Science.gov

Sample records for aerobic glucose metabolism

  1. A new model for the aerobic metabolism of yeast allows the detailed analysis of the metabolic regulation during glucose pulse.

    PubMed

    Kesten, Duygu; Kummer, Ursula; Sahle, Sven; Hübner, Katrin

    2015-11-01

    The onset of aerobic fermentation (the so-called Crabtree effect) in yeast has long been of interest. However, the underlying mechanisms at the metabolic level are not yet fully understood. We developed a detailed kinetic model of the aerobic central metabolism of Saccharomyces cerevisiae comprising glycolysis, TCA cycle and major transport reactions across the mitochondrial membrane to investigate this phenomenon. It is the first one of this extent in the literature. The model is able to reproduce experimental steady state fluxes and time-course behavior after a glucose pulse. Due to the lack of parameter identifiability in the model, we analyze a model ensemble consisting of a set of differently parameterized models for robust findings. The model predicts that the cooperativity of pyruvate decarboxylase with respect to pyruvate and the capacity difference between alcohol dehydrogenase and the pyruvate dehydrogenase bypass play a major role for the onset of the Crabtree effect.

  2. Stimulation of human neutrophil leukocyte aerobic glucose metabolism by purified chemotactic factors.

    PubMed Central

    Goetzl, E J; Austen, K F

    1974-01-01

    The interaction of human neutrophils adherent to plastic petri dishes with the purified chemotactic factors C5a and kallikrein increased their rate of aerobic glycolysis 25-120% and the activity of their hexose monophosphate shunt (HMPS) 100-600%, reaching a plateau after 2 hr at 37 degrees C. The stimulation of either pathway required a chemotactically active stimulus since neither C5 nor prekallikrein or inactivated kallikrein could enhance metabolic activity. Marked suppression of the neutrophil chemotactic response by preincubation with a chemotactic factor to achieve deactivation, 5 x 10(-7) M diisopropyl fluorophosphate, or the neutrophil immobilizing factor (NIF) did not prevent the stimulation of HMPS activity or glycolysis by chemotactic factors. The metabolic inhibitors iodoacetate and 6-aminonicotinamide at concentrations which blocked enhancement of glycolysis or HMPS activity, respectively, partially suppressed the chemotactic response of neutrophils to the chemotactic factors. The capacity of a chemotactic factor to stimulate glucose metabolism of human neutrophils is associated with a maximal chemotactic response, but this stimulation is not alone sufficient for chemotaxis. Images PMID:11344574

  3. Transport and metabolism of fumaric acid in Saccharomyces cerevisiae in aerobic glucose-limited chemostat culture.

    PubMed

    Shah, Mihir V; van Mastrigt, Oscar; Heijnen, Joseph J; van Gulik, Walter M

    2016-04-01

    Currently, research is being focused on the industrial-scale production of fumaric acid and other relevant organic acids from renewable feedstocks via fermentation, preferably at low pH for better product recovery. However, at low pH a large fraction of the extracellular acid is present in the undissociated form, which is lipophilic and can diffuse into the cell. There have been no studies done on the impact of high extracellular concentrations of fumaric acid under aerobic conditions in S. cerevisiae, which is a relevant issue to study for industrial-scale production. In this work we studied the uptake and metabolism of fumaric acid in S. cerevisiae in glucose-limited chemostat cultures at a cultivation pH of 3.0 (pH < pK). Steady states were achieved with different extracellular levels of fumaric acid, obtained by adding different amounts of fumaric acid to the feed medium. The experiments were carried out with the wild-type S. cerevisiae CEN.PK 113-7D and an engineered S. cerevisiae ADIS 244 expressing a heterologous dicarboxylic acid transporter (DCT-02) from Aspergillus niger, to examine whether it would be capable of exporting fumaric acid. We observed that fumaric acid entered the cells most likely via passive diffusion of the undissociated form. Approximately two-thirds of the fumaric acid in the feed was metabolized together with glucose. From metabolic flux analysis, an increased ATP dissipation was observed only at high intracellular concentrations of fumarate, possibly due to the export of fumarate via an ABC transporter. The implications of our results for the industrial-scale production of fumaric acid are discussed.

  4. Comprehensive analysis of glucose and xylose metabolism in Escherichia coli under aerobic and anaerobic conditions by (13)C metabolic flux analysis.

    PubMed

    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.

  5. Global gene expression analysis of glucose overflow metabolism in Escherichia coli and reduction of aerobic acetate formation.

    PubMed

    Veit, Andrea; Polen, Tino; Wendisch, Volker F

    2007-02-01

    During aerobic growth on glucose, Escherichia coli produces acetate in the so-called overflow metabolism. DNA microarray analysis was used to determine the global gene expression patterns of chemostat cultivations of E. coli MG1655 that were characterized by different acetate formation rates during aerobic growth on glucose. A correlation analysis identified that expression of ten genes (sdhCDAB, sucB, sucC, acnB, lpdA, fumC and mdh) encoding the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase, succinyl-CoA synthetase, aconitase, fumarase and malate dehydrogenase, respectively, and of the acs-yjcH-actP operon for acetate utilization correlated negatively with acetate formation. Relieving transcriptional control of the sdhCDAB-b0725-sucABCD operon by chromosomal promoter exchange mutagenesis yielded a strain with increased specific activities of the TCA cycle enzymes succinate dehydrogenase, alpha-ketoglutarate dehydrogenase and succinyl-CoA synthetase, which are encoded by this operon. The resulting strain produced less acetate and directed more carbon towards carbon dioxide formation than the parent strain MG1655 while maintaining high growth and glucose consumption rates.

  6. A 12 week aerobic exercise program improves fitness, hepatic insulin sensitivity and glucose metabolism in obese Hispanic adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    The rise in obesity related morbidity in children and adolescents requires urgent prevention and treatment strategies. Strictly controlled exercise programs might be useful tools to improve insulin sensitivity and glucose kinetics. Our objective was to test the hypothesis that a 12-wk aerobic exerci...

  7. Aerobic Metabolism of Streptococcus agalactiae

    PubMed Central

    Mickelson, M. N.

    1967-01-01

    Streptococcus agalactiae cultures possess an aerobic pathway for glucose oxidation that is strongly inhibited by cyanide. The products of glucose oxidation by aerobically grown cells of S. agalactiae 50 are lactic and acetic acids, acetylmethylcarbinol, and carbon dioxide. Glucose degradation products by aerobically grown cells, as percentage of glucose carbon, were 52 to 61% lactic acid, 20 to 23% acetic acid, 5.5 to 6.5% acetylmethylcarbinol, and 14 to 16% carbon dioxide. There was no evidence for a pentose cycle or a tricarboxylic acid cycle. Crude cell-free extracts of S. agalactiae 50 possessed a strong reduced nicotinamide adenine dinucleotide (NADH2) oxidase that is also cyanide-sensitive. Dialysis or ultrafiltration of the crude, cell-free extract resulted in loss of NADH2 oxidase activity. Oxidase activity was restored to the inactive extract by addition of the ultrafiltrate or by addition of menadione or K3Fe(CN)6. Noncytochrome iron-containing pigments were present in cell-free extracts of S. agalactiae. The possible participation of these pigments in the respiration of S. agalactiae is presently being studied. PMID:4291090

  8. The Transition from Aerobic to Anaerobic Metabolism.

    ERIC Educational Resources Information Center

    Skinner, James S.; McLellan, Thomas H.

    1980-01-01

    The transition from aerobic to anaerobic metabolism is discussed. More research is needed on different kinds of athletes and athletic activities and how they may affect aerobic and anaerobic metabolisms. (CJ)

  9. Glucose metabolism and hyperglycemia.

    PubMed

    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 <7%. The measurement of the HbA1c concentration is considered the gold standard for assessing long-term glycemia; however, it does not reveal any information on the extent or frequency of blood glucose excursions, but provides an overall mean value only. Postprandial hyperglycemia occurs frequently in patients with diabetes receiving active treatment and can occur even when metabolic control is apparently good. Interventional studies indicate that reducing postmeal glucose excursions is as important as controlling fasting plasma glucose in persons with diabetes and impaired glucose tolerance. Evidence exists for a causal relation between postmeal glucose increases and microvascular and macrovascular outcomes; therefore, it is not surprising that treatment with different compounds that have specific effects on postprandial glucose 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.

  10. Liver glucose metabolism in humans

    PubMed Central

    Adeva-Andany, María M.; Pérez-Felpete, Noemi; Fernández-Fernández, Carlos; Donapetry-García, Cristóbal; Pazos-García, Cristina

    2016-01-01

    Information about normal hepatic glucose metabolism may help to understand pathogenic mechanisms underlying obesity and diabetes mellitus. In addition, liver glucose metabolism is involved in glycosylation reactions and connected with fatty acid metabolism. The liver receives dietary carbohydrates directly from the intestine via the portal vein. Glucokinase phosphorylates glucose to glucose 6-phosphate inside the hepatocyte, ensuring that an adequate flow of glucose enters the cell to be metabolized. Glucose 6-phosphate may proceed to several metabolic pathways. During the post-prandial period, most glucose 6-phosphate is used to synthesize glycogen via the formation of glucose 1-phosphate and UDP–glucose. Minor amounts of UDP–glucose are used to form UDP–glucuronate and UDP–galactose, which are donors of monosaccharide units used in glycosylation. A second pathway of glucose 6-phosphate metabolism is the formation of fructose 6-phosphate, which may either start the hexosamine pathway to produce UDP-N-acetylglucosamine or follow the glycolytic pathway to generate pyruvate and then acetyl-CoA. Acetyl-CoA may enter the tricarboxylic acid (TCA) cycle to be oxidized or may be exported to the cytosol to synthesize fatty acids, when excess glucose is present within the hepatocyte. Finally, glucose 6-phosphate may produce NADPH and ribose 5-phosphate through the pentose phosphate pathway. Glucose metabolism supplies intermediates for glycosylation, a post-translational modification of proteins and lipids that modulates their activity. Congenital deficiency of phosphoglucomutase (PGM)-1 and PGM-3 is associated with impaired glycosylation. In addition to metabolize carbohydrates, the liver produces glucose to be used by other tissues, from glycogen breakdown or from de novo synthesis using primarily lactate and alanine (gluconeogenesis). PMID:27707936

  11. Aerobic sugar metabolism in the spoilage yeast Zygosaccharomyces bailii.

    PubMed

    Merico, Annamaria; Capitanio, Daniele; Vigentini, Ileana; Ranzi, Bianca Maria; Compagno, Concetta

    2003-12-01

    Despite the importance of some Zygosaccharomyces species as agents causing spoilage of food, the carbon and energy metabolism of most of them is yet largely unknown. This is the case with Zygosaccharomyces bailii. In this study the occurrence of the Crabtree effect in the petite-negative yeast Z. bailii ATCC 36947 was investigated. In this yeast the aerobic ethanol production is strictly dependent on the carbon source utilised. In glucose-limited continuous cultures a very low level of ethanol was produced. In fructose-limited continuous cultures ethanol was produced at a higher level and its production increased with the dilution rate. As a consequence, on fructose the onset of respiro-fermentative metabolism caused a reduction in biomass yield. An immediate aerobic alcoholic fermentation in Z. bailii was observed during the transition from sugar limitation to sugar excess, both on glucose and on fructose. The analysis of some key enzymes of the fermentative metabolism showed a high level of acetyl-CoA synthetase in Z. bailii growing on fructose. At high dilution rates, the activities of glucose- and fructose-phosphorylating enzymes, as well as of pyruvate decarboxylase and alcohol dehydrogenase, were higher in cells during growth on fructose than on glucose.

  12. Antihypertensive drugs and glucose metabolism

    PubMed Central

    Rizos, Christos V; Elisaf, Moses S

    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 and β-blockers have an overall disadvantageous effect on glucose metabolism. Of note, carvedilol as well as nebivolol seem to differentiate themselves from the rest of the β-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. PMID:25068013

  13. Effect of Modified Atmosphere Composition on the Metabolism of Glucose by Brochothrix thermosphacta

    PubMed Central

    Pin, Carmen; García de Fernando, Gonzalo D.; Ordóñez, Juan A.

