of acute events and conduct to a misdiagnosis of IME.

  2. Glucose metabolism in completed suicide: a forensic-pathological pilot study

    Science.gov (United States)

    Forsman, Jonas; Keltanen, Terhi; Liberg, Benny; Sajantila, Antti; Masterman, Thomas; Lindroos, Katarina

    2017-01-01

    Aim To determine whether antemortem blood levels of glycated hemoglobin (HbA1c) and glucose predict completed suicide and, by extension, whether markers of glucose metabolism might be associated with a prosuicidal trait or state. Method From consecutively performed autopsies, samples of blood and vitreous humor from 17 suicide victims and 27 non-suicide controls were compared with regard to levels of glucose, lactate, and HbA1c. Results Mean HbA1c was higher and mean estimated blood glucose was lower among suicide victims, although tests revealed no significant differences (P = 0.171 and P = 0.395, respectively). HbA1c levels exceeding 48.0 mmol/mol, which were indicative of persistent hyperglycemia, were twice as common in suicide victims (59% vs 30%; P = 0.068). Conclusion The finding of this pilot study suggest that deranged glucose metabolism may reflect biological events antecedent to, or concomitant with, completed suicide, with the following clinical implications: recurring hyperglycemia due to defective glucose transport, which may give rise to depression and suicidal ideation, and elevated HbA1c levels, which may represent an assayable correlate to neurobiological conditions predisposing to suicide. PMID:28252873

  3. Berberine improves glucose metabolism in diabetic rats by inhibition of hepatic gluconeogenesis.

    Directory of Open Access Journals (Sweden)

    Xuan Xia

    Full Text Available Berberine (BBR is a compound originally identified in a Chinese herbal medicine Huanglian (Coptis chinensis French. It improves glucose metabolism in type 2 diabetic patients. The mechanisms involve in activation of adenosine monophosphate activated protein kinase (AMPK and improvement of insulin sensitivity. However, it is not clear if BBR reduces blood glucose through other mechanism. In this study, we addressed this issue by examining liver response to BBR in diabetic rats, in which hyperglycemia was induced in Sprague-Dawley rats by high fat diet. We observed that BBR decreased fasting glucose significantly. Gluconeogenic genes, Phosphoenolpyruvate carboxykinase (PEPCK and Glucose-6-phosphatase (G6Pase, were decreased in liver by BBR. Hepatic steatosis was also reduced by BBR and expression of fatty acid synthase (FAS was inhibited in liver. Activities of transcription factors including Forkhead transcription factor O1 (FoxO1, sterol regulatory element-binding protein 1c (SREBP1 and carbohydrate responsive element-binding protein (ChREBP were decreased. Insulin signaling pathway was not altered in the liver. In cultured hepatocytes, BBR inhibited oxygen consumption and reduced intracellular adenosine triphosphate (ATP level. The data suggest that BBR improves fasting blood glucose by direct inhibition of gluconeogenesis in liver. This activity is not dependent on insulin action. The gluconeogenic inhibition is likely a result of mitochondria inhibition by BBR. The observation supports that BBR improves glucose metabolism through an insulin-independent pathway.

  4. Association between serum uric acid and different states of glucose metabolism and glomerular filtration rate

    Institute of Scientific and Technical Information of China (English)

    CAI Xiao-ling; HAN Xue-yao; JI Li-nong

    2010-01-01

    Background Recently, it has been suggested that the serum uric acid (SUA) level decreased in diabetic patients. The aim of this study was to explore the association between SUA level and different state of glucose metabolism and glomerular filtration rate (GFR) reflected by the simplified Modification of Diet in Renal Disease (MDRD) equation and to test the hypothesis that high MDRD is one of the determinants of SUA level.Methods This cross-sectional study included 2373 subjects in Beijing who underwent a 75 g oral glucose tolerance test (OGTT) for screening of diabetes. According to the states of glucose metabolism, they were divided into normal glucose tolerance, impaired glucose regulation and diabetes.Results Multiple stepwise linear regression analysis showed that adjusted by gender, SUA was positively correlated with body mass index (BMI), waist/hippo ratio, systolic blood pressure (SBP) and triglyceride, meanwhile negatively correlated with age, hemoglobin A1c, fasting insulin and MDRD. There was an increasing trend in SUA concentration and a decreasing trend in MDRD when the levels of fasting plasma glucose (FPG) increased from low to high up to the FPG level of 8.0 mmol/L; thereafter, the SUA concentration started to decrease with further increases in FPG levels, and the MDRD started to increase with further increases in FPG levels.Conclusion This study confirmed the previous finding that SUA decreased in diabetes and provided the supporting evidence that the increased MDRD might contribute to the fall of SUA.

  5. Quantification of pathways of glucose utilization and balance of energy metabolism of rabbit reticulocytes.

    Science.gov (United States)

    Siems, W; Müller, M; Dumdey, R; Holzhütter, H G; Rathmann, J; Rapoport, S M

    1982-06-01

    In this work it is demonstrated that glucose constitutes the main substrate of energy metabolism of rabbit reticulocytes under aerobic conditions in the presence of 5 mM glucose. Amino acids and fatty acids are minor sources of energy. The shares of processes utilizing glucose in reticulocytes were estimated from tracer experiments. A new mathematical technique used permits the derivation of closed terms for the specific radioactivity of single positions of C atoms of the metabolites of the citrate cycle. By means of regression analysis, the undetermined flux rates in the citrate cycle were calculated. On the basis of the data an overall balance sheet of glucose utilization and of ATP generation is given. About 45% of the glucose of reticulocytes is catabolized via the citrate cycle, about the same percentage yields lactate. Only 2% of the glucose was oxidized in the oxidative pentose pathway whereas the remainder is used for the formation of serine and glycine required for hemoglobin synthesis. These results are related to knowledge about the main processes utilizing ATP in reticulocytes, i.e. the synthesis of hemoglobin and the energy-dependent proteolysis. Our approach to the investigation of metabolic relations in the reticulocytes can be applied to other tissues in which equilibria between large metabolite pools play a role.

  6. Bace1 activity impairs neuronal glucose metabolism: rescue by beta-hydroxybutyrate and lipoic acid

    Directory of Open Access Journals (Sweden)

    John A Findlay

    2015-10-01

    Full Text Available Glucose hypometabolism and impaired mitochondrial function in neurons have been suggested to play early and perhaps causative roles in Alzheimer’s disease (AD pathogenesis. Activity of the aspartic acid protease, beta-site amyloid precursor protein (APP cleaving enzyme 1 (BACE1, responsible for beta amyloid peptide generation, has recently been demonstrated to modify glucose metabolism. We therefore examined, using a human neuroblastoma (SH-SY5Y cell line, whether increased BACE1 activity is responsible for a reduction in cellular glucose metabolism. Overexpression of active BACE1, but not a protease-dead mutant BACE1, protein in SH-SY5Y cells reduced glucose oxidation and the basal oxygen consumption rate, which was associated with a compensatory increase in glycolysis. Increased BACE1 activity had no effect on the mitochondrial electron transfer process but was found to diminish substrate delivery to the mitochondria by inhibition of key mitochondrial decarboxylation reaction enzymes. This BACE1 activity-dependent deficit in glucose oxidation was alleviated by the presence of beta hydroxybutyrate or α-lipoic acid. Consequently our data indicate that raised cellular BACE1 activity drives reduced glucose oxidation in a human neuronal cell line through impairments in the activity of specific tricarboxylic acid cycle enzymes. Because this bioenergetic deficit is recoverable by neutraceutical compounds we suggest that such agents, perhaps in conjunction with BACE1 inhibitors, may be an effective therapeutic strategy in the early-stage management or treatment of AD.

  7. Rewiring of embryonic glucose metabolism via suppression of PFK-1 and aldolase during mouse chorioallantoic branching

    Science.gov (United States)

    Sugiura, Yuki; Honda, Kurara; Kondo, Koki; Miura, Masayuki

    2017-01-01

    Adapting the energy metabolism state to changing bioenergetic demands is essential for mammalian development accompanying massive cell proliferation and cell differentiation. However, it remains unclear how developing embryos meet the changing bioenergetic demands during the chorioallantoic branching (CB) stage, when the maternal-fetal exchange of gases and nutrients is promoted. In this study, using metabolome analysis with mass-labeled glucose, we found that developing embryos redirected glucose carbon flow into the pentose phosphate pathway via suppression of the key glycolytic enzymes PFK-1 and aldolase during CB. Concomitantly, embryos exhibited an increase in lactate pool size and in the fractional contribution of glycolysis to lactate biosynthesis. Imaging mass spectrometry visualized lactate-rich tissues, such as the dorsal or posterior neural tube, somites and head mesenchyme. Furthermore, we found that the heterochronic gene Lin28a could act as a regulator of the metabolic changes observed during CB. Perturbation of glucose metabolism rewiring by suppressing Lin28a downregulation resulted in perinatal lethality. Thus, our work demonstrates that developing embryos rewire glucose metabolism following CB for normal development. PMID:28049690

  8. Conservation of the Nrf2-Mediated Gene Regulation of Proteasome Subunits and Glucose Metabolism in Zebrafish

    Directory of Open Access Journals (Sweden)

    Vu Thanh Nguyen

    2016-01-01

    Full Text Available The Keap1-Nrf2 system is an evolutionarily conserved defense mechanism against oxidative and xenobiotic stress. Besides the exogenous stress response, Nrf2 has been found to regulate numerous cellular functions, including protein turnover and glucose metabolism; however, the evolutionary origins of these functions remain unknown. In the present study, we searched for novel target genes associated with the zebrafish Nrf2 to answer this question. A microarray analysis of zebrafish embryos that overexpressed Nrf2 revealed that 115 candidate genes were targets of Nrf2, including genes encoding proteasome subunits and enzymes involved in glucose metabolism. A real-time quantitative PCR suggested that the expression of 3 proteasome subunits (psma3, psma5, and psmb7 and 2 enzymes involved in glucose metabolism (pgd and fbp1a were regulated by zebrafish Nrf2. We thus next examined the upregulation of these genes by an Nrf2 activator, diethyl maleate, using Nrf2 mutant zebrafish larvae. The results of real-time quantitative PCR and whole-mount in situ hybridization showed that all of these 5 genes were upregulated by diethyl maleate treatment in an Nrf2-dependent manner, especially in the liver. These findings implied that the Nrf2-mediated regulation of the proteasome subunits and glucose metabolism is evolutionarily conserved among vertebrates.

  9. Co-ordination of hepatic and adipose tissue lipid metabolism after oral glucose

    DEFF Research Database (Denmark)

    Bülow, J; Simonsen, L; Wiggins, D;

    1999-01-01

    The integration of lipid metabolism in the splanchnic bed and in subcutaneous adipose tissue before and after ingestion of a 75 g glucose load was studied by Fick's principle in seven healthy subjects. Six additional subjects were studied during a hyperinsulinemic euglycemic clamp. Release of non...

  10. Effect of opium on glucose metabolism and lipid profiles in rats with streptozotocin-induced diabetes

    NARCIS (Netherlands)

    Sadeghian, Saeed; Boroumand, Mohammad Ali; Sotoudeh-Anvari, Maryam; Rahbani, Shahram; Sheikhfathollahi, Mahmood; Abbasi, Ali

    2009-01-01

    Background: This experimental study was performed to determine the impact of opium use on serum lipid profile and glucose metabolism in rats with streptozotocin-induced diabetes. Material and methods: To determine the effect of opium, 20 male rats were divided into control (n = 10) and opium-treated

  11. Brain Size and Cerebral Glucose Metabolic Rate in Nonspecific Retardation and Down Syndrome.

    Science.gov (United States)

    Haier, Richard J.; And Others

    1995-01-01

    Brain size and cerebral glucose metabolic rate were determined for 10 individuals with mild mental retardation (MR), 7 individuals with Down syndrome (DS), and 10 matched controls. MR and DS groups both had brain volumes of about 80% compared to controls, with variance greatest within the MR group. (SLD)

  12. Sleep deprivation and its impact on circadian rhythms and glucose metabolism

    NARCIS (Netherlands)

    Jha, P.K.

    2016-01-01

    The mammalian master pacemaker is located in the hypothalamic suprachiasmatic nucleus (SCN). The SCN generates rhythms of behavioural and metabolic processes throughout the body via both endocrine and neuronal outputs. For example, daily rhythms of sleep-wake, fasting-feeding, plasma glucose, glucos

  13. Brain-derived neurotrophic factor, impaired glucose metabolism, and bipolar disorder course

    DEFF Research Database (Denmark)

    Mansur, Rodrigo B; Santos, Camila M; Rizzo, Lucas B

    2016-01-01

    OBJECTIVES: The neurotrophin brain-derived neurotrophic factor (BDNF) has been proposed as a potential biomarker in bipolar disorder (BD). However, current evidence is limited and results have been highly heterogeneous. This study aimed to assess the moderating effect of impaired glucose metabolism...

  14. Glucose and maltose metabolism in MIG1-disrupted and MAL-constitutive strains of Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Klein, Christopher; Olsson, Lisbeth; Rønnow, B;

    1997-01-01

    The alleviation of glucose control of maltose metabolism brought about by MIG1 disruption was compared to that by MAL overexpression in a haploid Saccharomyces cerevisiae strain. The sugar consumption profiles during cultivation of the wild type, single transformants and a double transformant in ...

  15. Low Cerebral Glucose Metabolism: A Potential Predictor for the Severity of Vascular Parkinsonism and Parkinson's Disease.

    Science.gov (United States)

    Xu, Yunqi; Wei, Xiaobo; Liu, Xu; Liao, Jinchi; Lin, Jiaping; Zhu, Cansheng; Meng, Xiaochun; Xie, Dongsi; Chao, Dongman; Fenoy, Albert J; Cheng, Muhua; Tang, Beisha; Zhang, Zhuohua; Xia, Ying; Wang, Qing

    2015-11-01

    This study explored the association between cerebral metabolic rates of glucose (CMRGlc) and the severity of Vascular Parkinsonism (VP) and Parkinson's disease (PD). A cross-sectional study was performed to compare CMRGlc in normal subjects vs. VP and PD patients. Twelve normal subjects, 22 VP, and 11 PD patients were evaluated with the H&Y and MMSE, and underwent 18F-FDG measurements. Pearson's correlations were used to identify potential associations between the severity of VP/PD and CMRGlc. A pronounced reduction of CMRGlc in the frontal lobe and caudate putamen was detected in patients with VP and PD when compared with normal subjects. The VP patients displayed a slight CMRGlc decrease in the caudate putamen and frontal lobe in comparison with PD patients. These decreases in CMRGlc in the frontal lobe and caudate putamen were significantly correlated with the VP patients' H&Y, UPDRS II, UPDRS III, MMSE, cardiovascular, and attention/memory scores. Similarly, significant correlations were observed in patients with PD. This is the first clinical study finding strong evidence for an association between low cerebral glucose metabolism and the severity of VP and PD. Our findings suggest that these changes in glucose metabolism in the frontal lobe and caudate putamen may underlie the pathophysiological mechanisms of VP and PD. As the scramble to find imaging biomarkers or predictors of the disease intensifies, a better understanding of the roles of cerebral glucose metabolism may give us insight into the pathogenesis of VP and PD.

  16. Effect of Antibiotics on Gut Microbiota, Gut Hormones and Glucose Metabolism

    DEFF Research Database (Denmark)

    Mikkelsen, Kristian H; Frost, Morten; Bahl, Martin Iain;

    2015-01-01

    The gut microbiota has been designated as an active regulator of glucose metabolism and metabolic phenotype in a number of animal and human observational studies. We evaluated the effect of removing as many bacteria as possible by antibiotics on postprandial physiology in healthy humans. Meal tests...... and glucose tolerant males. Faecal samples were collected for culture-based assessment of changes in gut microbiota composition. Acute and dramatic reductions in the abundance of a representative set of gut bacteria was seen immediately following the antibiotic course, but no changes in postprandial glucose...... tolerance, insulin secretion or plasma lipid concentrations were found. Apart from an acute and reversible increase in peptide YY secretion, no changes were observed in postprandial gut hormone release. As evaluated by selective cultivation of gut bacteria, a broad-spectrum 4-day antibiotics course...

  17. A community-based exercise intervention transitions metabolically abnormal obese adults to a metabolically healthy obese phenotype

    Directory of Open Access Journals (Sweden)

    Dalleck LC

    2014-08-01

    Full Text Available Lance C Dalleck,1,3 Gary P Van Guilder,2,3 Tara B Richardson,1 Donald L Bredle,3 Jeffrey M Janot31Recreation, Exercise, and Sport Science Department, Western State Colorado University, Gunnison, CO, USA; 2Department of Health and Nutritional Sciences, South Dakota State University, Brookings, SD, USA; 3Department of Kinesiology, University of Wisconsin-Eau Claire, Eau Claire, WI, USABackground: Lower habitual physical activity and poor cardiorespiratory fitness are common features of the metabolically abnormal obese (MAO phenotype that contribute to increased cardiovascular disease risk. The aims of the present study were to determine 1 whether community-based exercise training transitions MAO adults to metabolically healthy, and 2 whether the odds of transition to metabolically healthy were larger for obese individuals who performed higher volumes of exercise and/or experienced greater increases in fitness.Methods and results: Metabolic syndrome components were measured in 332 adults (190 women, 142 men before and after a supervised 14-week community-based exercise program designed to reduce cardiometabolic risk factors. Obese (body mass index ≥30 kg · m2 adults with two to four metabolic syndrome components were classified as MAO, whereas those with no or one component were classified as metabolically healthy but obese (MHO. After community exercise, 27/68 (40% MAO individuals (P<0.05 transitioned to metabolically healthy, increasing the total number of MHO persons by 73% (from 37 to 64. Compared with the lowest quartiles of relative energy expenditure and change in fitness, participants in the highest quartiles were 11.6 (95% confidence interval: 2.1–65.4; P<0.05 and 7.5 (95% confidence interval: 1.5–37.5; P<0.05 times more likely to transition from MAO to MHO, respectively.Conclusion: Community-based exercise transitions MAO adults to metabolically healthy. MAO adults who engaged in higher volumes of exercise and experienced the

  18. Study on abnormal iron metabolism and iron overload in patients with aplastic anemia

    Institute of Scientific and Technical Information of China (English)

    金朋

    2013-01-01

    Objective To investigate the abnormalities of iron metabolism,the prevalence and risk factors of iron overload and clinical characteristics of patients with aplastic anemia (AA) .Methods A cross-sectional study was conducted on 520 newly diagnosed AA patients.Results Iron overload was observed in 66 (13%) of 520 AA patients,in which a higher prevalence of iron overload was seen not only in patients with infections (19/86,22%) than those without infections (47/434,11%,P<0.01) ,but also in patients with hepatitis associated AA

  19. Germinated Pigmented Rice (Oryza Sativa L. cv. Superhongmi Improves Glucose and Bone Metabolisms in Ovariectomized Rats

    Directory of Open Access Journals (Sweden)

    Soo Im Chung

    2016-10-01

    Full Text Available The effect of germinated Superhongmi, a reddish brown pigmented rice cultivar, on the glucose profile and bone turnover in the postmenopausal-like model of ovariectomized rats was determined. The ovariectomized Sprague-Dawley rats were randomly divided into three dietary groups (n = 10: normal control diet (NC and normal diet supplemented with non-germinated Superhongmi (SH or germinated Superhongmi (GSH rice powder. After eight weeks, the SH and GSH groups showed significantly lower body weight, glucose and insulin concentrations, levels of bone resorption markers and higher glycogen and 17-β-estradiol contents than the NC group. The glucose metabolism improved through modulation of adipokine production and glucose-regulating enzyme activities. The GSH rats exhibited a greater hypoglycemic effect and lower bone resorption than SH rats. These results demonstrate that germinated Superhongmi rice may potentially be useful in the prevention and management of postmenopausal hyperglycemia and bone turnover imbalance.

  20. Impact of polymorphisms in WFS1 on prediabetic phenotypes in a population-based sample of middle-aged people with normal and abnormal glucose regulation

    DEFF Research Database (Denmark)

    Sparsø, T; Andersen, G; Albrechtsen, Anders

    2008-01-01

    interaction of WFS1 rs734312 on insulin release and insulin resistance we introduced Hotelling's T (2) test. Assuming bivariate normal distribution, we constructed standard error ellipses of the insulinogenic index and HOMA-IR when stratified according to glucose tolerance status around the means of each WFS1...... rs734312 genotype level. The interaction term between individuals with normal glucose tolerance and abnormal glucose regulation on the insulinogenic index and HOMA-IR was significantly associated with the traits (p = 0.0017). CONCLUSIONS/INTERPRETATION: Type 2 diabetes-associated risk alleles of WFS1...... are associated with estimates of a decreased pancreatic beta cell function among middle-aged individuals with abnormal glucose regulation....

  1. 冠心病患者不同糖代谢对糖餐后甘油三酯的影响%Relationship between plasma triglyceride levels and glucose metabolism after oral glucose load in patients with coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    郑晓敏; 李瑞杰; 李莉; 刘翠平; 陈晓燕; 徐世莹; 王亚娟

    2013-01-01

    This paper observed the levels of plasma triglyceride and glucose after oral glucose load in patients with coronary artery disease (CAD).An oral glucose tolerance test (OGTT)was performed in 237 CAD patients,plasma lipids,glucose and insulin were quantified in fasting and postprandial samples.According to fasting and postprandial glucose level,patients were divided into three groups,normal group,impaired glucose tolerance (IGT) group and diabetes mellitus (DM) group.The total prevalence of abnormal glucose metabolism was 72.15% in patient with CAD.The levels of plasma triglyceride decreased 2 h after glucose test.The change of the levels of plasma triglyceride between 0h and 2 h were strongly associated with insulin levels and HOMA-IR.The levels of plasma triglyceride in DM and IGT group were significant higher than those in normal UA group (1.88 ± 1.71,1.86 ± 1.28 vs 1.32-±0.78,respectively) (P <0.05).The levels of plasma triglyceride 2 h after glucose test in all groups were significant decreased,especially in IGT group.The observed decrease of triglycerides after glucose load in subjects with signs of insulin resistance suggests that post -glucose triglyceride change is a potential novel biomarker for early detection of metabolic risk.%评估冠心病患者75 g葡萄糖负荷后糖脂代谢变化.对237例冠心病患者行糖耐量试验,检测餐后2h血糖、胰岛素及血脂.将患者根据空腹及OGTT2 h血糖结果分为血糖正常组、糖耐量异常组及糖尿病组.冠心病患者中糖调节异常者占72.15%.冠心病患者糖餐后甘油三酯明显下降,与胰岛素水平及HOMA-IR相关.IGT组及糖尿病组空腹甘油三酯明显高于血糖正常组,服糖后2h各组甘油三酯水平均下降,其中IGT组下降最为明显.表明冠心病患者糖餐后2h甘油三酯水平可以作为胰岛素抵抗的新指标.

  2. Cubilin dysfunction causes abnormal metabolism of the steroid hormone 25(OH) vitamin D(3).

    Science.gov (United States)

    Nykjaer, A; Fyfe, J C; Kozyraki, R; Leheste, J R; Jacobsen, C; Nielsen, M S; Verroust, P J; Aminoff, M; de la Chapelle, A; Moestrup, S K; Ray, R; Gliemann, J; Willnow, T E; Christensen, E I

    2001-11-20

    Steroid hormones are central regulators of a variety of biological processes. According to the free hormone hypothesis, steroids enter target cells by passive diffusion. However, recently we demonstrated that 25(OH) vitamin D(3) complexed to its plasma carrier, the vitamin D-binding protein, enters renal proximal tubules by receptor-mediated endocytosis. Knockout mice lacking the endocytic receptor megalin lose 25(OH) vitamin D(3) in the urine and develop bone disease. Here, we report that cubilin, a membrane-associated protein colocalizing with megalin, facilitates the endocytic process by sequestering steroid-carrier complexes on the cellular surface before megalin-mediated internalization of the cubilin-bound ligand. Dogs with an inherited disorder affecting cubilin biosynthesis exhibit abnormal vitamin D metabolism. Similarly, human patients with mutations causing cubilin dysfunction exhibit urinary excretion of 25(OH) vitamin D(3). This observation identifies spontaneous mutations in an endocytic receptor pathway affecting cellular uptake and metabolism of a steroid hormone.

  3. Increased adiposity, dysregulated glucose metabolism and systemic inflammation in Galectin-3 KO mice.

    Directory of Open Access Journals (Sweden)

    Jingbo Pang

    Full Text Available Obesity and type 2 diabetes are associated with increased production of Galectin-3 (Gal-3, a protein that modulates inflammation and clearance of glucose adducts. We used Lean and Diet-induced Obese (DIO WT and Gal-3 KO mice to investigate the role of Gal-3 in modulation of adiposity, glucose metabolism and inflammation. Deficiency of Gal-3 lead to age-dependent development of excess adiposity and systemic inflammation, as indicated by elevated production of acute-phase proteins, number of circulating pro-inflammatory Ly6C(high monocytes and development of neutrophilia, microcytic anemia and thrombocytosis in 20-week-old Lean and DIO male Gal-3 KO mice. This was associated with impaired fasting glucose, heightened response to a glucose tolerance test and reduced adipose tissue expression of adiponectin, Gal-12, ATGL and PPARγ, in the presence of maintained insulin sensitivity and hepatic expression of gluconeogenic enzymes in 20-week-old Gal-3 KO mice compared to their diet-matched WT controls. Expression of PGC-1α and FGF-21 in the liver of Lean Gal-3 KO mice was comparable to that observed in DIO animals. Impaired fasting glucose and altered responsiveness to a glucose load preceded development of excess adiposity and systemic inflammation, as demonstrated in 12-week-old Gal-3 KO mice. Finally, a role for the microflora in mediating the fasting hyperglycemia, but not the excessive response to a glucose load, of 12-week-old Gal-3 KO mice was demonstrated by administration of antibiotics. In conclusion, Gal-3 is an important modulator of glucose metabolism, adiposity and inflammation.

  4. Effect of insulin and glucose on adenosine metabolizing enzymes in human B lymphocytes.

    Science.gov (United States)

    Kocbuch, Katarzyna; Sakowicz-Burkiewicz, Monika; Grden, Marzena; Szutowicz, Andrzej; Pawelczyk, Tadeusz

    2009-01-01

    In diabetes several aspects of immunity are altered, including the immunomodulatory action of adenosine. Our study was undertaken to investigate the effect of different glucose and insulin concentrations on activities of adenosine metabolizing enzymes in human B lymphocytes line SKW 6.4. The activity of adenosine deaminase in the cytosolic fraction was very low and was not affected by different glucose concentration, but in the membrane fraction of cells cultured with 25 mM glucose it was decreased by about 35% comparing to the activity in cells maintained in 5 mM glucose, irrespective of insulin concentration. The activities of 5'-nucleotidase (5'-NT) and ecto-5'-NT in SKW 6.4 cells depended on insulin concentration, but not on glucose. Cells cultured with 10(-8) M insulin displayed an about 60% lower activity of cytosolic 5'-NT comparing to cells maintained at 10(-11) M insulin. The activity of ecto-5'-NT was decreased by about 70% in cells cultured with 10(-8) M insulin comparing to cells grown in 10(-11) M insulin. Neither insulin nor glucose had an effect on adenosine kinase (AK) activity in SKW 6.4 cells or in human B cells isolated from peripheral blood. The extracellular level of adenosine and inosine during accelerated catabolism of cellular ATP depended on glucose, but not on insulin concentration. Concluding, our study demonstrates that glucose and insulin differentially affect the activities of adenosine metabolizing enzymes in human B lymphocytes, but changes in those activities do not correlate with the adenosine level in cell media during accelerated ATP catabolism, implying that nucleoside transport is the primary factor determining the extracellular level of adenosine.

  5. Glucose metabolism in batch and continuous cultures of Gluconacetobacter diazotrophicus PAL 3.

    Science.gov (United States)

    Luna, María F; Bernardelli, Cecilia E; Galar, María L; Boiardi, José L

    2006-03-01

    Periplasmic glucose oxidation (by way of a pyrrolo-quinoline-quinone [PQQ]-linked glucose dehydrogenase [GDH]) was observed in continuous cultures of Gluconacetobacter diazotrophicus regardless of the carbon source (glucose or gluconate) and the nitrogen source (N(2) or NH(3)). Its synthesis was stimulated by conditions of high energetic demand (i.e., N(2)-fixation) and/or C-limitation. Under C-excess conditions, PQQ-GDH synthesis increased with the glucose concentration in the culture medium. In batch cultures, PQQ-GDH was actively expressed in very early stages with higher activities under conditions of N(2)-fixation. Hexokinase activity was almost absent under any culture condition. Cytoplasmic nicotinamide adenine dinucleotide (NAD)-linked glucose dehydrogenase (GDH) was expressed in continuous cultures under all tested conditions, and its synthesis increased with the glucose concentration. In contrast, low activities of this enzyme were detected in batch cultures. Periplasmic oxidation, by way of PQQ-GDH, seems to be the principal pathway for metabolism of glucose in G. Diazotrophicus, and NAD-GDH is an alternative route under certain environmental conditions.

  6. Effect of breakfast skipping on diurnal variation of energy metabolism and blood glucose.

    Science.gov (United States)

    Kobayashi, Fumi; Ogata, Hitomi; Omi, Naomi; Nagasaka, Shoichiro; Yamaguchi, Sachiko; Hibi, Masanobu; Tokuyama, Kumpei

    2014-01-01

    Epidemiological studies suggest an association between breakfast skipping and body weight gain, insulin resistance or type 2 diabetes. Time when meal is consumed affects postprandial increase in energy expenditure and blood glucose, and breakfast skipping may reduce 24 h energy expenditure and elevate blood glucose level. The present study evaluated the effect of breakfast skipping on diurnal variation of energy metabolism and blood glucose. The skipped breakfast was compensated by following big meals at lunch and supper. In a randomized repeated-measure design with or without breakfast, eight males stayed twice in a room-size respiratory chamber. Blood glucose was recorded with a continuous glucose monitoring system. Breakfast skipping did not affect 24 h energy expenditure, fat oxidation and thermic effect of food, but increased overall 24 h average of blood glucose (83 ± 3 vs 89 ± 2 mg/dl, P breakfast skipping. These observations suggest that changes in glucose homeostasis precede that of energy balance, in the potential sequence caused by breakfast skipping, if this dietary habit has any effect on energy balance.:

  7. Regional changes in glucose metabolism during brain development from the age of 6 years.

    Science.gov (United States)

    Van Bogaert, P; Wikler, D; Damhaut, P; Szliwowski, H B; Goldman, S

    1998-07-01

    Positron emission tomography (PET) with [18F]fluorodeoxyglucose (FDG) studies of 42 subjects ages 6 to 38 years were analyzed using statistical parametric mapping to identify age-related changes in regional distribution of glucose metabolism adjusted for global activity. Whereas adults were normal volunteers, children had idiopathic epilepsy. We studied polynomial expansions of age to identify nonlinear effects and found that adjusted glucose metabolism varied very significantly in the thalamus and the anterior cingulate cortex and to a lesser degree in the basal ganglia, the mesencephalon, and the insular, posterior cingulate, frontal, and postcentral cortices. Regression plots slowed that the best fit was not linear: adjusted glucose metabolism increased mainly before the age of 25 years and then remained relatively stable. Effects persisted when anti-epileptic drug intake and sleep during the FDG uptake were considered as confounding covariates. To determine if the metabolic changes observed were not due to the epileptic condition of the children, PET data obtained in adults with temporal lobe epilepsy were compared with those in our group of normal adult subjects, resulting in the absence of mapping in the age-related regions. This study suggests that brain maturation from the age of 6 years gives rise to a relative increase of synaptic activities in the thalamus, possibly as a consequence of improved corticothalamic connections. Increased metabolic activity in the anterior cingulate cortex is probably related to these thalamic changes and suggests that the limbic system is involved in the processes of brain maturation.

  8. NMR ({sup 1}H and {sup 13}C) based signatures of abnormal choline metabolism in oral squamous cell carcinoma with no prominent Warburg effect

    Energy Technology Data Exchange (ETDEWEB)

    Bag, Swarnendu, E-mail: Swarna.bag@gmail.com [School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Banerjee, Deb Ranjan, E-mail: debranjan2@gmail.com [Department of Chemistry, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Basak, Amit, E-mail: absk@chem.iitkgp.ernet.in [Department of Chemistry, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Das, Amit Kumar, E-mail: amitk@hijli.iitkgp.ernet.in [Department of Biotechnology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India); Pal, Mousumi, E-mail: drmpal62@gmail.com [Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal (India); Banerjee, Rita, E-mail: ritabanerjee@outlook.com [Department of Science and Technology, New Mehrauli Road, New Delhi 110016 (India); Paul, Ranjan Rashmi, E-mail: dr_rsspaul@yahoo.co.in [Department of Oral and Maxillofacial Pathology, Guru Nanak Institute of Dental Sciences and Research, Kolkata, West Bengal (India); Chatterjee, Jyotirmoy, E-mail: jchatterjee.iitkgp@gmail.com [School of Medical Science and Technology, Indian Institute of Technology-Kharagpur, 721302 West Bengal (India)

    2015-04-17

    At functional levels, besides genes and proteins, changes in metabolome profiles are instructive for a biological system in health and disease including malignancy. It is understood that metabolomic alterations in association with proteomic and transcriptomic aberrations are very fundamental to unravel malignant micro-ambient criticality and oral cancer is no exception. Hence deciphering intricate dimensions of oral cancer metabolism may be contributory both for integrated appreciation of its pathogenesis and to identify any critical but yet unexplored dimension of this malignancy with high mortality rate. Although several methods do exist, NMR provides higher analytical precision in identification of cancer metabolomic signature. Present study explored abnormal signatures in choline metabolism in oral squamous cell carcinoma (OSCC) using {sup 1}H and {sup 13}C NMR analysis of serum. It has demonstrated down-regulation of choline with concomitant up-regulation of its break-down product in the form of trimethylamine N-oxide in OSCC compared to normal counterpart. Further, no significant change in lactate profile in OSCC possibly indicated that well-known Warburg effect was not a prominent phenomenon in such malignancy. Amongst other important metabolites, malonate has shown up-regulation but D-glucose, saturated fatty acids, acetate and threonine did not show any significant change. Analyzing these metabolomic findings present study proposed trimethyl amine N-oxide and malonate as important metabolic signature for oral cancer with no prominent Warburg effect. - Highlights: • NMR ({sup 1}H and {sup 13}C) study of Oral Squamous cell Carcinoma Serum. • Abnormal Choline metabolomic signatures. • Up-regulation of Trimethylamine N-oxide. • Unchanged lactate profile indicates no prominent Warburg effect. • Proposed alternative glucose metabolism path through up-regulation of malonate.

  9. Cerebral blood flow, oxygen and glucose metabolism with PET in progressive supranuclear palsy

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Makoto; Ichiya, Yuici; Kuwabara, Yasuo (Kyushu Univ., Fukuoka (Japan). Faculty of Medicine) (and others)

    1989-11-01

    Cerebral blood flow, cerebral oxygen metabolic rate and cerebral glucose metabolic rate were measured with positron emission tomography (PET) in four patients with progressive supranuclear palsy (PSP). Decreased blood flow and hypometabolism of oxygen and glucose were found in both subcortical and cortical regions, particularly in the striatum including the head of the caudate nucleus and the frontal cortex. The coupling between blood flow and metabolism was preserved even in the regions which showed decreased blood flow and hypometabolism. These findings indicated the hypofunction, as revealed by decreased blood flow and hypometablolism on PET, both in the striatum and the frontal cortex, and which may underlie the pathophysiological mechanism of motor and mental disturbance in PSP. (author).

  10. Deoxyglucose method for the estimation of local myocardial glucose metabolism with positron computed tomography

    Energy Technology Data Exchange (ETDEWEB)

    Ratib, O.; Phelps, M.E.; Huang, S.C.; Henze, E.; Selin, C.E.; Schelbert, H.R.

    1981-01-01

    The deoxyglucose method originally developed for measurements of the local cerebral metabolic rate for glucose has been investigated in terms of its application to studies of the heart with positron computed tomography (PCT) and FDG. Studies were performed in dogs to measure the tissue kinetics of FDG with PCT and by direct arterial-venous sampling. The operational equation developed in our laboratory as an extension of the Sokoloff model was used to analyze the data. The FDG method accurately predicted the true MMRGlc even when the glucose metabolic rate was normal but myocardial blood flow (MBF) was elevated 5 times the control value or when metabolism was reduced to 10% of normal and MBF increased 5 times normal. Improvements in PCT resolution are required to improve the accuracy of the estimates of the rate constants and the MMRGlc.

  11. Determination of patterns of regional cerebral glucose metabolism in normal aging and dementia

    Energy Technology Data Exchange (ETDEWEB)

    Alavi, A.; Chawluk, J.; Hurtig, H.; Dann, R.; Rosen, M.; Kushner, M.; Silver, F.; Reivich, M.

    1985-05-01

    Regional cerebral metabolic rates for glucose (rCMRGlc) were measured using 18F-FDG and positron emission tomography (PET) in 14 patients with probable Alzheimer's disease (AD) (age=64), 9 elderly controls (age=61), and 9 young controls (age=28). PET studies were performed without sensory stimulation or deprivation. Metabolic rates in individual brain regions were determined using an atlas overlay. Relative metabolic rates (rCMRGl c/global CMRGlc) were determined for all subjects. Comparison of young and elderly controls demonstrated significant decreases in frontal metabolism (rho<0.005) and right inferior parietal (IP) metabolism (rho<0.02) with normal aging. Patients with mild-moderate AD (NMAD) (n=8) when compared to age-matched controls, showed further reduction in right IP metabolism (rho<0.02). SAD patients also demonstrated metabolic decrements in left hemisphere language areas (rho<0.01). This latter finding is consistent with language disturbance observed late in the course of the disease. Out data reveal progressive changes in patterns of cerebral glucose utilization with aging and demential with reflect salient clinical features of these processes.

  12. Expression changes of hippocampal energy metabolism enzymes contribute to behavioural abnormalities during chronic morphine treatment

    Institute of Scientific and Technical Information of China (English)

    Xiao-Lan Chen; Jing-Gen Liu; Gang Lu; Ying-Xia Gong; Liang-Cai Zhao; Jie Chen; Zhi-Qiang Chi; Yi-Ming Yang; Zhong Chen; Qing-lin Li

    2007-01-01

    Dependence and impairment of learning and memory are two well-established features caused by abused drugs such as opioids. The hippocampus is an important region associated with both drug dependence and learning and memory. However, the molecular events in hippocampus following exposure to abused drugs such as opioids are not well understood. Here we examined the effect of chronic morphine treatment on hippocampal protein expression by proteomic analyses. We found that chronic exposure of mice to morphine for 10 days produced robust morphine withdrawal jumping and memory impairment, and also resulted in a significant downregulation of hippocampal protein levels of three metabolic enzymes, including Fe-S protein 1 of NADH dehydrogenase, dihydrolipoamide acetyltransferase or E2 component of the pyruvate dehydrogenase complex and lactate dehydrogenase 2. Further real-time quantitative PCR analyses confirmed that the levels of the corresponding mRNAs were also remarkably reduced. Consistent with these findings, lower ATP levels and an impaired ability to convert glucose into ATP were also observed in the hippocampus of chronically treated mice. Opioid antagonist naltrexone administrated concomitantly with morphine significantly suppressed morphine withdrawal jumping and reversed the downregulation of these proteins. Acute exposure to morphine also produced robust morphine withdrawal jumping and significant memory impairment, but failed to decrease the expression of these three proteins. Intrahippocampal injection of D-glucose before morphine administration significantly enhanced ATP levels and suppressed morphine withdrawal jumping and memory impairment in acute morphine-treated but not in chronic morphine-treated mice. Intraperitoneal injection of high dose of D-glucose shows a similar effect on morphine-induced withdrawal jumping as the central treatment. Taken together, our results suggest that reduced expression of the three metabolic enzymes in the hippocampus as

  13. Human regional cerebral glucose metabolism during non-rapid eye movement sleep in relation to waking.

    Science.gov (United States)

    Nofzinger, Eric A; Buysse, Daniel J; Miewald, Jean M; Meltzer, Carolyn C; Price, Julie C; Sembrat, Robert C; Ombao, Hernando; Reynolds, Charles F; Monk, Timothy H; Hall, Martica; Kupfer, David J; Moore, Robert Y

    2002-05-01

    Sleep is an essential human function. Although the function of sleep has generally been regarded to be restorative, recent data indicate that it also plays an important role in cognition. The neurobiology of human sleep is most effectively analysed with functional imaging, and PET studies have contributed substantially to our understanding of both rapid eye movement (REM) and non-rapid eye movement (NREM) sleep. In this study, PET was used to determine patterns of regional glucose metabolism in NREM sleep compared with waking. We hypothesized that brain structures related to waking cognitive function would show a persistence of function into the NREM sleep state. Fourteen healthy subjects (age range 21-49 years; 10 women, 4 men) underwent concurrent EEG sleep studies and [(18)F]fluoro-2-deoxy-D-glucose PET scans during waking and NREM sleep. Whole-brain glucose metabolism declined significantly from waking to NREM sleep. Relative decreases in regional metabolism from waking to NREM sleep occurred in wide areas of frontal, parietal, temporal and occipital association cortex, primary visual cortex, and in anterior/dorsomedial thalamus. After controlling for the whole-brain declines in absolute metabolism, relative increases in regional metabolism from waking to NREM were found bilaterally in the dorsal pontine tegmentum, hypothalamus, basal forebrain, ventral striatum, anterior cingulate cortex and extensive regions of the mesial temporal lobe, including the amygdala and hippocampus, and in the right dorsal parietal association cortex and primary somatosensory and motor cortices. The reductions in relative metabolism in NREM sleep compared with waking are consistent with prior findings from blood flow studies. The relative increases in glucose utilization in the basal forebrain, hypothalamus, ventral striatum, amygdala, hippocampus and pontine reticular formation are new observations that are in accordance with the view that NREM sleep is important to brain

  14. Acute Alcohol Intoxication Decreases Glucose Metabolism but Increases Acetate Uptake in the Human Brain

    Science.gov (United States)

    Volkow, Nora D.; Kim, Sung Won; Wang, Gene-Jack; Alexoff, David; Logan, Jean; Muench, Lisa; Shea, Colleen; Telang, Frank; Fowler, Joanna S.; Wong, Christopher; Benveniste, Helene; Tomasi, Dardo

    2012-01-01

    Alcohol intoxication results in marked reductions in brain glucose metabolism, which we hypothesized reflect not just its GABAergic enhancing effects but also metabolism of acetate as an alternative brain energy source. To test this hypothesis we separately assessed the effects of alcohol intoxication on brain glucose and acetate metabolism using Positron Emission Tomography (PET). We found that alcohol intoxication significantly decreased whole brain glucose metabolism (measured with FDG) with the largest decrements in cerebellum and occipital cortex and the smallest in thalamus. In contrast, alcohol intoxication caused a significant increase in [1-11C]acetate brain uptake (measured as standard uptake value, SUV), with the largest increases occurring in cerebellum and the smallest in thalamus. In heavy alcohol drinkers [1-11C]acetate brain uptake during alcohol challenge trended to be higher than in occasional drinkers (p <0.06) and the increases in [1-11C]acetate uptake in cerebellum with alcohol were positively associated with the reported amount of alcohol consumed (r=0.66, p<0.01). Our findings corroborate a reduction of brain glucose metabolism during intoxication and document an increase in brain acetate uptake. The opposite changes observed between regional brain metabolic decrements and regional increases in [1-11C]acetate uptake support the hypothesis that during alcohol intoxication the brain may rely on acetate as an alternative brain energy source and provides preliminary evidence that heavy alcohol exposures may facilitate the use of acetate as an energy substrate. These findings raise the question of the potential therapeutic benefits that increasing plasma acetate concentration (ie ketogenic diets) may have in alcoholics undergoing alcohol detoxification. PMID:22947541

  15. Cerebral blood flow and metabolic abnormalities in Alzheimer's disease

    Energy Technology Data Exchange (ETDEWEB)

    Matsuda, Hiroshi [National Center of Neurology and Psychiatry, Kodaira, Tokyo (Japan). National Center Hospital for Mental, Nervous, and Muscular Disorders

    2001-04-01

    In this review I summarize observations of PET and SPECT studies about cerebral blood flow and metabolic abnormalities in Alzheimer's disease (AD). In very early AD flow or metabolism reduces first in the posterior cingulate gyrus and precuneus. This reduction may arise from functional deafferentation caused by primary neural degeneration in the remote area of the entorhinal cortex that is the first to be pathologically affected in AD. Then medial temporal structures and parietotemporal association cortex show flow or metabolic reduction as disease processes. The reason why flow or metabolism in medial temporal structures shows delay in starting to reduce in spite of the earliest pathological affection remains to be elucidated. It is likely that anterior cingulate gyrus is functionally involved, since attention is the first non-memory domain to be affected, before deficits in language and visuospatial functions. However few reports have described involvement in the anterior cingulate gyrus. Relationship between cerebral blood flow or metabolism and apolipoprotein E (APOE) genotype has been investigated. Especially, the APOE{epsilon}4 allele has been reported to increase risk and to lower onset age as a function of the inherited dose of the {epsilon}4 allele. Reduction of flow or metabolism in the posterior cingulate gyrus and precuneus has been reported even in presymptomatic nondemented subjects who were cognitively normal and had at least a single {epsilon}4 allele. On the contrary the relation of {epsilon}4 allele to the progression rate of AD has been controversial from neuroimaging approaches. PET and SPECT imaging has become to be quite useful for assessing therapeutical effects of newly introduced treatment for AD. Recent investigations observed significant regional flow increase after donepezil hydrochloride treatment. Most of these observations have been made by applying computer assisted analysis of three-dimensional stereotactic surface projection

  16. Bile acid sequestration reduces plasma glucose levels in db/db mice by increasing its metabolic clearance rate.

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    Maxi Meissner

    Full Text Available AIMS/HYPOTHESIS: Bile acid sequestrants (BAS reduce plasma glucose levels in type II diabetics and in murine models of diabetes but the mechanism herein is unknown. We hypothesized that sequestrant-induced changes in hepatic glucose metabolism would underlie reduced plasma glucose levels. Therefore, in vivo glucose metabolism was assessed in db/db mice on and off BAS using tracer methodology. METHODS: Lean and diabetic db/db mice were treated with 2% (wt/wt in diet Colesevelam HCl (BAS for 2 weeks. Parameters of in vivo glucose metabolism were assessed by infusing [U-(13C]-glucose, [2-(13C]-glycerol, [1-(2H]-galactose and paracetamol for 6 hours, followed by mass isotopologue distribution analysis, and related to metabolic parameters as well as gene expression patterns. RESULTS: Compared to lean mice, db/db mice displayed an almost 3-fold lower metabolic clearance rate of glucose (p = 0.0001, a ∼300% increased glucokinase flux (p = 0.001 and a ∼200% increased total hepatic glucose production rate (p = 0.0002. BAS treatment increased glucose metabolic clearance rate by ∼37% but had no effects on glucokinase flux nor total hepatic or endogenous glucose production. Strikingly, BAS-treated db/db mice displayed reduced long-chain acylcarnitine content in skeletal muscle (p = 0.0317 but not in liver (p = 0.189. Unexpectedly, BAS treatment increased hepatic FGF21 mRNA expression 2-fold in lean mice (p = 0.030 and 3-fold in db/db mice (p = 0.002. CONCLUSIONS/INTERPRETATION: BAS induced plasma glucose lowering in db/db mice by increasing metabolic clearance rate of glucose in peripheral tissues, which coincided with decreased skeletal muscle long-chain acylcarnitine content.

  17. Ozone induces glucose intolerance and systemic metabolic effects in young and aged brown Norway rats

    Energy Technology Data Exchange (ETDEWEB)

    Bass, V. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Gordon, C.J.; Jarema, K.A.; MacPhail, R.C. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Cascio, W.E. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Phillips, P.M. [Toxicity Assessment Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Ledbetter, A.D.; Schladweiler, M.C. [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Andrews, D. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Miller, D. [Curriculum in Toxicology, University of North Carolina, Chapel Hill, NC (United States); Doerfler, D.L. [Research Cores Unit, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States); Kodavanti, U.P., E-mail: kodavanti.urmila@epa.gov [Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, NC (United States)

    2013-12-15

    Air pollutants have been associated with increased diabetes in humans. We hypothesized that ozone would impair glucose homeostasis by altering insulin signaling and/or endoplasmic reticular (ER) stress in young and aged rats. One, 4, 12, and 24 month old Brown Norway (BN) rats were exposed to air or ozone, 0.25 or 1.0 ppm, 6 h/day for 2 days (acute) or 2 d/week for 13 weeks (subchronic). Additionally, 4 month old rats were exposed to air or 1.0 ppm ozone, 6 h/day for 1 or 2 days (time-course). Glucose tolerance tests (GTT) were performed immediately after exposure. Serum and tissue biomarkers were analyzed 18 h after final ozone for acute and subchronic studies, and immediately after each day of exposure in the time-course study. Age-related glucose intolerance and increases in metabolic biomarkers were apparent at baseline. Acute ozone caused hyperglycemia and glucose intolerance in rats of all ages. Ozone-induced glucose intolerance was reduced in rats exposed for 13 weeks. Acute, but not subchronic ozone increased α{sub 2}-macroglobulin, adiponectin and osteopontin. Time-course analysis indicated glucose intolerance at days 1 and 2 (2 > 1), and a recovery 18 h post ozone. Leptin increased day 1 and epinephrine at all times after ozone. Ozone tended to decrease phosphorylated insulin receptor substrate-1 in liver and adipose tissues. ER stress appeared to be the consequence of ozone induced acute metabolic impairment since transcriptional markers of ER stress increased only after 2 days of ozone. In conclusion, acute ozone exposure induces marked systemic metabolic impairments in BN rats of all ages, likely through sympathetic stimulation. - Highlights: • Air pollutants have been associated with increased diabetes in humans. • Acute ozone exposure produces profound metabolic alterations in rats. • Age influences metabolic risk factors in aging BN rats. • Acute metabolic effects are reversible and repeated exposure reduces these effects. • Ozone

  18. Serotonergic dysfunctions and abnormal iron metabolism: Relevant to mental fatigue of Parkinson disease.

    Science.gov (United States)

    Zuo, Li-Jun; Yu, Shu-Yang; Hu, Yang; Wang, Fang; Piao, Ying-Shan; Lian, Teng-Hong; Yu, Qiu-Jin; Wang, Rui-Dan; Li, Li-Xia; Guo, Peng; Du, Yang; Zhu, Rong-Yan; Jin, Zhao; Wang, Ya-Jie; Wang, Xiao-Min; Chan, Piu; Chen, Sheng-Di; Wang, Yong-Jun; Zhang, Wei

    2016-12-01

    Fatigue is a very common non-motor symptom in Parkinson disease (PD) patients. It included physical fatigue and mental fatigue. The potential mechanisms of mental fatigue involving serotonergic dysfunction and abnormal iron metabolism are still unknown. Therefore, we evaluated the fatigue symptoms, classified PD patients into fatigue group and non-fatigue group, and detected the levels of serotonin, iron and related proteins in CSF and serum. In CSF, 5-HT level is significantly decreased and the levels of iron and transferrin are dramatically increased in fatigue group. In fatigue group, mental fatigue score is negatively correlated with 5-HT level in CSF, and positively correlated with the scores of depression and excessive daytime sleepiness, and disease duration, also, mental fatigue is positively correlated with the levels of iron and transferrin in CSF. Transferrin level is negatively correlated with 5-HT level in CSF. In serum, the levels of 5-HT and transferrin are markedly decreased in fatigue group; mental fatigue score exhibits a negative correlation with 5-HT level. Thus serotonin dysfunction in both central and peripheral systems may be correlated with mental fatigue through abnormal iron metabolism. Depression, excessive daytime sleepiness and disease duration were the risk factors for mental fatigue of PD.

  19. Danthron activates AMP-activated protein kinase and regulates lipid and glucose metabolism in vitro

    Institute of Scientific and Technical Information of China (English)

    Rong ZHOU; Ling WANG; Xing XU; Jing CHEN; Li-hong HU; Li-li CHEN; Xu SHEN

    2013-01-01

    Aim:To discover the active compound on AMP-activated protein kinase (AMPK) activation and investigate the effects of the active compound 1,8-dihydroxyanthraquinone (danthron) from the traditional Chinese medicine rhubarb on AMPK-mediated lipid and glucose metabolism in vitro.Methods:HepG2 and C2C12 cells were used.Cell viability was determined using MTT assay.Real-time PCR was performed to measure the gene expression.Western blotting assay was applied to investigate the protein phosphorylation level.Enzymatic assay kits were used to detect the total cholesterol (TC),triglyceride (TG) and glucose contents.Results:Danthron (0.1,1,and 10 μmol/L) dose-dependently promoted the phosphorylation of AMPK and acetyl-CoA carboxylase (ACC)in both HepG2 and C2C12 cells.Meanwhile,danthron treatment significantly reduced the lipid synthesis related sterol regulatory element-binding protein 1c (SREBP1c) and fatty acid synthetase (FAS) gene expressions,and the TC and TG levels.In addition,danthron treatment efficiently increased glucose consumption.The actions of danthron on lipid and glucose metabolism were abolished or reversed by co-treatment with the AMPK inhibitor compound C.Conclusion:Danthron effectively reduces intracellular lipid contents and enhanced glucose consumption in vitro via activation of AMPK signaling pathway.

  20. Lactate as a cerebral metabolic fuel for glucose-6-phosphatase deficient children.

    Science.gov (United States)

    Fernandes, J; Berger, R; Smit, G P

    1984-04-01

    The main substrates for brain energy metabolism were measured in blood samples taken from the carotid artery and the internal jugular bulb of four children with glycogen storage disease caused by deficiency of glucose-6-phosphatase. Multiple paired arterial and venous blood samples were analyzed for glucose, lactate, pyruvate, D-beta-hydroxybutyrate, acetoacetate, glycerol and O2, and the arteriovenous differences of the concentrations were calculated. In the first three patients the substrates were measured in two successive conditions with lower and higher glucose-intake, respectively, inducing reciprocally higher and lower concentrations of blood lactate. In the fourth patient medium chain triglycerides were administered simultaneously with the glucose-containing gastric drip feeding. Lactate appeared to be taken up significantly. It consumed, if completely oxidized, between 40-50% of the total O2 uptake in most cases. Only once in one patient the uptake of lactate switched to its release, when the blood lactate level decreased to normal. D-beta-hydroxybutyrate and acetoacetate arteriovenous (A-V) differences were small to negligible and these ketone bodies, therefore, did not contribute substantially to the brain's energy expenditure. Glycerol was not metabolized by the brain. Lactate thus appeared to be the second brain fuel next to glucose. It may protect the brain against fuel depletion in case of hypoglycemia.

  1. Epigallocatechin gallate affects glucose metabolism and increases fitness and lifespan in Drosophila melanogaster.

    Science.gov (United States)

    Wagner, Anika E; Piegholdt, Stefanie; Rabe, Doerte; Baenas, Nieves; Schloesser, Anke; Eggersdorfer, Manfred; Stocker, Achim; Rimbach, Gerald

    2015-10-13

    In this study, we tested whether a standardized epigallocatechin-3-gallate (EGCG) rich green tea extract (comprising > 90% EGCG) affects fitness and lifespan as well as parameters of glucose metabolism and energy homeostasis in the fruit fly, Drosophila melanogaster. Following the application of the green tea extract a significant increase in the mean lifespan (+ 3.3 days) and the 50% survival (+ 4.3 days) as well as improved fitness was detected. These effects went along an increased expression of Spargel, the homolog of mammalian PGC1α, which has been reported to affect lifespan in flies. Intriguingly, in flies, treatment with the green tea extract decreased glucose concentrations, which were accompanied by an inhibition of α-amylase and α-glucosidase activity. Computational docking analysis proved the potential of EGCG to dock into the substrate binding pocket of α-amylase and to a greater extent into α-glucosidase. Furthermore, we demonstrate that EGCG downregulates insulin-like peptide 5 and phosphoenolpyruvate carboxykinase, major regulators of glucose metabolism, as well as the Drosophila homolog of leptin, unpaired 2. We propose that a decrease in glucose metabolism in connection with an upregulated expression of Spargel contribute to the better fitness and the extended lifespan in EGCG-treated flies.

  2. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One-Carbon Cycle Energy Producing Pathway.

    Science.gov (United States)

    Varma, Vijayalakshmi; Boros, László G; Nolen, Greg T; Chang, Ching-Wei; Wabitsch, Martin; Beger, Richard D; Kaput, Jim

    2015-06-16

    Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS) preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001). However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA) cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway) one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes.

  3. Fructose Alters Intermediary Metabolism of Glucose in Human Adipocytes and Diverts Glucose to Serine Oxidation in the One–Carbon Cycle Energy Producing Pathway

    Directory of Open Access Journals (Sweden)

    Vijayalakshmi Varma

    2015-06-01

    Full Text Available Increased consumption of sugar and fructose as sweeteners has resulted in the utilization of fructose as an alternative metabolic fuel that may compete with glucose and alter its metabolism. To explore this, human Simpson-Golabi-Behmel Syndrome (SGBS preadipocytes were differentiated to adipocytes in the presence of 0, 1, 2.5, 5 or 10 mM of fructose added to a medium containing 5 mM of glucose representing the normal blood glucose concentration. Targeted tracer [1,2-13C2]-d-glucose fate association approach was employed to examine the influence of fructose on the intermediary metabolism of glucose. Increasing concentrations of fructose robustly increased the oxidation of [1,2-13C2]-d-glucose to 13CO2 (p < 0.000001. However, glucose-derived 13CO2 negatively correlated with 13C labeled glutamate, 13C palmitate, and M+1 labeled lactate. These are strong markers of limited tricarboxylic acid (TCA cycle, fatty acid synthesis, pentose cycle fluxes, substrate turnover and NAD+/NADP+ or ATP production from glucose via complete oxidation, indicating diminished mitochondrial energy metabolism. Contrarily, a positive correlation was observed between glucose-derived 13CO2 formed and 13C oleate and doses of fructose which indicate the elongation and desaturation of palmitate to oleate for storage. Collectively, these results suggest that fructose preferentially drives glucose through serine oxidation glycine cleavage (SOGC pathway one-carbon cycle for NAD+/NADP+ production that is utilized in fructose-induced lipogenesis and storage in adipocytes.

  4. GLUCOSE AND LACTATE METABOLISM IN THE AWAKE AND STIMULATED RAT: A 13C-NMR STUDY.

    Directory of Open Access Journals (Sweden)

    Denys eSampol

    2013-05-01

    Full Text Available Glucose is the major energetic substrate for the brain but evidence has accumulated during the last 20 years that lactate produced by astrocytes could be an additional substrate for neurons. However, little information exists about this lactate shuttle in vivo in activated and awake animals. We designed an experiment in which the cortical barrel field (S1BF was unilaterally activated during infusion of both glucose and lactate (alternatively labeled with 13C in rats. At the end of stimulation (1h, both S1BF areas were removed and analyzed by HR-MAS NMR spectroscopy to compare glucose and lactate metabolism in the activated area versus the non-activated one. In combination with microwave irradiation, HR-MAS spectroscopy is a powerful technical approach to study brain lactate metabolism in vivo.Using in vivo 14C-2-deoxyglucose and autoradiography, we confirmed that whisker stimulation was effective since we observed a 40% increase in glucose uptake in the activated S1BF area compared to the ipsilateral one.We first determined that lactate observed on spectra of biopsies did not arise from post-mortem metabolism. 1H-NMR data indicated that during brain activation, there was an average 2.4-fold increase in lactate content in the activated area. When [1-13C]glucose+lactate were infused, 13C-NMR data showed an increase in 13C-labeled lactate during brain activation, as well as an increase in lactate C3-specific enrichment. This result demonstrates that the increase in lactate observed on 1H-NMR spectra originates from newly synthesized lactate from the labeled precursor ([1-13C]glucose. It also shows that this additional lactate does not arise from an increase in blood lactate uptake since it would otherwise be unlabeled. These results are in favor of intracerebral lactate production during brain activation in vivo, which could be a supplementary fuel for neurons.

  5. Myocardial glucose transporters and glycolytic metabolism during ischemia in hyperglycemic diabetic swine.

    Science.gov (United States)

    Stanley, W C; Hall, J L; Smith, K R; Cartee, G D; Hacker, T A; Wisneski, J A

    1994-01-01

    We assessed the effects of 4 weeks of streptozocin-induced diabetes on regional myocardial glycolytic metabolism during ischemia in anesthetized open-chest domestic swine. Diabetic animals were hyperglycemic (12.0 +/- 2.1 v 6.6 +/- .5 mmol/L), and had lower fasting insulin levels (27 +/- 8 v 79 +/- 19 pmol/L). Myocardial glycolytic metabolism was studied with coronary flow controlled by an extracorporeal perfusion circuit. Left anterior descending coronary artery (LAD) flow was decreased by 50% for 45 minutes and left circumflex (CFX) flow was constant. Myocardial glucose uptake and extraction were measured with D-[6-3H]-2-deoxyglucose (DG) and myocardial blood flow was measured with microspheres. The rate of glucose conversion to lactate and lactate uptake and output were assessed with a continuous infusion of [6-14C]glucose and [U-13C]lactate into the coronary perfusion circuit. Both diabetic and nondiabetic animals had sharp decreases in subendocardial blood flow during ischemia (from 1.21 +/- .10 to 0.43 +/- .08 mL.g-1.min-1 in the nondiabetic group, and from 1.30 +/- .15 to 0.55 +/- .11 in the diabetic group). Diabetes had no significant effect on myocardial glucose uptake or glucose conversion to lactate under either well-perfused or ischemic conditions. Forty-five minutes of ischemia resulted in significant glycogen depletion in the subendocardium in both nondiabetic and diabetic animals, with no differences between the two groups. Glycolytic metabolism is not impaired in hyperglycemic diabetic swine after 1 month of the disease when compared with that in normoglycemic nondiabetic animals. The myocardial content of the insulin-regulatable glucose transporter (GLUT 4) was measured in left ventricular biopsies.(ABSTRACT TRUNCATED AT 250 WORDS)

  6. Diabetes, Glucose Metabolism, and Glaucoma: The 2005–2008 National Health and Nutrition Examination Survey

    Science.gov (United States)

    Zhao, Di; Cho, Juhee; Kim, Myung Hun; Friedman, David; Guallar, Eliseo

    2014-01-01

    Background Diabetes may affect vascular autoregulation of the retina and optic nerve and may be associated with an increased risk of glaucoma,but the association of prediabetes, insulin resistance, markers of glucose metabolismwith glaucoma has not beenevaluated in general population samples. Objective To examine the relation between diabetes, pre-diabetes, metabolic syndrome and its components and the levels of fasting glucose, HbA1c and HOMA-IR with the prevalence of glaucoma in the general U.S. population. Methods Cross-sectional study of 3,299 adult men and women from the 2005–2008 National Health and NutritionExamination Survey (NHANES). The presence of diabetes, prediabetes, the metabolic syndrome and its individual components and biomarkers of glucose metabolisms were based on standardized questionnaire and physical exam data and laboratory tests. The history of glaucoma was assessed through questionnaire during the home interview. Results Diabetes was strongly associated with prevalent glaucoma.In fully adjusted models, the odds ratiofor glaucoma comparing participants with diabetes with participants in the reference group with neither pre-diabetes nor diabetes was 2.12 (95% CI: 1.23, 3.67). The corresponding odd ratio comparing participants with pre-diabetes to those in the reference group was 1.01 (95% CI: 0.57, 1.82). Patients with 5 or more years of diabetes duration hadan OR for glaucoma of 3.90 (95% CI: 1.63, 9.32) compared with patients with <5 years of diabetes duration. We also found a hockey-stick shaped associations between biomarkers of glucose metabolisms and the prevalence of glaucoma. Conclusions Diabetes was associated with higher risk of glaucoma. Participants without diabetes but at the higher levels of fasting glucose, fasting insulin, HbA1c and HOMA-IR spectrum may also be at greater risk of glaucoma. PMID:25393836

  7. Effect of peripheral 5-HT on glucose and lipid metabolism in wether sheep.

    Directory of Open Access Journals (Sweden)

    Hitoshi Watanabe

    Full Text Available In mice, peripheral 5-HT induces an increase in the plasma concentrations of glucose, insulin and bile acids, and a decrease in plasma triglyceride, NEFA and cholesterol concentrations. However, given the unique characteristics of the metabolism of ruminants relative to monogastric animals, the physiological role of peripheral 5-HT on glucose and lipid metabolism in sheep remains to be established. Therefore, in this study, we investigated the effect of 5-HT on the circulating concentrations of metabolites and insulin using five 5-HT receptor (5HTR antagonists in sheep. After fasting for 24 h, sheep were intravenously injected with 5-HT, following which-, plasma glucose, insulin, triglyceride and NEFA concentrations were significantly elevated. In contrast, 5-HT did not affect the plasma cholesterol concentration, and it induced a decrease in bile acid concentrations. Increases in plasma glucose and insulin concentrations induced by 5-HT were attenuated by pre-treatment with Methysergide, a 5HTR 1, 2 and 7 antagonist. Additionally, decreased plasma bile acid concentrations induced by 5-HT were blocked by pre-treatment with Ketanserin, a 5HTR 2A antagonist. However, none of the 5HTR antagonists inhibited the increase in plasma triglyceride and NEFA levels induced by 5-HT. On the other hand, mRNA expressions of 5HTR1D and 1E were observed in the liver, pancreas and skeletal muscle. These results suggest that there are a number of differences in the physiological functions of peripheral 5-HT with respect to lipid metabolism between mice and sheep, though its effect on glucose metabolism appears to be similar between these species.

  8. Diabetes, glucose metabolism, and glaucoma: the 2005-2008 National Health and Nutrition Examination Survey.

    Directory of Open Access Journals (Sweden)

    Di Zhao

    Full Text Available BACKGROUND: Diabetes may affect vascular autoregulation of the retina and optic nerve and may be associated with an increased risk of glaucoma,but the association of prediabetes, insulin resistance, markers of glucose metabolismwith glaucoma has not beenevaluated in general population samples. OBJECTIVE: To examine the relation between diabetes, pre-diabetes, metabolic syndrome and its components and the levels of fasting glucose, HbA1c and HOMA-IR with the prevalence of glaucoma in the general U.S. population. METHODS: Cross-sectional study of 3,299 adult men and women from the 2005-2008 National Health and NutritionExamination Survey (NHANES. The presence of diabetes, prediabetes, the metabolic syndrome and its individual components and biomarkers of glucose metabolisms were based on standardized questionnaire and physical exam data and laboratory tests. The history of glaucoma was assessed through questionnaire during the home interview. RESULTS: Diabetes was strongly associated with prevalent glaucoma.In fully adjusted models, the odds ratiofor glaucoma comparing participants with diabetes with participants in the reference group with neither pre-diabetes nor diabetes was 2.12 (95% CI: 1.23, 3.67. The corresponding odd ratio comparing participants with pre-diabetes to those in the reference group was 1.01 (95% CI: 0.57, 1.82. Patients with 5 or more years of diabetes duration hadan OR for glaucoma of 3.90 (95% CI: 1.63, 9.32 compared with patients with <5 years of diabetes duration. We also found a hockey-stick shaped associations between biomarkers of glucose metabolisms and the prevalence of glaucoma. CONCLUSIONS: Diabetes was associated with higher risk of glaucoma. Participants without diabetes but at the higher levels of fasting glucose, fasting insulin, HbA1c and HOMA-IR spectrum may also be at greater risk of glaucoma.