    2002-01-01

    The influence of atmosphere composition on the metabolism of Brochothrix thermosphacta was studied by analyzing the consumption of glucose and the production of ethanol, acetic and lactic acids, acetaldehyde, and diacetyl-acetoin under atmospheres containing different combinations of carbon dioxide and oxygen. When glucose was metabolized under oxygen-free atmospheres, lactic acid was one of the main end products, while under atmospheres rich in oxygen mainly acetoin-diacetyl was produced. The proportions of the total consumed glucose used for the production of acetoin (aerobic metabolism) and lactic acid (anaerobic metabolism) were used to decide whether aerobic or anaerobic metabolism predominated at a given atmosphere composition. The boundary conditions between dominantly anaerobic and aerobic metabolisms were determined by logistic regression. The metabolism of glucose by B. thermosphacta was influenced not only by the oxygen content of the atmosphere but also by the carbon dioxide content. At high CO2 percentages, glucose metabolism remained anaerobic under greater oxygen contents. PMID:12200298

  14. Effect of modified atmosphere composition on the metabolism of glucose by Brochothrix thermosphacta.

    PubMed

    Pin, Carmen; García de Fernando, Gonzalo D; Ordóñez, Juan A

    2002-09-01

    The influence of atmosphere composition on the metabolism of Brochothrix thermosphacta was studied by analyzing the consumption of glucose and the production of ethanol, acetic and lactic acids, acetaldehyde, and diacetyl-acetoin under atmospheres containing different combinations of carbon dioxide and oxygen. When glucose was metabolized under oxygen-free atmospheres, lactic acid was one of the main end products, while under atmospheres rich in oxygen mainly acetoin-diacetyl was produced. The proportions of the total consumed glucose used for the production of acetoin (aerobic metabolism) and lactic acid (anaerobic metabolism) were used to decide whether aerobic or anaerobic metabolism predominated at a given atmosphere composition. The boundary conditions between dominantly anaerobic and aerobic metabolisms were determined by logistic regression. The metabolism of glucose by B. thermosphacta was influenced not only by the oxygen content of the atmosphere but also by the carbon dioxide content. At high CO(2) percentages, glucose metabolism remained anaerobic under greater oxygen contents.

  15. Glucose metabolism and cardiac hypertrophy

    PubMed Central

    Kolwicz, Stephen C.; Tian, Rong

    2011-01-01

    The most notable change in the metabolic profile of hypertrophied hearts is an increased reliance on glucose with an overall reduced oxidative metabolism, i.e. a reappearance of the foetal metabolic pattern. In animal models, this change is attributed to the down-regulation of the transcriptional cascades promoting gene expression for fatty acid oxidation and mitochondrial oxidative phosphorylation in adult hearts. Impaired myocardial energetics in cardiac hypertrophy also triggers AMP-activated protein kinase (AMPK), leading to increased glucose uptake and glycolysis. Aside from increased reliance on glucose as an energy source, changes in other glucose metabolism pathways, e.g. the pentose phosphate pathway, the glucosamine biosynthesis pathway, and anaplerosis, are also noted in the hypertrophied hearts. Studies using transgenic mouse models and pharmacological compounds to mimic or counter the switch of substrate preference in cardiac hypertrophy have demonstrated that increased glucose metabolism in adult heart is not harmful and can be beneficial when it provides sufficient fuel for oxidative metabolism. However, improvement in the oxidative capacity and efficiency rather than the selection of the substrate is likely the ultimate goal for metabolic therapies. PMID:21502371

  16. Changes in Glucose and Glutamine Lymphocyte Metabolisms Induced by Type I Interferon α

    PubMed Central

    Navarro, Francisco; Bacurau, Aline V. N.; Vanzelli, Andréa; Meneguello-Coutinho, Marcela; Uchida, Marco C.; Moraes, Milton R.; Almeida, Sandro S.; Wasinski, Frederick; Barros, Carlos C.; Würtele, Martin; Araújo, Ronaldo C.; Costa Rosa, Luís F. B.; Bacurau, Reury F. P.

    2010-01-01

    In lymphocytes (LY), the well-documented antiproliferative effects of IFN-α are associated with inhibition of protein synthesis, decreased amino acid incorporation, and cell cycle arrest. However, the effects of this cytokine on the metabolism of glucose and glutamine in these cells have not been well investigated. Thus, mesenteric and spleen LY of male Wistar rats were cultured in the presence or absence of IFN-α, and the changes on glucose and glutamine metabolisms were investigated. The reduced proliferation of mesenteric LY was accompanied by a reduction in glucose total consumption (35%), aerobic glucose metabolism (55%), maximal activity of glucose-6-phosphate dehydrogenase (49%), citrate synthase activity (34%), total glutamine consumption (30%), aerobic glutamine consumption (20.3%) and glutaminase activity (56%). In LY isolated from spleen, IFNα also reduced the proliferation and impaired metabolism. These data demonstrate that in LY, the antiproliferative effects of IFNα are associated with a reduction in glucose and glutamine metabolisms. PMID:21234393

  17. Glucose metabolism in gastric cancer: The cutting-edge

    PubMed Central

    Yuan, Lian-Wen; Yamashita, Hiroharu; Seto, Yasuyuki

    2016-01-01

    Glucose metabolism in gastric cancer cells differs from that of normal epithelial cells. Upregulated aerobic glycolysis (Warburg effect) in gastric cancer meeting the demands of cell proliferation is associated with genetic mutations, epigenetic modification and proteomic alteration. Understanding the mechanisms of aerobic glycolysis may contribute to our knowledge of gastric carcinogenesis. Metabolomic studies offer novel, convenient and practical tools in the search for new biomarkers for early detection, diagnosis, prognosis, and chemosensitivity prediction of gastric cancer. Interfering with the process of glycolysis in cancer cells may provide a new and promising therapeutic strategy for gastric cancer. In this article, we present a brief review of recent studies of glucose metabolism in gastric cancer, with primary focus on the clinical applications of new biomarkers and their potential therapeutic role in gastric cancer. PMID:26877609

  18. Impact of early fructose intake on metabolic profile and aerobic capacity of rats

    PubMed Central

    2011-01-01

    Background Metabolic syndrome is a disease that today affects millions of people around the world. Therefore, it is of great interest to implement more effective procedures for preventing and treating this disease. In search of a suitable experimental model to study the role of exercise in prevention and treatment of metabolic syndrome, this study examined the metabolic profile and the aerobic capacity of rats kept early in life on a fructose-rich diet, a substrate that has been associated with metabolic syndrome. Methods We used adult female Wistar rats fed during pregnancy and lactation with two diets: balanced or fructose-rich 60%. During breastfeeding, the pups were distributed in small (4/mother) or adequate (8/mother) litters. At 90 days of age, they were analyzed with respect to: glucose tolerance, peripheral insulin sensitivity, aerobic capacity and serum glucose, insulin, triglycerides, total cholesterol, LDL cholesterol and HDL cholesterol concentrations as well as measures of glycogen synthesis and glucose oxidation by the soleus muscle. Results It was found that the fructose rich diet led the animals to insulin resistance. The fructose fed rats kept in small litters also showed dyslipidemia, with increased serum concentrations of total cholesterol and triglycerides. Conclusion Neither the aerobic capacity nor the glucose oxidation rates by the skeletal muscle were altered by fructose-rich diet, indicating that the animal model evaluated is potentially interesting for the study of the role of exercise in metabolic syndrome. PMID:21223589

  19. Oxidative metabolism: glucose versus ketones.

    PubMed

    Prince, Allison; Zhang, Yifan; Croniger, Colleen; Puchowicz, Michelle

    2013-01-01

    The coupling of upstream oxidative processes (glycolysis, beta-oxidation, CAC turnover) to mitochondrial oxidative phosphorylation (OXPHOS) under the driving conditions of energy demand by the cell results in the liberation of free energy as ATP. Perturbations in glycolytic CAC or OXPHOS can result in pathology or cell death. To better understand whole body energy expenditure during chronic ketosis, we used a diet-induced rat model of ketosis to determine if high-fat-carbohydrate-restricted "ketogenic" diet results in changes in total energy expenditure (TEE). Consistent with previous reports of increased energy expenditure in mice, we hypothesized that rats fed ketogenic diet for 3 weeks would result in increased resting energy expenditure due to alterations in metabolism associated with a "switch" in energy substrate from glucose to ketone bodies. The rationale is ketone bodies are a more efficient fuel than glucose. Indirect calorimetric analysis revealed a moderate increase in VO2 and decreased VCO2 and heat with ketosis. These results suggest ketosis induces a moderate uncoupling state and less oxidative efficiency compared to glucose oxidation.

  20. Sex steroids and glucose metabolism.

    PubMed

    Allan, Carolyn A

    2014-01-01

    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.

  1. Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress.

    PubMed

    Kim, Nam Hee; Cha, Yong Hoon; Lee, Jueun; Lee, Seon-Hyeong; Yang, Ji Hye; Yun, Jun Seop; Cho, Eunae Sandra; Zhang, Xianglan; Nam, Miso; Kim, Nami; Yuk, Young-Su; Cha, So Young; Lee, Yoonmi; Ryu, Joo Kyung; Park, Sunghyouk; Cheong, Jae-Ho; Kang, Sang Won; Kim, Soo-Youl; Hwang, Geum-Sook; Yook, Jong In; Kim, Hyun Sil

    2017-02-08

    Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial-mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP.

  2. Snail reprograms glucose metabolism by repressing phosphofructokinase PFKP allowing cancer cell survival under metabolic stress

    PubMed Central

    Kim, Nam Hee; Cha, Yong Hoon; Lee, Jueun; Lee, Seon-Hyeong; Yang, Ji Hye; Yun, Jun Seop; Cho, Eunae Sandra; Zhang, Xianglan; Nam, Miso; Kim, Nami; Yuk, Young-Su; Cha, So Young; Lee, Yoonmi; Ryu, Joo Kyung; Park, Sunghyouk; Cheong, Jae-Ho; Kang, Sang Won; Kim, Soo-Youl; Hwang, Geum-Sook; Yook, Jong In; Kim, Hyun Sil

    2017-01-01

    Dynamic regulation of glucose flux between aerobic glycolysis and the pentose phosphate pathway (PPP) during epithelial–mesenchymal transition (EMT) is not well-understood. Here we show that Snail (SNAI1), a key transcriptional repressor of EMT, regulates glucose flux toward PPP, allowing cancer cell survival under metabolic stress. Mechanistically, Snail regulates glycolytic activity via repression of phosphofructokinase, platelet (PFKP), a major isoform of cancer-specific phosphofructokinase-1 (PFK-1), an enzyme involving the first rate-limiting step of glycolysis. The suppression of PFKP switches the glucose flux towards PPP, generating NADPH with increased metabolites of oxidative PPP. Functionally, dynamic regulation of PFKP significantly potentiates cancer cell survival under metabolic stress and increases metastatic capacities in vivo. Further, knockdown of PFKP rescues metabolic reprogramming and cell death induced by loss of Snail. Thus, the Snail-PFKP axis plays an important role in cancer cell survival via regulation of glucose flux between glycolysis and PPP. PMID:28176759

  3. Circadian control of glucose metabolism.

    PubMed

    Kalsbeek, Andries; la Fleur, Susanne; Fliers, Eric

    2014-07-01

    The incidence of obesity and type 2 diabetes mellitus (T2DM) has risen to epidemic proportions. The pathophysiology of T2DM is complex and involves insulin resistance, pancreatic β-cell dysfunction and visceral adiposity. It has been known for decades that a disruption of biological rhythms (which happens the most profoundly with shift work) increases the risk of developing obesity and T2DM. Recent evidence from basal studies has further sparked interest in the involvement of daily rhythms (and their disruption) in the development of obesity and T2DM. Most living organisms have molecular clocks in almost every tissue, which govern rhythmicity in many domains of physiology, such as rest/activity rhythms, feeding/fasting rhythms, and hormonal secretion. Here we present the latest research describing the specific role played by the molecular clock mechanism in the control of glucose metabolism and speculate on how disruption of these tissue clocks may lead to the disturbances in glucose homeostasis.

  4. Exercise training reverses impaired skeletal muscle metabolism induced by artificial selection for low aerobic capacity

    PubMed Central

    Lessard, Sarah J.; Rivas, Donato A.; Stephenson, Erin J.; Yaspelkis, Ben B.; Koch, Lauren G.; Britton, Steven L.