  9. Methylglyoxal alters glucose metabolism and increases AGEs content in C6 glioma cells.

    Science.gov (United States)

    Hansen, Fernanda; de Souza, Daniela Fraga; Silveira, Simone da Luz; Hoefel, Ana Lúcia; Fontoura, Júlia Bijoldo; Tramontina, Ana Carolina; Bobermin, Larissa Daniele; Leite, Marina Concli; Perry, Marcos Luiz Santos; Gonçalves, Carlos Alberto

    2012-12-01

    Methylglyoxal is a dicarbonyl compound that is physiologically produced by enzymatic and non-enzymatic reactions. It can lead to cytotoxicity, which is mainly related to Advanced Glycation End Products (AGEs) formation. Methylglyoxal and AGEs are involved in the pathogenesis of Neurodegenerative Diseases (ND) and, in these situations, can cause the impairment of energetic metabolism. Astroglial cells play critical roles in brain metabolism and the appropriate functioning of astrocytes is essential for the survival and function of neurons. However, there are only a few studies evaluating the effect of methylglyoxal on astroglial cells. The aim of this study was to evaluate the effect of methylglyoxal exposure, over short (1 and 3 h) and long term (24 h) periods, on glucose, glycine and lactate metabolism in C6 glioma cells, as well as investigate the glyoxalase system and AGEs formation. Glucose uptake and glucose oxidation to CO(2) increased in 1 h and the conversion of glucose to lipids increased at 3 h. In addition, glycine oxidation to CO(2) and conversion of glycine to lipids increased at 1 h, whereas the incorporation of glycine in proteins decreased at 1 and 3 h. Methylglyoxal decreased glyoxalase I and II activities and increased AGEs content within 24 h. Lactate oxidation and lactate levels were not modified by methylglyoxal exposure. These data provide evidence that methylglyoxal may impair glucose metabolism and can affect glyoxalase activity. In periods of increased methylglyoxal exposure, such alterations could be exacerbated, leading to further increases in intracellular methylglyoxal and AGEs, and therefore triggering and/or worsening ND.

  10. Cereal Processing Influences Postprandial Glucose Metabolism as Well as the GI Effect

    OpenAIRE

    2015-01-01

    Objective: Technological processes may influence the release of glucose in starch. The aim of this study was to compare the metabolic response and the kinetics of appearance of exogenous glucose from 2 cereal products consumed at breakfast. Methods: Twenty-five healthy men were submitted to a randomized, open, crossover study that was divided into 2 parts: 12 of the 25 subjects were included in the “isotope part,” and the 13 other subjects were included in the “glycemic part.” On test days, s...

  11. Effect of abomasal glucose infusion on splanchnic amino acid metabolism in periparturient dairy cows

    DEFF Research Database (Denmark)

    Larsen, Mogens; Kristensen, Niels Bastian

    2009-01-01

    Six Holstein cows fitted with ruminal cannulas and permanent indwelling catheters in the portal vein, hepatic vein, mesenteric vein, and an artery were used to study the effects of abomasal glucose infusion on splanchnic AA metabolism. The experimental design was a split plot, with cow as the whole...... plot, treatment as the whole-plot factor and days in milk (DIM) as the subplot factor. Cows were assigned to 1 of 2 treatments: control or infusion of 1,500 g/d of glucose into the abomasum from the day of calving to 29 DIM....

  12. TAp63 is a master transcriptional regulator of lipid and glucose metabolism

    Science.gov (United States)

    Su, Xiaohua; Gi, Young Jin; Chakravarti, Deepavali; Chan, Io Long; Zhang, Aijun; Xia, Xuefeng; Tsai, Kenneth Y.; Flores, Elsa R.

    2012-01-01

    SUMMARY TAp63 prevents premature aging suggesting a link to genes that regulate longevity. Further characterization of TAp63−/− mice revealed that these mice develop obesity, insulin resistance, and glucose intolerance, similar to those seen in mice lacking two key metabolic regulators, Silent information regulator T1 (Sirt1) and AMPK. While the roles of Sirt1 and AMPK in metabolism have been well studied, their upstream regulators are not well understood. We found that TAp63 is important in regulating energy metabolism by accumulating in response to metabolic stress and transcriptionally activating Sirt1, AMPKα2, and LKB1 resulting in increased fatty acid synthesis and decreased fatty acid oxidation. Moreover, we found that TAp63 lowers blood glucose levels in response to metformin. Restoration of Sirt1, AMPKα2, and LKB1 in TAp63−/− mice rescued some of the metabolic defects of the TAp63−/− mice. Our study defines a role for TAp63 in metabolism and weight control. PMID:23040072

  13. Visceral adiposity influences glucose and glycogen metabolism in control and hyperlipidic-fed animals

    Directory of Open Access Journals (Sweden)

    Danielle Kaiser de Souza

    2013-04-01

    Full Text Available Introduction: Evidences suggest that fat intake, visceral obesity and intracellular lipids are related to insulin impairment. Objective: The objective of the present paper was correlate visceral obesity and metabolic alterations in control (CTR and hyperlipidic cafeteria diet (CFT fed animals. Methods: After 6 months of diet treatment, liver and muscle of the male rats were utilized to determined glucose uptake and glycogen metabolism after administration of 0.4I U/kg insulin in vivo, and correlate the visceral adiposity to these two parameters. Results: Ample range of physiologic answers to body composition in metabolic profile of the both diets was found. No differences were found in glycemia and triacylglycerol after insulin action in both groups, however CFT group accumulated higher adiposity, mostly visceral fat, and showed lower glycogen content in the liver. We also found an inverse correlation between visceral adiposity and glucose uptake and a decrease of the glycogen synthase active form in the liver. CTR animals demonstrated an inverse correlation between glucose uptake and visceral adiposity in the muscle. Discussion and conclusion: It was observed a variability of metabolic alterations in animals which can be related to degree of accumulation of abdominal adiposity and ingestion of diet fats. Further studies will be required to clarify the reasons for the observed liver alterations in CFT and muscle alterations in CTR animals.

  14. Metabolic Characteristics of a Glucose-Utilizing Shewanella oneidensis Strain Grown under Electrode-Respiring Conditions.

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    Gen Nakagawa

    Full Text Available In bioelectrochemical systems, the electrode potential is an important parameter affecting the electron flow between electrodes and microbes and microbial metabolic activities. Here, we investigated the metabolic characteristics of a glucose-utilizing strain of engineered Shewanella oneidensis under electrode-respiring conditions in electrochemical reactors for gaining insight into how metabolic pathways in electrochemically active bacteria are affected by the electrode potential. When an electrochemical reactor was operated with its working electrode poised at +0.4 V (vs. an Ag/AgCl reference electrode, the engineered S. oneidensis strain, carrying a plasmid encoding a sugar permease and glucose kinase of Escherichia coli, generated current by oxidizing glucose to acetate and produced D-lactate as an intermediate metabolite. However, D-lactate accumulation was not observed when the engineered strain was grown with a working electrode poised at 0 V. We also found that transcription of genes involved in pyruvate and D-lactate metabolisms was upregulated at a high electrode potential compared with their transcription at a low electrode potential. These results suggest that the carbon catabolic pathway of S. oneidensis can be modified by controlling the potential of a working electrode in an electrochemical bioreactor.

  15. Metabolic responses to exercise on land and in water following glucose ingestion.

    Science.gov (United States)

    Kurobe, Kazumichi; Kousaka, Ayaka; Ogita, Futoshi; Matsumoto, Naoyuki

    2016-12-26

    Although aerobic exercise after a meal decreases postprandial blood glucose, the differences in glucose response between land and aquatic exercise are unclear. Thus, we examined the effect of different modes of exercise with same energy expenditure following glucose ingestion on carbohydrate metabolism. Ten healthy sedentary men (age, 22 ± 1 years) participated in this study. All subjects performed each of three exercise modes (cycling, walking and aquatic exercise) for 30 min after ingestion of a 75-g glucose solution with 1-2 weeks between trials. The exercise intensity was set at 40% of the maximum oxygen uptake that occurred during cycling. The velocity during walking and the target heart rate during aquatic exercise were predetermined in a pretest. The plasma glucose concentration at 30 min after exercise was significantly lower with aquatic exercise compared to that with cycling and walking (Pexercise modes in respiratory exchange ratio. On the other hand, serum free fatty acid concentration with aquatic exercise was significantly higher at 120 min after exercise compared with that after walking (Pexercise reduces postprandial blood glucose compared with both cycling and walking with the same energy expenditure. Aquatic exercise shows potential as an exercise prescription to prevent postprandial hyperglycaemia.

  16. Cross feeding of glucose metabolism byproducts of Escherichia coli human gut isolates and probiotic strains affect survival of Vibrio cholerae.

    Science.gov (United States)

    Sengupta, Chirantana; Ekka, Manjula; Arora, Saurabh; Dhaware, Prashant D; Chowdhury, Rukhsana; Raychaudhuri, Saumya

    2017-01-01

    Vibrio cholerae converts glucose into either acid or the neutral end product acetoin and its survival in carbohydrate enriched media is linked to the nature of the byproducts produced. It has been demonstrated in this study that Escherichia coli strain isolated from the gut of healthy human volunteers and the commonly used probiotic E. coli Nissle strain that metabolize glucose to acidic byproducts drastically reduce the survival of V. cholerae strains irrespective of their glucose sensitivity and acetoin production status. Accordingly, E. coli glucose transport mutants that produce lower amounts of acidic metabolites had little effect on the survival of V. cholerae in cocultures. Thus, cross feeding of byproducts of glucose metabolism by heterologous bacteria modulates the survival of V. cholerae in glucose rich medium suggesting that composition of the gut microbiota could influence the outcome of V. cholerae infection especially when glucose based ORS is administered.

  17. Beneficiary effect of Tinospora cordifolia against high-fructose diet induced abnormalities in carbohydrate and lipid metabolism in Wistar rats.

    Science.gov (United States)

    Reddy, S Sreenivasa; Ramatholisamma, P; Ramesh, B; Baskar, R; Saralakumari, D

    2009-10-01

    High intake of dietary fructose has been shown to exert a number of adverse metabolic eff ects in humans and experimental animals. The present study was designed to investigate the eff ect of the aqueous extract of Tinospora cordifolia stem (TCAE) on the adverse eff ects of fructose loading toward carbohydrate and lipid metabolism in rats. Adult male Wistar rats of body weight around 200 g were divided into four groups, two of which were fed with starch diet and the other two with high fructose (66 %) diet. Plant extract of TC (400 mg/kg/day) was administered orally to each group of the starch fed rats and the highfructose fed rats. At the end of 60 days of experimental period, biochemical parameters related to carbohydrate and lipid metabolism were assayed. Hyperglycemia, hyperinsulinemia, hypertriglyceridemia, insulin resistance, and elevated levels of hepatic total lipids, cholesterol, triglycerides, and free fatty acids (p TCAE treatment. Alterations in the activities of enzymes of glucose metabolism (hexokinase, phosphofructokinase, pyruvate kinase, glucose-6-phosphatase, fructose-1,6-bisphosphatase, and glucose-6-phosphate dehydrogenase) and lipid metabolism (fatty acid synthetase, lipoprotein lipase, and malic enzyme) as observed in the high fructose-fed rats were prevented with TCAE administration. In conclusion, our fi ndings indicate improvement of glucose and lipid metabolism in high-fructose fed rats by treatment with Tinospora cordifolia, and suggest that the plant can be used as an adjuvant for the prevention and/or management of insulin resistance and disorders related to it.

  18. Glycated albumin suppresses glucose-induced insulin secretion by impairing glucose metabolism in rat pancreatic β-cells

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    Muto Takashi

    2011-04-01

    Full Text Available Abstract Background Glycated albumin (GA is an Amadori product used as a marker of hyperglycemia. In this study, we investigated the effect of GA on insulin secretion from pancreatic β cells. Methods Islets were collected from male Wistar rats by collagenase digestion. Insulin secretion in the presence of non-glycated human albumin (HA and GA was measured under three different glucose concentrations, 3 mM (G3, 7 mM (G7, and 15 mM (G15, with various stimulators. Insulin secretion was measured with antagonists of inducible nitric oxide synthetase (iNOS, and the expression of iNOS-mRNA was investigated by real-time PCR. Results Insulin secretion in the presence of HA and GA was 20.9 ± 3.9 and 21.6 ± 5.5 μU/3 islets/h for G3 (P = 0.920, and 154 ± 9.3 and 126.1 ± 7.3 μU/3 islets/h (P = 0.046, for G15, respectively. High extracellular potassium and 10 mM tolbutamide abrogated the inhibition of insulin secretion by GA. Glyceraldehyde, dihydroxyacetone, methylpyruvate, GLP-1, and forskolin, an activator of adenylate cyclase, did not abrogate the inhibition. Real-time PCR showed that GA did not induce iNOS-mRNA expression. Furthermore, an inhibitor of nitric oxide synthetase, aminoguanidine, and NG-nitro-L-arginine methyl ester did not abrogate the inhibition of insulin secretion. Conclusion GA suppresses glucose-induced insulin secretion from rat pancreatic β-cells through impairment of intracellular glucose metabolism.

  19. Abnormality of peripheral nerve conduction velocity associated with illness course, symptoms and fasting blood glucose in patients with type 2 diabetes mellitus

    Institute of Scientific and Technical Information of China (English)

    Suijing Cui; Jinhua Qiu; Weiliang Luo

    2006-01-01

    BACKGROUND: It has shown that abnormality of peripheral nerve conduction velocity during onset of diabetes mellitus is not related to age and sex, but to symptoms, illness course and level of fasting blood glucose.OBJECTIVE: To measure correlation of abnormality of peripheral nerve conduction velocity with various illness courses, symptoms and levels of fasting blood glucose of patients with type 2 diabetes mellitus.DESIGN: Case analysis.SETTING: Department of Neurology, Central People's Hospital of Huizhou.PARTICIPANTS: A total of 128 patients who were diagnosed as type 2 diabetes mellitus were selected from Central People's Hospital of Huizhou from September 2001 to October 2005. There were 75 males and 53 females aged 32-83 years and the illness course ranged from 1 month to 20 years.METHODS: All 128 patients with type 2 diabetes mellitus received neuro-electrophysiological study and their clinical data were retrospectively analyzed to measure peripheral nerve conduction velocity and fasting blood glucose so as to investigate the correlation of peripheral nerve conduction velocity with clinical symptoms,illness course and levels of fasting blood glucose.MAIN OUTCOME MEASURES: Correlation of peripheral nerve conduction velocity with clinical symptoms, illness course and levels of fasting blood glucose.RESULTS: All 128 patients with type 2 diabetes mellitus were involved in the final analysis. ① Among 128patients, 114 patients had abnormality of peripheral nerve conduction velocity; 110 patients had clinical symptoms, including 102 patients having abnormality of peripheral nerve conduction velocity; 18 patients did not have clinical symptoms, including 12 patients having abnormality of peripheral nerve conduction velocity.There were significant differences between them (x2=8.275, P=0.04). ② Among 128 patients, illness course of 75 patients was equal to or less than 5 years, including 27 patients having abnormality of peripheral nerve conduction velocity

  20. Simultaneous Voltammetric Measurements of Glucose and Dopamine Demonstrate the Coupling of Glucose Availability with Increased Metabolic Demand in the Rat Striatum.

    Science.gov (United States)

    Smith, Samantha K; Lee, Christie A; Dausch, Matthew E; Horman, Brian M; Patisaul, Heather B; McCarty, Gregory S; Sombers, Leslie A

    2017-02-15

    Cerebral blood flow ensures delivery of nutrients, such as glucose, to brain sites with increased metabolic demand. However, little is known about rapid glucose dynamics at discrete locations during neuronal activation in vivo. Acute exposure to many substances of abuse elicits dopamine release and neuronal activation in the striatum; however, the concomitant changes in striatal glucose remain largely unknown. Recent developments have combined fast-scan cyclic voltammetry with glucose oxidase enzyme modified carbon-fiber microelectrodes to enable the measurement of glucose dynamics with subsecond temporal resolution in the mammalian brain. This work evaluates several waveforms to enable the first simultaneous detection of endogenous glucose and dopamine at single recording sites. These molecules, one electroactive and one nonelectroactive, were found to fluctuate in the dorsal striatum in response to electrical stimulation of the midbrain and systemic infusion of cocaine/raclopride. The data reveal the second-by-second dynamics of these species in a striatal microenvironment, and directly demonstrate the coupling of glucose availability with increased metabolic demand. This work provides a foundation that will enable detailed investigation of local mechanisms that regulate the coupling of cerebral blood flow with metabolic demand under normal conditions, and in animal studies of drug abuse and addiction.

  1. Metabolic flux profiling of recombinant protein secreting Pichia pastoris growing on glucose:methanol mixtures

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    Jordà Joel

    2012-05-01

    Full Text Available Abstract Background The methylotrophic yeast Pichia pastoris has emerged as one of the most promising yeast hosts for the production of heterologous proteins. Mixed feeds of methanol and a multicarbon source instead of methanol as sole carbon source have been shown to improve product productivities and alleviate metabolic burden derived from protein production. Nevertheless, systematic quantitative studies on the relationships between the central metabolism and recombinant protein production in P. pastoris are still rather limited, particularly when growing this yeast on mixed carbon sources, thus hampering future metabolic network engineering strategies for improved protein production. Results The metabolic flux distribution in the central metabolism of P. pastoris growing on a mixed feed of glucose and methanol was analyzed by Metabolic Flux Analysis (MFA using 13C-NMR-derived constraints. For this purpose, we defined new flux ratios for methanol assimilation pathways in P. pastoris cells growing on glucose:methanol mixtures. By using this experimental approach, the metabolic burden caused by the overexpression and secretion of a Rhizopus oryzae lipase (Rol in P. pastoris was further analyzed. This protein has been previously shown to trigger the unfolded protein response in P. pastoris. A series of 13C-tracer experiments were performed on aerobic chemostat cultivations with a control and two different Rol producing strains growing at a dilution rate of 0.09 h−1 using a glucose:methanol 80:20 (w/w mix as carbon source. The MFA performed in this study reveals a significant redistristribution of carbon fluxes in the central carbon metabolism when comparing the two recombinant strains vs the control strain, reflected in increased glycolytic, TCA cycle and NADH regeneration fluxes, as well as higher methanol dissimilation rates. Conclusions Overall, a further 13C-based MFA development to characterise the central metabolism of methylotrophic

  2. A comprehensive metabolic profile of cultured astrocytes using isotopic transient metabolic flux analysis and 13C-labeled glucose

    Directory of Open Access Journals (Sweden)

    Ana I Amaral

    2011-09-01

    Full Text Available Metabolic models have been used to elucidate important aspects of brain metabolism in recent years. This work applies for the first time the concept of isotopic transient 13C metabolic flux analysis (MFA to estimate intracellular fluxes of cultured astrocytes. This methodology comprehensively explores the information provided by 13C labeling time-courses of intracellular metabolites after administration of a 13C labeled substrate. Cells were incubated with medium containing [1-13C]glucose for 24 h and samples of cell supernatant and extracts collected at different time-points were then analyzed by mass spectrometry and/or HPLC. Metabolic fluxes were estimated by fitting a carbon labeling network model to isotopomer profiles experimentally determined. Both the fast isotopic equilibrium of glycolytic metabolite pools and the slow labeling dynamics of TCA cycle intermediates are described well by the model. The large pools of glutamate and aspartate which are linked to the TCA cycle via reversible aminotransferase reactions are likely to be responsible for the observed delay in equilibration of TCA cycle intermediates. Furthermore, it was estimated that 11% of the glucose taken up by astrocytes was diverted to the pentose phosphate pathway. In addition, considerable fluxes through pyruvate carboxylase (PC (PC/pyruvate dehydrogenase (PDH ratio = 0.5, malic enzyme (5% of the total pyruvate production and catabolism of branched-chained amino acids (contributing with ~40% to total acetyl-CoA produced confirmed the significance of these pathways to astrocytic metabolism. Consistent with the need of maintaining cytosolic redox potential, the fluxes through the malate-aspartate shuttle and the PDH pathway were comparable. Finally, the estimated glutamate/α-ketoglutarate exchange rate (~0.7 µmol.mg prot-1.h-1 was similar to the TCA cycle flux. In conclusion, this work demonstrates the potential of isotopic transient MFA for a comprehensive analysis of

  3. A metabolic trade-off between phosphate and glucose utilization in Escherichia coli.

    Science.gov (United States)

    Behrends, Volker; Maharjan, Ram P; Ryall, Ben; Feng, Lu; Liu, Bin; Wang, Lei; Bundy, Jacob G; Ferenci, Thomas

    2014-11-01

    Getting the most out of available nutrients is a key challenge that all organisms face. Little is known about how they optimize and balance the simultaneous utilization of multiple elemental resources. We investigated the effects of long-term phosphate limitation on carbon metabolism of the model organism Escherichia coli using chemostat cultures. We profiled metabolic changes in the growth medium over time and found evidence for an increase in fermentative metabolism despite the aerobic conditions. Using full-genome sequencing and competition experiments, we found that fitness under phosphate-limiting conditions was reproducibly increased by a mutation preventing flux through succinate in the tricarboxylic acid cycle. In contrast, these mutations reduced competitive ability under carbon limitation, and thus reveal a conflicting metabolic benefit in the role of the TCA cycle in environments limited by inorganic phosphate and glucose.

  4. Adaptive mutations in sugar metabolism restore growth on glucose in a pyruvate decarboxylase negative yeast strain

    DEFF Research Database (Denmark)

    Zhang, Yiming; Liu, Guodong; Engqvist, Martin K. M.

    2015-01-01

    DNA sequencing. Among these genetic changes, 4 genes were found to carry point mutations in at least two of the evolved strains: MTH1 encoding a negative regulator of the glucose-sensing signal transduction pathway, HXT2 encoding a hexose transporter, CIT1 encoding a mitochondrial citrate synthase...... further increased the maximum specific growth rate to 0.069 h-1. Conclusions: In this study, possible evolving mechanisms of Pdc negative strains on glucose were investigated by genome sequencing and reverse engineering. The non-synonymous mutations in MTH1 alleviated the glucose repression by repressing...... expression of several hexose transporter genes. The non-synonymous mutations in HXT2 and CIT1 may function in the presence of mutated MTH1 alleles and could be related to an altered central carbon metabolism in order to ensure production of cytosolic acetyl-CoA in the Pdc negative strain....

  5. Tumor glucose metabolism imaged in vivo in small animals with whole-body photoacoustic computed tomography

    Science.gov (United States)

    Chatni, Muhammad Rameez; Xia, Jun; Sohn, Rebecca; Maslov, Konstantin; Guo, Zijian; Zhang, Yu; Wang, Kun; Xia, Younan; Anastasio, Mark; Arbeit, Jeffrey; Wang, Lihong V.

    2012-07-01

    With the increasing use of small animals for human disease studies, small-animal whole-body molecular imaging plays an important role in biomedical research. Currently, none of the existing imaging modalities can provide both anatomical and glucose molecular information, leading to higher costs of building dual-modality systems. Even with image co-registration, the spatial resolution of the molecular imaging modality is not improved. Utilizing a ring-shaped confocal photoacoustic computed tomography system, we demonstrate, for the first time, that both anatomy and glucose uptake can be imaged in a single modality. Anatomy was imaged with the endogenous hemoglobin contrast, and glucose metabolism was imaged with a near-infrared dye-labeled 2-deoxyglucose.

  6. Further studies of the influence of apolipoprotein B alleles on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Bentzen, Joan; Poulsen, Pernille; Vaag, Allan

    2003-01-01

    The effect of five genetic polymorphisms in the apolipoprotein B gene on parameters of lipid and glucose metabolism was assessed in 564 Danish mono- and dizygotic twins. Genotypes in apolipoprotein B T71I (ApaLI RFLP), A591V (AluI RFLP), L2712P (MvaI RFLP), R3611Q (MspI RFLP), and E4154K (Eco...... on the insulin-to-glucose ratio (p = 0.04), and E4154K (EcoRI RFLP) influenced HOMAbeta (p = 0.04). Significant interactions were observed between genotype in T71I (ApaLI RFLP), A591V (AluI RFLP), R3611Q (MspI RFLP), and E4154K (EcoRI RFLP) and glucose tolerance on lipid-related parameters (0.03

  7. Hydroxytyrosol prevents diet-induced metabolic syndrome and attenuates mitochondrial abnormalities in obese mice.

    Science.gov (United States)

    Cao, Ke; Xu, Jie; Zou, Xuan; Li, Yuan; Chen, Cong; Zheng, Adi; Li, Hao; Li, Hua; Szeto, Ignatius Man-Yau; Shi, Yujie; Long, Jiangang; Liu, Jiankang; Feng, Zhihui

    2014-02-01

    A Mediterranean diet rich in olive oil has profound influence on health outcomes including metabolic syndrome. However, the active compound and detailed mechanisms still remain unclear. Hydroxytyrosol (HT), a major polyphenolic compound in virgin olive oil, has received increased attention for its antioxidative activity and regulation of mitochondrial function. Here, we investigated whether HT is the active compound in olive oil exerting a protective effect against metabolic syndrome. In this study, we show that HT could prevent high-fat-diet (HFD)-induced obesity, hyperglycemia, hyperlipidemia, and insulin resistance in C57BL/6J mice after 17 weeks supplementation. Within liver and skeletal muscle tissues, HT could decrease HFD-induced lipid deposits through inhibition of the SREBP-1c/FAS pathway, ameliorate HFD-induced oxidative stress by enhancing antioxidant enzyme activities, normalize expression of mitochondrial complex subunits and mitochondrial fission marker Drp1, and eventually inhibit apoptosis activation. Moreover, in muscle tissue, the levels of mitochondrial carbonyl protein were decreased and mitochondrial complex activities were significantly improved by HT supplementation. In db/db mice, HT significantly decreased fasting glucose, similar to metformin. Notably, HT decreased serum lipid, at which metformin failed. Also, HT was more effective at decreasing the oxidation levels of lipids and proteins in both liver and muscle tissue. Similar to the results in the HFD model, HT decreased muscle mitochondrial carbonyl protein levels and improved mitochondrial complex activities in db/db mice. Our study links the olive oil component HT to diabetes and metabolic disease through changes that are not limited to decreases in oxidative stress, suggesting a potential pharmaceutical or clinical use of HT in metabolic syndrome treatment.

  8. Selective and Efficient Elimination of Vibrio cholerae with a Chemical Modulator that Targets Glucose Metabolism

    Science.gov (United States)

    Oh, Young Taek; Kim, Hwa Young; Kim, Eun Jin; Go, Junhyeok; Hwang, Wontae; Kim, Hyoung Rae; Kim, Dong Wook; Yoon, Sang Sun

    2016-01-01

    Vibrio cholerae, a Gram-negative bacterium, is the causative agent of pandemic cholera. Previous studies have shown that the survival of the seventh pandemic El Tor biotype V. cholerae strain N16961 requires production of acetoin in a glucose-rich environment. The production of acetoin, a neutral fermentation end-product, allows V. cholerae to metabolize glucose without a pH drop, which is mediated by the production of organic acid. This finding suggests that inhibition of acetoin fermentation can result in V. cholerae elimination by causing a pH imbalance under glucose-rich conditions. Here, we developed a simple high-throughput screening method and identified an inducer of medium acidification (iMAC). Of 8364 compounds screened, we identified one chemical, 5-(4-chloro-2-nitrobenzoyl)-6-hydroxy-1,3-dimethylpyrimidine-2,4(1H,3H)-dione, that successfully killed glucose-metabolizing N16961 by inducing acidic stress. When N16961 was grown with abundant glucose in the presence of iMAC, acetoin production was completely suppressed and concomitant accumulation of lactate and acetate was observed. Using a beta-galactosidase activity assay with a single-copy palsD::lacZ reporter fusion, we show that that iMAC likely inhibits acetoin production at the transcriptional level. Thin-layer chromatography revealed that iMAC causes a significantly reduced accumulation of intracellular (p)ppGpp, a bacterial stringent response alarmone known to positively regulate acetoin production. In vivo bacterial colonization and fluid accumulation were also markedly decreased after iMAC treatment. Finally, we demonstrate iMAC-induced bacterial killing for 22 different V. cholerae strains belonging to diverse serotypes. Together, our results suggest that iMAC, acting as a metabolic modulator, has strong potential as a novel antibacterial agent for treatment against cholera. PMID:27900286

  9. Sympathetic overactivity precedes metabolic dysfunction in a fructose model of glucose intolerance in mice.

    Science.gov (United States)

    De Angelis, Katia; Senador, Danielle D; Mostarda, Cristiano; Irigoyen, Maria C; Morris, Mariana

    2012-04-15

    Consumption of high levels of fructose in humans and animals leads to metabolic and cardiovascular dysfunction. There are questions as to the role of the autonomic changes in the time course of fructose-induced dysfunction. C57/BL male mice were given tap water or fructose water (100 g/l) to drink for up to 2 mo. Groups were control (C), 15-day fructose (F15), and 60-day fructose (F60). Light-dark patterns of arterial pressure (AP) and heart rate (HR), and their respective variabilities were measured. Plasma glucose, lipids, insulin, leptin, resistin, adiponectin, and glucose tolerance were quantified. Fructose increased systolic AP (SAP) at 15 and 60 days during both light (F15: 123 ± 2 and F60: 118 ± 2 mmHg) and dark periods (F15: 136 ± 4 and F60: 136 ± 5 mmHg) compared with controls (light: 111 ± 2 and dark: 117 ± 2 mmHg). SAP variance (VAR) and the low-frequency component (LF) were increased in F15 (>60% and >80%) and F60 (>170% and >140%) compared with C. Cardiac sympatho-vagal balance was enhanced, while baroreflex function was attenuated in fructose groups. Metabolic parameters were unchanged in F15. However, F60 showed significant increases in plasma glucose (26%), cholesterol (44%), triglycerides (22%), insulin (95%), and leptin (63%), as well as glucose intolerance. LF of SAP was positively correlated with SAP. Plasma leptin was correlated with triglycerides, insulin, and glucose tolerance. Results show that increased sympathetic modulation of vessels and heart preceded metabolic dysfunction in fructose-consuming mice. Data suggest that changes in autonomic modulation may be an initiating mechanism underlying the cluster of symptoms associated with cardiometabolic disease.

  10. Sexual dimorphism in glucose and lipid metabolism during fasting, hypoglycemia and exercise

    Directory of Open Access Journals (Sweden)

    Maka S Hedrington

    2015-04-01

    Full Text Available Sexually dimorphic physiologic responses occur during fasting, hypoglycemia and exercise. The areas covered in this mini review include studies that have used isotopic tracer methods and/or euglycemic clamp studies to investigate substrate metabolism during the above common physiologic stress. Women have greater reliance on lipid metabolism during fasting, hypoglycemia and exercise while men exhibit preference of carbohydrate utilization. Plasma glucose concentrations were shown to be lower, while free fatty acids (FFA and lipolysis higher in women compared to men after fasting. Hypoglycemia resulted in significantly reduced epinephrine, norepinephrine, glucagon, growth hormone, pancreatic polypeptide and hepatic glucose production responses in females as compared to males. Sexual dimorphism during exercise was demonstrated by higher glycerol and FFA responses in women compared to men and higher carbohydrate oxidation rate in men. Mechanisms that can increase lipolytic rates in women include higher total fat mass, enhanced lipolytic sensitivity to epinephrine and increased activation of β adrenergic receptors.

  11. Dietary Fiber-Induced Improvement in Glucose Metabolism Is Associated with Increased Abundance of Prevotella

    DEFF Research Database (Denmark)

    Kovatcheva-Datchary, Petia; Nilsson, Anne; Akrami, Rozita

    2015-01-01

    The gut microbiota plays an important role in human health by interacting with host diet, but there is substantial inter-individual variation in the response to diet. Here we compared the gut microbiota composition of healthy subjects who exhibited improved glucose metabolism following 3-day...... consumption of barley kernel-based bread (BKB) with those who responded least to this dietary intervention. The Prevotella/Bacteroides ratio was higher in responders than non-responders after BKB. Metagenomic analysis showed that the gut microbiota of responders was enriched in Prevotella copri and had...... increased potential to ferment complex polysaccharides after BKB. Finally, germ-free mice transplanted with microbiota from responder human donors exhibited improved glucose metabolism and increased abundance of Prevotella and liver glycogen content compared with germ-free mice that received non...

  12. Impact of expression of EMP enzymes on glucose metabolism in Zymomonas mobilis.

    Science.gov (United States)

    Chen, Rachel Ruizhen; Agrawal, Manoj; Mao, Zichao

    2013-06-01

    Zymomonas mobilis is the only known microorganism that utilizes the Entner-Doudoroff (ED) pathway anaerobically. In this work, we investigated whether the overexpression of a phosphofructokinase (PFK), the only missing Embden-Meyerhof-Parnas (EMP) pathway enzyme, could establish the pathway in this organism. Introduction of a pyrophosphate-dependent PFK, along with co-expression of homologous fructose-1,6-bisphosphate aldolase and triosephosphate isomerase, did not result in an EMP flux to any appreciable level. However, the metabolism of glucose was impacted significantly. Eight percent of glucose was metabolized to form a new metabolite, dihydroxyacetone. Reducing flux through the ED pathway by as much as 40 % through antisense of a key enzyme, ED aldolase, did not result in a fully functional EMP pathway, suggesting that the ED pathway, especially the lower arm, downstream from glyceraldehyde-3-phosphate, is very rigid, possibly due to redox balance.