    2011-01-01

    We have used a novel model of genetically imparted endurance exercise capacity and metabolic health to study the genetic and environmental contributions to skeletal muscle glucose and lipid metabolism. We hypothesized that metabolic abnormalities associated with low intrinsic running capacity would be ameliorated by exercise training. Selective breeding for 22 generations resulted in rat models with a fivefold difference in intrinsic aerobic capacity. Low (LCR)- and high (HCR)-capacity runners remained sedentary (SED) or underwent 6 wk of exercise training (EXT). Insulin-stimulated glucose transport, insulin signal transduction, and rates of palmitate oxidation were lower in LCR SED vs. HCR SED (P < 0.05). Decreases in glucose and lipid metabolism were associated with decreased β2-adrenergic receptor (β2-AR), and reduced expression of Nur77 target proteins that are critical regulators of muscle glucose and lipid metabolism [uncoupling protein-3 (UCP3), fatty acid transporter (FAT)/CD36; P < 0.01 and P < 0.05, respectively]. EXT reversed the impairments to glucose and lipid metabolism observed in the skeletal muscle of LCR, while increasing the expression of β2-AR, Nur77, GLUT4, UCP3, and FAT/CD36 (P < 0.05) in this tissue. However, no metabolic improvements were observed following exercise training in HCR. Our results demonstrate that metabolic impairments resulting from genetic factors (low intrinsic aerobic capacity) can be overcome by an environmental intervention (exercise training). Furthermore, we identify Nur77 as a potential mechanism for improved skeletal muscle metabolism in response to EXT. PMID:21048074

  5. Sirtuins in glucose and lipid metabolism

    PubMed Central

    Ye, Xin; Li, Meiting; Hou, Tianyun; Gao, Tian; Zhu, Wei-guo; Yang, Yang

    2017-01-01

    Sirtuins are evolutionarily conserved protein, serving as nicotinamide adenine dinucleotide-dependent deacetylases or adenosine diphosphate-ribosyltransferases. The mammalian sirtuins family, including SIRT1~7, is involved in many biological processes such as cell survival, proliferation, senescence, stress response, genome stability and metabolism. Evidence accumulated over the past two decades has indicated that sirtuins not only serve as important energy status sensors but also protect cells against metabolic stresses. In this review, we summarize the background of glucose and lipid metabolism concerning sirtuins and discuss the functions of sirtuins in glucose and lipid metabolism. We also seek to highlight the biological roles of certain sirtuins members in cancer metabolism. PMID:27659520

  6. Role of multifaceted regulators in cancer glucose metabolism and their clinical significance

    PubMed Central

    Zhao, Luqing; Mao, Yitao; Zhao, Yuelong; Cao, Ya; Chen, Xiang

    2016-01-01

    Aberrant glucose metabolism, “aerobic glycolysis” or “Warburg effect”, is a hallmark of human cancers. There is a cluster of “multifaceted regulators”, which plays a pivotal role in the regulation of glucose metabolism. They can not only modulate the activities of specific enzymes, but also act as transcriptional activators to regulate the expression of metabolism related genes. Additionally, they can crosstalk with other key factors involved in glucose metabolism and work together to initiate multiple oncogenic processes. These “multifaceted regulators”, especially p53, HIF-1, TIGAR and microRNA, will be focused in this review. And we will comprehensively illustrate their regulatory effects on cancer glucose metabolism, and further elaborate on their clinical significance. In-depth elucidation the role of “multifaceted regulators” in cancer glucose metabolism will provide us novel insights in cancer research field and offer promising therapeutic targets for anti-cancer therapies. PMID:26934324

  7. Glucose Transporters in Cardiac Metabolism and Hypertrophy

    PubMed Central

    Shao, Dan; Tian, Rong

    2016-01-01

    The heart is adapted to utilize all classes of substrates to meet the high-energy demand, and it tightly regulates its substrate utilization in response to environmental changes. Although fatty acids are known as the predominant fuel for the adult heart at resting stage, the heart switches its substrate preference toward glucose during stress conditions such as ischemia and pathological hypertrophy. Notably, increasing evidence suggests that the loss of metabolic flexibility associated with increased reliance on glucose utilization contribute to the development of cardiac dysfunction. The changes in glucose metabolism in hypertrophied hearts include altered glucose transport and increased glycolysis. Despite the role of glucose as an energy source, changes in other nonenergy producing pathways related to glucose metabolism, such as hexosamine biosynthetic pathway and pentose phosphate pathway, are also observed in the diseased hearts. This article summarizes the current knowledge regarding the regulation of glucose transporter expression and translocation in the heart during physiological and pathological conditions. It also discusses the signaling mechanisms governing glucose uptake in cardiomyocytes, as well as the changes of cardiac glucose metabolism under disease conditions. PMID:26756635

  8. Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis.

    PubMed

    Liu, T; Kishton, R J; Macintyre, A N; Gerriets, V A; Xiang, H; Liu, X; Abel, E D; Rizzieri, D; Locasale, J W; Rathmell, J C

    2014-10-16

    The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. In particular, a wide range of both solid and liquid tumors use aerobic glycolysis to supply energy and support cell growth. This metabolic program leads to high rates of glucose consumption through glycolysis with secretion of lactate even in the presence of oxygen. Identifying the limiting events in aerobic glycolysis and the response of cancer cells to metabolic inhibition is now essential to exploit this potential metabolic dependency. Here, we examine the role of glucose uptake and the glucose transporter Glut1 in the metabolism and metabolic stress response of BCR-Abl+ B-cell acute lymphoblastic leukemia cells (B-ALL). B-ALL cells were highly glycolytic and primary human B-ALL samples were dependent on glycolysis. We show B-ALL cells express multiple glucose transporters and conditional genetic deletion of Glut1 led to a partial loss of glucose uptake. This reduced glucose transport capacity, however, was sufficient to metabolically reprogram B-ALL cells to decrease anabolic and increase catabolic flux. Cell proliferation decreased and a limited degree of apoptosis was also observed. Importantly, Glut1-deficient B-ALL cells failed to accumulate in vivo and leukemic progression was suppressed by Glut1 deletion. Similarly, pharmacologic inhibition of aerobic glycolysis with moderate doses of 2-deoxyglucose (2-DG) slowed B-ALL cell proliferation, but extensive apoptosis only occurred at high doses. Nevertheless, 2-DG induced the pro-apoptotic protein Bim and sensitized B-ALL cells to the tyrosine kinase inhibitor Dasatinib in vivo. Together, these data show that despite expression of multiple glucose transporters, B-ALL cells are reliant on Glut1 to maintain aerobic glycolysis and anabolic metabolism. Further, partial inhibition of glucose metabolism is sufficient to sensitize cancer cells to specifically targeted therapies, suggesting

  9. Glucose transporter 1-mediated glucose uptake is limiting for B-cell acute lymphoblastic leukemia anabolic metabolism and resistance to apoptosis

    PubMed Central

    Liu, T; Kishton, R J; Macintyre, A N; Gerriets, V A; Xiang, H; Liu, X; Abel, E D; Rizzieri, D; Locasale, J W; Rathmell, J C

    2014-01-01

    The metabolic profiles of cancer cells have long been acknowledged to be altered and to provide new therapeutic opportunities. In particular, a wide range of both solid and liquid tumors use aerobic glycolysis to supply energy and support cell growth. This metabolic program leads to high rates of glucose consumption through glycolysis with secretion of lactate even in the presence of oxygen. Identifying the limiting events in aerobic glycolysis and the response of cancer cells to metabolic inhibition is now essential to exploit this potential metabolic dependency. Here, we examine the role of glucose uptake and the glucose transporter Glut1 in the metabolism and metabolic stress response of BCR-Abl+ B-cell acute lymphoblastic leukemia cells (B-ALL). B-ALL cells were highly glycolytic and primary human B-ALL samples were dependent on glycolysis. We show B-ALL cells express multiple glucose transporters and conditional genetic deletion of Glut1 led to a partial loss of glucose uptake. This reduced glucose transport capacity, however, was sufficient to metabolically reprogram B-ALL cells to decrease anabolic and increase catabolic flux. Cell proliferation decreased and a limited degree of apoptosis was also observed. Importantly, Glut1-deficient B-ALL cells failed to accumulate in vivo and leukemic progression was suppressed by Glut1 deletion. Similarly, pharmacologic inhibition of aerobic glycolysis with moderate doses of 2-deoxyglucose (2-DG) slowed B-ALL cell proliferation, but extensive apoptosis only occurred at high doses. Nevertheless, 2-DG induced the pro-apoptotic protein Bim and sensitized B-ALL cells to the tyrosine kinase inhibitor Dasatinib in vivo. Together, these data show that despite expression of multiple glucose transporters, B-ALL cells are reliant on Glut1 to maintain aerobic glycolysis and anabolic metabolism. Further, partial inhibition of glucose metabolism is sufficient to sensitize cancer cells to specifically targeted therapies, suggesting

  10. The Role of Glucose Metabolism and Glucose-Associated Signalling in Cancer

    PubMed Central

    Wittig, Rainer; Coy, Johannes F.

    2007-01-01

    Aggressive carcinomas ferment glucose to lactate even in the presence of oxygen. This particular metabolism, termed aerobic glycolysis, the glycolytic phenotype, or the Warburg effect, was discovered by Nobel laureate Otto Warburg in the 1920s. Since these times, controversial discussions about the relevance of the fermentation of glucose by tumours took place; however, a majority of cancer researchers considered the Warburg effect as a non-causative epiphenomenon. Recent research demonstrated, that several common oncogenic events favour the expression of the glycolytic phenotype. Moreover, a suppression of the phenotypic features by either substrate limitation, pharmacological intervention, or genetic manipulation was found to mediate potent tumour-suppressive effects. The discovery of the transketolase-like 1 (TKTL1) enzyme in aggressive cancers may deliver a missing link in the interpretation of the Warburg effect. TKTL1-activity could be the basis for a rapid fermentation of glucose in aggressive carcinoma cells via the pentose phosphate pathway, which leads to matrix acidification, invasive growth, and ultimately metastasis. TKTL1 expression in certain non-cancerous tissues correlates with aerobic formation of lactate and rapid fermentation of glucose, which may be required for the prevention of advanced glycation end products and the suppression of reactive oxygen species. There is evidence, that the activity of this enzyme and the Warburg effect can be both protective or destructive for the organism. These results place glucose metabolism to the centre of pathogenesis of several civilisation related diseases and raise concerns about the high glycaemic index of various food components commonly consumed in western diets. PMID:19812737

  11. Metabolic Effects of Aerobic Training and Resistance Training in Type 2 Diabetic Subjects

    PubMed Central

    Bacchi, Elisabetta; Negri, Carlo; Zanolin, Maria Elisabetta; Milanese, Chiara; Faccioli, Niccolò; Trombetta, Maddalena; Zoppini, Giacomo; Cevese, Antonio; Bonadonna, Riccardo C.; Schena, Federico; Bonora, Enzo; Lanza, Massimo; Moghetti, Paolo

    2012-01-01

    OBJECTIVE To assess differences between the effects of aerobic and resistance training on HbA1c (primary outcome) and several metabolic risk factors in subjects with type 2 diabetes, and to identify predictors of exercise-induced metabolic improvement. RESEARCH DESIGN AND METHODS Type 2 diabetic patients (n = 40) were randomly assigned to aerobic training or resistance training. Before and after 4 months of intervention, metabolic phenotypes (including HbA1c, glucose clamp–measured insulin sensitivity, and oral glucose tolerance test–assessed β-cell function), body composition by dual-energy X-ray absorptiometry, visceral (VAT) and subcutaneous (SAT) adipose tissue by magnetic resonance imaging, cardiorespiratory fitness, and muscular strength were measured. RESULTS After training, increase in peak oxygen consumption (VO2peak) was greater in the aerobic group (time-by-group interaction P = 0.045), whereas increase in strength was greater in the resistance group (time-by-group interaction P < 0.0001). HbA1c was similarly reduced in both groups (−0.40% [95% CI −0.61 to −0.18] vs. −0.35% [−0.59 to −0.10], respectively). Total and truncal fat, VAT, and SAT were also similarly reduced in both groups, whereas insulin sensitivity and lean limb mass were similarly increased. β-Cell function showed no significant changes. In multivariate analyses, improvement in HbA1c after training was independently predicted by baseline HbA1c and by changes in VO2peak and truncal fat. CONCLUSIONS Resistance training, similarly to aerobic training, improves metabolic features and insulin sensitivity and reduces abdominal fat in type 2 diabetic patients. Changes after training in VO2peak and truncal fat may be primary determinants of exercise-induced metabolic improvement. PMID:22344613

  12. Cellular hallmarks reveal restricted aerobic metabolism at thermal limits

    PubMed Central

    Neves, Aitana; Busso, Coralie; Gönczy, Pierre

    2015-01-01

    All organisms live within a given thermal range, but little is known about the mechanisms setting the limits of this range. We uncovered cellular features exhibiting signature changes at thermal limits in Caenorhabditis elegans embryos. These included changes in embryo size and shape, which were also observed in Caenorhabditis briggsae, indicating evolutionary conservation. We hypothesized that such changes could reflect restricted aerobic capacity at thermal limits. Accordingly, we uncovered that relative respiration in C. elegans embryos decreases at the thermal limits as compared to within the thermal range. Furthermore, by compromising components of the respiratory chain, we demonstrated that the reliance on aerobic metabolism is reduced at thermal limits. Moreover, embryos thus compromised exhibited signature changes in size and shape already within the thermal range. We conclude that restricted aerobic metabolism at the thermal limits contributes to setting the thermal range in a metazoan organism. DOI: http://dx.doi.org/10.7554/eLife.04810.001 PMID:25929283

  13. The immediate effects of a single bout of aerobic exercise on oral glucose tolerance across the glucose tolerance continuum

    PubMed Central

    Knudsen, Sine H.; Karstoft, Kristian; Pedersen, Bente K.; van Hall, Gerrit; Solomon, Thomas P. J.

    2014-01-01

    Abstract We investigated glucose tolerance and postprandial glucose fluxes immediately after a single bout of aerobic exercise in subjects representing the entire glucose tolerance continuum. Twenty‐four men with normal glucose tolerance (NGT), impaired glucose tolerance (IGT), or type 2 diabetes (T2D; age: 56 ± 1 years; body mass index: 27.8 ± 0.7 kg/m2, P > 0.05) underwent a 180‐min oral glucose tolerance test (OGTT) combined with constant intravenous infusion of [6,6‐2H2]glucose and ingestion of [U‐13C]glucose, following 1 h of exercise (50% of peak aerobic power) or rest. In both trials, plasma glucose concentrations and kinetics, insulin, C‐peptide, and glucagon were measured. Rates (mg kg−1 min−1) of glucose appearance from endogenous (RaEndo) and exogenous (oral glucose; RaOGTT) sources, and glucose disappearance (Rd) were determined. We found that exercise increased RaEndo, RaOGTT, and Rd (all P < 0.0001) in all groups with a tendency for a greater (~20%) peak RaOGTT value in NGT subjects when compared to IGT and T2D subjects. Accordingly, following exercise, the plasma glucose concentration during the OGTT was increased in NGT subjects (P < 0.05), while unchanged in subjects with IGT and T2D. In conclusion, while a single bout of moderate‐intensity exercise increased the postprandial glucose response in NGT subjects, glucose tolerance following exercise was preserved in the two hyperglycemic groups. Thus, postprandial plasma glucose responses immediately following exercise are dependent on the underlying degree of glycemic control. PMID:25168869

  14. Glucose metabolism in rat retinal pigment epithelium.

    PubMed

    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.

  15. MicroRNA 33 Regulates Glucose Metabolism

    PubMed Central

    Ramírez, Cristina M.; Goedeke, Leigh; Rotllan, Noemi; Yoon, Je-Hyun; Cirera-Salinas, Daniel; Mattison, Julie A.; Suárez, Yajaira; de Cabo, Rafael; Gorospe, Myriam

    2013-01-01

    Metabolic diseases are characterized by the failure of regulatory genes or proteins to effectively orchestrate specific pathways involved in the control of many biological processes. In addition to the classical regulators, recent discoveries have shown the remarkable role of small noncoding RNAs (microRNAs [miRNAs]) in the posttranscriptional regulation of gene expression. In this regard, we have recently demonstrated that miR-33a and miR33b, intronic miRNAs located within the sterol regulatory element-binding protein (SREBP) genes, regulate lipid metabolism in concert with their host genes. Here, we show that miR-33b also cooperates with SREBP1 in regulating glucose metabolism by targeting phosphoenolpyruvate carboxykinase (PCK1) and glucose-6-phosphatase (G6PC), key regulatory enzymes of hepatic gluconeogenesis. Overexpression of miR-33b in human hepatic cells inhibits PCK1 and G6PC expression, leading to a significant reduction of glucose production. Importantly, hepatic SREBP1c/miR-33b levels correlate inversely with the expression of PCK1 and G6PC upon glucose infusion in rhesus monkeys. Taken together, these results suggest that miR-33b works in concert with its host gene to ensure a fine-tuned regulation of lipid and glucose homeostasis, highlighting the clinical potential of miR-33a/b as novel therapeutic targets for a range of metabolic diseases. PMID:23716591

  16. Glucose and fructose metabolism in Zymomonas anaerobia

    PubMed Central

    McGill, D. J.; Dawes, E. A.

    1971-01-01

    Isotopic and enzymic evidence indicates that Zymomonas anaerobia ferments glucose via the Entner–Doudoroff pathway. The molar growth yields with glucose (5.89) and fructose (5.0) are lower than those for the related organism Zymomonas mobilis and the observed linear growth suggests that energetically uncoupled growth occurs. A survey of enzymes of carbohydrate metabolism revealed the presence of weak phosphofructokinase and fructose 1,6-diphosphate aldolase activities but phosphoketolase, transketolase and transaldolase were not detected. Fermentation balances for glucose and fructose are reported; acetaldehyde accumulated in both fermentations, to a greater extent with fructose which also yielded glycerol and dihydroxyacetone as minor products. PMID:4259336

  17. Toxic and inhibitory effects of trichloroethylene aerobic co-metabolism on phenol-grown aerobic granules.

    PubMed

    Zhang, Yi; Tay, JooHwa

    2015-04-09

    Aerobic granule, a form of microbial aggregate, exhibits good potential in degrading toxic and recalcitrant substances. In this study, the inhibitory and toxic effects of trichloroethylene (TCE), a model compound for aerobic co-metabolism, on phenol-grown aerobic granules were systematically studied, using respiratory activities after exposure to TCE as indicators. High TCE concentration did not exert positive or negative effects on the subsequent endogenous respiration rate or phenol dependent specific oxygen utilization rate (SOUR), indicating the absence of solvent stress and induction effect on phenol-hydroxylase. Phenol-grown aerobic granules exhibited a unique response to TCE transformation product toxicity, that small amount of TCE transformation enhanced the subsequent phenol SOUR. Granules that had transformed between 1.3 and 3.7 mg TCE gSS(-1) showed at most 53% increase in the subsequent phenol SOUR, and only when the transformation exceeded 6.6 mg TCE gSS(-1) did the SOUR dropped below that of the control. This enhancing effect was found to sustain throughout several phenol dosages, and TCE transformation below the toxicity threshold also lessened the granules' sensitivity to higher phenol concentration. The unique toxic effect was possibly caused by the granule's compact structure as a protection barrier against the diffusive transformation product(s) of TCE co-metabolism.

  18. Glucose metabolism in fish: a review.

    PubMed

    Polakof, Sergio; Panserat, Stéphane; Soengas, José L; Moon, Thomas W

    2012-12-01

    Teleost fishes represent a highly diverse group consisting of more than 20,000 species living across all aquatic environments. This group has significant economical, societal and environmental impacts, yet research efforts have concentrated primarily on salmonid and cyprinid species. This review examines carbohydrate/glucose metabolism and its regulation in these model species including the role of hormones and diet. Over the past decade, molecular tools have been used to address some of the downstream components of these processes and these are incorporated to better understand the roles played by carbohydrates and their regulatory paths. Glucose metabolism remains a contentious area as many fish species are traditionally considered glucose intolerant and, therefore, one might expect that the use and storage of glucose would be considered of minor importance. However, the actual picture is not so clear since the apparent intolerance of fish to carbohydrates is not evident in herbivorous and omnivorous species and even in carnivorous species, glucose is important for specific tissues and/or for specific activities. Thus, our aim is to up-date carbohydrate metabolism in fish, placing it to the context of these new experimental tools and its relationship to dietary intake. Finally, we suggest that new research directions ultimately will lead to a better understanding of these processes.

  19. A combined continuous and interval aerobic training improves metabolic syndrome risk factors in men

    PubMed Central

    Sari-Sarraf, Vahid; Aliasgarzadeh, Akbar; Naderali, Mohammad-Mahdi; Esmaeili, Hamid; Naderali, Ebrahim K

    2015-01-01

    Individuals with metabolic syndrome have significantly higher risk of cardiovascular disease and type 2 diabetes leading to premature death mortality. Metabolic syndrome has a complex etiology; thus, it may require a combined and multi-targeted aerobic exercise regimen to improve risk factors associated with it. Therefore, the aim of this study was to evaluate the effect of combined continuous and interval aerobic training on patients with metabolic syndrome. Thirty adult male with metabolic syndrome (54±8 years) were randomly divided into two groups: test training group (TTG; n=15) and control group (CG; n=15). Subjects in TTG performed combined continuous and interval aerobic training using a motorized treadmill three times per week for 16 weeks. Subjects in CG were advised to continue with their normal activities of life. Twenty-two men completed the study (eleven men in each group). At the end of the study, in TTG, there were significant (for all, P<0.05) reductions in total body weight (−3.2%), waist circumference (−3.43 cm), blood pressure (up to −12.7 mmHg), and plasma insulin, glucose, and triacylglyceride levels. Moreover, there were significant (for all, P<0.05) increases VO2max (−15.3%) and isometric strength of thigh muscle (28.1%) and high-density lipoprotein in TTG. None of the above indices were changed in CG at the end of 16-week study period. Our study suggests that adoption of a 16-week combined continuous and interval aerobic training regimen in men with metabolic syndrome could significantly reduce cardiovascular risk factors in these patients. PMID:26056487

  20. Thermodynamics of Microbial Growth Coupled to Metabolism of Glucose, Ethanol, Short-Chain Organic Acids, and Hydrogen ▿ †

    PubMed Central

    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

  1. Diabetes and Altered Glucose Metabolism with Aging

    PubMed Central

    Kalyani, Rita Rastogi; Egan, Josephine M.

    2013-01-01

    I. Synopsis Diabetes and impaired glucose tolerance affect a substantial proportion of older adults. While the aging process can be associated with alterations in glucose metabolism, including both relative insulin resistance and islet cell dysfunction, abnormal glucose metabolism is not a necessary component of aging. Instead, older adults with diabetes and altered glucose status likely represent a vulnerable subset of the population at high-risk for complications and adverse geriatric syndromes such as accelerated muscle loss, functional disability, frailty, and early mortality. Goals for treatment of diabetes in the elderly include control of hyperglycemia, prevention and treatment of diabetic complications, avoidance of hypoglycemia and preservation of quality of life. Given the heterogeneity of the elderly population with regards to the presence of comorbidities, life expectancy, and functional status, an individualized approach to diabetes management is often appropriate. A growing area of research seeks to explore associations of dysglycemia and insulin resistance with the development of adverse outcomes in the elderly and may ultimately inform guidelines on the use of future glucose-lowering therapies in this population. PMID:23702405

  2. Transcriptional Regulation of Aerobic Metabolism in Pichia pastoris Fermentation

    PubMed Central

    Zhang, Biao; Li, Baizhi; Chen, Dai; Zong, Jie; Sun, Fei; Qu, Huixin; Liang, Chongyang

    2016-01-01

    In this study, we investigated the classical fermentation process in Pichia pastoris based on transcriptomics. We utilized methanol in pichia yeast cell as the focus of our study, based on two key steps: limiting carbon source replacement (from glycerol to methonal) and fermentative production of exogenous proteins. In the former, the core differential genes in co-expression net point to initiation of aerobic metabolism and generation of peroxisome. The transmission electron microscope (TEM) results showed that yeast gradually adapted methanol induction to increased cell volume, and decreased density, via large number of peroxisomes. In the fermentative production of exogenous proteins, the Gene Ontology (GO) mapping results show that PAS_chr2-1_0582 played a vital role in regulating aerobic metabolic drift. In order to confirm the above results, we disrupted PAS_chr2-1_0582 by homologous recombination. Alcohol consumption was equivalent to one fifth of the normal control, and fewer peroxisomes were observed in Δ0582 strain following methanol induction. In this study we determined the important core genes and GO terms regulating aerobic metabolic drift in Pichia, as well as developing new perspectives for the continued development within this field. PMID:27537181

  3. Glucose intolerance, metabolic syndrome, and neuropathy.

    PubMed

    Cortez, Melissa; Singleton, J Robinson; Smith, A Gordon

    2014-01-01

    There is increasing evidence that impaired glucose tolerance (IGT) or metabolic syndrome may result in peripheral nerve injury, although the exact relationship between the conditions is still being characterized. There is animal model, epidemiologic, and clinical evidence to suggest a pathophysiologic relationship between neuropathy and metabolic syndrome, along with its components including obesity, dyslipidemia, and insulin resistance. IGT and metabolic syndrome are associated with subclinical nerve damage or are typically painful and sensory predominant, although autonomic involvement may also occur. Because there is often preferential small fiber injury and nerve conduction studies may be relatively insensitive, skin biopsy with assessment of intraepidermal nerve fiber density is often used to confirm the diagnosis. Treatment of metabolic syndrome and IGT-associated neuropathies should include diet and exercise counseling, maintenance of normoglycemia, and targeted pharmacologic therapy for modifiable risk factors. Further research is required to fully elucidate the complex pathophysiology, as well as identify optimal diagnostic and treatment approaches.

  4. Melatonin and glucose metabolism: clinical relevance.

    PubMed

    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.

  5. Regulation of Blood Glucose by Hypothalamic Pyruvate Metabolism

    NASA Astrophysics Data System (ADS)

    Lam, Tony K. T.; Gutierrez-Juarez, Roger; Pocai, Alessandro; Rossetti, Luciano

    2005-08-01

    The brain keenly depends on glucose for energy, and mammalians have redundant systems to control glucose production. An increase in circulating glucose inhibits glucose production in the liver, but this negative feedback is impaired in type 2 diabetes. Here we report that a primary increase in hypothalamic glucose levels lowers blood glucose through inhibition of glucose production in rats. The effect of glucose requires its conversion to lactate followed by stimulation of pyruvate metabolism, which leads to activation of adenosine triphosphate (ATP)-sensitive potassium channels. Thus, interventions designed to enhance the hypothalamic sensing of glucose may improve glucose homeostasis in diabetes.

  6. Berberine improves glucose metabolism through induction of glycolysis.

    PubMed

    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.