  13. Prevalence of depression in individuals with impaired glucose metabolism or undiagnosed diabetes

    DEFF Research Database (Denmark)

    Nouwen, Arie; Nefs, Giesje; Caramlau, Isabela

    2011-01-01

    diagnosed type 2 diabetes (PDD) has not been the subject of a systematic review/meta-analysis. This study examined the prevalence of depression in IGM and UDD subjects relative to each other and to NGM and PDD subjects by reviewing the literature and conducting a meta-analysis of studies on this topic....... RESEARCH DESIGN AND METHODS: EMBASE and MEDLINE databases were searched for articles published up to May 2010. All studies that compared the prevalence of depression in subjects with IGM and UDD were included. Odds ratios (ORs) were calculated using fixed and random-effects models. RESULTS: The meta......OBJECTIVE: Meta-analyses have shown that the risk for depression is elevated in type 2 diabetes. Whether this risk in individuals with impaired glucose metabolism (IGM) or undiagnosed diabetes (UDD) is elevated relative to normal glucose metabolism (NGM) or decreased relative to previously...

  14. The Association of Hypertension with Obesity and Metabolic Abnormalities among Chinese Children

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    Haiquan Xu

    2011-01-01

    Full Text Available A total of 8898 Chinese children (4580 boys and 4318 girls aged 7–13 years in 6 cities of east China were recruited. Data on height, weight, waist circumference, blood pressure, serum lipid profiles, glucose, and insulin were collected. The overall prevalence of hypertension was 11.1%. Overweight and obese children had a higher risk of developing hypertension than their counterparts (29.1%, 17.4%, and 7.8%, resp. (P=0.0001. The means levels of triglycerides, glucose, insulin, and HOMA-IR (1.0 mmol/L, 4.5 mmol/L, 8.4 mU/mL and 1.7, resp. among hypertensive children were all significantly higher than their normotensive counterparts (0.8 mmol/L, 4.5 mmol/L, 5.9 mU/mL, and 1.2, resp. (P=0.0001. Compared with the healthy children, the risk (odds ratio, OR of having hypertension among children with high triglycerides, hyperglycemia, and metabolic syndrome was 1.4 (95% confidence interval (CI: 1.0–2.0, P=0.0334, 1.5 (95% CI: 0.9–2.5, P=0.0890, and 2.8 (95%CI: 1.5–5.4, P=0.0014, respectively, after controlling for age, gender, BMI, income level, parents' education level and puberty. In conclusion, overweight and obese children have higher risk of having hypertension and children with dyslipidemia, hyperglycemia, and metabolic syndrome and higher HOMA-IR have higher risk of developing hypertension.

  15. [Study of regional cerebral glucose metabolism, in man, while awake or asleep, by positron emission tomography].

    Science.gov (United States)

    Franck, G; Salmon, E; Poirrier, R; Sadzot, B; Franco, G

    1987-03-01

    Measurements of regional cerebral glucose uptake by the 18F-fluorodeoxyglucose technique (18FDG) and positron emission tomography (PET) along with polygraph recordings were made serially during relaxed wakefulness and different stages of nocturnal sleep in two right-handed normal volunteers. During stage III-IV sleep, values declined diffusely in both hemispheric regions (-31%), thalamus (-33%), cerebellum (-33%) and brain stem (-25%). During paradoxical sleep regional values increased diffusely compared with slow wave sleep. Compared to wakefulness, regional metabolic values seemed to increase but the results were more variable from one volunteer to the other. These preliminary data indicate important regional alterations in cerebral metabolism between sleep states.

  16. [Comparative characteristics of glucose metabolism in the liver of rats under acute alcohol and morphine intoxication].

    Science.gov (United States)

    Lelevich, S V

    2011-01-01

    The comparative analysis effect of acute alcohol and morphine intoxications on rats on hepatic glycolysis and pentose phosphate pathway was done. The dose-dependent inhibitory effect of ethanol on activity of limiting enzymes of these metabolic ways, as well as anaerobic reorientation of glucose metabolism was recognised with the increase of the dose of the intake alcohol. Morfine (10 mg/kg) activated enymes of glycolysis and pentose phosphate pathway, but in contrast to ethanol it did not influence these parameters at the dose 20 or 40 mg/kg.

  17. Associations of fatty acids in cerebrospinal fluid with peripheral glucose concentrations and energy metabolism.

    Directory of Open Access Journals (Sweden)

    Reiner Jumpertz

    Full Text Available Rodent experiments have emphasized a role of central fatty acid (FA species, such as oleic acid, in regulating peripheral glucose and energy metabolism. Thus, we hypothesized that central FAs are related to peripheral glucose regulation and energy expenditure in humans. To test this we measured FA species profiles in cerebrospinal fluid (CSF and plasma of 32 individuals who stayed in our clinical inpatient unit for 6 days. Body composition was measured by dual energy X-ray absorptiometry and glucose regulation by an oral glucose test (OGTT followed by measurements of 24 hour (24EE and sleep energy expenditure (SLEEP as well as respiratory quotient (RQ in a respiratory chamber. CSF was obtained via lumbar punctures; FA concentrations were measured by liquid chromatography/mass spectrometry. As expected, FA concentrations were higher in plasma compared to CSF. Individuals with high concentrations of CSF very-long-chain saturated FAs had lower rates of SLEEP. In the plasma moderate associations of these FAs with higher 24EE were observed. Moreover, CSF monounsaturated long-chain FA (palmitoleic and oleic acid concentrations were associated with lower RQs and lower glucose area under the curve during the OGTT. Thus, FAs in the CSF strongly correlated with peripheral metabolic traits. These physiological parameters were most specific to long-chain monounsaturated (C16:1, C18:1 and very-long-chain saturated (C24:0, C26:0 FAs.Together with previous animal experiments these initial cross-sectional human data indicate that central FA species are linked to peripheral glucose and energy homeostasis.

  18. A palatable hyperlipidic diet causes obesity and affects brain glucose metabolism in rats

    Directory of Open Access Journals (Sweden)

    Motoyama Caio SM

    2011-09-01

    Full Text Available Abstract Background We have previously shown that either the continuous intake of a palatable hyperlipidic diet (H or the alternation of chow (C and an H diet (CH regimen induced obesity in rats. Here, we investigated whether the time of the start and duration of these feeding regimens are relevant and whether they affect brain glucose metabolism. Methods Male Wistar rats received C, H, or CH diets during various periods of their life spans: days 30-60, days 30-90, or days 60-90. Experiments were performed the 60th or the 90th day of life. Rats were killed by decapitation. The glucose, insulin, leptin plasma concentration, and lipid content of the carcasses were determined. The brain was sliced and incubated with or without insulin for the analysis of glucose uptake, oxidation, and the conversion of [1-14C]-glucose to lipids. Results The relative carcass lipid content increased in all of the H and CH groups, and the H30-60 and H30-90 groups had the highest levels. Groups H30-60, H30-90, CH30-60, and CH30-90 exhibited a higher serum glucose level. Serum leptin increased in all H groups and in the CH60-90 and CH30-90 groups. Serum insulin was elevated in the H30-60, H60-90, CH60-90, CH30-90 groups. Basal brain glucose consumption and hypothalamic insulin receptor density were lower only in the CH30-60 group. The rate of brain lipogenesis was increased in the H30-90 and CH30-90 groups. Conclusion These findings indicate that both H and CH diet regimens increased body adiposity independent treatment and the age at which treatment was started, whereas these diets caused hyperglycemia and affected brain metabolism when started at an early age.

  19. The Cut-off Values of Triglycerides and Glucose Index for Metabolic Syndrome in American and Korean Adolescents.

    Science.gov (United States)

    Moon, Shinje; Park, Joon Sung; Ahn, Youhern

    2017-03-01

    The aim of this study was to establish ethnic- and gender-specific cut-off values of triglycerides and glucose index (TyG index) for clinical usefulness in a representative sample of Mexican American, Non-Hispanic White, Non-Hispanic Black, and Korean adolescents. The data were collected from datasets of the National Health and Nutrition Examination Survey between 1999 and 2012, and the Korean National Health and Nutrition Examination Survey between 2005 and 2013. Receiver operating characteristic curve analysis was used to find valid cut-off values of the TyG index for metabolic syndrome. The total number of eligible participants was 3,164 in the US and 4,873 in Korea. The optimal cut-off value with the Cook et al. definition revealed 8.55 in Mexican American, 8.55 in Non-Hispanic White, 8.35 in Non-Hispanic Black, and 8.45 in Korean, respectively. The cut-off value with the de Ferranti et al. definition was 8.45, 8.45, 8.15, and 8.35, and the cut-off value with the International Diabetes Federation definition was 8.65, 8.65, 8.15, and 8.55, respectively. These findings may be clinically useful for evaluating insulin resistance for determining metabolic abnormalities in adolescents.

  20. Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach

    Energy Technology Data Exchange (ETDEWEB)

    Mazzetti, Marta Blanca; Taira, Maria Cristina; Lelli, Sandra Marcela; Viale, Leonor Carmen San Martin de [Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428BGA, Ciudad Autonoma Buenos Aires (Argentina); Dascal, Eduardo; Basabe, Juan Carlos [Centro de Investigaciones Endocrinologicas (CEDIE). Hospital de Ninos, Dr. Ricardo Gutierrez, C1425EDF, Ciudad Autonoma Buenos Aires (Argentina)

    2004-01-01

    Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative

  1. Elevation in Tanis expression alters glucose metabolism and insulin sensitivity in H4IIE cells.

    Science.gov (United States)

    Gao, Yuan; Walder, Ken; Sunderland, Terry; Kantham, Lakshmi; Feng, Helen C; Quick, Melissa; Bishara, Natalie; de Silva, Andrea; Augert, Guy; Tenne-Brown, Janette; Collier, Gregory R

    2003-04-01

    Increased hepatic glucose output and decreased glucose utilization are implicated in the development of type 2 diabetes. We previously reported that the expression of a novel gene, Tanis, was upregulated in the liver during fasting in the obese/diabetic animal model Psammomys obesus. Here, we have further studied the protein and its function. Cell fractionation indicated that Tanis was localized in the plasma membrane and microsomes but not in the nucleus, mitochondria, or soluble protein fraction. Consistent with previous gene expression data, hepatic Tanis protein levels increased more significantly in diabetic P. obesus than in nondiabetic controls after fasting. We used a recombinant adenovirus to increase Tanis expression in hepatoma H4IIE cells and investigated its role in metabolism. Tanis overexpression reduced glucose uptake, basal and insulin-stimulated glycogen synthesis, and glycogen content and attenuated the suppression of PEPCK gene expression by insulin, but it did not affect insulin-stimulated insulin receptor phosphorylation or triglyceride synthesis. These results suggest that Tanis may be involved in the regulation of glucose metabolism, and increased expression of Tanis could contribute to insulin resistance in the liver.

  2. Molecular mechanism of hepatitis C virus-induced glucose metabolic disorders

    Directory of Open Access Journals (Sweden)

    Ikuo eShoji

    2012-01-01

    Full Text Available Hepatitis C virus (HCV infection causes not only intrahepatic diseases but also extrahepatic manifestations, including metabolic disorders. Chronic HCV infection is often associated with type 2 diabetes. However, the precise mechanism underlying this association is still unclear. Glucose is transported into hepatocytes via glucose transporter 2 (GLUT2. Hepatocytes play a crucial role in maintaining plasma glucose homeostasis via the gluconeogenic and glycolytic pathways. We have been investigating the molecular mechanism of HCV-related type 2 diabetes using HCV RNA replicon cells and HCV J6/JFH1 system. We found that HCV replication down-regulates cell surface expression of GLUT2 at the transcriptional level. We also found that HCV infection promotes hepatic gluconeogenesis in HCV J6/JFH1-infected Huh-7.5 cells. HCV infection transcriptionally up-regulated the genes for PEPCK and G6Pase, the rate-limiting enzymes for hepatic gluconeogenesis. Gene expression of PEPCK and G6Pase was regulated by the transcription factor forkhead box O1 (FoxO1 in HCV-infected cells. Phosphorylation of FoxO1 at Ser319 was markedly diminished in HCV-infected cells, resulting in increased nuclear accumulation of FoxO1. HCV NS5A protein was directly linked with the FoxO1-dependent increased gluconeogenesis. This paper will discuss the current model of HCV-induced glucose metabolic disorders.

  3. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role

    OpenAIRE

    Hage, Mirella P.; Al-Badri, Marwa R.; Azar, Sami T.

    2014-01-01

    Hydroxychloroquine (HCQ), a commonly used antimalarial drug in rheumatic diseases, has shown favorable metabolic effects on both glucose control and lipid profiles. We describe a case of a young woman with type 1 diabetes whose glycemic control was optimized with the introduction of HCQ as a treatment for her Sjogren syndrome in addition to a subtle yet measurable improvement in her lipid profile. An increasing body of evidence supports the beneficial impacts of HCQ in various ancillary condi...

  4. Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study

    OpenAIRE

    Strand, Linn Beate; Carnethon, Mercedes; Biggs, Mary Lou; Djoussé, Luc; Kaplan, Robert C.; David S Siscovick; Robbins, John A.; Redline, Susan; Patel, Sanjay R.; Janszky, Imre; Mukamal, Kenneth J.

    2015-01-01

    OBJECTIVE We examined the associations of symptoms of sleep-disordered breathing (SDB), which was defined as loud snoring, stopping breathing for a while during sleep, and daytime sleepiness, and insomnia with glucose metabolism and incident type 2 diabetes in older adults. RESEARCH DESIGN AND METHODS Between 1989 and 1993, the Cardiovascular Health Study recruited 5,888 participants ≥65 years of age from four U.S. communities. Participants reported SDB and insomnia symptoms yearly through 19...

  5. Nosocomial pneumonia caused by a glucose-metabolizing strain of Neisseria cinerea.

    OpenAIRE

    Boyce, J M; Taylor, M R; Mitchell, E B; Knapp, J S

    1985-01-01

    We describe what appears to be the first reported case of nosocomial pneumonia caused by Neisseria cinerea. The isolate metabolized glucose when tested in BACTEC Neisseria Differentiation Kits (Johnston Laboratories), but did not produce detectable acid in cystine-Trypticase (BBL Microbiology Systems) agar medium or in modified oxidation-fermentation medium. Clinical laboratories that rely on the BACTEC method for differentiation of pathogenic neisseriae should be aware of the fact that N. ci...

  6. Cerebral perfusion and glucose metabolism in Alzheimer's disease and frontotemporal dementia: two sides of the same coin?

    Energy Technology Data Exchange (ETDEWEB)

    Verfaillie, Sander C.J.; Adriaanse, Sofie M.; Binnewijzend, Maja A.A.; Benedictus, Marije R.; Ossenkoppele, Rik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Wattjes, Mike P.; Lammertsma, Adriaan A.; Boellaard, Ronald; Berckel, Bart N.M. van; Barkhof, Frederik [VU University Medical Centre, Department of Radiology and Nuclear Medicine, Amsterdam (Netherlands); Pijnenburg, Yolande A.L.; Scheltens, Philip [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); Flier, Wiesje M. van der [VU University Medical Centre, Alzheimer Centre and Department of Neurology, P.O. Box 7057, Amsterdam (Netherlands); VU University Medical Centre, Department of Epidemiology and Biostatistics, Amsterdam (Netherlands); Kuijer, Joost P.A. [VU University Medical Centre, Department of Physics and Medical Technology, Amsterdam (Netherlands)

    2015-10-15

    Alzheimer's disease (AD) and frontotemporal (FTD) dementia can be differentiated using [{sup 18}F]-2-deoxy-2-fluoro-D-glucose (FDG)-PET. Since cerebral blood flow (CBF) is related to glucose metabolism, our aim was to investigate the extent of overlap of abnormalities between AD and FTD. Normalized FDG-PET and arterial spin labelling (ASL-MRI)-derived CBF was measured in 18 AD patients (age, 64 ± 8), 12 FTD patients (age, 61 ± 8), and 10 controls (age, 56 ± 10). Voxel-wise comparisons, region-of-interest (ROI), correlation, and ROC curve analyses were performed. Voxel-wise comparisons showed decreased CBF and FDG uptake in AD compared with controls and FTD in both precuneus and inferior parietal lobule (IPL). Compared with controls and AD, FTD patients showed both hypometabolism and hypoperfusion in medial prefrontal cortex (mPFC). ASL and FDG were related in precuneus (r = 0.62, p < 0.001), IPL (r = 0.61, p < 0.001), and mPFC across groups (r = 0.74, p < 001). ROC analyses indicated comparable performance of perfusion and metabolism in the precuneus (AUC, 0.72 and 0.74), IPL (0.85 and 0.94) for AD relative to FTD, and in the mPFC in FTD relative to AD (both 0.68). Similar patterns of hypoperfusion and hypometabolism were observed in regions typically associated with AD and FTD, suggesting that ASL-MRI provides information comparable to FDG-PET. (orig.)

  7. Zonation of glucose and fatty acid metabolism in the liver : Mechanism and metabolic consequences

    NARCIS (Netherlands)

    Hijmans, Brenda S.; Greffiorst, Aldo; Oosterveer, Maaike H.; Groen, Albert K.

    2014-01-01

    The liver is generally considered as a relatively homogeneous organ containing four different cell types. It is however well-known that the liver is not homogeneous and consists of clearly demarcated metabolic zones. Hepatocytes from different zones show phenotypical heterogeneity in metabolic featu

  8. Abnormal bone and mineral metabolism in kidney transplant patients--a review

    DEFF Research Database (Denmark)

    Sprague, S.M.; Belozeroff, V.; Danese, M.D.

    2008-01-01

    for English language articles published between January 1990 and October 2006 that contained Medical Subject Headings and key words related to secondary or persistent hyperparathyroidism and kidney transplant. RESULTS: Parathyroid hormone levels decreased significantly during the first 3 months after......BACKGROUND/AIMS: Abnormal bone and mineral metabolism is common in patients with kidney failure and often persists after successful kidney transplant. METHODS: To better understand the natural history of this disease in transplant patients, we reviewed the literature by searching MEDLINE...... transplant but typically stabilized at elevated values after 1 year. Calcium tended to increase after transplant and then stabilize at the higher end of the normal range within 2 months. Phosphorus decreased rapidly to within or below normal levels after surgery and hypophosphatemia, if present, resolved...

  9. Effects of over-expressing resistin on glucose and lipid metabolism in mice

    Institute of Scientific and Technical Information of China (English)

    You LIU; Qun WANG; Ying-bin PAN; Zhi-jie GAO; Yan-fen LIU; Shao-hong CHEN

    2008-01-01

    Resistin, a newly discovered peptide hormone mainly secreted by adipose tissues, is present at high levels in serum of obese mice and may be a potential link between obesity and insulin resistance in rodents. However, some studies of rat and mouse models have associated insulin resistance and obesity with decreased resistin expression. In humans, no relationship between resistin level and insulin resistance or adiposity was observed. This suggests that additional studies are necessary to determine the specific role of resistin in the regulation of energy metabolism and adipogenesis. In the present study, we investigated the effect of resistin in vivo on glucose and lipid metabolism by over-expressing resistin in mice by intramuscular injection of a recombinant eukaryotic expression vector pcDNA3.1-Retn encoding porcine resistin gene. After injection, serum resistin and serum glucose (GLU) levels were significantly increased in the pcDNA3.1-Retn-treated mice; there was an obvious difference in total cholesterol (TC) level between the experiment and the control groups on Day 30. In pcDNA3.1-Retn-treated mice, both free fatty acid (FFA) and high density lipoprotein (HDL) cholesterol levels were markedly lower than those of control, whereas HDL cholesterol and triglyceride (TG) levels did not differ between the two groups. Furthermore, lipase activity was expressly lower on Day 20. Our data suggest that resistin over-expressed in mice might be responsible for insulin resistance and parameters related to glucose and lipid metabolism were changed accordingly.

  10. Olanzapine-induced changes in glucose metabolism are independent of the melanin-concentrating hormone system.

    Science.gov (United States)

    Girault, Elodie M; Toonen, Pim W; Eggels, Leslie; Foppen, Ewout; Ackermans, Mariëtte T; la Fleur, Susanne E; Fliers, Eric; Kalsbeek, Andries

    2013-11-01

    Atypical antipsychotic drugs such as Olanzapine (Ola) induce weight gain and metabolic changes associated with the development of type 2 diabetes. The mechanisms underlying these undesired side-effects are currently unknown. Chagnon et al. showed that the common allele rs7973796 of the prepro-melanin-concentrating hormone (PMCH) gene is associated with a greater body mass index in Ola-treated schizophrenic patients. As PMCH encodes for the orexigenic neuropeptide melanin-concentrating hormone (MCH), it was hypothesized that MCH is involved in Ola-induced metabolic changes. We have recently reported that the intragastric infusion of Ola results in hyperglycaemia and insulin resistance in male rats. In order to test in vivo the possible involvement of the PMCH gene in the pathogenesis of Ola side-effects, we administered Ola intragastrically in wild-type (WT) and PMCH knock-out (KO) rats. Our results show that glucose and corticosterone levels, as well as endogenous glucose production, are elevated by the infusion of Ola in both WT and KO animals. Thus, the lack of MCH does not seem to affect the acute effects of Ola on glucose metabolism. On the other hand, these effects might be obliterated by compensatory changes in other hypothalamic systems. In addition, possible modulatory effects of the MCH KO on the long term effects of Ola, i.e. increased adiposity, body weight gain, have not been investigated yet.

  11. Epithelial and Mesenchymal Tumor Compartments Exhibit In Vivo Complementary Patterns of Vascular Perfusion and Glucose Metabolism

    Directory of Open Access Journals (Sweden)

    Mirco Galiè

    2007-11-01

    Full Text Available Glucose transport and consumption are increased in tumors, and this is considered a diagnostic index of malignancy. However, there is recent evidence that carcinoma-associated stromal cells are capable of aerobic metabolism with low glucose consumption, at least partly because of their efficient vascular supply. In the present study, using dynamic contrast-enhanced magnetic resonance imaging and [F-18]fluorodeoxyglucose (FDG positron emission tomography (PET, we mapped in vivo the vascular supply and glucose metabolism in syngeneic experimental models of carcinoma and mesenchymal tumor. We found that in both tumor histotypes, regions with high vascular perfusion exhibited a significantly lower FDG uptake. This reciprocity was more conspicuous in carcinomas than in mesenchymal tumors, and regions with a high-vascular/low-FDG uptake pattern roughly overlapped with a stromal capsule and intratumoral large connectival septa. Accordingly, mesenchymal tumors exhibited a higher vascular perfusion and a lower FDG uptake than carcinomas. Thus, we provide in vivo evidence of vascular/metabolic reciprocity between epithelial and mesenchymal histotypes in tumors, suggesting a new intriguing aspect of epithelial-stromal interaction. Our results suggests that FDG-PET-based clinical analysis can underestimate the malignity or tumor extension of carcinomas exhibiting any trait of “mesenchymalization” such as desmoplasia or epithelial-mesenchymal transition.

  12. Metabolic abnormalities in skeletal muscle of patients receiving zidovudine therapy observed by 31P in vivo magnetic resonance spectroscopy.

    OpenAIRE

    Sinnwell, T M; Sivakumar, K.; Soueidan, S; Jay, C; Frank, J.A.; McLaughlin, A C; Dalakas, M C

    1995-01-01

    Patients on long-term zidovudine (AZT) therapy experience muscle fatigue and weakness attributed to AZT-induced mitochondrial toxicity in skeletal muscle. To determine if the clinico-pathological abnormalities in these patients correspond to abnormal muscle energy metabolism, we used 31P in vivo magnetic resonance spectroscopy to follow phosphorylated metabolites during exercise. We studied 19 normal volunteers, 6 HIV-positive patients never treated with AZT, and 9 HIV-positive patients who h...

  13. Electrocardiographic left ventricular hypertrophy without echocardiographic abnormalities evaluated by myocardial perfusion and fatty acid metabolic imaging

    Energy Technology Data Exchange (ETDEWEB)

    Narita, Michihiro; Kurihara, Tadashi [Sumitomo Hospital, Osaka (Japan)

    2000-01-01

    The pathophysiologic process in patients with electrocardiographic left ventricular hypertrophy with ST, T changes but without echocardiographic abnormalities was investigated by myocardial perfusion imaging and fatty acid metabolic imaging. Exercise stress {sup 99m}Tc-methoxy-isobutyl isonitrile (MIBI) imaging and rest {sup 123}I-beta-methyl-p-iodophenyl pentadecanoic acid (BMIPP) imaging were performed in 59 patients with electrocardiographic hypertrophy including 29 without apparent cause including hypertension and echocardiographic hypertrophy, and 30 with essential hypertension. Coronary angiography was performed in 6 patients without hypertension and 4 with hypertension and biopsy specimens were obtained from the left ventricular apex from 6 patients without hypertension. Myocardial perfusion and {sup 123}I-BMIPP images were classified into 3 types: normal, increased accumulation of the isotope at the left ventricular apex (high uptake) and defect. Transient perfusion abnormality and apical defect observed by {sup 123}I-BMIPP imaging were more frequent in patients without hypertension than in patients with hypertension (32% vs. 17%, p=0.04671 in perfusion; 62% vs. 30%, p=0.0236 in {sup 123}I-BMIPP). Eighteen normotensive patients with apical defect by {sup 123}I-BMIPP imaging included 3 of 10 patients with normal perfusion at exercise, 6 of 10 patients with high uptake and 9 of 9 patients with perfusion defect. The defect size revealed by {sup 123}I-BMIPP imaging was greater than that of the perfusion abnormality. Coronary stenoses were not observed and myocardial specimens showed myocardial disarray with hypertrophy. Moreover, 9 patients with hypertension and apical defects by {sup 123}I-BMIPP showed 3 different types of perfusion. Many patients without hypertension show a pathologic process similar to hypertrophic cardiomyopathy. Perfusion and {sup 123}I-BMIPP imaging are useful for the identification of these patients. (author)

  14. Reduced thalamic volume in preterm infants is associated with abnormal white matter metabolism independent of injury

    Energy Technology Data Exchange (ETDEWEB)

    Wisnowski, Jessica L. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Ceschin, Rafael C. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); University of Pittsburgh, Department of Biomedical Informatics, Pittsburgh, PA (United States); Choi, So Young [University of Southern California, Brain and Creativity Institute, Los Angeles, CA (United States); Schmithorst, Vincent J. [University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Painter, Michael J. [University of Pittsburgh, Department of Pediatrics, Division of Neurology, Childrens Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States); Nelson, Marvin D. [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Blueml, Stefan [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); Rudi Schulte Research Institute, Santa Barbara, CA (United States); Panigrahy, Ashok [Children' s Hospital Los Angeles, Department of Radiology, Los Angeles, CA (United States); University of Pittsburgh, Department of Pediatric Radiology, Children' s Hospital of Pittsburgh of UPMC, Pittsburgh, PA (United States)

    2015-05-01

    Altered thalamocortical development is hypothesized to be a key substrate underlying neurodevelopmental disabilities in preterm infants. However, the pathogenesis of this abnormality is not well-understood. We combined magnetic resonance spectroscopy of the parietal white matter and morphometric analyses of the thalamus to investigate the association between white matter metabolism and thalamic volume and tested the hypothesis that thalamic volume would be associated with diminished N-acetyl-aspartate (NAA), a measure of neuronal/axonal maturation, independent of white matter injury. Data from 106 preterm infants (mean gestational age at birth: 31.0 weeks ± 4.3; range 23-36 weeks) who underwent MR examinations under clinical indications were included in this study. Linear regression analyses demonstrated a significant association between parietal white matter NAA concentration and thalamic volume. This effect was above and beyond the effect of white matter injury and age at MRI and remained significant even when preterm infants with punctate white matter lesions (pWMLs) were excluded from the analysis. Furthermore, choline, and among the preterm infants without pWMLs, lactate concentrations were also associated with thalamic volume. Of note, the associations between NAA and choline concentration and thalamic volume remained significant even when the sample was restricted to neonates who were term-equivalent age or older. These observations provide convergent evidence of a neuroimaging phenotype characterized by widespread abnormal thalamocortical development and suggest that the pathogenesis may involve impaired axonal maturation. (orig.)

  15. Role of glucose and ketone bodies in the metabolic control of experimental brain cancer.

    Science.gov (United States)

    Seyfried, T N; Sanderson, T M; El-Abbadi, M M; McGowan, R; Mukherjee, P

    2003-10-06

    Brain tumours lack metabolic versatility and are dependent largely on glucose for energy. This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and elevate ketone bodies in the CT-2A syngeneic malignant mouse astrocytoma. C57BL/6J mice were fed either a standard diet unrestricted (SD-UR), a ketogenic diet unrestricted (KD-UR), the SD restricted to 40% (SD-R), or the KD restricted to 40% of the control standard diet (KD-R). Body weights, tumour weights, plasma glucose, beta-hydroxybutyrate (beta-OHB), and insulin-like growth factor 1 (IGF-1) were measured 13 days after tumour implantation. CT-2A growth was rapid in both the SD-UR and KD-UR groups, but was significantly reduced in both the SD-R and KD-R groups by about 80%. The results indicate that plasma glucose predicts CT-2A growth and that growth is dependent more on the amount than on the origin of dietary calories. Also, restriction of either diet significantly reduced the plasma levels of IGF-1, a biomarker for angiogenesis and tumour progression. Owing to a dependence on plasma glucose, IGF-1 was also predictive of CT-2A growth. Ketone bodies are proposed to reduce stromal inflammatory activities, while providing normal brain cells with a nonglycolytic high-energy substrate. Our results in a mouse astrocytoma suggest that malignant brain tumours are potentially manageable with dietary therapies that reduce glucose and elevate ketone bodies.

  16. Evaluation of hepatic glucose metabolism via gluconeogenesis and glycogenolysis after oral administration of insulin nanoparticles.

    Science.gov (United States)

    Woitiski, Camile B; Neufeld, Ronald J; Soares, Ana F; Figueiredo, Isabel V; Veiga, Francisco J; Carvalho, Rui A

    2012-12-01

    Nanoparticles were designed to promote insulin intestinal absorption via the oral route, to increase portal insulin levels to better mimic the physiological pathway, providing enhanced glucose control through glycogenolysis and gluconeogenesis. Nanoparticles were formulated with insulin encapsulated in the core material consisting of alginate and dextran sulfate, associated with poloxamer and subsequently coated with chitosan then albumin. A spherical and slightly rough core was observed in electron micrographs with the appearance of a concentration gradient of the polysaccharide structure toward the periphery of the nanoparticle. Atomic force microscopy showed that the fully formed nanoparticles are about 200 nm in diameter with smooth and spherical morphology. Histopathological analysis of organs and tissues of diabetic rats dosed daily for 15 days with insulin nanoparticles was used to evaluate toxicological issues. No morphological or pathological alterations were observed in rat liver, spleen, pancreas, kidney or intestinal sections. Following, the effect of nanoencapsulated insulin on inhibiting hepatic gluconeogenesis was evaluated after a single insulin administration and oral glucose tolerance test, which represents a significant metabolic challenge to the liver. Alterations in the hepatic glucose metabolism of fasted streptozotocin-diabetic rats were determined by the percent contribution of glycogenolysis and gluconeogenesis, measured by using metabolic tracers, however similar gluconeogenesis contribution to the hepatic metabolism was observed between diabetic rats receiving nanoencapsulated insulin or insulin solution. The metabolic results may be explained by the inability of a single dose in shifting the gluconeogenesis/glycogenolysis contributions, sampling time, fasting period or by influence of the kidney enzymes and impairment in insulin signaling observed in stz-diabetic rats.

  17. Glucose metabolism in obstructive sleep apnea syndrome%阻塞性睡眠呼吸暂停综合征患者葡萄糖代谢研究

    Institute of Scientific and Technical Information of China (English)

    刘宇; 汪鲁华; 古丽扎尔·买买提明

    2011-01-01

    Objective To observe glucose metabolism changes in patients with obstructive sleep apnea syndrome. Methods A total of 162 patients were diagnosed with polysomnography, and 50 healthy vonlunteers were as controls. Oral glucose tolerance test, fasting insulin and C-reactive protein were measured to observe the impaired fasting glucose and impaired glucose tolerance. Results The incidences of diabetes mellitus, abnormal glucose tolerance and C-reactive protein were higher in patients with obstructive sleep apnea syndrome than those in controls. Conclusion Glucose metabolism is abnormal in obstructive sleep apnea syndrome, and is properly related to inflammation.%目的:观察阻塞性睡眠呼吸暂停综合征(obstructive sleep apnea syndrome,OSAS)患者葡萄糖代谢情况.方法:用多导睡眠图检查确诊的重度OSAS患者162例(OSAS组),行口服糖耐量试验检查、空腹胰岛素及C反应蛋白测定,观察空腹血糖受损及糖耐量异常.并选择同期健康体检者50例作为对照组.结果:OSAS组糖尿病、糖耐量异常发病率及C反应蛋白水平明显高于对照组.结论:OSAS患者存在明显的糖代谢紊乱,可能与炎症有关.

  18. Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study.

    Directory of Open Access Journals (Sweden)

    Jennifer Kriebel

    Full Text Available Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10(-5 and 0.047. In addition, DNA methylation at cg06500161 (annotated to ABCG1 was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10(-5 and 3.0x10(-3. Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI (B-H-adjusted p-values = 0.047. Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1 was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10(-9. Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and

  19. Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study.