  7. Role of exercise intensity on GLUT4 content, aerobic fitness and fasting plasma glucose in type 2 diabetic mice.

    PubMed

    Cunha, Verusca Najara; de Paula Lima, Mérica; Motta-Santos, Daisy; Pesquero, Jorge Luiz; de Andrade, Rosangela Vieira; de Almeida, Jeeser Alves; Araujo, Ronaldo Carvalho; Grubert Campbell, Carmen Silvia; Lewis, John E; Simões, Herbert Gustavo

    2015-10-01

    Type 2 diabetes mellitus (T2D) results in several metabolic and cardiovascular dysfunctions, clinically characterized by hyperglycaemia due to lower glucose uptake and oxidation. Physical exercise is an effective intervention for glycaemic control. However, the effects of exercising at different intensities have not yet been addressed. The present study analysed the effects of 8 weeks of training performed at different exercise intensities on type 4 glucose transporters (GLUT4) content and glycaemic control of T2D (ob/ob) and non-diabetic mice (ob/OB). The animals were divided into six groups, with four groups being subjected either to low-intensity (ob/obL and ob/OBL: 3% body weight, three times/week/40 min) or high-intensity (ob/obH and ob/OBH: 6% body weight, three times per week per 20 min) swimming training. An incremental swimming test was performed to measure aerobic fitness. After the training intervention period, glycaemia and the content of GLUT4 were quantified. Although both training intensities were beneficial, the high-intensity regimen induced a more significant improvement in GLUT4 levels and glycaemic profile compared with sedentary controls (p < 0.05). Only animals in the high-intensity exercise group improved aerobic fitness. Thus, our study shows that high-intensity training was more effective for increasing GLUT4 content and glycaemia reduction in insulin-resistant mice, perhaps because of a higher metabolic demand imposed by this form of exercise.

  8. Impaired glucose metabolism in hypertensive patients.

    PubMed

    Fragachan, F; Perez-Acuña, F; Monsalve, P; Sanabria, A

    1990-01-01

    the free glucose pool at zero time. A significantly higher level was found in hypertensives with pathological Kg values, again indicating an impairment in glucose metabolism in this group: 90.6 +/- 26.5 vs. 65.0 +/- 5.4 g (p less than 0.0001). Another study showed an estimate of the mean cellular glucose uptake (MCUg) per minute and per kilogram body weight. The MCUg following glucose loading decreased considerably in hypertensives with pathological Kg values. The percentage reduction ranged between 50 and 55% hypertensives with pathological Kg values 4.1 +/- 0.8, and normotensives with normal Kg values, 8.0 +/- 0.6 (p less than 0.0001).(ABSTRACT TRUNCATED AT 400 WORDS)

  9. Aerobic exercise improves cognition for older adults with glucose intolerance, a risk factor for Alzheimer's disease.

    PubMed

    Baker, Laura D; Frank, Laura L; Foster-Schubert, Karen; Green, Pattie S; Wilkinson, Charles W; McTiernan, Anne; Cholerton, Brenna A; Plymate, Stephen R; Fishel, Mark A; Watson, G Stennis; Duncan, Glen E; Mehta, Pankaj D; Craft, Suzanne

    2010-01-01

    Impaired glucose regulation is a defining characteristic of type 2 diabetes mellitus (T2DM) pathology and has been linked to increased risk of cognitive impairment and dementia. Although the benefits of aerobic exercise for physical health are well-documented, exercise effects on cognition have not been examined for older adults with poor glucose regulation associated with prediabetes and early T2DM. Using a randomized controlled design, twenty-eight adults (57-83 y old) meeting 2-h tolerance test criteria for glucose intolerance completed 6 months of aerobic exercise or stretching, which served as the control. The primary cognitive outcomes included measures of executive function (Trails B, Task Switching, Stroop, Self-ordered Pointing Test, and Verbal Fluency). Other outcomes included memory performance (Story Recall, List Learning), measures of cardiorespiratory fitness obtained via maximal-graded exercise treadmill test, glucose disposal during hyperinsulinemic-euglycemic clamp, body fat, and fasting plasma levels of insulin, cortisol, brain-derived neurotrophic factor, insulin-like growth factor-1, amyloid-β (Aβ40 and Aβ42). Six months of aerobic exercise improved executive function (MANCOVA, p=0.04), cardiorespiratory fitness (MANOVA, p=0.03), and insulin sensitivity (p=0.05). Across all subjects, 6-month changes in cardiorespiratory fitness and insulin sensitivity were positively correlated (p=0.01). For Aβ42, plasma levels tended to decrease for the aerobic group relative to controls (p=0.07). The results of our study using rigorous controlled methodology suggest a cognition-enhancing effect of aerobic exercise for older glucose intolerant adults. Although replication in a larger sample is needed, our findings potentially have important therapeutic implications for a growing number of adults at increased risk of cognitive decline.

  10. Lactate is released and taken up by isolated rabbit vagus nerve during aerobic metabolism.

    PubMed

    Véga, C; Poitry-Yamate, C L; Jirounek, P; Tsacopoulos, M; Coles, J A

    1998-07-01

    To determine if lactate is produced during aerobic metabolism in peripheral nerve, we incubated pieces of rabbit vagus nerve in oxygenated solution containing D-[U-14C]glucose while stimulating electrically. After 30 min, nearly all the radioactivity in metabolites in the nerve was in lactate, glucose 6-phosphate, glutamate, and aspartate. Much lactate was released to the bath: 8.2 pmol (microg dry wt)(-1) from the exogenous glucose and 14.2 pmol (microg dry wt)(-1) from endogenous substrates. Lactate release was not increased when bath PO2 was decreased, indicating that it did not come from anoxic tissue. When the bath contained [U-14C]lactate at a total concentration of 2.13 mM and 1 mM glucose, 14C was incorporated in CO2 and glutamate. The initial rate of formation of CO2 from bath lactate was more rapid than its formation from bath glucose. The results are most readily explained by the hypothesis that has been proposed for brain tissue in which glial cells supply lactate to neurons.

  11. Focal adhesion kinase-promoted tumor glucose metabolism is associated with a shift of mitochondrial respiration to glycolysis.

    PubMed

    Zhang, J; Gao, Q; Zhou, Y; Dier, U; Hempel, N; Hochwald, S N

    2016-04-14

    Cancer cells often gains a growth advantage by taking up glucose at a high rate and undergoing aerobic glycolysis through intrinsic cellular factors that reprogram glucose metabolism. Focal adhesion kinase (FAK), a key transmitter of growth factor and anchorage stimulation, is aberrantly overexpressed or activated in most solid tumors, including pancreatic ductal adenocarcinomas (PDACs). We determined whether FAK can act as an intrinsic driver to promote aerobic glycolysis and tumorigenesis. FAK inhibition decreases and overexpression increases intracellular glucose levels during unfavorable conditions, including growth factor deficiency and cell detachment. Amplex glucose assay, fluorescence and carbon-13 tracing studies demonstrate that FAK promotes glucose consumption and glucose-to-lactate conversion. Extracellular flux analysis indicates that FAK enhances glycolysis and decreases mitochondrial respiration. FAK increases key glycolytic proteins, including enolase, pyruvate kinase M2 (PKM2), lactate dehydrogenase and monocarboxylate transporter. Furthermore, active/tyrosine-phosphorylated FAK directly binds to PKM2 and promotes PKM2-mediated glycolysis. On the other hand, FAK-decreased levels of mitochondrial complex I can result in reduced oxidative phosphorylation (OXPHOS). Attenuation of FAK-enhanced glycolysis re-sensitizes cancer cells to growth factor withdrawal, decreases cell viability and reduces growth of tumor xenografts. These observations, for the first time, establish a vital role of FAK in cancer glucose metabolism through alterations in the OXPHOS-to-glycolysis balance. Broadly targeting the common phenotype of aerobic glycolysis and more specifically FAK-reprogrammed glucose metabolism will disrupt the bioenergetic and biosynthetic supply for uncontrolled growth of tumors, particularly glycolytic PDAC.

  12. Anaerobic Metabolism: Linkages to Trace Gases and Aerobic Processes

    NASA Astrophysics Data System (ADS)

    Megonigal, J. P.; Hines, M. E.; Visscher, P. T.

    2003-12-01

    Life evolved and flourished in the absence of molecular oxygen (O2). As the O2 content of the atmosphere rose to the present level of 21% beginning about two billion years ago, anaerobic metabolism was gradually supplanted by aerobic metabolism. Anaerobic environments have persisted on Earth despite the transformation to an oxidized state because of the combined influence of water and organic matter. Molecular oxygen diffuses about 104 times more slowly through water than air, and organic matter supports a large biotic O2 demand that consumes the supply faster than it is replaced by diffusion. Such conditions exist in wetlands, rivers, estuaries, coastal marine sediments, aquifers, anoxic water columns, sewage digesters, landfills, the intestinal tracts of animals, and the rumen of herbivores. Anaerobic microsites are also embedded in oxic environments such as upland soils and marine water columns. Appreciable rates of aerobic respiration are restricted to areas that are in direct contact with air or those inhabited by organisms that produce O2.Rising atmospheric O2 reduced the global area of anaerobic habitat, but enhanced the overall rate of anaerobic metabolism (at least on an area basis) by increasing the supply of electron donors and acceptors. Organic carbon production increased dramatically, as did oxidized forms of nitrogen, manganese, iron, sulfur, and many other elements. In contemporary anaerobic ecosystems, nearly all of the reducing power is derived from photosynthesis, and most of it eventually returns to O2, the most electronegative electron acceptor that is abundant. This photosynthetically driven redox gradient has been thoroughly exploited by aerobic and anaerobic microorganisms for metabolism. The same is true of hydrothermal vents (Tunnicliffe, 1992) and some deep subsurface environments ( Chapelle et al., 2002), where thermal energy is the ultimate source of the reducing power.Although anaerobic habitats are currently a small fraction of Earth

  13. Disturbance of aerobic metabolism accompanies neurobehavioral changes induced by nickel in mice.

    PubMed

    He, Min-Di; Xu, Shang-Cheng; Zhang, Xin; Wang, Yan; Xiong, Jia-Chuan; Zhang, Xiao; Lu, Yong-Hui; Zhang, Lei; Yu, Zheng-Ping; Zhou, Zhou

    2013-09-01

    The oral ingestion of soluble nickel compounds leads to neurological symptoms in humans. Deficiencies in aerobic metabolism induced by neurotoxic stimulus can cause an energy crisis in the brain that results in a variety of neurotoxic effects. In the present study, we focused on the aerobic metabolic states to investigate whether disturbance of aerobic metabolism was involved in nickel-induced neurological effects in mice. Mice were orally administered nickel chloride, and neurobehavioral performance was evaluated using the Morris water maze and open field tests at different time points. Aerobic metabolic states in the cerebral cortex were analyzed at the same time points at which neurobehavioral changes were evident. We found that nickel exposure caused deficits in both spatial memory and exploring activity in mice and that nickel was deposited in their cerebral cortex. Deficient aerobic metabolism manifested as decreased O2 consumption and ATP concentrations, lactate and NADH accumulation, and oxidative stress. Meanwhile, the activity of prototypical iron-sulfur clusters (ISCs) containing enzymes that are known to control aerobic metabolism, including complex I and aconitase, and the expression of ISC assembly scaffold protein (ISCU) were inhibited following nickel deposition. Overall, these data suggest that aerobic metabolic disturbances, which accompanied the neurobehavioral changes, may participate in nickel-induced neurologic effects. The inactivation of ISC containing metabolic enzymes may result in the disturbance of aerobic metabolism. A better understanding of how nickel impacts the energy metabolic processes may provide insight into the prevention of nickel neurotoxicity.

  14. Targeting glucose metabolism for healthy aging

    PubMed Central

    Brewer, Rachel A.; Gibbs, Victoria K.; Smith, Daniel L.

    2016-01-01

    Advancing age is the greatest single risk factor for numerous chronic diseases. Thus, the ability to target the aging process can facilitate improved healthspan and potentially lifespan. Lack of adequate glucoregulatory control remains a recurrent theme accompanying aging and chronic disease, while numerous longevity interventions result in maintenance of glucoregulatory control. In this review, we propose targeting glucose metabolism to enhance regulatory control as a means to ameliorate the aging process. We highlight that calorie restriction improves glucoregulatory control and extends both lifespan and healthspan in model organisms, but we also indicate more practical interventions (i.e., calorie restriction mimetics) are desirable for clinical application in humans. Of the calorie restriction mimetics being investigated, we focus on the type 2 diabetes drug acarbose, an α-glucosidase inhibitor that when taken with a meal, results in reduced enzymatic degradation and absorption of glucose from complex carbohydrates. We discuss alternatives to acarbose that yield similar physiologic effects and describe dietary sources (e.g., sweet potatoes, legumes, and berries) of bioactive compounds with α-glucosidase inhibitory activity. We indicate future research should include exploration of how non-caloric compounds like α-glucosidase inhibitors modify macronutrient metabolism prior to disease onset, which may guide nutritional/lifestyle interventions to support health and reduce age-related disease risk. PMID:28035340

  15. Glucose metabolism in different regions of the rat brain under hypokinetic stress influence

    NASA Technical Reports Server (NTRS)

    Konitzer, K.; Voigt, S.

    1980-01-01

    Glucose metabolism in rats kept under long term hypokinetic stress was studied in 7 brain regions. Determination was made of the regional levels of glucose, lactate, glutamate, glutamine, aspartate, gamma-aminobutyrate and the incorporation of C-14 from plasma glucose into these metabolites, in glycogen and protein. From the content and activity data the regional glucose flux was approximated quantitatively. Under normal conditions the activity gradient cortex and frontal pole cerebellum, thalamus and mesencephalon, hypothalamus and pons and medulla is identical with that of the regional blood supply (measured with I131 serum albumin as the blood marker). Within the first days of immobilization a functional hypoxia occurred in all brain regions and the utilization of cycle amino acids for protein synthesis was strongly diminished. After the first week of stress the capillary volumes of all regions increased, aerobic glucose metabolism was enhanced (factors 1.3 - 2.0) and the incorporation of glucose C-14 via cycle amino acids into protein was considerably potentiated. The metabolic parameters normalized between the 7th and 11th week of stress. Blood supply and metabolic rate increased most in the hypothalamus.

  16. Acute effects of aerobic exercise intensity on arterial stiffness after glucose ingestion in young men.

    PubMed

    Kobayashi, Ryota; Hashimoto, Yuto; Hatakeyama, Hiroyuki; Okamoto, Takanobu

    2016-10-18

    Arterial stiffness increases after glucose ingestion. Acute low- and moderate-intensity aerobic exercise decreases arterial stiffness. However, the acute effects of 30 min of cycling at low- and moderate-intensity [25% (LE trial) and 65% (ME trial) peak oxygen uptake, respectively] on arterial stiffness at 30, 60 and 120 min of a postexercise glucose ingestion. Ten healthy young men (age, 22·4 ± 0·5 years) performed LE and ME trials on separate days in a randomized controlled crossover fashion. Carotid-femoral (aortic) pulse wave velocity (PWV), femoral-ankle (leg) PWV, carotid augmentation index (AIx) and carotid blood pressure (BP) (applanation tonometry), brachial and ankle BP (oscillometric device), heart rate (HR) (electrocardiography), blood glucose (UV-hexokinase method) and blood insulin (CLEIA method) levels were measured at before (baseline) and at 30, 60 and 120 min after the 75-g OGTT. Leg PWV, ankle pulse pressure and BG levels significantly increased from baseline after the 75-g OGTT in the LE trial (P<0·05), but not in the ME trial. Insulin levels and HR significantly increased from baseline after the 75-g OGTT in both trials (P<0·05). Aortic PWV, carotid AIx, brachial BP and carotid BP did not change from baseline after the 75-g OGTT in both trials. The present findings indicate that aerobic exercise at moderate intensity before glucose ingestion suppresses increases leg arterial stiffness after glucose ingestion.

  17. Brain areas and pathways in the regulation of glucose metabolism.

    PubMed

    Diepenbroek, Charlene; Serlie, Mireille J; Fliers, Eric; Kalsbeek, Andries; la Fleur, Susanne E

    2013-01-01

    Glucose is the most important source of fuel for the brain and its concentration must be kept within strict boundaries to ensure the organism's optimal fitness. To maintain glucose homeostasis, an optimal balance between glucose uptake and glucose output is required. Besides managing acute changes in plasma glucose concentrations, the brain controls a daily rhythm in glucose concentrations. The various nuclei within the hypothalamus that are involved in the control of both these processes are well known. However, novel studies indicate an additional role for brain areas that are originally appreciated in other processes than glucose metabolism. Therefore, besides the classic hypothalamic pathways, we will review cortico-limbic brain areas and their role in glucose metabolism.

  18. Advances in glucose metabolism research in colorectal cancer

    PubMed Central

    Fang, Sitian; Fang, Xiao

    2016-01-01

    Cancer cells uptake glucose at a higher rate and produce lactic acid rather than metabolizing pyruvate through the tricarboxylic acid cycle. This adaptive metabolic shift is termed the Warburg effect. Recently progress had been made regarding the mechanistic understanding of glucose metabolism and associated diagnostic and therapeutic methods, which have been investigated in colorectal cancer. The majority of novel mechanisms involve important glucose metabolism associated genes and miRNA regulation. The present review discusses the contribution of these research results to facilitate with the development of novel diagnosis and anticancer treatment options. PMID:27602209

  19. The metabolic impact of extracellular nitrite on aerobic metabolism of Paracoccus denitrificans.

    PubMed

    Hartop, K R; Sullivan, M J; Giannopoulos, G; Gates, A J; Bond, P L; Yuan, Z; Clarke, T A; Rowley, G; Richardson, D J

    2017-02-07

    Nitrite, in equilibrium with free nitrous acid (FNA), can inhibit both aerobic and anaerobic growth of microbial communities through bactericidal activities that have considerable potential for control of microbial growth in a range of water systems. There has been much focus on the effect of nitrite/FNA on anaerobic metabolism and so, to enhance understanding of the metabolic impact of nitrite/FNA on aerobic metabolism, a study was undertaken with a model denitrifying bacterium Paracoccus denitrificans PD1222. Extracellular nitrite inhibits aerobic growth of P. denitrificans in a pH-dependent manner that is likely to be a result of both nitrite and free nitrous acid (pKa = 3.25) and subsequent reactive nitrogen oxides generated from the intracellular passage of FNA into P. denitrificans. Increased expression of a gene encoding a flavohemoglobin protein (Fhp) (Pden_1689) was observed in response to extracellular nitrite. Construction and analysis of a deletion mutant established Fhp to be involved in endowing nitrite/FNA resistance at high extracellular nitrite concentrations. Global transcriptional analysis confirmed nitrite-dependent expression of fhp and indicated that P. denitrificans expressed a number of stress response systems associated with protein, DNA and lipid repair. It is therefore suggested that nitrite causes a pH-dependent stress response that is due to the production of associated reactive nitrogen species, such as nitric oxide from the internalisation of FNA.

  20. Glucose metabolic gene expression in growth hormone transgenic coho salmon.

    PubMed

    Panserat, Stéphane; Kamalam, Biju Sam; Fournier, Jeanne; Plagnes-Juan, Elisabeth; Woodward, Krista; Devlin, Robert H

    2014-04-01

    Salmonids are generally known to be glucose intolerant. However, previous studies have shown that growth hormone (GH) transgenic coho salmon display modified nutritional regulation of glycolysis and lipogenesis compared to non-transgenic fish, suggesting the potential for better use of glucose in GH transgenic fish. To examine this in detail, GH transgenic and non-transgenic coho salmon were subjected to glucose tolerance test and subsequent metabolic assessments. After intra-peritoneal injection of 250mg/kg glucose, we analysed post-injection kinetics of glycaemia and expression of several key target genes highly involved in glucose homeostasis in muscle and liver tissues. Our data show no significant differences in plasma glucose levels during peak hyperglycaemia (3-6h after injection), demonstrating a similar glucose tolerance between transgenic and non transgenic. However, and unrelated to the hyperglycaemic episode, GH transgenic fish return to a slightly lower basal glycaemia values 24h after injection. Correspondingly, GH transgenic fish exhibited higher mRNA levels of glucokinase (GK) and glucose-6-phosphate dehydrogenase (G6PDH) in liver, and glucose transporter (GLUT4) in muscle. These data suggest that these metabolic actors may be involved in different glucose use in GH transgenic fish, which would be expected to influence the glucose challenge response. Overall, our data demonstrate that GH transgenic coho salmon may be a pertinent animal model for further study of glucose metabolism in carnivorous fish.

  1. Metabolic effects of glycerol supplementation and aerobic physical training on Wistar rats.

    PubMed

    Andrade, Eric Francelino; Lobato, Raquel Vieira; Araújo, Ticiana Vasques; Orlando, Débora Ribeiro; Gomes, Núbia Ferreira; Alvarenga, Renata Ribeiro; Rogatto, Gustavo Puggina; Zangeronimo, Márcio Gilberto; Pereira, Luciano José

    2014-09-01

    We evaluated the effects of oral glycerol supplementation on trained rats fed a normal diet. Wistar rats were distributed among 6 groups in a completely randomized 2 × 3 factorial design. The animals were subjected to 6 weeks of aerobic training. In the last 4 weeks, the animals' diet was supplemented with saline, glucose, or glycerol. Data were subjected to one-way analysis of variance (ANOVA) followed by a Student-Newmann-Keuls test, with values for P < 0.05 considered statistically significant. The change in body mass was lower in the trained groups, and their food and water consumption were higher. Glycerol supplementation resulted in an increase in the levels of triacylglycerol (TAG) and total cholesterol, as well as in the area and diameter of adipocytes. When associated with training, these parameters were similar to those of other trained groups. Levels of low-density lipoprotein + very-low-density lipoprotein cholesterol decreased in the trained animals that received glycerol compared with the non-trained ones. Glycerol consumption caused a reduction in food intake and increased the villous:crypt (V:C) ratio. No changes in glycemia, high density lipoproteins, or density of adipocytes were observed. Supplementation with glycerol together with aerobic physical training promoted beneficial metabolic effects. However, in non-trained rats glycerol increased the diameter and area of adipocytes, as well as the levels of TAG and total cholesterol.

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

    PubMed

    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.

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

    PubMed

    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.

  4. Proteome analysis of aerobic and fermentative metabolism in Rhizobium etli CE3.

    PubMed

    Encarnación, Sergio; Guzmán, Yudith; Dunn, Michael F; Hernández, Magdalena; del Carmen Vargas, Maria; Mora, Jaime

    2003-06-01

    Rhizobium etli undergoes a transition from an aerobic to a fermentative metabolism during successive subcultures in minimal medium. This metabolic transition does not occur in cells subcultured in rich medium, or in minimal medium containing either biotin or thiamine. In this report, we characterize the aerobic and fermentative metabolism of R. etli using proteome analysis. According to their synthesis patterns in response to aerobic (rich medium, minimal medium with biotin or minimal medium with thiamine) or fermentative (minimal medium without supplements) growth conditions, proteins were assigned to five different classes: (i) proteins produced only in aerobic conditions (e.g., catalase-peroxidase KatG and the E2 component of pyruvate dehydrogenase); (ii) protein produced under both conditions but strongly induced in aerobic metabolism (e.g., malate dehydrogenase and the succinyl-CoA synthetase beta subunit); (iii) proteins that were induced equally under all conditions tested (e.g., AniA, DnaK, and GroEL); (iv) proteins downregulated during aerobic metabolism, and (v) proteins specific to only one of the conditions analyzed. Northern blotting studies of katG expression confirmed the proteome data for this protein. The negative regulation of carbon metabolism proteins observed in fermentative metabolism is consistent with the drastic physiological changes which occur during this process.

  5. Cell based metabolic barriers to glucose diffusion: macrophages and continuous glucose monitoring.

    PubMed

    Klueh, Ulrike; Frailey, Jackman T; Qiao, Yi; Antar, Omar; Kreutzer, Donald L

    2014-03-01

    It is assumed that MQ are central to glucose sensor bio-fouling and therefore have a major negative impact on continuous glucose monitoring (CGM) performance in vivo. However to our knowledge there is no data in the literature to directly support or refute this assumption. Since glucose and oxygen (O2) are key to glucose sensor function in vivo, understanding and controlling glucose and O2 metabolic activity of MQ is likely key to successful glucose sensor performance. We hypothesized that the accumulation of MQ at the glucose sensor-tissue interface will act as "Cell Based Metabolic Barriers" (CBMB) to glucose diffusing from the interstitial tissue compartment to the implanted glucose sensor and as such creating an artificially low sensor output, thereby compromising sensor function and CGM. Our studies demonstrated that 1) direct injections of MQ at in vivo sensor implantation sites dramatically decreased sensor output (measured in nA), 2) addition of MQ to glucose sensors in vitro resulted in a rapid and dramatic fall in sensor output and 3) lymphocytes did not affect sensor function in vitro or in vivo. These data support our hypothesis that MQ can act as metabolic barriers to glucose and O2 diffusion in vivo and in vitro.

  6. Regulators of Glucose Metabolism in CD4(+) and CD8(+) T Cells.

    PubMed

    Palmer, Clovis S; Hussain, Tabinda; Duette, Gabriel; Weller, Thomas J; Ostrowski, Matias; Sada-Ovalle, Isabel; Crowe, Suzanne M

    2016-11-01

    Much like cancer cells, activated T cells undergo various metabolic changes that allow them to grow and proliferate rapidly. By adopting aerobic glycolysis upon activation, T cells effectively prioritize efficiency in biosynthesis over energy generation. There are distinct differences in the way CD4(+) and CD8(+) T cells process activation signals. CD8(+) effector T cells are less dependent on Glut1 and oxygen levels compared to their CD4(+) counterparts. Similarly the downstream signaling by TCR also differs in both effector T cell types. Recent studies have explored PI3K/Akt, mTORC, HIF1α, p70S6K and Bcl-6 signaling in depth providing definition of the crucial roles of these regulators in glucose metabolism. These new insights may allow improved therapeutic manipulation against inflammatory conditions that are associated with dysfunctional T-cell metabolism such as autoimmune disorders, metabolic syndrome, HIV, and cancers.