    Science.gov (United States)

    Kriebel, Jennifer; Herder, Christian; Rathmann, Wolfgang; Wahl, Simone; Kunze, Sonja; Molnos, Sophie; Volkova, Nadezda; Schramm, Katharina; Carstensen-Kirberg, Maren; Waldenberger, Melanie; Gieger, Christian; Peters, Annette; Illig, Thomas; Prokisch, Holger; Roden, Michael; Grallert, Harald

    2016-01-01

    Epigenetic regulation has been postulated to affect glucose metabolism, insulin sensitivity and the risk of type 2 diabetes. Therefore, we performed an epigenome-wide association study for measures of glucose metabolism in whole blood samples of the population-based Cooperative Health Research in the Region of Augsburg F4 study using the Illumina HumanMethylation 450 BeadChip. We identified a total of 31 CpG sites where methylation level was associated with measures of glucose metabolism after adjustment for age, sex, smoking, and estimated white blood cell proportions and correction for multiple testing using the Benjamini-Hochberg (B-H) method (four for fasting glucose, seven for fasting insulin, 25 for homeostasis model assessment-insulin resistance [HOMA-IR]; B-H-adjusted p-values between 9.2x10(-5) and 0.047). In addition, DNA methylation at cg06500161 (annotated to ABCG1) was associated with all the aforementioned phenotypes and 2-hour glucose (B-H-adjusted p-values between 9.2x10(-5) and 3.0x10(-3)). Methylation status of additional three CpG sites showed an association with fasting insulin only after additional adjustment for body mass index (BMI) (B-H-adjusted p-values = 0.047). Overall, effect strengths were reduced by around 30% after additional adjustment for BMI, suggesting that this variable has an influence on the investigated phenotypes. Furthermore, we found significant associations between methylation status of 21 of the aforementioned CpG sites and 2-hour insulin in a subset of samples with seven significant associations persisting after additional adjustment for BMI. In a subset of 533 participants, methylation of the CpG site cg06500161 (ABCG1) was inversely associated with ABCG1 gene expression (B-H-adjusted p-value = 1.5x10(-9)). Additionally, we observed an enrichment of the top 1,000 CpG sites for diabetes-related canonical pathways using Ingenuity Pathway Analysis. In conclusion, our study indicates that DNA methylation and diabetes

  20. Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving.

    Science.gov (United States)

    Weber, C; Schäff, C T; Kautzsch, U; Börner, S; Erdmann, S; Görs, S; Röntgen, M; Sauerwein, H; Bruckmaier, R M; Metges, C C; Kuhla, B; Hammon, H M

    2016-08-01

    Dairy cows undergo significant metabolic and endocrine changes during the transition from pregnancy to lactation, and impaired insulin action influences nutrient partitioning toward the fetus and the mammary gland. Because impaired insulin action during transition is thought to be related to elevated body condition and body fat mobilization, we hypothesized that over-conditioned cows with excessive body fat mobilization around calving may have impaired insulin metabolism compared with cows with low fat mobilization. Nineteen dairy cows were grouped according to their average concentration of total liver fat (LFC) after calving in low [LLFC; LFC 24.4% total fat/DM; n=10) fat-mobilizing cows. Blood samples were taken from wk 7 antepartum (ap) to wk 5 postpartum (pp) to determine plasma concentrations of glucose, insulin, glucagon, and adiponectin. We applied euglycemic-hyperinsulinemic (EGHIC) and hyperglycemic clamps (HGC) in wk 5 ap and wk 3 pp to measure insulin responsiveness in peripheral tissue and pancreatic insulin secretion during the transition period. Before and during the pp EGHIC, [(13)C6] glucose was infused to determine the rate of glucose appearance (GlucRa) and glucose oxidation (GOx). Body condition, back fat thickness, and energy-corrected milk were greater, but energy balance was lower in HLFC than in LLFC. Plasma concentrations of glucose, insulin, glucagon, and adiponectin decreased at calving, and this was followed by an immediate increase of glucagon and adiponectin after calving. Insulin concentrations ap were higher in HLFC than in LLFC cows, but the EGHIC indicated no differences in peripheral insulin responsiveness among cows ap and pp. However, GlucRa and GOx:GlucRa during the pp EGHIC were greater in HLFC than in LLFC cows. During HGC, pancreatic insulin secretion was lower, but the glucose infusion rate was higher pp than ap in both groups. Plasma concentrations of nonesterified fatty acids decreased during HGC and EGHIC, but in both

  1. Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes

    Science.gov (United States)

    Garcia-Carbonell, Ricard; Divakaruni, Ajit S.; Lodi, Alessia; Vicente-Suarez, Ildefonso; Saha, Arindam; Cheroutre, Hilde; Boss, Gerry R.; Tiziani, Stefano; Murphy, Anne N.; Guma, Monica

    2016-01-01

    Objective Up-regulation of glucose metabolism has been implicated not only in tumor cell growth but also in immune cells upon activation. However, little is known about the metabolite profile in rheumatoid arthritis (RA), particularly in fibroblast-like synoviocytes (FLS). This study was undertaken to evaluate whether changes in glucose metabolism in RA FLS could play a role in inflammation and joint damage. Methods Synovium and FLS were obtained from patients with RA and patients with osteoarthritis (OA). The rate of glycolysis after stimulation of FLS with lipopolysaccharide and platelet-derived growth factor BB was measured using glycolysis stress test technology. FLS function was evaluated using a glycolysis inhibitor, 2-deoxy-D-glucose (2-DG). After stimulation of the FLS, a migration scratch assay, MTT assay, and enzyme-linked immunosorbent assay were performed to measure the effect of 2-DG on FLS migration, viability of the FLS, and cytokine secretion, respectively. IRDye 800CW 2-DG was used to assess glucose uptake in the arthritic joints and stromal cells of mice after K/BxN mouse serum transfer. The mice were injected daily, intraperitoneally, with 3-bromopyruvate (BrPa; 5 mg/kg) to assess the effect of inhibition of glycolysis in vivo. Results Compared to human OA FLS, the balance between glycolysis and oxidative phosphorylation was shifted toward glycolysis in RA FLS. Glucose transporter 1 (GLUT1) messenger RNA (mRNA) expression correlated with baseline functions of the RA FLS. Glucose deprivation or incubation of the FLS with glycolytic inhibitors impaired cytokine secretion and decreased the rate of proliferation and migration of the cells. In a mouse model of inflammatory arthritis, GLUT1 mRNA expression in the synovial lining cells was observed, and increased levels of glucose uptake and glycolytic gene expression were detected in the stromal compartment of the arthritic mouse joints. Inhibition of glycolysis by BrPa, administered in vivo

  2. Effects of Cooling and Supplemental Bovine Somatotropin on Milk Production relating to Body Glucose Metabolism and Utilization of Glucose by the Mammary Gland in Crossbred Holstein Cattle

    Directory of Open Access Journals (Sweden)

    Siravit Sitprija

    2010-01-01

    Full Text Available Problem statement: The low milk yield and shorter persistency of lactation of dairy cattle is the major problem for the dairy practices in the tropics. High environmental temperatures and rapid decline of plasma growth hormone level can influence milk production. Regulation of the milk yield of animals is mainly based on the mechanisms governing the quantity of glucose extracted by the mammary gland for lactose biosynthetic pathways. The mechanism(s underlying the effects of cooling and supplemental bovine somatotropin on milk production relating to body glucose metabolism and intracellular metabolism of glucose in the mammary gland of crossbred Holstein cattle in the tropics have not been investigated to date. Approach: Ten crossbred 87.5% Holstein cows were divided into two groups of five animals each. Animals were housed in Normal Shade barn (NS as non-cooled cows and cows in the second group were housed in barn which was equipped with a two Misty-Fan cooling system (MF as cooled cows. Supplementation of recombinant bovine Somatotropin (rbST (POSILAC, 500 mg per cow were performed in both groups to study body glucose metabolism and the utilization of glucose in the mammary gland using a continuous infusion of [3-3H] glucose and [U- 14C] glucose as markers in early, mid and late stages of lactation. Results: Milk yield significantly increased in both groups during supplemental rbST with a high level of mammary blood flow. Body glucose turnover rates were not significant different between cooled and non-cooled cows whether supplemental rbST or not. The glucose taken up by the mammary gland of both non-cooled and cooled cows increased flux through the lactose synthesis and the pentose cycle pathway with significant increases in NADPH formation for fatty acid synthesis during rbST supplementation. The utilization of glucose carbon incorporation into milk appeared to increase in milk lactose and milk triacylglycerol but not for

  3. Fast dynamic response of the fermentative metabolism of Escherichia coli to aerobic and anaerobic glucose pulses.

    Science.gov (United States)

    Lara, Alvaro R; Taymaz-Nikerel, Hilal; Mashego, Mlawule R; van Gulik, Walter M; Heijnen, Joseph J; Ramírez, Octavio T; van Winden, Wouter A

    2009-12-15

    The response of Escherichia coli cells to transient exposure (step increase) in substrate concentration and anaerobiosis leading to mixed-acid fermentation metabolism was studied in a two-compartment bioreactor system consisting of a stirred tank reactor (STR) connected to a mini-plug-flow reactor (PFR: BioScope, 3.5 mL volume). Such a system can mimic the situation often encountered in large-scale, fed-batch bioreactors. The STR represented the zones of a large-scale bioreactor that are far from the point of substrate addition and that can be considered as glucose limited, whereas the PFR simulated the region close to the point of substrate addition, where glucose concentration is much higher than in the rest of the bioreactor. In addition, oxygen-poor and glucose-rich regions can occur in large-scale bioreactors. The response of E. coli to these large-scale conditions was simulated by continuously pumping E. coli cells from a well stirred, glucose limited, aerated chemostat (D = 0.1 h(-1)) into the mini-PFR. A glucose pulse was added at the entrance of the PFR. In the PFR, a total of 11 samples were taken in a time frame of 92 s. In one case aerobicity in the PFR was maintained in order to evaluate the effects of glucose overflow independently of oxygen limitation. Accumulation of acetate and formate was detected after E. coli cells had been exposed for only 2 s to the glucose-rich (aerobic) region in the PFR. In the other case, the glucose pulse was also combined with anaerobiosis in the PFR. Glucose overflow combined with anaerobiosis caused the accumulation of formate, acetate, lactate, ethanol, and succinate, which were also detected as soon as 2 s after of exposure of E. coli cells to the glucose and O(2) gradients. This approach (STR-mini-PFR) is useful for a better understanding of the fast dynamic phenomena occurring in large-scale bioreactors and for the design of modified strains with an improved behavior under large-scale conditions.

  4. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse, human glioblastomas in the mouse brain in vivo

    Science.gov (United States)

    Marin-Valencia, Isaac; Yang, Chendong; Mashimo, Tomoyuki; Cho, Steve; Baek, Hyeonman; Yang, Xiao-Li; Rajagopalan, Kartik N.; Maddie, Melissa; Vemireddy, Vamsidhara; Zhao, Zhenze; Cai, Ling; Good, Levi; Tu, Benjamin P.; Hatanpaa, Kimmo J.; Mickey, Bruce E.; Matés, José M.; Pascual, Juan M.; Maher, Elizabeth A.; Malloy, Craig R.; DeBerardinis, Ralph J.; Bachoo, Robert M.

    2012-01-01

    SUMMARY Dysregulated metabolism is a hallmark of cancer cell lines, but little is known about the fate of glucose and other nutrients in tumors growing in their native microenvironment. To study tumor metabolism in vivo, we used an orthotopic mouse model of primary human glioblastoma (GBM). We infused 13C-labeled nutrients into mice bearing three independent GBM lines, each with a distinct set of mutations. All three lines displayed glycolysis, as expected for aggressive tumors. They also displayed unexpected metabolic complexity, oxidizing glucose via pyruvate dehydrogenase and the citric acid cycle, and using glucose to supply anaplerosis and other biosynthetic activities. Comparing the tumors to surrounding brain revealed obvious metabolic differences, notably the accumulation of a large glutamine pool within the tumors. Many of these same activities were conserved in cells cultured ex vivo from the tumors. Thus GBM cells utilize mitochondrial glucose oxidation during aggressive tumor growth in vivo. PMID:22682223

  5. Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress

    Energy Technology Data Exchange (ETDEWEB)

    Liao, Y.Y.; Seto, K.; Saito, H.; Kawakami, M.

    A study was made of the effect of acupuncture on citrate and glucose metabolism in the liver in terms of incorporation of /sup 14/C-1, 5-citric acid and /sup 14/C-u-glucose in some metabolites. The effect of acupuncture on citrate metabolism in the liver under control conditions was such as to increase production of G and reduce that of KB, FC and FFA. No effect of acupuncture on glucose metabolism in the liver under such conditions was observed. Both citrate and glucose metabolism were affected to a marked extent by immobilization stress or exposure to heat or cold. The deleterious effect of these types of stress was less prominent in animals receiving acupuncture at the Tsu-San-Li locus than in those treated otherwise or receiving no treatment.

  6. Short-Term Treatment with Bisphenol-A Leads to Metabolic Abnormalities in Adult Male Mice

    Science.gov (United States)

    Batista, Thiago M.; Alonso-Magdalena, Paloma; Vieira, Elaine; Amaral, Maria Esmeria C.; Cederroth, Christopher R.; Nef, Serge; Quesada, Ivan; Carneiro, Everardo M.; Nadal, Angel

    2012-01-01

    Bisphenol-A (BPA) is one of the most widespread endocrine disrupting chemicals (EDC) used as the base compound in the manufacture of polycarbonate plastics. Although evidence points to consider exposure to BPA as a risk factor for insulin resistance, its actions on whole body metabolism and on insulin-sensitive tissues are still unclear. The aim of the present work was to study the effects of low doses of BPA in insulin-sensitive peripheral tissues and whole body metabolism in adult mice. Adult mice were treated with subcutaneous injection of 100 µg/kg BPA or vehicle for 8 days. Whole body energy homeostasis was assessed with in vivo indirect calorimetry. Insulin signaling assays were conducted by western blot analysis. Mice treated with BPA were insulin resistant and had increased glucose-stimulated insulin release. BPA-treated mice had decreased food intake, lower body temperature and locomotor activity compared to control. In skeletal muscle, insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit was impaired in BPA-treated mice. This impairment was associated with a reduced insulin-stimulated Akt phosphorylation in the Thr308 residue. Both skeletal muscle and liver displayed an upregulation of IRS-1 protein by BPA. The mitogen-activated protein kinase (MAPK) signaling pathway was also impaired in the skeletal muscle from BPA-treated mice. In the liver, BPA effects were of lesser intensity with decreased insulin-stimulated tyrosine phosphorylation of the insulin receptor β subunit. In conclusion, short-term treatment with low doses of BPA slows down whole body energy metabolism and disrupts insulin signaling in peripheral tissues. Thus, our findings support the notion that BPA can be considered a risk factor for the development of type 2 diabetes. PMID:22470480

  7. Complex Patterns of Metabolic and Ca2+ Entrainment in Pancreatic Islets by Oscillatory Glucose

    OpenAIRE

    Pedersen, Morten Gram; Mosekilde, Erik; Polonsky, Kenneth S.; Luciani, Dan Seriano

    2013-01-01

    Glucose-stimulated insulin secretion is pulsatile and driven by intrinsic oscillations in metabolism, electrical activity, and Ca2+in pancreatic islets. Periodic variations in glucose can entrain islet Ca2+ and insulin secretion, possibly promoting interislet synchronization. Here, we used fluorescence microscopy to demonstrate that glucose oscillations can induce distinct 1:1 and 1:2 entrainment of oscillations (one and two oscillations for each period of exogenous stimulus, respectively) in...

  8. Abomasal amino acid infusion in postpartum dairy cows: Effect on whole-body, splanchnic, and mammary glucose metabolism

    DEFF Research Database (Denmark)

    Galindo, C; Larsen, Mogens; Ouellet, D R

    2015-01-01

    Nine Holstein cows fitted with rumen cannulas and indwelling catheters in splanchnic blood vessels were used to study the effects of supplementing AA on milk lactose secretion, whole-body rate of appearance (WB-Ra) of glucose, and tissue metabolism of glucose, lactate, glycerol, and β-OH-butyrate...

  9. Alcohol Decreases Baseline Brain Glucose Metabolism More in Heavy Drinkers Than Controls But Has No Effect on Stimulation-Induced Metabolic Increases

    Science.gov (United States)

    Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S.; Benveniste, Helene; Tomasi, Dardo

    2015-01-01

    During alcohol intoxication, the human brain increases metabolism of acetate and decreases metabolism of glucose as energy substrate. Here we hypothesized that chronic heavy drinking facilitates this energy substrate shift both for baseline and stimulation conditions. To test this hypothesis, we compared the effects of alcohol intoxication (0.75 g/kg alcohol vs placebo) on brain glucose metabolism during video stimulation (VS) versus when given with no stimulation (NS), in 25 heavy drinkers (HDs) and 23 healthy controls, each of whom underwent four PET-18FDG scans. We showed that resting whole-brain glucose metabolism (placebo-NS) was lower in HD than controls (13%, p = 0.04); that alcohol (compared with placebo) decreased metabolism more in HD (20 ± 13%) than controls (9 ± 11%, p = 0.005) and in proportion to daily alcohol consumption (r = 0.36, p = 0.01) but found that alcohol did not reduce the metabolic increases in visual cortex from VS in either group. Instead, VS reduced alcohol-induced decreases in whole-brain glucose metabolism (10 ± 12%) compared with NS in both groups (15 ± 13%, p = 0.04), consistent with stimulation-related glucose metabolism enhancement. These findings corroborate our hypothesis that heavy alcohol consumption facilitates use of alternative energy substrates (i.e., acetate) for resting activity during intoxication, which might persist through early sobriety, but indicate that glucose is still favored as energy substrate during brain stimulation. Our findings are consistent with reduced reliance on glucose as the main energy substrate for resting brain metabolism during intoxication (presumably shifting to acetate or other ketones) and a priming of this shift in HDs, which might make them vulnerable to energy deficits during withdrawal. PMID:25698759

  10. Abnormal polyamine metabolism in hereditary muscular dystrophies: effect of human growth hormone.

    Science.gov (United States)

    Rudman, D; Kutner, M H; Chawla, R K; Goldsmith, M A

    1980-01-01

    Previous studies showed hyperre-sponsiveness to human growth hormone (hGH) in men with myotonic or limb girdle dystrophies (MMD or LGD). Because polyamines may mediate some actions of hGH, we have now investigated polyamine metabolism in these and other dystrophies. Under metabolic balance study conditions, serum and urine levels of putrescine (Pu), spermidine (Sd), spermine (Sm), and cadaverine (Cd) were measured in six normal men (36-44 yr), four men with MMD (38-44 yr), and three men with LGD (30-36 yr), before and during treatment with 0.532 U/kg body wt ((3/4)/d) of hGH. Daily balances of N, P, and K were also monitored. In the normal subjects, hGH did not influence elemental balances or serum and urine polyamines. In MMD, hGH caused significant retention of N, P, and K (P muscular dystrophy, age 8-13, did not differ from those in five age-matched normal boys. Skeletal muscle polyamines were measured in five men (31-40 yr) without muscle disease and in three men with LGD (30-38 yr). Average concentrations of Pu, Sd, Sm, and Cd were 46, 306, 548, and 61 nmol/g wet wt in LGD and 1, 121, 245, and 14 in the normal subjects, respectively (P muscular dystrophy and in age- and sex-matched normal controls. Pu, Sd, Sm, and Cd levels were two to three times higher than normal in muscle, but did not differ in liver, kidney, and brain. Similar findings were made in male hamsters with hereditary dystrophy and in their controls. The abnormality in hamster muscle polyamines appeared between 1 and 6 wk of age and persisted or intensified until 30 wk. These data reveal abnormalities of polyamine metabolism in men with MMD, in men with LGD, and in mice or hamsters with hereditary muscular dystrophy. The polyamine disorder could be related to dystrophic patients' hyperresponsiveness to hGH.

  11. Effects of sleep disruption and high fat intake on glucose metabolism in mice.

    Science.gov (United States)

    Ho, Jacqueline M; Barf, R Paulien; Opp, Mark R

    2016-06-01

    Poor sleep quality or quantity impairs glycemic control and increases risk of disease under chronic conditions. Recovery sleep may offset adverse metabolic outcomes of accumulated sleep debt, but the extent to which this occurs is unclear. We examined whether recovery sleep improves glucose metabolism in mice subjected to prolonged sleep disruption, and whether high fat intake during sleep disruption exacerbates glycemic control. Adult male C57BL/6J mice were subjected to 18-h sleep fragmentation daily for 9 days, followed by 1 day of recovery. During sleep disruption, one group of mice was fed a high-fat diet (HFD) while another group was fed standard laboratory chow. Insulin sensitivity and glucose tolerance were assessed by insulin and glucose tolerance testing at baseline, after 3 and 7 days of sleep disruption, and at the end of the protocol after 24h of undisturbed sleep opportunity (recovery). To characterize changes in sleep architecture that are associated with sleep debt and recovery, we quantified electroencephalogram (EEG) recordings during sleep fragmentation and recovery periods from an additional group of mice. We now report that 9 days of 18-h daily sleep fragmentation significantly reduces rapid eye movement sleep (REMS) and non-rapid eye movement sleep (NREMS). Mice respond with increases in REMS, but not NREMS, during the daily 6-h undisturbed sleep opportunity. However, both REMS and NREMS increase significantly during the 24-h recovery period. Although sleep disruption alone has no effect in this protocol, high fat feeding in combination with sleep disruption impairs glucose tolerance, effects that are reversed by recovery sleep. Insulin sensitivity modestly improves after 3 days of sleep fragmentation and after 24h of recovery, with significantly greater improvements in mice exposed to HFD during sleep disruption. Improvements in both glucose tolerance and insulin sensitivity are associated with NREMS rebound, raising the possibility that this

  12. Cocoa and Whey Protein Differentially Affect Markers of Lipid and Glucose Metabolism and Satiety.

    Science.gov (United States)

    Campbell, Caroline L; Foegeding, E Allen; Harris, G Keith

    2016-03-01

    Food formulation with bioactive ingredients is a potential strategy to promote satiety and weight management. Whey proteins are high in leucine and are shown to decrease hunger ratings and increase satiety hormone levels; cocoa polyphenolics moderate glucose levels and slow digestion. This study examined the effects of cocoa and whey proteins on lipid and glucose metabolism and satiety in vitro and in a clinical trial. In vitro, 3T3-L1 preadipocytes were treated with 0.5-100 μg/mL cocoa polyphenolic extract (CPE) and/or 1-15 mM leucine (Leu) and assayed for lipid accumulation and leptin production. In vivo, a 6-week clinical trial consisted of nine panelists (age: 22.6 ± 1.7; BMI: 22.3 ± 2.1) consuming chocolate-protein beverages once per week, including placebo, whey protein isolate (WPI), low polyphenolic cocoa (LP), high polyphenolic cocoa (HP), LP-WPI, and HP-WPI. Measurements included blood glucose and adiponectin levels, and hunger ratings at baseline and 0.5-4.0 h following beverage consumption. At levels of 50 and 100 μg/mL, CPE significantly inhibited preadipocyte lipid accumulation by 35% and 50%, respectively, and by 22% and 36% when combined with 15 mM Leu. Leu treatment increased adipocyte leptin production by 26-37%. In the clinical trial, all beverages significantly moderated blood glucose levels 30 min postconsumption. WPI beverages elicited lowest peak glucose levels and HP levels were significantly lower than LP. The WPI and HP beverage treatments significantly increased adiponectin levels, but elicited no significant changes in hunger ratings. These trends suggest that combinations of WPI and cocoa polyphenols may improve markers of metabolic syndrome and satiety.

  13. Investigation of (/sup 18/F)2-fluoro-2-deoxyglucose for the measure of myocardial glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Phelps, M.E.; Hoffman, E.J.; Selin, C.; Huang, S.C.; Robinson, G.; MacDonald, N.; Schelbert, H.; Kuhl, D.E.

    1978-12-01

    Fluorine-18-labeled 2-deoxyglucose (FDG) was studied as a glucose analog for the measure of myocardial glucose metabolism. Myocardial uptake and retention, blood clearance, species dependence (dog, monkey, man), and effect of diet on uptake were investigated. Normal myocardial uptake of FDG was 3 to 4% of injected dose in dog and monkey, and 1 to 4% in man, compared with brain uptakes of 1.5 to 3% in dog, 5 to 6% in monkey, and 4 to 8% in man. The myocardial metabolic rate (MR) for glucose in the nonfasting (glycolytic) state was 2.8 times that in the fasting (ketogenic) state. Human subjects showed higher myocardial uptake after a normal meal than after a meal containing mostly free fatty acids (FFA). Blood clearance was rapid with initial clearance t/sub 1/2/ of 0.2 to 0.3 min, followed by a t/sub 1/2/ of 8.4 +- 1.2 min in dog and 11.6 +- 1.1 min in man. A small third component had half-times of 59 +- 10 min and 88 +- 4 min in dog and man, respectively. With the ECAT positron tomograph, high image-contrast ratios were found between heart and blood (dog 3.5/1, man 14/1), heart and lung (dog 9/1, man 20/1), and heart and liver (dog 15/1, man 10/1). The FDG was taken up rapidly by the myocardium without any significant tissue clearance over a 4-hr period. The FDG exhibited excellent imaging properties. Average counting rates of 12K, 20K, and 40K c/min-mCi injected are obtained in human subjects with high, medium, and low resolutions of the ECAT tomograph. Determination of glucose and FFA MR in vivo with EACT provides a method for investigation and assessment of changing aerobic and anaerobic metabolic rates in ischemic heart disease in man.

  14. A favorable effect of hydroxychloroquine on glucose and lipid metabolism beyond its anti-inflammatory role.

    Science.gov (United States)

    Hage, Mirella P; Al-Badri, Marwa R; Azar, Sami T

    2014-08-01

    Hydroxychloroquine (HCQ), a commonly used antimalarial drug in rheumatic diseases, has shown favorable metabolic effects on both glucose control and lipid profiles. We describe a case of a young woman with type 1 diabetes whose glycemic control was optimized with the introduction of HCQ as a treatment for her Sjogren syndrome in addition to a subtle yet measurable improvement in her lipid profile. An increasing body of evidence supports the beneficial impacts of HCQ in various ancillary conditions, including diabetes mellitus and dyslipidemia. However, mechanisms of action responsible for these effects remain ill-defined and may include alterations in insulin metabolism and signaling through cellular receptors. These favorable metabolic effects of HCQ and further understanding of underlying mechanisms may provide an additional rational for its use in rheumatic diseases, conditions associated with an elevated cardiovascular risk.

  15. Impact of switching from lopinavir/ritonavir to boosted and un-boosted atazanavir on glucose metabolism: the ATAzanavir & GLUcose metabolism (ATAGLU) study.

    Science.gov (United States)

    d'Ettorre, Gabriella; Ceccarelli, Giancarlo; Zaccarelli, Mauro; Ascoli-Bartoli, Tommaso; Bianchi, Luigi; Bellelli, Valeria; De Girolamo, Gabriella; Serafino, Sara; Giustini, Noemi; Mastroianni, Claudio M; Vullo, Vincenzo

    2016-07-01

    Previous studies have reported that protease inhibitors (PIs) can contribute to glycaemic alterations. However, there are few trials examining the direct effect of a single PI. The objective of the study was to evaluate the modifications of glucose and lipid profiles after a switch from lopinavir/ritonavir (LPV/r) to atazanavir, used as ritonavir-boosted (ATV/r) or un-boosted. We conducted a retrospective observational cohort study on the effect of ATV/(r) on glycaemic metabolism (ATAGLU) in patients with undetectable levels of HIV-RNA who switched from LPV/r. In total, 235 patients treated for 48 weeks with LPV/r plus two nucleoside reverse transcriptase inhibitors (NRTIs) and with undetectable HIV-RNA were included: 134 continued LPV/r after the initial 48 weeks and 101 switched to ATV(/r) (18.3% to ATV; 24.7% to ATV/r). A significant decrease in mean glucose level and insulin resistance was observed in patients who switched to ATV(/r). The mean cholesterol triglyceride levels increased in the LPV/r group and decreased among the patients who switched. A significant increase of CD4 T cells with undetectable levels of HIV-RNA was observed in all groups. The long-term results obtained in this real-life study suggest that patients who have achieved initial suppression on a regimen including LPV/r + two NRTIs can switch to ATV/(r) + two NRTIs with an improvement in lipid and glycaemic metabolism.

  16. Detection of serum iron and zinc levels in patients with type 2 diabetes mellitus and their relationship with glucose and lipid metabolism

    Institute of Scientific and Technical Information of China (English)

    Xiao-Yong Tang; Wan-Fen Zhong

    2016-01-01

    Objective:To study the blood iron and zinc levels in patients with type 2 diabetes mellitus and their relationship with glucose and lipid metabolism.Methods:Patients with type 2 diabetes mellitus were enrolled in T2DM group and healthy people were enrolled in control group. T2DM patients were divided into low iron and zinc group and high iron and zinc group with the median of serum iron and zinc contents as the standard. Serum trace elements contents and glucose and lipid metabolism indicators were detected.Results:T2DM patients’ blood iron contents were significantly higher than those of the control group while the zinc contents were significantly lower than those of the control group. Copper, calcium and magnesium contents had no significant difference between two groups of patients. HbA1c%, glucagon and HOMA-IR as well as apoB, apoE, ApoM, leptin and vaspin contents in high iron group were higher than those in low iron group while serum insulin, GLP-1, GIP, ApoA1, APN and HOMA-β levels were lower than those in low iron group. HbA1c%, glucagon, HOMA-IR, apoB, apoE, ApoM, leptin and vaspin contents in high zinc group were lower than those in low zinc group while serum insulin, GLP-1, GIP, ApoA1, APN and HOMA-β levels were higher than those in low zinc group.Conclusions: the serum iron level was abnormally high and the zinc content was abnormally low in patients with type 2 diabetes mellitus. Serum iron and zinc levels were closely related to the glucose and lipid metabolism.

  17. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states [version 1; referees: 2 approved, 1 approved with reservations

    Directory of Open Access Journals (Sweden)

    Richard J. Naftalin

    2016-04-01

    Full Text Available A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD, non-alcoholic steatohepatitis, (NASH and type 2 diabetes mellitus, (T2DM demonstrates how when glucagon-like peptide-1, (GLP-1 is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU. When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.   Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.  This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic

  18. Voxel-based statistical analysis of cerebral glucose metabolism in patients with permanent vegetative state after acquired brain injury

    Institute of Scientific and Technical Information of China (English)

    Yong Wook Kim; Hyoung Seop Kim; Young-Sil An; Sang Hee Im

    2010-01-01

    Background Permanent vegetative state is defined as the impaired level of consciousness longer than 12 months after traumatic causes and 3 months after non-traumatic causes of brain injury. Although many studies assessed the cerebral metabolism in patients with acute and persistent vegetative state after brain injury, few studies investigated the cerebral metabolism in patients with permanent vegetative state. In this study, we performed the voxel-based analysis of cerebral glucose metabolism and investigated the relationship between regional cerebral glucose metabolism and the severity of impaired consciousness in patients with permanent vegetative state after acquired brain injury.Methods We compared the regional cerebral glucose metabolism as demonstrated by F-18 fluorodeoxyglucose positron emission tomography from 12 patients with permanent vegetative state after acquired brain injury with those from 12 control subjects. Additionally, covariance analysis was performed to identify regions where decreased changes in regional cerebral glucose metabolism significantly correlated with a decrease of level of consciousness measured by JFK-coma recovery scare. Statistical analysis was performed using statistical parametric mapping.Results Compared with controls, patients with permanent vegetative state demonstrated decreased cerebral glucose metabolism in the left precuneus, both posterior cingulate cortices, the left superior parietal lobule (Pcorrected <0.001), and increased cerebral glucose metabolism in the both cerebellum and the right supramarginal cortices (Pcorrected <0.001). In the covariance analysis, a decrease in the level of consciousness was significantly correlated with decreased cerebral glucose metabolism in the both posterior cingulate cortices (Puncorrected <0.005).Conclusion Our findings suggest that the posteromedial parietal cortex, which are part of neural network for consciousness, may be relevant structure for pathophysiological mechanism

  19. Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry.

    Science.gov (United States)

    Sheng, Zhenyu; Santiago, Ammy M; Thomas, Mark P; Routh, Vanessa H

    2014-09-01

    Lateral hypothalamic area (LHA) orexin neurons modulate reward-based feeding by activating ventral tegmental area (VTA) dopamine (DA) neurons. We hypothesize that signals of peripheral energy status influence reward-based feeding by modulating the glucose sensitivity of LHA orexin glucose-inhibited (GI) neurons. This hypothesis was tested using electrophysiological recordings of LHA orexin-GI neurons in brain slices from 4 to 6week old male mice whose orexin neurons express green fluorescent protein (GFP) or putative VTA-DA neurons from C57Bl/6 mice. Low glucose directly activated ~60% of LHA orexin-GFP neurons in both whole cell and cell attached recordings. Leptin indirectly reduced and ghrelin directly enhanced the activation of LHA orexin-GI neurons by glucose decreases from 2.5 to 0.1mM by 53±12% (n=16, PFasting increased activation of LHA orexin-GI neurons by decreased glucose, as would be predicted by these hormonal effects. We also evaluated putative VTA-DA neurons in a novel horizontal slice preparation containing the LHA and VTA. Decreased glucose increased the frequency of spontaneous excitatory post-synaptic currents (sEPSCs; 125 ± 40%, n=9, P<0.05) and action potentials (n=9; P<0.05) in 45% (9/20) of VTA DA neurons. sEPSCs were completely blocked by AMPA and NMDA glutamate receptor antagonists (CNQX 20 μM, n=4; APV 20μM, n=4; respectively), demonstrating that these sEPSCs were mediated by glutamatergic transmission onto VTA DA neurons. Orexin-1 but not 2 receptor antagonism with SB334867 (10μM; n=9) and TCS-OX2-29 (2μM; n=5), respectively, blocks the effects of decreased glucose on VTA DA neurons. Thus, decreased glucose increases orexin-dependent excitatory glutamate neurotransmission onto VTA DA neurons. These data suggest that the glucose sensitivity of LHA orexin-GI neurons links metabolic state and reward-based feeding.

  20. Regional cerebral glucose metabolism in frontotemporal dementia: a study with FDG PET

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    Cho, S. S.; Jeong, J.; Kang, S. J.; Na, D. L.; Choe, Y. S.; Lee, K. H.; Choi, Y.; Kim, B. T.; Kim, S. E. [Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of)

    2002-07-01

    Frontotemporal dementia (FTD) is a common cause of presenile dementia. We investigated the regional cerebral glucose metabolic impairments in patients with FTD using FDG PET. We analysed the regional metabolic patterns on FDG PET images obtained from 30 patients with FTD and age- and sex-matched 15 patients with Alzheimers disease (AD) and 11 healthy subjects using SPM99. We also compared the inter-hemispheric metabolic asymmetry among the three groups by counting the total metabolic activity of each hemisphere and computing asymmetry index (AL) between hemispheres. The hypometabolic brain regions in FTD patients compared with healthy controls were as follows: superior middle and medial frontal lobules, superior and middle temporal lobules, anterior and posterior cingulate gyri, uncus, insula, lateral globus pallidus and thalamus. The regions with decreased metabolism in FTD patients compared with AD patients were as follows: superior, inferior and medial frontal lobules, anterior cingulate gyrus, and caudate nucleus. Twenty-five (83%) out of the 30 FTD patients had AI values that was beyond the 95% confidence interval of the AI values obtained from healthy controls; 10 patients had hypometabolism more severe on the right and 15 patients had the opposite pattern. In comparison, 10 (67%) out of the 15 AD patients had asymmetric metabolism. Our SPM analysis of FDG PET revealed additional areas of decreased metabolism in FTD patients compared with prior studies using the ROI method, involving frontal, temporal, cingulate gyrus, corpus callosum, uncus, insula, and some subcortical areas. The inter-hemispheric metabolic asymmetry was common in FTD patients, which can be another metabolic feature that helps differentiate FTD from AD.

  1. (1H-NMR spectroscopy revealed Mycobacterium tuberculosis caused abnormal serum metabolic profile of cattle.

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    Yingyu Chen

    Full Text Available To re-evaluate virulence of Mycobacterium tuberculosis (M. tb in cattle, we experimentally infected calves with M. tb andMycobacterium bovisvia intratracheal injection at a dose of 2.0×10(7 CFU and observed the animals for 33 weeks. The intradermal tuberculin test and IFN-γin vitro release assay showed that both M. tb and M. bovis induced similar responses. Immunohistochemical staining of pulmonary lymph nodes indicated that the antigen MPB83 of both M. tb and M. bovis were similarly distributed in the tissue samples. Histological examinations showed all of the infected groups exhibited neutrophil infiltration to similar extents. Although the infected cattle did not develop granulomatous inflammation, the metabolic profiles changed significantly, which were characterized by a change in energy production pathways and increased concentrations of N-acetyl glycoproteins. Glycolysis was induced in the infected cattle by decreased glucose and increased lactate content, and enhanced fatty acid β-oxidation was induced by decreased TG content, and decreased gluconeogenesis indicated by the decreased concentration of glucogenic and ketogenic amino acids promoted utilization of substances other than glucose as energy sources. In addition, an increase in acute phase reactive serum glycoproteins, together with neutrophil infiltration and increased of IL-1β production indicated an early inflammatory response before granuloma formation. In conclusion, this study indicated that both M. tb and M.bovis were virulent to cattle. Therefore, it is likely that cattle with M. tb infections would be critical to tuberculosis transmission from cattle to humans. Nuclear magnetic resonance was demonstrated to be an efficient method to systematically evaluate M. tb and M. bovi sinfection in cattle.

  2. The Role of Glucose Metabolism on Porcine Oocyte Cytoplasmic Maturation and Its Possible Mechanisms

    Science.gov (United States)

    Kwon, Jeong-Woo; Jin, Yong-Xun; Park, Shun-Ha; Wang, Hai-Yang; Sun, Tian-Yi; Zhang, Jia-Bao; Kim, Nam-Hyung

    2016-01-01

    In the present study, we investigated the potential role of glucose and pyruvate in the cytoplasmic maturation of porcine oocytes by investigating the effect of glucose and/or pyruvate supplementation, in the presence or absence of 10% porcine follicular fluid (PFF), on meiotic maturation and subsequent embryo development. In the absence of 10% PFF, without exogenous addition of glucose and pyruvate, the medium seemed unable to support maturation. In the presence of 10% PFF, the addition of 5.6 mM glucose and/or 2 mM pyruvate during in vitro maturation of cumulus enclosed oocytes increased MII oocyte and blastocyst rates. In contrast, oocytes denuded of cumulus cells were not able to take full advantage of the glucose in the medium, as only pyruvate was able to increase the MII rate and the subsequent early embryo developmental ability. Treatment of cumulus enclosed oocytes undergoing maturation with 200 μM dehydroepiandrosterone (DHEA), a pentose phosphate pathway inhibitor, or 2 μM iodoacetate (IA), a glycolysis inhibitor, significantly reduced GHS, intra-oocyte ATP, maternal gene expression, and MPF activity levels. DHEA was also able to increase ROS and reduce the levels of NADPH. Moreover, blastocysts of the DHEA- or IA-treated groups presented higher apoptosis rates and markedly lower cell proliferation cell rates than those of the non-treated group. In conclusion, our results suggest that oocytes maturing in the presence of 10% PFF can make full use of energy sources through glucose metabolism only when they are accompanied by cumulus cells, and that pentose phosphate pathway (PPP) and glycolysis promote porcine oocyte cytoplasmic maturation by supplying energy, regulating maternal gene expression, and controlling MPF activity. PMID:27997591

  3. Acute effects of concentric and eccentric exercise on glucose metabolism and interleukin-6 concentration in healthy males.

    Science.gov (United States)

    Philippe, M; Krüsmann, P J; Mersa, L; Eder, E M; Gatterer, H; Melmer, A; Ebenbichler, C; Burtscher, M

    2016-06-01

    Acute muscle-damaging eccentric exercise (EE) negatively affects glucose metabolism. On the other hand, long-term eccentric endurance exercise seems to result in equal or superior positive effects on glucose metabolism compared to concentric endurance exercise. However, it is not known if acute non-muscle-damaging EE will have the same positive effects on glucose metabolism as acute concentric exercise (CE). Interleukin-6 (IL-6) released from the exercising muscles may be involved in the acute adaptations of glucose metabolism after CE and non-muscle-damaging EE. The aim of this study was to assess acute effects of uphill walking (CE) and non-muscle-damaging downhill walking (EE) on glucose metabolism and IL-6 secretion. Seven sedentary non-smoking, healthy males participated in a crossover trial consisting of a 1 h uphill (CE) and a 1 h downhill (EE) walking block on a treadmill. Venous blood samples were drawn before (pre), directly after (acute) and 24 h after (post) exercise. An oral glucose tolerance test (OGTT) was performed before and 24 h after exercise. Glucose tolerance after 1 and 2 hours significantly improved 24 hours after CE (-10.12±3.22%: P=0.039; -13.40±8.24%: P=0.028). After EE only the 1-hour value was improved (-5.03±5.48%: P=0.043). Acute IL-6 concentration rose significantly after CE but not after EE. We conclude that both a single bout of CE and a single bout of non-muscle-damaging EE elicit positive changes in glucose tolerance even in young, healthy subjects. Our experiment indicates that the overall metabolic cost is a major trigger for acute adaptations of glucose tolerance after exercise, but only the IL-6 production during EE was closely related to changes in glycaemic control.

  4. Vitamin C inhibits leptin secretion and some glucose/lipid metabolic pathways in primary rat adipocytes.

    Science.gov (United States)

    Garcia-Diaz, D F; Campion, J; Milagro, F I; Boque, N; Moreno-Aliaga, M J; Martinez, J A

    2010-07-01

    Antioxidant-based treatments are emerging as an interesting approach to possibly counteract obesity fat accumulation complications, since this is accompanied by an increased systemic oxidative stress. The aim of this study was to analyze specific metabolic effects of vitamin C (VC) on epididymal primary rat adipocytes. Cells were isolated and incubated for 72 h in culture medium, in the absence or presence of 1.6 nM insulin, within a range of VC concentrations (5-1000 microM). Glucose- and lipid-related variables as well as the secretion/expression patterns of several obesity-related genes were assessed. It was observed that VC dose dependently inhibited glucose uptake and lactate production, and also reduced glycerol release in both control and insulin-treated cells. Also, VC caused a dramatic concentration-dependent fall in leptin secretion especially in insulin-stimulated cells. In addition, VC (200 microM) induced Cdkn1a and Casp8, partially inhibited Irs3, and together with insulin drastically reduced Gpdh (listed as Gpd1 in the MGI database) gene expressions. Finally, VC and insulin down-regulatory effects were observed on extracellular and intracellular reactive oxygen species production respectively. In summary, this experimental assay describes a specific effect of VC in isolated rat adipocytes on glucose and fat metabolism, and on the secretion/expression of important obesity-related proteins.

  5. Effect of phenolic acids on glucose and organic acid metabolism by lactic acid bacteria from wine.

    Science.gov (United States)

    Campos, Francisco M; Figueiredo, Ana R; Hogg, Tim A; Couto, José A

    2009-06-01

    The influence of phenolic (p-coumaric, caffeic, ferulic, gallic and protocatechuic) acids on glucose and organic acid metabolism by two strains of wine lactic acid bacteria (Oenococcus oeni VF and Lactobacillus hilgardii 5) was investigated. Cultures were grown in modified MRS medium supplemented with different phenolic acids. Cellular growth was monitored and metabolite concentrations were determined by HPLC-RI. Despite the strong inhibitory effect of most tested phenolic acids on the growth of O. oeni VF, the malolactic activity of this strain was not considerably affected by these compounds. While less affected in its growth, the capacity of L. hilgardii 5 to degrade malic acid was clearly diminished. Except for gallic acid, the addition of phenolic acids delayed the metabolism of glucose and citric acid in both strains tested. It was also found that the presence of hydroxycinnamic acids (p-coumaric, caffeic and ferulic) increased the yield of lactic and acetic acid production from glucose by O. oeni VF and not by L. hilgardii 5. The results show that important oenological characteristics of wine lactic acid bacteria, such as the malolactic activity and the production of volatile organic acids, may be differently affected by the presence of phenolic acids, depending on the bacterial species or strain.

  6. Inflammation in metabolic syndrome and type 2 diabetes: Impact of dietary glucose.

    Science.gov (United States)

    Kempf, Kerstin; Rose, Bettina; Herder, Christian; Kleophas, Ursula; Martin, Stephan; Kolb, Hubert

    2006-11-01

    Chronic overnutrition combined with a lack of exercise is the main cause for the rapidly increasing prevalence of overweight and obesity. It seems accepted that adipositis (macrophage infiltration and inflammation of adipose tissue in obesity) and systemic low grade inflammation affect the pathogenesis of the metabolic syndrome or type 2 diabetes mellitus (T2DM). Therefore, modern weight reduction programs additionally focus on strategies to attenuate the inflammation state. Exercise is one major factor, which contributes to the reduction of both the incidence of T2DM and inflammation, and the immunomodulatory effects of exercise are supported by similarly beneficial effects of dietary changes. In this context, glucose is the most extensively studied nutrient and current investigations focus on postprandial glucose-induced inflammation, one possible reason why hyperglycemia is detrimental. Indeed, glucose may modulate the mRNA expression and serum concentrations of immune parameters but these alterations rapidly normalize in normoglycemic subjects. In case of an impaired metabolic state, however, postprandial hyperglycemia increases magnitude and duration of systemic inflammatory responses, which probably promotes the development of T2DM and of cardiovascular disease.

  7. Diacylglycerol kinase ϵ deficiency preserves glucose tolerance and modulates lipid metabolism in obese mice.

    Science.gov (United States)

    Mannerås-Holm, Louise; Schönke, Milena; Brozinick, Joseph T; Vetterli, Laurène; Bui, Hai-Hoang; Sanders, Philip; Nascimento, Emmani B M; Björnholm, Marie; Chibalin, Alexander V; Zierath, Juleen R

    2017-02-28

    Diacylglycerol kinases (DGKs) catalyze the phosphorylation and conversion of DAG into phosphatidic acid. DGK isozymes have unique primary structures, expression patterns, subcellular localizations, regulatory mechanisms and DAG preferences. DGKε has a hydrophobic segment that promotes its attachment to membranes and shows substrate specificity for DAG with an arachidonoyl acyl chain in the sn-2 position of the substrate. We determined the role of DGKε in the regulation of energy and glucose homeostasis in relation to diet-induced insulin resistance and obesity using DGKε deficient (KO) and wild-type mice. Lipidomic analysis revealed elevated unsaturated and saturated DAG species in skeletal muscle of DGKε KO mice, which was paradoxically associated with increased glucose tolerance. While skeletal muscle insulin sensitivity was unaltered, whole body respiratory exchange ratio was reduced, and abundance of mitochondrial markers was increased, indicating a greater reliance on fat oxidation and intracellular lipid metabolism in DGKε KO mice. Thus, the increased intracellular lipids in skeletal muscle from DGKε KO mice may undergo rapid turnover due to increased mitochondrial function and lipid oxidation, rather than storage, which in turn may preserve insulin sensitivity. In conclusion, DGKε plays a role in glucose and energy homeostasis by modulating lipid metabolism in skeletal muscle.

  8. Comprehensive analysis of glucose and xylose metabolism in Escherichia coli under aerobic and anaerobic conditions by (13)C metabolic flux analysis.

    Science.gov (United States)

    Gonzalez, Jacqueline E; Long, Christopher P; Antoniewicz, Maciek R

    2017-01-01

    Glucose and xylose are the two most abundant sugars derived from the breakdown of lignocellulosic biomass. While aerobic glucose metabolism is relatively well understood in E. coli, until now there have been only a handful of studies focused on anaerobic glucose metabolism and no (13)C-flux studies on xylose metabolism. In the absence of experimentally validated flux maps, constraint-based approaches such as MOMA and RELATCH cannot be used to guide new metabolic engineering designs. In this work, we have addressed this critical gap in current understanding by performing comprehensive characterizations of glucose and xylose metabolism under aerobic and anaerobic conditions, using recent state-of-the-art techniques in (13)C metabolic flux analysis ((13)C-MFA). Specifically, we quantified precise metabolic fluxes for each condition by performing parallel labeling experiments and analyzing the data through integrated (13)C-MFA using the optimal tracers [1,2-(13)C]glucose, [1,6-(13)C]glucose, [1,2-(13)C]xylose and [5-(13)C]xylose. We also quantified changes in biomass composition and confirmed turnover of macromolecules by applying [U-(13)C]glucose and [U-(13)C]xylose tracers. We demonstrated that under anaerobic growth conditions there is significant turnover of lipids and that a significant portion of CO2 originates from biomass turnover. Using knockout strains, we also demonstrated that β-oxidation is critical for anaerobic growth on xylose. Quantitative analysis of co-factor balances (NADH/FADH2, NADPH, and ATP) for different growth conditions provided new insights regarding the interplay of energy and redox metabolism and the impact on E. coli cell physiology.

  9. Clinical Observation of Patients with Cardiovascular Medicine Sugar Metabolic Abnormality%心血管内科患者糖代谢异常的临床观察

    Institute of Scientific and Technical Information of China (English)

    高学军

    2014-01-01

    Objective To analyze the clinical study of carbohydrate metabolism in Department of internal medicine, cardiovascular abnormality. Methods 82 patients of this hospital cardiovascular department of internal medicine patients, in which 32 cases were diagnosed as diabetic patients, 50 cases of non diabetic patients, wil give a fasting blood glucose test results as the control group, wil give the oral glucose tolerance test results as the study group, recording and analysis of two groups of diagnostic rate and accuracy. Results The study group detection diagnosis rate was significantly higher than the control group, with significant dif erence ( <0.05);the study group detection accuracy higher than that of the control group, with significant dif erence ( < 0.05). Conclusion The application of oral glucose tolerance test diagnosis rate and accuracy rate of abnormal glucose metabolism is high, can avoid missed diagnosis and misdiagnosis.%目的:分析心血管内科患者糖代谢异常的临床研究。方法对本院诊治的心血管内科患者82例,其中32例被确诊为糖尿病患者,非糖尿病患者有50例,将给予空腹血糖测试结果作为对照组,将给予口服葡萄糖耐量试验测试结果作为研究组,记录并分析两组诊断确诊率和准确性情况。结果研究组检测确诊率明显高于对照组,比较差异具有统计学意义(P<0.05);研究组检测准确性比对照组高,比较差异具有统计学意义(P<0.05)。结论应用口服葡萄糖耐量试验测试糖代谢异常的确诊率和准确性均较好,能够避免漏诊和误诊。

  10. Arctigenin preferentially induces tumor cell death under glucose deprivation by inhibiting cellular energy metabolism.

    Science.gov (United States)

    Gu, Yuan; Qi, Chunting; Sun, Xiaoxiao; Ma, Xiuquan; Zhang, Haohao; Hu, Lihong; Yuan, Junying; Yu, Qiang

    2012-08-15

    Selectively eradicating cancer cells with minimum adverse effects on normal cells is a major challenge in the development of anticancer therapy. We hypothesize that nutrient-limiting conditions frequently encountered by cancer cells in poorly vascularized solid tumors might provide an opportunity for developing selective therapy. In this study, we investigated the function and molecular mechanisms of a natural compound, arctigenin, in regulating tumor cell growth. We demonstrated that arctigenin selectively promoted glucose-starved A549 tumor cells to undergo necrosis by inhibiting mitochondrial respiration. In doing so, arctigenin elevated cellular level of reactive oxygen species (ROS) and blocked cellular energy metabolism in the glucose-starved tumor cells. We also demonstrated that cellular ROS generation was caused by intracellular ATP depletion and played an essential role in the arctigenin-induced tumor cell death under the glucose-limiting condition. Furthermore, we combined arctigenin with the glucose analogue 2-deoxyglucose (2DG) and examined their effects on tumor cell growth. Interestingly, this combination displayed preferential cell-death inducing activity against tumor cells compared to normal cells. Hence, we propose that the combination of arctigenin and 2DG may represent a promising new cancer therapy with minimal normal tissue toxicity.

  11. Liver-specific deletion of Ppp2cα enhances glucose metabolism and insulin sensitivity.

    Science.gov (United States)

    Xian, Li; Hou, Siyuan; Huang, Zan; Tang, An; Shi, Peiliang; Wang, Qinghua; Song, Anying; Jiang, Shujun; Lin, Zhaoyu; Guo, Shiying; Gao, Xiang

    2015-04-01

    Protein phosphatase 2A (PP2A) is a key negative regulator of phosphatidylinositol 3-kinase/Akt pathway. Previous study showed that, in the liver, the catalytic subunit of PP2A (PP2Ac) is closely associated with insulin resistance syndrome, which is characterized by glucose intolerance and dyslipidemia. Here we studied the role of liver PP2Ac in glucose metabolism and evaluated whether PP2Ac is a suitable therapeutic target for treating insulin resistance syndrome. Liver-specific Ppp2cα knockout mice (Ppp2cα(loxp/loxp): Alb) exhibited improved glucose homeostasis compared with littermate controls in both normal and high-fat diet conditions, despite no significant changes in body weight and liver weight under chow diet. Ppp2cα(loxp/loxp): Alb mice showed enhanced glycogen deposition, serum triglyceride, cholesterol, low density lipoprotein and high density lipoprotein, activated insulin signaling, decreased expressions of gluconeogenic genes G6P and PEPCK, and lower liver triglyceride. Liver-specific Ppp2cα knockout mice showed enhanced glucose homeostasis and increased insulin sensitivity by activation of insulin signaling through Akt. These findings suggest that inhibition of hepatic Ppp2cα may be a useful strategy for the treatment of insulin resistance syndrome.

  12. The Effect of Exercise on Glucose Metabolism in Patients with Type 2 Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Tuba Tulay Koca

    2015-09-01

    Full Text Available Diabetes mellitus is one of the major causes of disability and death due to the complications accompanying this disease. The incidence of type 2 diabetes mellitus and insulin resistance has increased worldwide during the last decades, despite the development of effective drug therapy and improved clinical diagnoses. Recent epidemiological studies indicate that individuals who maintain a physically active lifestyle are much less likely to develop impaired glucose tolerance and diabetes mellitus. Additional to protective effect of physical activity for individuals at highest risk of developing diabetes mellitus, physical activity has positive impacts on fasting glucose, insulin sensitivity and blood glucose level for patients with overt diabetes. The essential mechanism of exercises is enhancing sensitivity of insulin on pheripheral tissues (especially skeletal muscle. With exercise training significant improvements in glucose metabolism is observed in many of these studies. Especially, the improvements in insulin sensitivity with exercise training observed better in high magnitude of aerobic exercises. Also adaptation of patients is very high to combined type exercises. However worldwide standardization of these training programmes in many of the studies is lacking and current practice in daily life is unsatisfactory. [Archives Medical Review Journal 2015; 24(3.000: 306-316

  13. Effect of guar gum on glucose and lipid metabolism in white sea bream Diplodus sargus.

    Science.gov (United States)

    Enes, P; Pousão-Ferreira, P; Salmerón, C; Capilla, E; Navarro, I; Gutiérrez, J; Oliva-Teles, A

    2013-04-01

    The aim of this study was to assess the role of soluble non-starch polysaccharide (guar gum) on white sea bream Diplodus sargus, glucose and lipid metabolism. A control diet was formulated to contain 40 % crude protein, 14 % crude lipids and 35 % pregelatinized maize starch, and three other diets were formulated similar to the control diet except for guar gum, which was included at 4 % (diet GG4), 8 % (diet GG8) or 12 % (diet GG12). Diets were fed to the fish for 9 weeks on a pair-feeding scheme. Guar gum had no effect on growth performance, feed efficiency, glycaemia, cholesterolaemia and plasma triacylglyceride levels. Hepatic glucokinase and pyruvate kinase activities, liver glycogen content and liver insulin-like growth factor-I gene expression were not affected by dietary guar gum, while fructose-1,6-bisphosphatase activity was lower in fish fed guar gum-supplemented diets. Hepatic glucose-6-phosphate dehydrogenase activity was higher in fish fed diets GG4 and GG8 than in the control group. Overall, data suggest that in contrast to mammals guar gum had no effect on white sea bream glucose utilization and in lowering plasma cholesterol and triacylglyceride levels. However, it seems to contribute to lower endogenous glucose production.

  14. Developmental role for endocannabinoid signaling in regulating glucose metabolism and growth.

    Science.gov (United States)

    Li, Zhiying; Schmidt, Sarah F; Friedman, Jeffrey M

    2013-07-01

    Treatment of ob/ob (obese) mice with a cannabinoid receptor 1 (Cnr1) antagonist reduces food intake, suggesting a role for endocannabinoid signaling in leptin action. We further evaluated the role of endocannabinoid signaling by analyzing the phenotype of Cnr1 knockout ob/ob mice. Double mutant animals show a more severe growth retardation than ob/ob mice with similar levels of adiposity and reduced IGF-I levels without alterations of growth hormone (GH) levels. The double mutant mice are also significantly more glucose intolerant than ob/ob mice. This is in contrast to treatment of ob/ob mice with a Cnr1 antagonist that had no effect on glucose metabolism, suggesting a possible requirement for endocannabinoid signaling during development for normal glucose homeostasis. Double mutant animals also showed similar leptin sensitivity as ob/ob mice, suggesting that there are developmental changes that compensate for the loss of Cnr1 signaling. These data establish a role for Cnr1 during development and suggest that compensatory changes during development may mitigate the requirement for Cnr1 in mediating the effects of leptin. The data also suggest a developmental role for Cnr1 to promote growth, regulate the GH/IGF-I axis, and improve β-cell function and glucose homeostasis in the setting of leptin deficiency.

  15. Effect of pinitol on glucose metabolism and adipocytokines in uncontrolled type 2 diabetes.

    Science.gov (United States)

    Kim, Mi Jin; Yoo, Kwang Ha; Kim, Ji Hoon; Seo, Young Tak; Ha, Byung Wook; Kho, Jang Hyun; Shin, Young Goo; Chung, Choon Hee

    2007-09-01

    Pinitol (3-O-methyl-D-chiro-inositol) was identified in putative insulin mediator fractions that have hypoglycemic activity, and appears to mimic the act effects of insulin by acting downstream in the insulin signaling pathway. We evaluated the effect of pinitol therapy in type 2 diabetic patients who were poorly controlled with hypoglycemic drugs, such as sulfonylurea, metformin and/or insulin. Twenty type 2 diabetic patients were enrolled in our study. Fasting glucose, fasting c-peptide, total cholesterol, triglyceride, and HDL- and LDL-cholesterol were checked before and after a 12-week pinitol treatment (20 mg kg(-1)day(-1)). All subjects continued their current medications during the study. Adipocytokines, such as adiponectin, leptin, free fatty acids, and c-reactive protein (CRP) were checked before and after pinitol treatment. After pinitol treatment, fasting glucose, post-prandial glucose levels, and hemoglobin A1c were significantly decreased (Ppinitol treatment. In the unresponsive group, serum c-peptide levels were higher than in the responsive group. Twelve weeks of pinitol treatment altered glucose metabolism, but not lipid profiles or adipocytokine levels, in type 2 diabetic patients. Additional research is needed to define the physiological and potential therapeutic effects of pinitol administration.

  16. Evaluation of Chios mastic gum on lipid and glucose metabolism in diabetic mice.

    Science.gov (United States)

    Georgiadis, Ioannis; Karatzas, Theodore; Korou, Laskarina-Maria; Agrogiannis, George; Vlachos, Ioannis S; Pantopoulou, Alkisti; Tzanetakou, Irene P; Katsilambros, Nikolaos; Perrea, Despina N

    2014-03-01

    Chios mastic gum (MG), a resin produced from Pistacia lentiscus var. Chia, is reported to possess beneficial cardiovascular and hepatoprotective properties. This study investigated the effect of crude Chios MG on metabolic parameters in diabetic mice. Streptozotocin-induced diabetic 12-week-old male C57bl/6 mice were assigned to three groups: NC (n=9) control; LdM (n=9) animals receiving low dose mastic for 8 weeks (20 mg/kg body weight [BW]); and HdM (n=9) animals receiving high dose mastic (500 mg/kg BW) for the same period. Serum lipid and glucose levels were determined at baseline, at 4 and 8 weeks. Serum total protein, adiponectin, and resistin levels were also measured at the end of the experiment. Histopathological examination for liver, kidney, aorta, and heart lesions was performed. After 4 weeks, MG administration resulted in decreased serum glucose and triglyceride levels in both LdM and HdM, whereas BW levels were reduced in LdM group compared with controls. At the end of the experiment, LdM presented significantly lower serum glucose, cholesterol, low-density lipoprotein cholesterol, and triglyceride levels and improved high-density lipoprotein cholesterol levels compared with control group. HdM group had ameliorated serum triglyceride levels. Hepatic steatosis observed in control group was partially reversed in LdM and HdM groups. MG administered in low dosages improves glucose and lipid disturbances in diabetic mice while alleviating hepatic damage.

  17. Metabolic Control of Type 2 Diabetes by Targeting the GLUT4 Glucose Transporter: Intervention Approaches.

    Science.gov (United States)

    Alam, Fahmida; Islam, Md Asiful; Khalil, Md Ibrahim; Gan, Siew Hua

    2016-01-01

    Type 2 diabetes mellitus (T2DM), the most common form of diabetes, is characterized by insulin resistance in the hepatic and peripheral tissues. Glucose transporter 4 (GLUT4) plays a major role in the pathophysiology of T2DM. Its defective expression or translocation to the peripheral cell plasma membrane in T2DM patients hinders the entrance of glucose into the cell for energy production. In addition to suitable drugs, an appropriate diet and/or exercise can be implemented to target the increase in GLUT4 expression, GLUT4 concentrations and GLUT4 translocation to the cell surface when managing the glucose metabolism of T2DM patients. In this review, we discussed successful intervention strategies that were individually administered or coupled with diet and/or exercise and affected the expression and translocation of GLUT4 in T2DM while reducing the excess glucose load from the blood. Additionally, some potentially good synthetic and natural compounds, which can activate the insulin-independent GLUT4 signaling pathways for the efficient management of T2DM, are highlighted as possible targets or emerging alternative sources for future anti-diabetic drug development.

  18. Effects of a training program at the crossover point on the cluster of metabolic abnormalities and cardiovascular risk factors

    Directory of Open Access Journals (Sweden)

    Jérémy B. Coquart

    2014-12-01

    Full Text Available The present study examined the effects of a training program at a special exercise intensity—the crossover point of substrate utilization (COP—on the metabolic abnormalities and cardiovascular risk factors in obese women with metabolic syndrome (MetS. Eighteen postmenopausal obese women with MetS (age, 54.8 ± 8.4 years; height, 160 ± 6 cm followed a 12-week training program consisting of three 45-minute sessions/wk on a cycle ergometer. The intensity imposed during the training sessions corresponded to COP. Before and after the training program, anthropometric, biological, and blood pressure data were collected and compared. After the training program, body mass (88.4 ± 12.3 kg vs. 85.7 ± 11.1 kg, fat mass (43.2 ± 4.8% vs. 41.8 ± 4.8% body mass, body mass index (34.3 ± 3.9 kg/m2 vs. 33.2 ± 3.6 kg/m2, and waist circumference (105 ± 10 cm vs. 100 ± 9 cm were significantly lower (p < 0.01. Moreover, fasting plasma glucose was significantly lower after the training program (114 ± 20 mg/dL vs. 107 ± 15 mg/dL; p = 0.02 and the quantitative insulin-sensitivity check index was significantly higher (0.58 ± 0.08 vs. 0.61 ± 0.05; p = 0.05. A significant reduction in systolic blood pressure was also observed (141 ± 15 mmHg vs. 129 ± 11 mmHg; p = 0.02. After the program, the number of patients with fasting plasma hyperglycemia and arterial hypertension was significantly decreased by 54.4% and 44.4%, respectively, and the number of patients with MetS was nonsignificantly reduced by 22.2% (p = 0.10. The present study shows that a training program at COP is an efficient means to treat MetS.

  19. Glucose metabolic changes in the prefrontal cortex are associated with HPA axis response to a psychosocial stressor.

    Science.gov (United States)

    Kern, Simone; Oakes, Terrence R; Stone, Charles K; McAuliff, Emelia M; Kirschbaum, Clemens; Davidson, Richard J

    2008-05-01

    The prefrontal cortex (PFC) has been well known for its role in higher order cognition, affect regulation and social reasoning. Although the precise underpinnings have not been sufficiently described, increasing evidence also supports a prefrontal involvement in the regulation of the hypothalamus-pituitary-adrenal (HPA) axis. Here we investigate the PFC's role in HPA axis regulation during a psychosocial stress exposure in 14 healthy humans. Regional brain metabolism was assessed using positron emission tomography (PET) and injection of fluoro-18-deoxyglucose (FDG). Depending on the exact location within the PFC, increased glucose metabolic rate was associated with lower or higher salivary cortisol concentration in response to a psychosocial stress condition. Metabolic glucose rate in the rostral medial PFC (mPFC) (Brodman area (BA) 9 and BA 10) was negatively associated with stress-induced salivary cortisol increases. Furthermore, metabolic glucose rate in these regions was inversely coupled with changes in glucose metabolic rate in other areas, known to be involved in HPA axis regulation such as the amygdala/hippocampal region. In contrast, metabolic glucose rate in areas more lateral to the mPFC was positively associated with saliva cortisol. Subjective ratings on task stressfulness, task controllability and self-reported dispositional mood states also showed positive and negative associations with the glucose metabolic rate in prefrontal regions. These findings suggest that in humans, the PFC is activated in response to psychosocial stress and distinct prefrontal metabolic glucose patterns are linked to endocrine stress measures as well as subjective ratings on task stressfulness, controllability as well as dispositional mood states.

  20. Glucose as the Sole Metabolic Fuel: Overcoming a Misconception Using Conceptual Change to Teach the Energy-Yielding Metabolism to Brazilian High School Students

    Science.gov (United States)

    Luz, Mauricio R. M. P.; Oliveira, Gabriel A.; Da Poian, Andrea T.