  7. Aerobic fermentation of D-glucose by an evolved cytochrome oxidase-deficient Escherichia coli strain.

    PubMed

    Portnoy, Vasiliy A; Herrgård, Markus J; Palsson, Bernhard Ø

    2008-12-01

    Fermentation of glucose to D-lactic acid under aerobic growth conditions by an evolved Escherichia coli mutant deficient in three terminal oxidases is reported in this work. Cytochrome oxidases (cydAB, cyoABCD, and cbdAB) were removed from the E. coli K12 MG1655 genome, resulting in the ECOM3 (E. coli cytochrome oxidase mutant) strain. Removal of cytochrome oxidases reduced the oxygen uptake rate of the knockout strain by nearly 85%. Moreover, the knockout strain was initially incapable of growing on M9 minimal medium. After the ECOM3 strain was subjected to adaptive evolution on glucose M9 medium for 60 days, a growth rate equivalent to that of anaerobic wild-type E. coli was achieved. Our findings demonstrate that three independently adaptively evolved ECOM3 populations acquired different phenotypes: one produced lactate as a sole fermentation product, while the other two strains exhibited a mixed-acid fermentation under oxic growth conditions with lactate remaining as the major product. The homofermenting strain showed a D-lactate yield of 0.8 g/g from glucose. Gene expression and in silico model-based analyses were employed to identify perturbed pathways and explain phenotypic behavior. Significant upregulation of ygiN and sodAB explains the remaining oxygen uptake that was observed in evolved ECOM3 strains. E. coli strains produced in this study showed the ability to produce lactate as a fermentation product from glucose and to undergo mixed-acid fermentation during aerobic growth.

  8. Akkermansia muciniphila mediates negative effects of IFNγ on glucose metabolism

    PubMed Central

    Greer, Renee L.; Dong, Xiaoxi; Moraes, Ana Carolina F.; Zielke, Ryszard A.; Fernandes, Gabriel R.; Peremyslova, Ekaterina; Vasquez-Perez, Stephany; Schoenborn, Alexi A.; Gomes, Everton P.; Pereira, Alexandre C.; Ferreira, Sandra R. G.; Yao, Michael; Fuss, Ivan J.; Strober, Warren; Sikora, Aleksandra E.; Taylor, Gregory A.; Gulati, Ajay S.; Morgun, Andrey; Shulzhenko, Natalia

    2016-01-01

    Cross-talk between the gut microbiota and the host immune system regulates host metabolism, and its dysregulation can cause metabolic disease. Here, we show that the gut microbe Akkermansia muciniphila can mediate negative effects of IFNγ on glucose tolerance. In IFNγ-deficient mice, A. muciniphila is significantly increased and restoration of IFNγ levels reduces A. muciniphila abundance. We further show that IFNγ-knockout mice whose microbiota does not contain A. muciniphila do not show improvement in glucose tolerance and adding back A. muciniphila promoted enhanced glucose tolerance. We go on to identify Irgm1 as an IFNγ-regulated gene in the mouse ileum that controls gut A. muciniphila levels. A. muciniphila is also linked to IFNγ-regulated gene expression in the intestine and glucose parameters in humans, suggesting that this trialogue between IFNγ, A. muciniphila and glucose tolerance might be an evolutionally conserved mechanism regulating metabolic health in mice and humans. PMID:27841267

  9. Glucose metabolism in pregnant sheep when placental growth is restricted

    SciTech Connect

    Owens, J.A.; Falconer, J.; Robinson, J.S. )

    1989-08-01

    The effect of restricting placental growth on glucose metabolism in pregnant sheep in late gestation was determined by primed constant infusions of D-(U-{sup 14}C)- and D-(2-{sup 3}H)glucose and antipyrine into fetuses of six control sheep and six sheep from which endometrial caruncles had been removed before pregnancy (caruncle sheep). In the latter, placental and fetal weights were reduced, as was the concentration of glucose in fetal arterial blood. Fetal glucose turnover in caruncle sheep was only 52-59% of that in controls, largely because of lower umbilical loss of glucose back to the placenta (38-39% of control) and lower fetal glucose utilization (61-74% of control). However, fetal glucose utilization on a weight-specific basis was similar in control and caruncle sheep. Significant endogenous glucose production occurred in control and caruncle fetal sheep. Maternal glucose production and partition of glucose between the gravid uterus and other maternal tissues were similar in control and caruncle sheep. In conclusion, when placental and fetal growth are restricted, fetal glucose utilization is maintained by reduced loss of glucose back to the placenta and mother and by maintaining endogenous glucose production.

  10. Exenatide Regulates Cerebral Glucose Metabolism in Brain Areas Associated With Glucose Homeostasis and Reward System.

    PubMed

    Daniele, Giuseppe; Iozzo, Patricia; Molina-Carrion, Marjorie; Lancaster, Jack; Ciociaro, Demetrio; Cersosimo, Eugenio; Tripathy, Devjit; Triplitt, Curtis; Fox, Peter; Musi, Nicolas; DeFronzo, Ralph; Gastaldelli, Amalia

    2015-10-01

    Glucagon-like peptide 1 receptors (GLP-1Rs) have been found in the brain, but whether GLP-1R agonists (GLP-1RAs) influence brain glucose metabolism is currently unknown. The study aim was to evaluate the effects of a single injection of the GLP-1RA exenatide on cerebral and peripheral glucose metabolism in response to a glucose load. In 15 male subjects with HbA1c of 5.7 ± 0.1%, fasting glucose of 114 ± 3 mg/dL, and 2-h glucose of 177 ± 11 mg/dL, exenatide (5 μg) or placebo was injected in double-blind, randomized fashion subcutaneously 30 min before an oral glucose tolerance test (OGTT). The cerebral glucose metabolic rate (CMRglu) was measured by positron emission tomography after an injection of [(18)F]2-fluoro-2-deoxy-d-glucose before the OGTT, and the rate of glucose absorption (RaO) and disposal was assessed using stable isotope tracers. Exenatide reduced RaO0-60 min (4.6 ± 1.4 vs. 13.1 ± 1.7 μmol/min ⋅ kg) and decreased the rise in mean glucose0-60 min (107 ± 6 vs. 138 ± 8 mg/dL) and insulin0-60 min (17.3 ± 3.1 vs. 24.7 ± 3.8 mU/L). Exenatide increased CMRglu in areas of the brain related to glucose homeostasis, appetite, and food reward, despite lower plasma insulin concentrations, but reduced glucose uptake in the hypothalamus. Decreased RaO0-60 min after exenatide was inversely correlated to CMRglu. In conclusion, these results demonstrate, for the first time in man, a major effect of a GLP-1RA on regulation of brain glucose metabolism in the absorptive state.

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

    SciTech Connect

    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.

  12. Metabolic reprogramming towards aerobic glycolysis correlates with greater proliferative ability and resistance to metabolic inhibition in CD8 versus CD4 T cells.

    PubMed

    Cao, Yilin; Rathmell, Jeffrey C; Macintyre, Andrew N

    2014-01-01

    T lymphocytes (T cells) undergo metabolic reprogramming after activation to provide energy and biosynthetic materials for growth, proliferation and differentiation. Distinct T cell subsets, however, adopt metabolic programs specific to support their needs. As CD4 T cells coordinate adaptive immune responses while CD8 T cells become cytotoxic effectors, we compared activation-induced proliferation and metabolic reprogramming of these subsets. Resting CD4 and CD8 T cells were metabolically similar and used a predominantly oxidative metabolism. Following activation CD8 T cells proliferated more rapidly. Stimulation led both CD4 and CD8 T cells to sharply increase glucose metabolism and adopt aerobic glycolysis as a primary metabolic program. Activated CD4 T cells, however, remained more oxidative and had greater maximal respiratory capacity than activated CD8 T cells. CD4 T cells were also associated with greater levels of ROS and increased mitochondrial content, irrespective of the activation context. CD8 cells were better able, however, to oxidize glutamine as an alternative fuel source. The more glycolytic metabolism of activated CD8 T cells correlated with increased capacity for growth and proliferation, along with reduced sensitivity of cell growth to metabolic inhibition. These specific metabolic programs may promote greater growth and proliferation of CD8 T cells and enhance survival in diverse nutrient conditions.

  13. Association of pentraxin 3 with insulin resistance and glucose response following maximal aerobic exercise in obese and normal-mass individuals.

    PubMed

    Slusher, Aaron L; Huang, Chun-Jung

    2016-07-01

    Pentraxin 3 (PTX3), a cardioprotective protein, has recently been shown to be associated with improved insulin resistance (IR) and glucose metabolism. Therefore, the primary purpose of this study was to examine whether or not increased plasma PTX3 following maximal aerobic exercise would differ between obese and normal-mass subjects, and its association with the homeostatic model assessment of insulin resistance (HOMA-IR) and glucose response. Twenty-five untrained obese (n = 13 [6 males and 7 females]) and normal-mass (n = 12 [5 males and 7 females]) subjects performed an acute bout of maximal aerobic exercise to assess maximal oxygen consumption (VO2max). At baseline, plasma PTX3 concentrations are decreased in obese compared with normal-mass subjects and are negatively associated with plasma insulin and HOMA-IR values. In response to maximal exercise, plasma PTX3 responses were similar in obese and normal-mass subjects while the intensity of plasma PTX3 response as indicated by area under the curve analysis (AUCi) was not associated with HOMA-IR or glucose AUCi. However, PTX3 AUCi was positively associated with cardiorespiratory fitness levels (relative VO2max). These findings suggest that PTX3 could serve as a biomarker for both metabolic health, as well as a measurement to monitor the effectiveness of exercise interventions in obesity.

  14. JAK-STAT signaling and myocardial glucose metabolism

    PubMed Central

    Frias, Miguel A; Montessuit, Christophe

    2013-01-01

    JAK-STAT signaling occurs in virtually every tissue of the body, and so does glucose metabolism. In this review, we summarize the regulation of glucose metabolism in the myocardium and ponder whether JAK-STAT signaling participates in this regulation. Despite a paucity of data directly pertaining to cardiac myocytes, we conclude that JAK-STAT signaling may contribute to the development of insulin resistance in the myocardium in response to various hormones and cytokines. PMID:24416656

  15. Hexose metabolism in pancreatic islets. Regulation of aerobic glycolysis and pyruvate decarboxylation.

    PubMed

    Malaisse, W J; Rasschaert, J; Conget, I; Sener, A

    1991-01-01

    1. D-Glucose (0.5-16.7 mM) preferentially stimulates aerobic glycolysis and D-[3,4-14C]glucose oxidation, relative to D-[5-3H]glucose utilization in rat pancreatic islets, the concentration dependency of such a preferential effect displaying a sigmoidal pattern. 2. Inorganic and organic calcium antagonists, as well as Ca2+ deprivation, only cause a minor decrease in the ratio between D-[3,4-14C]glucose oxidation and D-[5-3H]glucose utilization in islets exposed to a high concentration of the hexose (16.7 mM). 3. Non-glucidic nutrient secretagogues such as 2-aminobicyclo[2,2,1]heptane-2-carboxylate (BCH), 2-ketoisocaproate and 3-phenylpyruvate fail to stimulate aerobic glycolysis and D-[3,4-14C]glucose oxidation in islets exposed to 6.0 mM D-glucose. Nevertheless, BCH augments [1-14C]pyruvate and [2-14C]pyruvate oxidation. 4. The glucose-induced increment in the paired ratio between D-[3,4-14C]glucose oxidation and D-[5-3H]glucose utilization is impaired in the presence of either cycloheximide or ouabain. 5. These findings suggest that the preferential effect of D-glucose upon aerobic glycolysis and pyruvate decarboxylation is not attributable solely to a Ca(2+)-induced activation of FAD-linked glycerophosphate dehydrogenase and/or pyruvate dehydrogenase, but may also involve an ATP-modulated regulatory process.

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

    PubMed

    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 (P<0·05). However, there were no significant differences among the three exercise 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 (P<0·05). These results suggest that aquatic exercise 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.

  17. Regional cerebral glucose metabolism in patients with alcoholic Korsakoff's syndrome

    SciTech Connect

    Kessler, R.M.; Parker, E.S.; Clark, C.M.; Martin, P.R.; George, D.T.; Weingartner, H.; Sokoloff, L.; Ebert, M.H.; Mishkin, M.

    1985-05-01

    Seven alcoholic male subjects diagnosed as having Korsakoff's syndrome and eight age-matched male normal volunteers were studied with /sup 18/F 2-fluoro-2-deoxy-D-glucose (2/sup 18/FDG). All subjects were examined at rest with eyes covered in a quiet, darkened room. Serial plasma samples were obtained following injection of 4 to 5 mCi of 2/sup 18/FDG. Tomographic slices spaced at 10mm axial increments were obtained (in-plane resolution = 1.75 cm, axial resolution = 1.78 cm). Four planes were selected from each subject, and a total of 46 regions of interest were sampled and glucose metabolic rates for each region calculated. The mean glucose metalbolic rate for the 46 regions in the Korsakoff subjects was significantly lower than that in the normal controls (5.17 +- .43 versus 6.6 +- 1.31). A Q-component analysis, which examined each subject's regional rates relative to his mean rate, revealed two distinct patterns in the Korsakoff group. Glucose metabolism was significantly reduced in 37 of the 46 regions sampled. Reduced cerebral glucose metabolism in a nondemented group of subjects has not previously been reported. The reduction in cortical metabolism may be the result of damage to sub-cortical projecting systems. The differing patterns of cerebral metabolism in Korsakoff's syndrome suggests subgroups with differing neuropathology. Regions implicated in memory function, medial temporal, thalamic and medial prefrontal were among the regions reduced in metabolism.