    2013-01-01

    A misconception regarding the human metabolism has been shown to be widespread among high school students. The students consider glucose as the sole metabolic fuel, disregarding that lipids and amino acids can be oxidized for ATP production by human cells. This misconception seems to be a consequence of formal teaching in grade and high schools.…

  1. Dysfunctional protection against advanced glycation due to thiamine metabolism abnormalities in gestational diabetes.

    Science.gov (United States)

    Bartáková, Vendula; Pleskačová, Anna; Kuricová, Katarína; Pácal, Lukáš; Dvořáková, Veronika; Bělobrádková, Jana; Tomandlová, Marie; Tomandl, Josef; Kaňková, Kateřina

    2016-08-01

    While the pathogenic role of dicarbonyl stress and accelerated formation of advanced glycation end products (AGEs) to glucose intolerance and to the development of diabetic complications is well established, little is known about these processes in gestational diabetes mellitus (GDM), a condition pathogenically quite similar to type 2 diabetes. The aims of the present study were (i) to determine plasma thiamine and erythrocyte thiamine diphosphate (TDP) and transketolase (TKT) activity in pregnant women with and without GDM, (ii) to assess relationships between thiamine metabolism parameters and selected clinical, biochemical and anthropometric characteristics and, finally, (iii) to analyse relationship between variability in the genes involved in the regulation of transmembrane thiamine transport (i.e. SLC19A2 and SLC19A3) and relevant parameters of thiamine metabolism. We found significantly lower plasma BMI adjusted thiamine in women with GDM (P = 0.002, Mann-Whitney) while levels of erythrocyte TDP (an active TKT cofactor) in mid-trimester were significantly higher in GDM compared to controls (P = 0.04, Mann-Whitney). However, mid-gestational TKT activity - reflecting pentose phosphate pathway activity - did not differ between the two groups (P > 0.05, Mann-Whitney). Furthermore, we ascertained significant associations of postpartum TKT activity with SNPs SLC19A2 rs6656822 and SLC19A3 rs7567984 (P = 0.03 and P = 0.007, resp., Kruskal-Wallis). Our findings of increased thiamine delivery to the cells without concomitant increase of TKT activity in women with GDM therefore indicate possible pathogenic role of thiamine mishandling in GDM. Further studies are needed to determine its contribution to maternal and/or neonatal morbidity.

  2. Probing the metabolic network in bloodstream-form Trypanosoma brucei using untargeted metabolomics with stable isotope labelled glucose.

    Directory of Open Access Journals (Sweden)

    Darren J Creek

    2015-03-01

    Full Text Available Metabolomics coupled with heavy-atom isotope-labelled glucose has been used to probe the metabolic pathways active in cultured bloodstream form trypomastigotes of Trypanosoma brucei, a parasite responsible for human African trypanosomiasis. Glucose enters many branches of metabolism beyond glycolysis, which has been widely held to be the sole route of glucose metabolism. Whilst pyruvate is the major end-product of glucose catabolism, its transamination product, alanine, is also produced in significant quantities. The oxidative branch of the pentose phosphate pathway is operative, although the non-oxidative branch is not. Ribose 5-phosphate generated through this pathway distributes widely into nucleotide synthesis and other branches of metabolism. Acetate, derived from glucose, is found associated with a range of acetylated amino acids and, to a lesser extent, fatty acids; while labelled glycerol is found in many glycerophospholipids. Glucose also enters inositol and several sugar nucleotides that serve as precursors to macromolecule biosynthesis. Although a Krebs cycle is not operative, malate, fumarate and succinate, primarily labelled in three carbons, were present, indicating an origin from phosphoenolpyruvate via oxaloacetate. Interestingly, the enzyme responsible for conversion of phosphoenolpyruvate to oxaloacetate, phosphoenolpyruvate carboxykinase, was shown to be essential to the bloodstream form trypanosomes, as demonstrated by the lethal phenotype induced by RNAi-mediated downregulation of its expression. In addition, glucose derivatives enter pyrimidine biosynthesis via oxaloacetate as a precursor to aspartate and orotate.

  3. MAPK/ERK signaling regulates insulin sensitivity to control glucose metabolism in Drosophila.

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2011-12-01

    Full Text Available The insulin/IGF-activated AKT signaling pathway plays a crucial role in regulating tissue growth and metabolism in multicellular animals. Although core components of the pathway are well defined, less is known about mechanisms that adjust the sensitivity of the pathway to extracellular stimuli. In humans, disturbance in insulin sensitivity leads to impaired clearance of glucose from the blood stream, which is a hallmark of diabetes. Here we present the results of a genetic screen in Drosophila designed to identify regulators of insulin sensitivity in vivo. Components of the MAPK/ERK pathway were identified as modifiers of cellular insulin responsiveness. Insulin resistance was due to downregulation of insulin-like receptor gene expression following persistent MAPK/ERK inhibition. The MAPK/ERK pathway acts via the ETS-1 transcription factor Pointed. This mechanism permits physiological adjustment of insulin sensitivity and subsequent maintenance of circulating glucose at appropriate levels.

  4. Polychlorinated biphenyl exposure and glucose metabolism in Danish children aged 9 years

    DEFF Research Database (Denmark)

    Jensen, Tina K; Timmermann, Clara Amalie Gade; Rossing, Laura I;

    2014-01-01

    and participants: A total of 771 healthy Danish third grade school children aged 8-10 years in the municipality of Odense were recruited in 1997 through a two-stage cluster sampling from 25 different schools stratified according to location and socioeconomic character; 509 (9.7±0.8 years, 53% girls) had adequate......Context: Human exposure to polychlorinated biphenyls (PCBs) has been associated to type 2 diabetes in adults. Objectives: To determine whether concurrent serum PCB concentration was associated with markers of glucose metabolism in healthy children. Design: Cross-sectional study. Settings......-DDE. Conclusion: A strong inverse association between serum insulin and PCB exposure was found while fasting plasma glucose remained within the expected narrow range. Our findings suggest that PCB may not exert effect through decreased peripheral insulin sensitivity, as seen in obese and low fit children...

  5. Adiponectin regulates expression of hepatic genes critical for glucose and lipid metabolism.

    Science.gov (United States)

    Liu, Qingqing; Yuan, Bingbing; Lo, Kinyui Alice; Patterson, Heide Christine; Sun, Yutong; Lodish, Harvey F

    2012-09-04

    The effects of adiponectin on hepatic glucose and lipid metabolism at transcriptional level are largely unknown. We profiled hepatic gene expression in adiponectin knockout (KO) and wild-type (WT) mice by RNA sequencing. Compared with WT mice, adiponectin KO mice fed a chow diet exhibited decreased mRNA expression of rate-limiting enzymes in several important glucose and lipid metabolic pathways, including glycolysis, tricarboxylic acid cycle, fatty-acid activation and synthesis, triglyceride synthesis, and cholesterol synthesis. In addition, binding of the transcription factor Hnf4a to DNAs encoding several key metabolic enzymes was reduced in KO mice, suggesting that adiponectin might regulate hepatic gene expression via Hnf4a. Phenotypically, adiponectin KO mice possessed smaller epididymal fat pads and showed reduced body weight compared with WT mice. When fed a high-fat diet, adiponectin KO mice showed significantly reduced lipid accumulation in the liver. These lipogenic defects are consistent with the down-regulation of lipogenic genes in the KO mice.

  6. Persistence of disturbed thalamic glucose metabolism in a case of Wernicke-Korsakoff syndrome.

    Science.gov (United States)

    Fellgiebel, Andreas; Scheurich, Armin; Siessmeier, Thomas; Schmidt, Lutz G; Bartenstein, Peter

    2003-10-30

    We report the case of a 40-year-old alcoholic male patient, hospitalized with an acute ataxia of stance and gait, ocular muscle weakness with nystagmus and a global apathetic-confusional state. After admission, an amnestic syndrome with confabulation was also observed and diagnosis of Wernicke-Korsakoff syndrome was made. Under treatment with intravenous thiamine, the patient recovered completely from gaze weakness and ataxia, whereas a severe amnestic syndrome persisted. Fluorodeoxyglucose (FDG) positron emission tomography (PET) showed bilateral thalamic and severe bilateral temporal-parietal hypometabolism resembling a pattern typical for Alzheimer's disease. Longitudinal assessment of the alcohol-abstinent and thiamine-substituted patient revealed improvements of clinical state and neuropsychological performance that were paralleled by recovered cerebral glucose metabolism. In contrast to metabolic rates that increased between 7.1% (anterior cingulate, left) and 23.5% (parietal, left) in cortical areas during a 9-month remission period, thalamic glucose metabolism remained severely disturbed over time (change: left +0.2%, right +0.3%).

  7. High-density lipoprotein modulates glucose metabolism in patients with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Drew, Brian G; Duffy, Stephen J; Formosa, Melissa F

    2009-01-01

    kinase kinase and the AMP-activated protein kinase pathway. CONCLUSIONS: rHDL reduced plasma glucose in patients with type 2 diabetes mellitus by increasing plasma insulin and activating AMP-activated protein kinase in skeletal muscle. These findings suggest a role for HDL-raising therapies beyond......BACKGROUND: Low plasma high-density lipoprotein (HDL) is associated with elevated cardiovascular risk and aspects of the metabolic syndrome. We hypothesized that HDL modulates glucose metabolism via elevation of plasma insulin and through activation of the key metabolic regulatory enzyme, AMP...... baseline occurred during rHDL than during placebo (at 4 hours rHDL=-2.6+/-0.4; placebo=-2.1+/-0.3 mmol/L; P=0.018). rHDL increased plasma insulin (at 4 hours rHDL=3.4+/-10.0; placebo= -19.2+/-7.4 pmol/L; P=0.034) and also the homeostasis model assessment beta-cell function index (at 4 hours rHDL=18...

  8. Effects of the BET-inhibitor, RVX-208 on the HDL lipidome and glucose metabolism in individuals with prediabetes

    DEFF Research Database (Denmark)

    Siebel, Andrew L; Trinh, Si Khiang; Formosa, Melissa F

    2016-01-01

    particle size and distribution using NMR spectroscopy. An oral glucose tolerance test (OGTT) protocol with oral and infused stable isotope tracers was employed to assess postprandial plasma glucose, indices of insulin secretion and insulin sensitivity, glucose kinetics and lipolysis. Whole plasma and HDL...... (HDL lipidome) and glucose metabolism. MATERIALS AND METHODS: Twenty unmedicated males with prediabetes received 100mg b.i.d. RVX-208 and placebo for 29-33days separated by a wash-out period in a randomized, cross-over design trial. Plasma HDL-cholesterol and apoA-I were assessed as well as lipoprotein...

  9. The effect of microbial glucose metabolism on bytownite feldspar dissolution rates between 5 and 35 C

    Energy Technology Data Exchange (ETDEWEB)

    Welch, S.A.; Ullman, W.J.

    1999-10-01

    The rate of Si release from dissolving bytownite feldspar in abiotic batch reactors increased as temperatures increased from 5 to 35 C. Metabolically inert subsurface bacteria (bacteria in solution with no organic substrate) had no apparent effect on dissolution rates over this temperature range. When glucose was added to the microbial cultures, the bacteria responded by producing gluconic acid, which catalyzed the dissolution reaction by both proton- and ligand-promoted mechanisms. The metabolic production, excretion, and consumption of gluconic acid in the course of glucose oxidation, and therefore, the degree of microbial enhancement of mineral dissolution, depend on temperature. There was little accumulation of gluconic acid and therefore, no significant enhancement of mineral dissolution rates at 35 C compared to the abiotic controls. At 20 C, gluconate accumulated in the experimental solutions only at the beginning of the experiment and led to a twofold increase in dissolved Si release compared to the controls, primarily by the ligand-promoted dissolution mechanism. There was significant accumulation of gluconic acid in the 5 C experiment, which is reflected in a significant reduction in pH, leading to 20-fold increase in Si release, primarily attributable to the proton-promoted dissolution mechanism. These results indicate that bacteria and microbial metabolism can affect mineral dissolution rates in organic-rich, nutrient-poor environments; the impact of microbial metabolism on aluminum silicate dissolution rates may be greater at lower rather than at higher temperatures due to the metabolic accumulation of dissolution-enhancing protons and ligands in solution.

  10. Cannabidiol attenuates OGD/R-induced damage by enhancing mitochondrial bioenergetics and modulating glucose metabolism via pentose-phosphate pathway in hippocampal neurons

    Directory of Open Access Journals (Sweden)

    Shanshan Sun

    2017-04-01

    Full Text Available Deficient bioenergetics and diminished redox conservation have been implicated in the development of cerebral ischemia/reperfusion injury. In this study, the mechanisms underlying the neuroprotective effects of cannabidiol (CBD, a nonpsychotropic compound derived from Cannabis sativa with FDA-approved antiepilepsy properties, were studied in vitro using an oxygen–glucose-deprivation/reperfusion (OGD/R model in a mouse hippocampal neuronal cell line. CBD supplementation during reperfusion rescued OGD/R-induced cell death, attenuated intracellular ROS generation and lipid peroxidation, and simultaneously reversed the abnormal changes in antioxidant biomarkers. Using the Seahorse XFe24 Extracellular Flux Analyzer, we found that CBD significantly improved basal respiration, ATP-linked oxygen consumption rate, and the spare respiratory capacity, and augmented glucose consumption in OGD/R-injured neurons. The activation of glucose 6-phosphate dehydrogenase and the preservation of the NADPH/NADP+ ratio implies that the pentose-phosphate pathway is stimulated by CBD, thus protecting hippocampal neurons from OGD/R injury. This study is the first to document the neuroprotective effects of CBD against OGD/R insult, which depend in part on attenuating oxidative stress, enhancing mitochondrial bioenergetics, and modulating glucose metabolism via the pentose-phosphate pathway, thus preserving both energy and the redox balance.

  11. Effect of anterior nucleus of thalamus stimulation on glucose metabolism in hippocampus of epileptic rats

    Institute of Scientific and Technical Information of China (English)

    LIU Huan-guang; YANG An-chao; MENG Da-wei; ZHANG Kai; ZHANG Jian-guo

    2012-01-01

    Background Electrical stimulation of the anterior nucleus of the thalamus (ANT) appears to be effective against seizures.In this study,we investigated changes in glucose metabolism during high-frequency stimulation of ANT in epileptic rats.Methods Three groups of rats were used:(1) a stimulation group (n=12),(2) a sham stimulation group (n=12) with seizures induced by stereotactic administration of kainic acid (KA),and (3) a control group (n=12) with sham surgery.Concentric bipolar electrodes were stereotaxically implanted unilaterally in the ANT.High-frequency stimulation was performed in each group except the sham stimulation group.Microdialysis probes were lowered into the CA3 region of the hippocampus unilaterally but bilaterally in thestimulation group.The concentrations of glucose,lactate,and pyruvate in dialysate samples were determined by an ISCUS microdialysis analyzer.Results The extracellular concentrations of lactate and lactate/pyruvate ratio (LPR) of epileptic rats were significantly higher than in control rats (P=0.020,P=0.001; respectively).However,no significant difference in the concentration of glucose and pyruvate was found between these groups (P>0.05).Electrical stimulation of ANT induced decreases in lactate and LPR in the ipsilateral hippocampus (KA injected) of the stimulation group (P <0.05),but it did not influence the glucose metabolism in the contralateral hippocampus (P >0.05).Conclusions This study demonstrated that the glycolysis was inhibited in the ipsilateral hippocampus of epileptic rats during electrical ANT stimulation.These findings may provide useful information for better understanding the mechanism of ANT-deep brain stimulation.

  12. Resistance to chemotherapy is associated with altered glucose metabolism in acute myeloid leukemia

    Science.gov (United States)

    SONG, KUI; LI, MIN; XU, XIAOJUN; XUAN, LI; HUANG, GUINIAN; LIU, QIFA

    2016-01-01

    Altered glucose metabolism has been described as a cause of chemoresistance in multiple tumor types. The present study aimed to identify the expression profile of glucose metabolism in drug-resistant acute myeloid leukemia (AML) cells and provide potential strategies for the treatment of drug-resistant AML. Bone marrow and serum samples were obtained from patients with AML that were newly diagnosed or had relapsed. The messenger RNA expression of hypoxia inducible factor (HIF)-1α, glucose transporter (GLUT)1, and hexokinase-II was measured by quantitative polymerase chain reaction. The levels of LDH and β subunit of human F1-F0 adenosine triphosphate synthase (β-F1-ATPase) were detected by enzyme-linked immunosorbent and western blot assays. The HL-60 and HL-60/ADR cell lines were used to evaluate glycolytic activity and effect of glycolysis inhibition on cellular proliferation and apoptosis. Drug-resistant HL-60/ADR cells exhibited a significantly increased level of glycolysis compared with the drug-sensitive HL-60 cell line. The expression of HIF-1α, hexokinase-II, GLUT1 and LDH were increased in AML patients with no remission (NR), compared to healthy control individuals and patients with complete remission (CR) and partial remission. The expression of β-F1-ATPase in patients with NR was decreased compared with the expression in the CR group. Treatment of HL-60/ADR cells with 2-deoxy-D-glucose or 3-bromopyruvate increased in vitro sensitivity to Adriamycin (ADR), while treatment of HL-60 cells did not affect drug cytotoxicity. Subsequent to treatment for 24 h, apoptosis in these two cell lines showed no significant difference. However, glycolytic inhibitors in combination with ADR increased cellular necrosis. These findings indicate that increased glycolysis and low efficiency of oxidative phosphorylation may contribute to drug resistance. Targeting glycolysis is a viable strategy for modulating chemoresistance in AML. PMID:27347147

  13. Analysis of metabolism of 6FDG: a PET glucose transport tracer

    Energy Technology Data Exchange (ETDEWEB)

    Muzic, Raymond F., E-mail: raymond.muzic@case.edu [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Chandramouli, Visvanathan [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Huang, Hsuan-Ming [Department of Biomedical Engineering, Case Western Reserve University, Cleveland, OH 44106 (United States); Wu Chunying; Wang Yanming [Department of Radiology, Case Western Reserve University, Cleveland, OH 44106 (United States); Ismail-Beigi, Faramarz [Department of Medicine, Case Western Reserve University, Cleveland, OH 44106 (United States)

    2011-07-15

    Introduction: We are developing {sup 18}F-labeled 6-fluoro-6-deoxy-D-glucose ([{sup 18}F]6FDG) as a tracer of glucose transport. As part of this process it is important to characterize and quantify putative metabolites. In contrast to the ubiquitous positron emission tomography (PET) tracer {sup 18}F-labeled 2-fluoro-2-deoxy-D-glucose ([{sup 18}F]2FDG) which is phosphorylated and trapped intracellularly, the substitution of fluorine for a hydroxyl group at carbon-6 in [{sup 18}F]6FDG should prevent its phosphorylation. Consequently, [{sup 18}F]6FDG has the potential to trace the transport step of glucose metabolism without the confounding effects of phosphorylation and subsequent steps of metabolism. Herein the focus is to determine whether, and the degree to which, [{sup 18}F]6FDG remains unchanged following intravenous injection. Methods: Biodistribution studies were performed using 6FDG labeled with {sup 18}F or with the longer-lived radionuclides {sup 3}H and {sup 14}C. Tissues were harvested at 1, 6, and 24 h following intravenous administration and radioactivity was extracted from the tissues and analyzed using a combination of ion exchange columns, high-performance liquid chromatography, and chemical reactivity. Results: At the 1 h time-point, the vast majority of radioactivity in the liver, brain, heart, skeletal muscle, and blood was identified as 6FDG. At the 6-h and 24-h time points, there was evidence of a minor amount of radioactive material that appeared to be 6-fluoro-6-deoxy-D-sorbitol and possibly 6-fluoro-6-deoxy-D-gluconic acid. Conclusion: On the time scale typical of PET imaging studies radioactive metabolites of [{sup 18}F]6FDG are negligible.

  14. Detection of glycemic abnormalities in adolescents with beta thalassemia using continuous glucose monitoring and oral glucose tolerance in adolescents and young adults with β-thalassemia major: Pilot study

    Directory of Open Access Journals (Sweden)

    Ashraf T Soliman

    2013-01-01

    Full Text Available Background: Both insulin deficiency and resistance are reported in patients with β-thalassemia major (BTM. The use of continuous blood glucose monitoring (CGM, among the different methods for early detection of glycemic abnormalities, has not been studied thoroughly in these adolescents. Materials and Methods: To assess the oralglucose tolerance (OGT and 72-h continuous glucose concentration by the continuous glucose monitoring system (CGMS and calculate homeostatic model assessment (HOMA, and the quantitative insulin sensitivity check index (QUICKI was conducted in 16 adolescents with BTM who were receiving regular blood transfusions every 2-4 weeks and iron-chelation therapy since early childhood. Results: Sixteen adolescents with BTM (age: 19.75 ± 3 years were investigated. Using OGTT, (25% had impaired fasting blood (plasma glucose concentration (BG (>5.6 mmol/L. 2-h after the glucose load, one of them had BG = 16.2 mmol/L (diabetic and two had impaired glucose tolerance (IGT (BG > 7.8 and 11.1 mmol/L and 9 with IGT (56%. HOMA and QUICKI revealed levels 0.33 (0.36 ± 0.03, respectively, ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B% on one hand and the fasting and the 2-h BG (r=−0.6, and − 0.48, P < 0.01, respectively on the other hand. Neither fasting serum insulin nor c-peptide concentrations were correlated with fasting BG or ferritin levels. The average and maximum blood glucose levels during CGM were significantly correlated with the fasting BG (r = 0.68 and 0.39, respectively, with P < 0.01 and with the BG at 2-hour after oral glucose intake (r = 0.87 and 0.86 respectively, with P < 0.001. Ferritin concentrations were correlated with the fasting BG and the 2-h blood glucose levels in the OGTT (r = 0.52, and r = 0.43, respectively, P < 0.01 as well as with the average BG recorded by CGM (r = 0.75, P < 0.01. Conclusion: CGM has proven to

  15. Dynamic relationships between age, amyloid-β deposition, and glucose metabolism link to the regional vulnerability to Alzheimer's disease.

    Science.gov (United States)

    Oh, Hwamee; Madison, Cindee; Baker, Suzanne; Rabinovici, Gil; Jagust, William

    2016-08-01

    SEE HANSSON AND GOURAS DOI101093/AWW146 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: Although some brain regions such as precuneus and lateral temporo-parietal cortex have been shown to be more vulnerable to Alzheimer's disease than other areas, a mechanism underlying the differential regional vulnerability to Alzheimer's disease remains to be elucidated. Using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography imaging glucose metabolism and amyloid-β deposition, we tested whether and how life-long changes in glucose metabolism relate to amyloid-β deposition and Alzheimer's disease-related hypometabolism. Nine healthy young adults (age range: 20-30), 96 cognitively normal older adults (age range: 61-96), and 20 patients with Alzheimer's disease (age range: 50-90) were scanned using fluorodeoxyglucose and Pittsburgh compound B positron emission tomography. Among cognitively normal older subjects, 32 were further classified as amyloid-positive, with 64 as amyloid-negative. To assess the contribution of glucose metabolism to the regional vulnerability to amyloid-β deposition, we defined the highest and lowest metabolic regions in young adults and examined differences in amyloid deposition between these regions across groups. Two-way analyses of variance were conducted to assess regional differences in age and amyloid-β-related changes in glucose metabolism. Multiple regressions were applied to examine the association between amyloid-β deposition and regional glucose metabolism. Both region of interest and whole-brain voxelwise analyses were conducted to complement and confirm the results derived from the other approach. Regional differences in glucose metabolism between the highest and lowest metabolism regions defined in young adults (T = 12.85, P Alzheimer's disease-related hypometabolism was observed in brain regions that showed both age-invariance and amyloid-β-related increases in glucose metabolism. Our results indicate that although

  16. Thermodynamics of Microbial Growth Coupled to Metabolism of Glucose, Ethanol, Short-Chain Organic Acids, and Hydrogen ▿ †

    Science.gov (United States)

    Roden, Eric E.; Jin, Qusheng

    2011-01-01

    A literature compilation demonstrated a linear relationship between microbial growth yield and the free energy of aerobic and anaerobic (respiratory and/or fermentative) metabolism of glucose, ethanol, formate, acetate, lactate, propionate, butyrate, and H2. This relationship provides a means to estimate growth yields for modeling microbial redox metabolism in soil and sedimentary environments. PMID:21216913

  17. Circadian rhythms in glucose and lipid metabolism in nocturnal and diurnal mammals.

    Science.gov (United States)

    Kumar Jha, Pawan; Challet, Etienne; Kalsbeek, Andries

    2015-12-15

    Most aspects of energy metabolism display clear variations during day and night. This daily rhythmicity of metabolic functions, including hormone release, is governed by a circadian system that consists of the master clock in the suprachiasmatic nuclei of the hypothalamus (SCN) and many secondary clocks in the brain and peripheral organs. The SCN control peripheral timing via the autonomic and neuroendocrine system, as well as via behavioral outputs. The sleep-wake cycle, the feeding/fasting rhythm and most hormonal rhythms, including that of leptin, ghrelin and glucocorticoids, usually show an opposite phase (relative to the light-dark cycle) in diurnal and nocturnal species. By contrast, the SCN clock is most active at the same astronomical times in these two categories of mammals. Moreover, in both species, pineal melatonin is secreted only at night. In this review we describe the current knowledge on the regulation of glucose and lipid metabolism by central and peripheral clock mechanisms. Most experimental knowledge comes from studies in nocturnal laboratory rodents. Nevertheless, we will also mention some relevant findings in diurnal mammals, including humans. It will become clear that as a consequence of the tight connections between the circadian clock system and energy metabolism, circadian clock impairments (e.g., mutations or knock-out of clock genes) and circadian clock misalignments (such as during shift work and chronic jet-lag) have an adverse effect on energy metabolism, that may trigger or enhancing obese and diabetic symptoms.

  18. Emerging roles of the myocardin family of proteins in lipid and glucose metabolism.

    Science.gov (United States)

    Swärd, Karl; Stenkula, Karin G; Rippe, Catarina; Alajbegovic, Azra; Gomez, Maria F; Albinsson, Sebastian

    2016-09-01

    Members of the myocardin family bind to the transcription factor serum response factor (SRF) and act as coactivators controlling genes of relevance for myogenic differentiation and motile function. Binding of SRF to DNA is mediated by genetic elements called CArG boxes, found often but not exclusively in muscle and growth controlling genes. Studies aimed at defining the full spectrum of these CArG elements in the genome (i.e. the CArGome) have in recent years, unveiled unexpected roles of the myocardin family proteins in lipid and glucose homeostasis. This coactivator family includes the protein myocardin (MYOCD), the myocardin-related transcription factors A and B (MRTF-A/MKL1 and MRTF-B/MKL2) and MASTR (MAMSTR). Here we discuss growing evidence that SRF-driven transcription is controlled by extracellular glucose through activation of the Rho-kinase pathway and actin polymerization. We also describe data showing that adipogenesis is influenced by MLK activity through actions upstream of peroxisome proliferator-activated receptor γ with consequences for whole body fat mass and insulin sensitivity. The recently demonstrated involvement of myocardin coactivators in the biogenesis of caveolae, Ω-shaped membrane invaginations of importance for lipid and glucose metabolism, is finally discussed. These novel roles of myocardin proteins may open the way for new unexplored strategies to combat metabolic diseases such as diabetes, which, at the current incidence, is expected to reach 333 million people worldwide by 2025. This review highlights newly discovered roles of myocardin-related transcription factors in lipid and glucose metabolism as well as novel insights into their well-established role as mediators of stretch-dependent effects in smooth muscle. As co-factors for serum response factor (SRF), MKLs regulates transcription of genes involved in the contractile function of smooth muscle cells. In addition to mechanical stimuli, this regulation has now been found to

  19. Metabolic engineering of Corynebacterium glutamicum to produce GDP-L-fucose from glucose and mannose.

    Science.gov (United States)

    Chin, Young-Wook; Park, Jin-Byung; Park, Yong-Cheol; Kim, Kyoung Heon; Seo, Jin-Ho

    2013-06-01

    Wild-type Corynebacterium glutamicum was metabolically engineered to convert glucose and mannose into guanosine 5'-diphosphate (GDP)-L-fucose, a precursor of fucosyl-oligosaccharides, which are involved in various biological and pathological functions. This was done by introducing the gmd and wcaG genes of Escherichia coli encoding GDP-D-mannose-4,6-dehydratase and GDP-4-keto-6-deoxy-D-mannose-3,5-epimerase-4-reductase, respectively, which are known as key enzymes in the production of GDP-L-fucose from GDP-D-mannose. Coexpression of the genes allowed the recombinant C. glutamicum cells to produce GDP-L-fucose in a minimal medium containing glucose and mannose as carbon sources. The specific product formation rate was much higher during growth on mannose than on glucose. In addition, the specific product formation rate was further increased by coexpressing the endogenous phosphomanno-mutase gene (manB) and GTP-mannose-1-phosphate guanylyl-transferase gene (manC), which are involved in the conversion of mannose-6-phosphate into GDP-D-mannose. However, the overexpression of manA encoding mannose-6-phosphate isomerase, catalyzing interconversion of mannose-6-phosphate and fructose-6-phosphate showed a negative effect on formation of the target product. Overall, coexpression of gmd, wcaG, manB and manC in C. glutamicum enabled production of GDP-L-fucose at the specific rate of 0.11 mg g cell(-1) h(-1). The specific GDP-L-fucose content reached 5.5 mg g cell(-1), which is a 2.4-fold higher than that of the recombinant E. coli overexpressing gmd, wcaG, manB and manC under comparable conditions. Well-established metabolic engineering tools may permit optimization of the carbon and cofactor metabolisms of C. glutamicum to further improve their production capacity.

  20. Zonation of nitrogen and glucose metabolism gene expression upon acute liver damage in mouse.

    Directory of Open Access Journals (Sweden)

    Shahrouz Ghafoory

    Full Text Available Zonation of metabolic activities within specific structures and cell types is a phenomenon of liver organization and ensures complementarity of variant liver functions like protein production, glucose homeostasis and detoxification. To analyze damage and regeneration of liver tissue in response to a toxic agent, expression of liver specific enzymes was analyzed by in situ hybridization in mouse over a 6 days time course following carbon tetrachloride (CCl4 injection. CCl4 mixed with mineral oil was administered to BALB/c mice by intraperitoneal injection, and mice were sacrificed at different time points post injection. Changes in the expression of albumin (Alb, arginase (Arg1, glutaminase 2 (Gls2, Glutamine synthetase (Gs, glucose-6-phosphatase (G6pc, glycogen synthase 2 (Gys2, Glycerinaldehyd-3-phosphat-Dehydrogenase (Gapdh, Cytochrom p450 2E1 (Cyp2e1 and glucagon receptor (Gcgr genes in the liver were studied by in situ hybridization and qPCR. We observed significant changes in gene expression of enzymes involved in nitrogen and glucose metabolism and their local distribution following CCl4 injury. We also found that Cyp2e1, the primary metabolizing enzyme for CCl4, was strongly expressed in the pericentral zone during recovery. Furthermore, cells in the damaged area displayed distinct gene expression profiles during the analyzed time course and showed complete recovery with strong albumin production 6 days after CCl4 injection. Our results indicate that despite severe damage, liver cells in the damaged area do not simply die but instead display locally adjusted gene expression supporting damage response and recovery.

  1. Zonation of Nitrogen and Glucose Metabolism Gene Expression upon Acute Liver Damage in Mouse

    Science.gov (United States)

    Ghafoory, Shahrouz; Breitkopf-Heinlein, Katja; Li, Qi; Scholl, Catharina; Dooley, Steven; Wölfl, Stefan

    2013-01-01

    Zonation of metabolic activities within specific structures and cell types is a phenomenon of liver organization and ensures complementarity of variant liver functions like protein production, glucose homeostasis and detoxification. To analyze damage and regeneration of liver tissue in response to a toxic agent, expression of liver specific enzymes was analyzed by in situ hybridization in mouse over a 6 days time course following carbon tetrachloride (CCl4) injection. CCl4 mixed with mineral oil was administered to BALB/c mice by intraperitoneal injection, and mice were sacrificed at different time points post injection. Changes in the expression of albumin (Alb), arginase (Arg1), glutaminase 2 (Gls2), Glutamine synthetase (Gs), glucose-6-phosphatase (G6pc), glycogen synthase 2 (Gys2), Glycerinaldehyd-3-phosphat-Dehydrogenase (Gapdh), Cytochrom p450 2E1 (Cyp2e1) and glucagon receptor (Gcgr) genes in the liver were studied by in situ hybridization and qPCR. We observed significant changes in gene expression of enzymes involved in nitrogen and glucose metabolism and their local distribution following CCl4 injury. We also found that Cyp2e1, the primary metabolizing enzyme for CCl4, was strongly expressed in the pericentral zone during recovery. Furthermore, cells in the damaged area displayed distinct gene expression profiles during the analyzed time course and showed complete recovery with strong albumin production 6 days after CCl4 injection. Our results indicate that despite severe damage, liver cells in the damaged area do not simply die but instead display locally adjusted gene expression supporting damage response and recovery. PMID:24147127

  2. Regional cerebral blood flow and glucose metabolism following transient forebrain ischemia.

    Science.gov (United States)

    Pulsinelli, W A; Levy, D E; Duffy, T E

    1982-05-01

    Progressive brain damage after transient cerebral ischemia may be related to changes in postischemic cerebral blood flow and metabolism. Regional cerebral blood flow (rCBF) and cerebral glucose utilization (rCGU) were measured in adult rats prior to, during (only rCBF), and serially after transient forebrain ischemia. Animals were subjected to 30 minutes of forebrain ischemia by occluding both common carotid arteries 24 hours after cauterizing the vertebral arteries. Regional CBF was measured by the indicator-fractionation technique using 4-iodo-[14C]-antipyrine. Regional CGU was measured by the 2-[14C]deoxyglucose method. The results were correlated with the distribution and progression of ischemic neuronal damage in animals subjected to an identical ischemic insult. Cerebral blood flow to forebrain after 30 minutes of moderate to severe ischemia (less than 10% control CBF) was characterized by 5 to 15 minutes of hyperemia; rCBF then fell below normal and remained low for as long as 24 hours. Post-ischemic glucose utilization in the forebrain, except in the hippocampus, was depressed below control values at 1 hour and either remained low (neocortex, striatum) or gradually rose to normal (white matter) by 48 hours. In the hippocampus, glucose utilization equaled the control value at 1 hour and fell below control between 24 and 48 hours. The appearance of moderate to severe morphological damage in striatum and hippocampus coincided with a late rise of rCBF above normal and with a fall of rCGU; the late depression of rCGU was usually preceded by a period during which metabolism was increased relative to adjacent tissue. Further refinement of these studies may help identify salvageable brain after ischemia and define ways to manipulate CBF and metabolism in the treatment of stroke.

  3. EFFECT OF ACUPUNCTURE STIMULATION AT SANYINJIAO (SP 6) ON CEREBRAL GLUCOSE METABOLISM IN DYSMENORRHEA PATIENTS

    Institute of Scientific and Technical Information of China (English)

    GONG Ping; ZHANG Ming-min; JIANG Li-ming; WU Zhi-jian; WANG Wei; HUANG Guang-ying

    2006-01-01

    Objective: To study the central mechanism of acupuncture stimulation of Sanyinjiao ( 三阴交 SP6) in relieving dysmenorrhea. Methods: A total of 6 dysmenorrhea volunteer patients were subjected into this study. On the first positron emission tomography (PET) scan examination, they were assigned to pseudoacupuncture group by using the acupuncture needle just to prick the skin of Sanyinjiao (SP 6); while on the second PET scans, they were assigned to acupuncture group by inserting the needle into the same acupoint.18F fluorodeoxyglucose (18F-FDG) PET of the whole brain was performed during pseudo-acupuncture and real acupuncture of Sanyinjiao (SP 6). The acquired PET data were analyzed by using statistical parametric mapping (SPM) software to determine changes of glucose metabolism in different cerebral regions. The patient's pain intensity was rated by using 0- 10 numerical pain intensity scale. Results: After pseudo-acupuncture stimulation of Sanyinjiao (SP 6), no significant changes were found in the pain intensity ( P >0.05), while after real-acupuncture stimulation, the pain intensity declined significantly (P < 0.01 ). Following acupuncture of the right Sanyinjiao (SP 6), multiple cerebral regions involving pain were activated (increase of glucose metabolism), including ipsilateral lenticular nucleus (globus pallidus, putamen), ipsilateral cerebellum and insular lobe, bilateral dorsal thalamus, ipsilateral paracentral lobule, bilateral amygdaloid bodies, contralateral substantia nigra of the midbrain, bilateral second somatosensory (S Ⅱ ) areas, ispsilateral hippocampal gyrus, frontal part of the ipsilateral cingulated gyrus, and bilateral mammary bodies of the hypothalamus. In addition, fewer regions of the cerebral cortex responded with decrease of the glucose metabolism after real acupuncture.

  4. Glucose and Glycogen Metabolism in Brugia malayi Is Associated with Wolbachia Symbiont Fitness.

    Science.gov (United States)

    Voronin, Denis; Bachu, Saheed; Shlossman, Michael; Unnasch, Thomas R; Ghedin, Elodie; Lustigman, Sara

    2016-01-01

    Wolbachia are endosymbiotic bacteria found in the majority of arthropods and filarial nematodes of medical and veterinary importance. They have evolved a wide range of symbiotic associations. In filarial nematodes that cause human lymphatic filariasis (Wuchereria bancrofti, Brugia malayi) or onchocerciasis (Onchocerca volvulus), Wolbachia are important for parasite development, reproduction and survival. The symbiotic bacteria rely in part on nutrients and energy sources provided by the host. Genomic analyses suggest that the strain of Wolbachia found in B. malayi (wBm) lacks the genes for two glycolytic enzymes--6-phosphofructokinase and pyruvate kinase--and is thus potentially unable to convert glucose into pyruvate, an important substrate for energy generation. The Wolbachia surface protein, wBm00432, is complexed to six B. malayi glycolytic enzymes, including aldolase. In this study we characterized two B. malayi aldolase isozymes and found that their expression is dependent on Wolbachia fitness and number. We confirmed by immuno-transmission electron microscopy that aldolase is associated with the Wolbachia surface. RNAi experiments suggested that aldolase-2 plays a significant role in both Wolbachia survival and embryogenesis in B. malayi. Treatment with doxycycline reduced Wolbachia fitness and increased the amount of both glucose and glycogen detected in the filarial parasite, indicating that glucose metabolism and glycogen storage in B. malayi are associated with Wolbachia fitness. This metabolic co-dependency between Wolbachia and its filarial nematode indicates that glycolysis could be a shared metabolic pathway between the bacteria and B. malayi, and thus a potential new target for anti-filarial therapy.

  5. Comparison of Cerebral Glucose Metabolism between Possible and Probable Multiple System Atrophy

    Directory of Open Access Journals (Sweden)

    Kyum-Yil Kwon

    2009-05-01

    Full Text Available Background: To investigate the relationship between presenting clinical manifestations and imaging features of multisystem neuronal dysfunction in MSA patients, using 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET. Methods: We studied 50 consecutive MSA patients with characteristic brain MRI findings of MSA, including 34 patients with early MSA-parkinsonian (MSA-P and 16 with early MSA-cerebellar (MSA-C. The cerebral glucose metabolism of all MSA patients was evaluated in comparison with 25 age-matched controls. 18F-FDG PET results were assessed by the Statistic Parametric Mapping (SPM analysis and the regions of interest (ROI method. Results: The mean time from disease onset to 18F-FDG PET was 25.9±13.0 months in 34 MSA-P patients and 20.1±11.1 months in 16 MSA-C patients. Glucose metabolism of the putamen showed a greater decrease in possible MSA-P than in probable MSA-P (p=0.031. Although the Unified Multiple System Atrophy Rating Scale (UMSARS score did not differ between possible MSA-P and probable MSA-P, the subscores of rigidity (p=0.04 and bradykinesia (p= 0.008 were significantly higher in possible MSA-P than in probable MSA-P. Possible MSA-C showed a greater decrease in glucose metabolism of the cerebellum than probable MSA-C (p=0.016. Conclusions: Our results may suggest that the early neuropathological pattern of possible MSA with a predilection for the striatonigral or olivopontocerebellar system differs from that of probable MSA, which has prominent involvement of the autonomic nervous system in addition to the striatonigral or olivopontocerebellar system.

  6. Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

    Energy Technology Data Exchange (ETDEWEB)

    Bolado-Carrancio, A. [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain); Riancho, J.A. [Department of Internal Medicine, Hospital U.M. Valdecilla-IDIVAL, University of Cantabria, RETICEF, Santander (Spain); Sainz, J. [Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, Santander (Spain); Rodríguez-Rey, J.C., E-mail: rodriguj@unican.es [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain)

    2014-04-04

    Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity.

  7. Targeting Adipose Tissue Lipid Metabolism to Improve Glucose Metabolism in Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Johan W.E. Jocken

    2014-10-01

    Full Text Available With Type 2 diabetes mellitus and cardiovascular disease prevalence on the rise, there is a growing need for improved strategies to prevent or treat obesity and insulin resistance, both of which are major risk factors for these chronic diseases. Impairments in adipose tissue lipid metabolism seem to play a critical role in these disorders. In the classical picture of intracellular lipid breakdown, cytosolic lipolysis was proposed as the sole mechanism for triacylglycerol hydrolysis in adipocytes. Recent evidence suggests involvement of several hormones, membrane receptors, and intracellular signalling cascades, which has added complexity to the regulation of cytosolic lipolysis. Interestingly, a specific form of autophagy, called lipophagy, has been implicated as alternative lipolytic pathway. Defective regulation of cytosolic lipolysis and lipophagy might have substantial effects on lipid metabolism, thereby contributing to adipose tissue dysfunction, insulin resistance, and related cardiometabolic (cMet diseases. This review will discuss recent advances in our understanding of classical lipolysis and lipophagy in adipocyte lipid metabolism under normal and pathological conditions. Furthermore, the question of whether modulation of adipocyte lipolysis and lipophagy might be a potential therapeutic target to combat cMet disorders will be addressed.

  8. [Metabolic syndrome].

    Science.gov (United States)

    Mitsuishi, Masanori; Miyashita, Kazutoshi; Itoh, Hiroshi

    2009-02-01

    Metabolic syndrome, which is consisted of hypertension, dyslipidemia and impaired glucose tolerance, is one of the most significant lifestyle-related disorders that lead to cardiovascular diseases. Among many upstream factors that are related to metabolic syndrome, obesity, especially visceral obesity, plays an essential role in its pathogenesis. In recent studies, possible mechanisms which connect obesity to metabolic syndrome have been elucidated, such as inflammation, abnormal secretion of adipokines and mitochondrial dysfunction. In this review, we focus on the relationship between obesity and metabolic syndrome; and illustrate how visceral obesity contributes to, and how the treatments for obesity act on metabolic syndrome.

  9. The estrogen hypothesis of schizophrenia implicates glucose metabolism: association study in three independent samples

    DEFF Research Database (Denmark)

    Olsen, Line; Hansen, Thomas; Jakobsen, Klaus D.

    2008-01-01

    not feasible task. We undertook these challenges by using an established clinical paradigm, the estrogen hypothesis of schizophrenia, as the criterion to select candidates among the numerous genes experimentally implicated in schizophrenia. Bioinformatic tools were used to build and priorities the signaling...... networks implicated by the candidate genes resulting from the estrogen selection. We identified ten candidate genes using this approach that are all active in glucose metabolism and particularly in the glycolysis. Thus, we tested the hypothesis that variants of the glycolytic genes are associated...

  10. Effects of Chinese herbal medicine on plasma glucose, protein and energy metabolism in sheep

    Institute of Scientific and Technical Information of China (English)

    Xi Liang; Kyota Yamazaki; Mohammad Kamruzzaman; Xue Bi; Arvinda Panthee; Hiroaki Sano

    2014-01-01

    Background:The use of antibiotics in animal diets is facing negative feedback due to the hidden danger of drug residues to human health. Traditional Chinese herbal medicine has been used to replace antibiotics in the past two decades and played an increasingly important role in livestock production. The present study was carried out to assess the feeding effects of a traditional nourishing Chinese herbal medicine mixture on kinetics of plasma glucose, protein and energy metabolism in sheep. Ruminal fermentation characteristics were also determined. Methods:Four sheep were fed on either mixed hay (MH-diet) or MH-diet supplemented with 2%of Chinese herbal medicine (mixture of Astragalus root, Angelica root and Atractylodes rhizome;CHM-diet) over two 35-day periods using a crossover design. The turnover rate of plasma glucose was measured with an isotope dilution method using [U-13C]glucose. The rates of plasma leucine turnover and leucine oxidation, whole body protein synthesis (WBPS) and metabolic heat production were measured using the [1-13C]leucine dilution and open circuit calorimetry. Results:Body weight gain of sheep was higher (P=0.03) for CHM-diet than for MH-diet. Rumen pH was lower (P=0.02), concentration of rumen total volatile fatty acid tended to be higher (P=0.05) and acetate was higher (P=0.04) for CHM-diet than for MH-diet. Turnover rates of plasma glucose and leucine did not differ between diets. Oxidation rate of leucine tended to be higher (P=0.06) for CHM-diet than for MH-diet, but the WBPS did not differ between diets. Metabolic heat production tended to be greater (P=0.05) for CHM-diet than for MH-diet. Conclusions:The sheep fed on CHM-diet had a higher body weight gain and showed positive impacts on rumen fermentation and energy metabolism without resulting in any adverse response. Therefore, these results suggested that the Chinese herbal medicine mixture should be considered as a potential feed additive for sheep.

  11. PRIMARY PREVENTION OF DIABETES MELLITUS: CORRECTION OF EARLY DISORDERS OF GLUCOSE METABOLISM IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2015-12-01

    Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.

  12. PRIMARY PREVENTION OF DIABETES MELLITUS: CORRECTION OF EARLY DISORDERS OF GLUCOSE METABOLISM IN CARDIOLOGY PRACTICE

    Directory of Open Access Journals (Sweden)

    M. N. Mamedov

    2012-01-01

    Full Text Available Early glucose metabolism disorders (GMD are of interest in development of effective approaches to prevention of type 2 diabetes mellitus (DM. Data of international clinical trials shows that early GMD are an independent risk factor for cardiovascular disease. The possibilities of GMD prevention and early treatment are discussed. Antihyperglycemic medications classification, their mode of action and efficacy are presented from evidence-based medicine point of view. This data confirms that successful DM primary prevention at early stage of GMD reduces the risk of cardiovascular complications.

  13. Renal Denervation Normalizes Arterial Pressure With No Effect on Glucose Metabolism or Renal Inflammation in Obese Hypertensive Mice.

    Science.gov (United States)

    Asirvatham-Jeyaraj, Ninitha; Fiege, Jessica K; Han, Ruijun; Foss, Jason; Banek, Christopher T; Burbach, Brandon J; Razzoli, Maria; Bartolomucci, Alessandro; Shimizu, Yoji; Panoskaltsis-Mortari, Angela; Osborn, John W

    2016-10-01

    Hypertension often occurs in concurrence with obesity and diabetes mellitus, commonly referred to as metabolic syndrome. Renal denervation (RDNx) lowers arterial pressure (AP) and improves glucose metabolism in drug-resistant hypertensive patients with high body mass index. In addition, RDNx has been shown to reduce renal inflammation in the mouse model of angiotensin II hypertension. The present study tested the hypothesis that RDNx reduces AP and renal inflammation and improves glucose metabolism in obesity-induced hypertension. Eight-week-old C57BL/6J mice were fed either a low-fat diet (10 kcal%) or a high-fat diet (45 kcal%) for 10 weeks. Body weight, food intake, fasting blood glucose, and glucose metabolism (glucose tolerance test) were measured. In a parallel study, radiotelemeters were implanted in mice for AP measurement. High fat-fed C57BL/6J mice exhibited an inflammatory and metabolic syndrome phenotype, including increased fat mass, increased AP, and hyperglycemia compared with low-fat diet mice. RDNx, but not Sham surgery, normalized AP in high-fat diet mice (115.8±1.5 mm Hg in sham versus 96.6±6.7 mm Hg in RDNx). RDNx had no significant effect on AP in low-fat diet mice. Also, RDNx had no significant effect on glucose metabolism or renal inflammation as measured by the number of CD8, CD4, and T helper cells or levels of inflammatory cytokines in the kidneys. These results indicate that although renal nerves play a role in obesity-induced hypertension, they do not contribute to impaired glucose metabolism or renal inflammation in this model.

  14. Genetically obese rats with (SHR/N-cp) and without diabetes (LA/N-cp) share abnormal islet responses to glucose.

    Science.gov (United States)

    Timmers, K I; Voyles, N R; Recant, L

    1992-10-01

    To assess the effect of hyperglycemia on the function of islets obtained from obese rats, the behavior of isolated islets from LA/N-corpulent (nondiabetic obese) and SHR/N-corpulent (diabetic obese) male rats was examined and compared. Islets from both genetic models showed a left-shifted glucose dose-response curve for insulin release (concentrations for half-maximal release, 5 to 6 mmol/L v 12 to 13 mmol/L in LA/N lean littermates and 3 mmol/L v 10 mmol/L in lean SHR/N). When insulin release was expressed per unit islet volume, the fourfold to fivefold enlarged islets from both obese diabetic and obese nondiabetic rats showed decreased insulin secretory response in high (16.5 to 28 mmol/L) glucose concentrations, although the decrease was more severe in the diabetic rats. Glucose-stimulated insulin release by islets from both models was relatively resistant to inhibition by 1.2 mmol/L mannoheptulose (eg, 82% +/- 3% inhibition in LA/N lean v 16% +/- 8% in LA/N obese), although nearly complete inhibition was observed with 16 mmol/L mannoheptulose (96% v 85%, NS). Islets of obese diabetic rats were also resistant to the calcium-channel blocker, verapamil, suggesting an abnormal pathway of stimulus-secretion coupling for glucose. Glucose oxidation to carbon dioxide was increased in both obese models at all glucose concentrations when expressed per islet. In data expressed per unit volume, the larger islets from the obese-nondiabetic rats showed a left-shifted dose-response curve with an unchanged maximum rate of glucose oxidation at high (16.5 mmol/L) glucose concentrations.(ABSTRACT TRUNCATED AT 250 WORDS)

  15. Relationship between salivary cortisol levels and regional cerebral glucose metabolism in nondemented elderly subjects

    Energy Technology Data Exchange (ETDEWEB)

    Kwak, Young Bin; Cho, Sang Soo; Lee, Sung Ha; Chey, Jean Yung; Kim, Sang Eun [Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2004-07-01

    Cortisol is a primary stress hormone for flight-or-fight response in human. Increased levels of cortisol have been associated with memory and learning impairments. However, little is known about the role of cortisol on brain/cognitive functions in older adults. We compared regional cerebral glucose metabolism between elderly subjects with high and low cortisol levels using FDG PET. Salivary cortisol levels were measured four times during a day, and an average of the four measurements was used as the standard cortisol level for the analyses. From a population of 120 nondemented elderly subjects, 19 (mean age, 70.1{+-}4.9 y: 2 males and 17 females) were identified as the high (> mean + 1 SD of the total population) cortisol subjects (mean cortisol, 0.69{+-}0.09 {mu} g/dL), while 14 (mean age, 67.2{+-}4.5 y: all females) as the low (< mean 1 SD) cortisol (mean cortisol, 0.27{+-}0.03 {mu} g/dL). A voxel-wise comparison of FDG PET images from the high and low cortisol subjects was performed using SPM99. When compared with the low cortisol group, the high cortisol group had significant hypometabolism in the right middle temporal gyrus, left precuneus, right parahippocampal gyrus, right inferior temporal and superior temporal gyri (P < 0.01 uncorrected, k = 100). There was no significant increase of glucose metabolism in the high cortisol group compared with the low cortisol group (P < 0.01 uncorrected, k = 100). The high cortisol elderly subjects had hypometabolism in the parahippocampal and temporal gyri and precuneus, regions involved in memory and other cognitive functions. This may represent the preclinical metabolic correlates of forthcoming cognitive dysfunction associated with stress in the elderly. Longitudinal studies of brain metabolism and cognitive function are warranted.

  16. Glucose metabolism: focus on gut microbiota, the endocannabinoid system and beyond.

    Science.gov (United States)

    Cani, P D; Geurts, L; Matamoros, S; Plovier, H; Duparc, T

    2014-09-01

    The gut microbiota is now considered as a key factor in the regulation of numerous metabolic pathways. Growing evidence suggests that cross-talk between gut bacteria and host is achieved through specific metabolites (such as short-chain fatty acids) and molecular patterns of microbial membranes (lipopolysaccharides) that activate host cell receptors (such as toll-like receptors and G-protein-coupled receptors). The endocannabinoid (eCB) system is an important target in the context of obesity, type 2 diabetes (T2D) and inflammation. It has been demonstrated that eCB system activity is involved in the control of glucose and energy metabolism, and can be tuned up or down by specific gut microbes (for example, Akkermansia muciniphila). Numerous studies have also shown that the composition of the gut microbiota differs between obese and/or T2D individuals and those who are lean and non-diabetic. Although some shared taxa are often cited, there is still no clear consensus on the precise microbial composition that triggers metabolic disorders, and causality between specific microbes and the development of such diseases is yet to be proven in humans. Nevertheless, gastric bypass is most likely the most efficient procedure for reducing body weight and treating T2D. Interestingly, several reports have shown that the gut microbiota is profoundly affected by the procedure. It has been suggested that the consistent postoperative increase in certain bacterial groups such as Proteobacteria, Bacteroidetes and Verrucomicrobia (A. muciniphila) may explain its beneficial impact in gnotobiotic mice. Taken together, these data suggest that specific gut microbes modulate important host biological systems that contribute to the control of energy homoeostasis, glucose metabolism and inflammation in obesity and T2D.

  17. Prevalence of insulin resistance and the metabolic syndrome with alternative definitions of impaired fasting glucose.

    Science.gov (United States)

    Ford, Earl S; Abbasi, Fahim; Reaven, Gerald M

    2005-07-01

    We sought to evaluate the effect of the new definition of impaired fasting glucose (IFG = fasting glucose concentration 100-125 mg/dL among people without diabetes) on the ability to identify insulin resistance, as well as the prevalence of the metabolic syndrome in apparently healthy individuals. From the Stanford General Clinical Research Center data-base, we used data from 230 men and 260 women aged 19-79 years who had had an insulin suppression test to measure insulin resistance. From the Third National Health and Nutrition Examination Survey (1988-1994), we used data from 8814 participants aged > or =20 years to estimate the impact of adopting the new IFG criteria on the prevalence of the metabolic syndrome. Among the 490 participants, the prevalence of IFG increased from 5.5% under the old definition of IFG to 20.4% under the new definition. Using the old definition of IFG, the sensitivity, specificity, and positive predictive value (PPV) of IFG of identifying an individual as being insulin resistant were 10%, 97%, and 63%, respectively. Using the new definition, these parameters were 33%, 88%, and 61%, respectively. If the new IFG criteria were adopted, the prevalence of the metabolic syndrome would increase from 21.8% to 26.3%. The new definition of IFG expands the population with insulin resistance by almost four-fold and could expand the population with the metabolic syndrome by about 20%. The clinical and public health implications of the new IFG definition remain to be elucidated.

  18. Lymphocyte Glucose and Glutamine Metabolism as Targets of the Anti-Inflammatory and Immunomodulatory Effects of Exercise

    Directory of Open Access Journals (Sweden)

    Frederick Wasinski

    2014-01-01

    Full Text Available Glucose and glutamine are important energetic and biosynthetic nutrients for T and B lymphocytes. These cells consume both nutrients at high rates in a function-dependent manner. In other words, the pathways that control lymphocyte function and survival directly control the glucose and glutamine metabolic pathways. Therefore, lymphocytes in different functional states reprogram their glucose and glutamine metabolism to balance their requirement for ATP and macromolecule production. The tight association between metabolism and function in these cells was suggested to introduce the possibility of several pathologies resulting from the inability of lymphocytes to meet their nutrient demands under a given condition. In fact, disruptions in lymphocyte metabolism and function have been observed in different inflammatory, metabolic, and autoimmune pathologies. Regular physical exercise and physical activity offer protection against several chronic pathologies, and this benefit has been associated with the anti-inflammatory and immunomodulatory effects of exercise/physical activity. Chronic exercise induces changes in lymphocyte functionality and substrate metabolism. In the present review, we discuss whether the beneficial effects of exercise on lymphocyte function in health and disease are associated with modulation of the glucose and glutamine metabolic pathways.

  19. SU-E-J-122: Detecting Treatment-Induced Metabolic Abnormalities in Craniopharyngioma Patients Undergoing Surgery and Proton Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Hua, C; Shulkin, B; Li, Y; LI, X; Merchant, T [St. Jude Children' s Research Hospital, Memphis, TN (United States); Indelicato, D [University of Florida Proton Therapy Institute, Jacksonville, FL (United States); Boop, F [Semmes-Murphey Neurologic and Spine Institute, Memphis, TN (United States)

    2014-06-01

    Purpose: To identify treatment-induced defects in the brain of children with craniopharyngioma receiving surgery and proton therapy using fluorodeoxyglucose positron emission tomography (FDG PET). Methods: Forty seven patients were enrolled on a clinical trial for craniopharyngioma with serial imaging and functional evaluations. Proton therapy was delivered using the double-scattered beams with a prescribed dose of 54 Cobalt Gray Equivalent. FDG tracer uptake in each of 63 anatomical regions was computed after warping PET images to a 3D reference template in Talairach coordinates. Regional uptake was deemed significantly low or high if exceeding two standard deviations of normal population from the mean. For establishing the normal ranges, 132 children aged 1–20 years with noncentral nervous system related diseases and normal-appearing cerebral PET scans were analyzed. Age- and gender-dependent regional uptake models were developed by linear regression and confidence intervals were calculated. Results: Most common PET abnormality before proton therapy was significantly low uptake in the frontal lobe, the occipital lobe (particularly in cuneus), the medial and ventral temporal lobe, cingulate gyrus, caudate nuclei, and thalamus. They were related to injury from surgical corridors, tumor mass effect, insertion of a ventricular catheter, and the placement of an Ommaya reservoir. Surprisingly a significantly high uptake was observed in temporal gyri and the parietal lobe. In 13 patients who already completed 18-month PET scans, metabolic abnormalities improved in 11 patients from baseline. One patient had persistent abnormalities. Only one revealed new uptake abnormalities in thalamus, brainstem, cerebellum, and insula. Conclusion: Postoperative FDG PET of craniopharyngioma patients revealed metabolic abnormalities in specific regions of the brain. Proton therapy did not appear to exacerbate these surgery- and tumor-induced defects. In patients with persistent and

  20. Niclosamide reduces glucagon sensitivity via hepatic PKA inhibition in obese mice: Implications for glucose metabolism improvements in type 2 diabetes

    Science.gov (United States)

    Chowdhury, Md. Kamrul Hasan; Turner, Nigel; Bentley, Nicholas L.; Das, Abhirup; Wu, Lindsay E.; Richani, Dulama; Bustamante, Sonia; Gilchrist, Robert B.; Morris, Margaret J.; Shepherd, Peter R.; Smith, Greg C.

    2017-01-01

    Type 2 diabetes (T2D) is a global pandemic. Currently, the drugs used to treat T2D improve hyperglycemic symptom of the disease but the underlying mechanism causing the high blood glucose levels have not been fully resolved. Recently published data showed that salt form of niclosamide improved glucose metabolism in high fat fed mice via mitochondrial uncoupling. However, based on our previous work we hypothesised that niclosamide might also improve glucose metabolism via inhibition of the glucagon signalling in liver in vivo. In this study, mice were fed either a chow or high fat diet containing two different formulations of niclosamide (niclosamide ethanolamine salt - NENS or niclosamide - Nic) for 10 weeks. We identified both forms of niclosamide significantly improved whole body glucose metabolism without altering total body weight or body composition, energy expenditure or insulin secretion or sensitivity. Our study provides evidence that inhibition of the glucagon signalling pathway contributes to the beneficial effects of niclosamide (NENS or Nic) on whole body glucose metabolism. In conclusion, our results suggest that the niclosamide could be a useful adjunctive therapeutic strategy to treat T2D, as hepatic glucose output is elevated in people with T2D and current drugs do not redress this adequately. PMID:28054648

  1. Trace glucose and lipid metabolism in high androgen and high-fat diet induced polycystic ovary syndrome rats

    Directory of Open Access Journals (Sweden)

    Zhai Hua-Ling

    2012-01-01

    Full Text Available Abstract Background There is a high prevalence of diabetes mellitus (DM and dyslipidemia in women with polycystic ovary syndrome (PCOS. The purpose of this study was to investigate the role of different metabolic pathways in the development of diabetes mellitus in high-androgen female mice fed with a high-fat diet. Methods Female Sprague-Dawley rats were divided into 3 groups: the control group(C, n = 10; the andronate-treated group (Andronate, n = 10 (treated with andronate, 1 mg/100 g body weight/day for 8 weeks; and the andronate-treated and high-fat diet group (Andronate+HFD, n = 10. The rate of glucose appearance (Ra of glucose, gluconeogenesis (GNG, and the rate of glycerol appearance (Ra of glycerol were assessed with a stable isotope tracer. The serum sex hormone levels, insulin levels, glucose concentration, and the lipid profile were also measured. Results Compared with control group, both andronate-treated groups exhibited obesity with higher insulin concentrations (P P Conclusions Andronate with HFD rat model showed ovarian and metabolic features of PCOS, significant increase in glucose Ra, GNG, and lipid profiles, as well as normal blood glucose levels. Therefore, aberrant IR, increased glucose Ra, GNG, and lipid metabolism may represent the early-stage of glucose and lipid kinetics disorder, thereby might be used as potential early-stage treatment targets for PCOS.

  2. Delivery-corrected imaging of fluorescently-labeled glucose reveals distinct metabolic phenotypes in murine breast cancer.

    Directory of Open Access Journals (Sweden)

    Amy E Frees

    Full Text Available When monitoring response to cancer therapy, it is important to differentiate changes in glucose tracer uptake caused by altered delivery versus a true metabolic shift. Here, we propose an optical imaging method to quantify glucose uptake and correct for in vivo delivery effects. Glucose uptake was measured using a fluorescent D-glucose derivative 2-(N-(7-Nitrobenz-2-oxa-1,3-diazol-4-ylAmino-2-deoxy-D-glucose (2-NBDG in mice implanted with dorsal skin flap window chambers. Additionally, vascular oxygenation (SO2 was calculated using only endogenous hemoglobin contrast. Results showed that the delivery factor proposed for correction, "RD", reported on red blood cell velocity and injected 2-NBDG dose. Delivery-corrected 2-NBDG uptake (2-NBDG60/RD inversely correlated with blood glucose in normal tissue, indicating sensitivity to glucose demand. We further applied our method in metastatic 4T1 and nonmetastatic 4T07 murine mammary adenocarcinomas. The ratio 2-NBDG60/RD was increased in 4T1 tumors relative to 4T07 tumors yet average SO2 was comparable, suggesting a shift toward a "Warburgian" (aerobic glycolysis metabolism in the metastatic 4T1 line. In heterogeneous regions of both 4T1 and 4T07, 2-NBDG60/RD increased slightly but significantly as vascular oxygenation decreased, indicative of the Pasteur effect in both tumors. These data demonstrate the utility of delivery-corrected 2-NBDG and vascular oxygenation imaging for differentiating metabolic phenotypes in vivo.

  3. Abnormal skeletal metabolism and its changes after decopper therapy in patients with Wilson disease

    Institute of Scientific and Technical Information of China (English)

    Guang'e Yang; Minfan Hong; Bin Yang; Renmin Yang; Xun Wang

    2006-01-01

    BACKGROUND: Researches indicate that patients with Wilson disease(WD)have abnormal skeletal metabolism,which is induced by various factors.OBJECTIVE:To probe into the changing characteristics of abnormal skeletal metabolism in WD patients and observe the effect of decopper therapy.DESIGN:Case-contrast and self-control study.SETTING:Department of Neurology,Affiliated Hospital of Neurological Institute,Anhui College of Traditional Chinese Medicine.PARTICIPANTS:A total of 35 patients with WD including 21 males and 14 females aged from 10 to 42 years with the mean age of (20±8) years were selected from Department of Neurology, Affiliated Hospital of Neurological Institute,Anhui College of Traditional Chinese Medicine from September 2000 to February 2001.All the patients were in compliance with the diagnostic criteria:history of family heredity;cone symptoms in vitro,physical sign or liver symptoms;positive Kayser-Fleischer ring; serum copper protein<200 mg/L or A copper oxidase<0.2;urine copper>1.6 μmol/24 hours;liver copper>250μg/g(dry weight).The control group was selected from 25 cases of health individuals including 13 males and 12 females aged from 16 to 35 years with the mean age of (22±6) years.All patients who participated in the study were informed first and consented.METHODS:Patients in treatment group were treated with venous injection of 1.0 g sodium dimercaptosulfonate,once a day for totally 6 successive days.And then,patients rested for 2 days.This procedure mentioned above was regarded as a course, and the treatment lasted for 4-8 courses. Before and after injection of sodium dimercaptosulfonate,serum calcitonin(CT),osteocalcin(BGP),parathyroid hormone(PTH)and 1,25-(OH)2VitD3 were measured with radio-immunity method: blood, urine calcium,phosphorum and urine creatinine were measured with biochemical analyzer; urine dihydropyrimidine dehydrogenase(DPD) was detected with enzyme-immunity method;bone mineral density(BMD)was checked at the one

  4. EXPLORING THE MECHANISM OF ACUPUNCTURE IN THE TREATMENT OF STROKE FROM CHANGES OF GLUCOSE METABOLISM IN THE CEREBRAL MOTOR CENTER

    Institute of Scientific and Technical Information of China (English)

    石现; 左芳; 关玲

    2004-01-01

    Objective:To observe the effect of acupuncture on cerebral glucose metabolism in stroke patients.Methods:Changes of cerebral glucose metabolism before and after acupuncture stimulation were observed in six cases of stroke patients by using positron emission tomography (PET) scanner. Electroacupuncture (EA,4 Hz, continuous waves and duration of 20 min) was applied to Baihui (百会GV 20) and right Qubin (曲鬓GB 7). 18 Fluorine deoxyglucose (18FDG), a developer (radioactive form of glucose) for showing the levels of the brain functional activity was given to the patients intravenously. SPM software was used to deal with the data of each pixel point by unilateral t-test (Ts: P=0.05), then, the regions showing increase/decrease of the glucose metabolism were obtained.Results:After acupuncture stimulation, significant increase of glucose metabolism was found to be in the first somatic motor cortical region (MI), supplementary motor area (SMA), premotor area (PMC), and the superior parietal lobule (LPs) on the healthy side of the brain; while the decrease of glucose metabolism found in MI, PMC and LPs on the focus side. In addition to the cerebral regions related to the motor function, changes of glucose metabolism were also found in the parietal lobule and basal ganglion area, central parietal gyrus, superior parietal gyrus, putamen, cerebellum, etc..Conclusion:Acupuncture of Qubin (GB 7) and Baihui (GV 20) can activate motor-related cerebral structures in the bilateral cerebral hemisphere and induce excitement reaction of the potentially correlative motor area so as to compensate or assist the injured motor area to play a role in improving motor function in stroke patients.

  5. Gender differences in age-related decline in regional cerebral glucose metabolism

    Energy Technology Data Exchange (ETDEWEB)

    Bang, Seong Ae; Cho, Sang Soo; Yoon, Eun Jin; Park, Hyun Soo; Lee, Eun Ju; Kim, Yu Kyeong; Kim, Sang Sun [Seoul National Univ. College of Medicine, Seoul (Korea, Republic of)

    2007-07-01

    In this study, we investigated gender differences in age-related declines in regional cerebral glucose