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

    SciTech Connect

    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.

  19. STRATEGIES FOR THE AEROBIC CO-METABOLISM OF CHLORINATED SOLVENTS. (R825689C019)

    EPA Science Inventory

    Abstract

    Recent field and laboratory studies have evaluated the potential for aerobic co-metabolism of chlorinated solvents. Different co-metabolic substrates and different methods of application have been tried, including growing indigenous microbes in situ, an...

  20. Metabolomics of aerobic metabolism in mice selected for increased maximal metabolic rate

    PubMed Central

    Wone, Bernard; Donovan, Edward R.; Hayes, Jack P.

    2014-01-01

    Maximal aerobic metabolic rate (MMR) is an important physiological and ecological variable that sets an upper limit to sustained, vigorous activity. How the oxygen cascade from the external environment to the mitochondria may affect MMR has been the subject of much interest, but little is known about the metabolic profiles that underpin variation in MMR. We tested how seven generations of artificial selection for high mass-independent MMR affected metabolite profiles of two skeletal muscles (gastrocnemius and plantaris) and the liver. MMR was 12.3% higher in mass selected for high MMR than in controls. Basal metabolic rate was 3.5% higher in selected mice than in controls. Artificial selection did not lead to detectable changes in the metabolic profiles from plantaris muscle, but in the liver amino acids and tricarboxylic acid cycle (TCA cycle) metabolites were lower in high-MMR mice than in controls. In gastrocnemius, amino acids and TCA cycle metabolites were higher in high-MMR mice than in controls, indicating elevated amino acid and energy metabolism. Moreover, in gastrocnemius free fatty acids and triacylglycerol fatty acids were lower in high-MMR mice than in controls. Because selection for high MMR was associated with changes in the resting metabolic profile of both liver and gastrocnemius, the result suggests a possible mechanistic link between resting metabolism and MMR. In addition, it is well established that diet and exercise affect the composition of fatty acids in muscle. The differences that we found between control lines and lines selected for high MMR demonstrate that the composition of fatty acids in muscle is also affected by genetic factors. PMID:21982590

  1. Glucose metabolism in cultured trophoblasts from human placenta

    SciTech Connect

    Moe, A.J.; Farmer, D.R.; Nelson, D.M.; Smith, C.H. )

    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.

  2. In vivo metabolic response of glucose to dichloroacetate in humans.

    PubMed

    Brown, J A; Gore, D C

    1996-03-01

    Hyperglycemia is common in severely ill patients and is related principally to an increase in glucose production. Dichloroacetate (DCA), which is known to increase the rate of pyruvate oxidation, has been shown to lower plasma glucose concentrations in normal fasting subjects and in diabetics and thus may be efficacious in treating stress induced hyperglycemia. However, the mechanism by which DCA lowers the plasma glucose concentration in humans has not been elucidated. To examine the human in vivo metabolic alterations induced by DCA, six fasting volunteers were infused with 6,6-D2-glucose and indirect calorimetry was performed prior to and following DCA administration. Glucose, lactate, and alanine net balance across the leg were also quantitated. Following DCA administration, plasma glucose concentrations decreased by 9% due to a proportional decrease in the rate of glucose production (P < 0.05). DCA had no affect on glucose clearance or leg net balance; however, the rate of glucose oxidation increased by 24% from baseline (P < 0.05). This increase in glucose oxidation without a compensatory change in peripheral glucose consumption suggests an improved efficiency in peripheral glucose utilization induced by DCA. Plasma concentrations of lactate and alanine were also lowered by DCA (56% for lactate, 66% for alanine, P < 0.05) without a significant alteration in leg net balance. These results suggest that DCA may decrease gluconeogenesis by limiting the availability of the precursor substrates lactate and alanine. Thus dichloroacetate may be an appropriate alternative to insulin in correcting mild elevations in plasma glucose concentrations. Furthermore, DCA may be especially effective in severely ill patients where hyperglycemia is largely due to increases in gluconeogenesis.

  3. Signaling through the Phosphatidylinositol 3-Kinase (PI3K)/Mammalian Target of Rapamycin (mTOR) Axis Is Responsible for Aerobic Glycolysis mediated by Glucose Transporter in Epidermal Growth Factor Receptor (EGFR)-mutated Lung Adenocarcinoma.

    PubMed

    Makinoshima, Hideki; Takita, Masahiro; Saruwatari, Koichi; Umemura, Shigeki; Obata, Yuuki; Ishii, Genichiro; Matsumoto, Shingo; Sugiyama, Eri; Ochiai, Atsushi; Abe, Ryo; Goto, Koichi; Esumi, Hiroyasu; Tsuchihara, Katsuya

    2015-07-10

    Oncogenic epidermal growth factor receptor (EGFR) signaling plays an important role in regulating global metabolic pathways, including aerobic glycolysis, the pentose phosphate pathway (PPP), and pyrimidine biosynthesis. However, the molecular mechanism by which EGFR signaling regulates cancer cell metabolism is still unclear. To elucidate how EGFR signaling is linked to metabolic activity, we investigated the involvement of the RAS/MEK/ERK and PI3K/AKT/mammalian target of rapamycin (mTOR) pathways on metabolic alteration in lung adenocarcinoma (LAD) cell lines with activating EGFR mutations. Although MEK inhibition did not alter lactate production and the extracellular acidification rate, PI3K/mTOR inhibitors significantly suppressed glycolysis in EGFR-mutant LAD cells. Moreover, a comprehensive metabolomics analysis revealed that the levels of glucose 6-phosphate and 6-phosphogluconate as early metabolites in glycolysis and PPP were decreased after inhibition of the PI3K/AKT/mTOR pathway, suggesting a link between PI3K signaling and the proper function of glucose transporters or hexokinases in glycolysis. Indeed, PI3K/mTOR inhibition effectively suppressed membrane localization of facilitative glucose transporter 1 (GLUT1), which, instead, accumulated in the cytoplasm. Finally, aerobic glycolysis and cell proliferation were down-regulated when GLUT1 gene expression was suppressed by RNAi. Taken together, these results suggest that PI3K/AKT/mTOR signaling is indispensable for the regulation of aerobic glycolysis in EGFR-mutated LAD cells.

  4. Leptin and the CNS Control of Glucose Metabolism

    PubMed Central

    Morton, Gregory J.; Schwartz, Michael W.

    2012-01-01

    The regulation of body fat stores and blood glucose levels is critical for survival. This review highlights growing evidence that leptin action in the central nervous system (CNS) plays a key role in both processes. Investigation into underlying mechanisms has begun to clarify the physiological role of leptin in the control of glucose metabolism and raises interesting new possibilities for the treatment of diabetes and related disorders. PMID:21527729

  5. Regulation of Glucose Metabolism in Pseudomonas

    PubMed Central

    Daddaoua, Abdelali; Krell, Tino; Ramos, Juan-Luis

    2009-01-01

    In Pseudomonas putida, genes for the glucose phosphorylative pathway and the Entner-Doudoroff pathway are organized in two operons; one made up of the zwf, pgl, and eda genes and another consisting of the edd, glk, gltR2, and gltS genes. Divergently with respect to the edd gene is the gap-1 gene. Expression from Pzwf, Pedd, and Pgap is modulated by HexR in response to the availability of glucose in the medium. To study the regulatory process in greater detail we purified HexR and showed that it is a monomer in solution. Electrophoretic mobility shift assays and isothermal titration calorimetry assays were done showing that HexR recognizes the Pedd, Pzwf, and Pgap-1 promoters with affinity in the nanomolar range. DNA footprinting assays identified the binding site between +30 and +1 at Pzwf, between +16 and +41 at Pedd, and between −6 and +18 at Pgap-1. Based on DNA sequence alignment of the target sites and isothermal titration calorimetry data, two monomers of HexR bind to a pseudopalindrome with a consensus sequence of 5′-TTGTN7–8ACAA-3′. Binding of the Entner-Doudoroff pathway intermediate 2-keto-3-deoxy-6-phosphogluconate to HexR released the repressor from its target operators, whereas other chemicals such as glucose, glucose 6-phosphate, and 6-phosphogluconate did not induce complex dissociation. The phosphorylated effector is likely to be recognized by a sugar isomerase domain located at the C-terminal end of HexR, whereas the helix-turn-helix DNA binding domain of HexR exhibits high similarity to proteins of the RpiR family of regulators. PMID:19506074

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

    PubMed

    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.

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

    PubMed Central

    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. PMID:26582989

  8. Resistance to aerobic exercise training causes metabolic dysfunction and reveals novel exercise-regulated signaling networks.

    PubMed

    Lessard, Sarah J; Rivas, Donato A; Alves-Wagner, Ana B; Hirshman, Michael F; Gallagher, Iain J; Constantin-Teodosiu, Dumitru; Atkins, Ryan; Greenhaff, Paul L; Qi, Nathan R; Gustafsson, Thomas; Fielding, Roger A; Timmons, James A; Britton, Steven L; Koch, Lauren G; Goodyear, Laurie J

    2013-08-01

    Low aerobic exercise capacity is a risk factor for diabetes and a strong predictor of mortality, yet some individuals are "exercise-resistant" and unable to improve exercise capacity through exercise training. To test the hypothesis that resistance to aerobic exercise training underlies metabolic disease risk, we used selective breeding for 15 generations to develop rat models of low and high aerobic response to training. Before exercise training, rats selected as low and high responders had similar exercise capacities. However, after 8 weeks of treadmill training, low responders failed to improve their exercise capacity, whereas high responders improved by 54%. Remarkably, low responders to aerobic training exhibited pronounced metabolic dysfunction characterized by insulin resistance and increased adiposity, demonstrating that the exercise-resistant phenotype segregates with disease risk. Low responders had impaired exercise-induced angiogenesis in muscle; however, mitochondrial capacity was intact and increased normally with exercise training, demonstrating that mitochondria are not limiting for aerobic adaptation or responsible for metabolic dysfunction in low responders. Low responders had increased stress/inflammatory signaling and altered transforming growth factor-β signaling, characterized by hyperphosphorylation of a novel exercise-regulated phosphorylation site on SMAD2. Using this powerful biological model system, we have discovered key pathways for low exercise training response that may represent novel targets for the treatment of metabolic disease.

  9. Patterns of human local cerebral glucose metabolism during epileptic seizures

    SciTech Connect

    Engel, J. Jr.; Kuhl, D.E.; Phelps, M.E.

    1982-10-01

    Ictal patterns of local cerebral metabolic rate have been studied in epileptic patients by positron computed tomography with /sup 18/F-labeled 2-fluoro-2-deoxy-D-glucose. Partial seizures were associated with activation of anatomic structures unique to each patient studied. Ictal increases and decreases in local cerebral metabolism were observed. Scans performed during generalized convulsions induced by electroshock demonstrated a diffuse ictal increase and postictal decrease in cerebral metabolism. Petit mal absences were associated with a diffuse increase in cerebral metabolic rate. The ictal fluorodeoxyglucose patterns obtained from patients do not resemble autoradiographic patterns obtained from common experimental animal models of epilepsy.

  10. Effects of Aerobic Exercise on Postprandial Carbohydrate and Lipoprotein Metabolism Following Cookie Ingestion in Healthy Young Women.

    PubMed

    Hashimoto, Sayuki; Mizutani, Erika; Suzuki, Maiko; Yoshida, Akihiro; Naito, Michitaka

    2015-01-01

    We examined the acute effects of postprandial aerobic exercise on glucose and lipid metabolism following cookie ingestion. Fifteen healthy young women with a sedentary lifestyle, normal weight and apolipoprotein E3/3 participated. After a 12-h overnight fast, each subject ingested a cookie (1.53 g/kg, Meal Test C) and then performed two trials, one with postprandial exercise (E trial) and one without exercise (C trial), in a randomized crossover design. A single 30-min bout of walking exercise was performed 20 min after the cookie intake. Venous blood samples were drawn before (0 h) and 20 min and 1, 2, 4, and 6 h after cookie ingestion. The Δglucose concentration was not significantly different between the two trials, but the Δinsulin concentration at 1 h and the incremental area under the curve (IAUC) (0-2 h)-insulin in the E trial were significantly lower than in the C trial. The ratio of glucose/insulin at 1 h was significantly higher in the E trial than in the C trial. The ΔTG, ΔRLP-TG, ΔapoB48 and ΔRemL-C concentrations at 1 h in the E trial were significantly higher than in the C trial. The IAUC (0-2 h)-apoB48 in the E trial was significantly larger than in the C trial. Postprandial exercise showed an insulin-sparing effect following the cookie ingestion by increasing insulin sensitivity. However, postprandial exercise transiently stimulated the secretion of exogenous apoB48-containing lipoprotein during the early period, and no further effects were observed. These results suggest that postprandial aerobic exercise is effective for the promotion of postprandial carbohydrate metabolism, but not lipidemia.

  11. Glucose metabolic phenotype of pancreatic cancer

    PubMed Central

    Chan, Anthony KC; Bruce, Jason IE; Siriwardena, Ajith K

    2016-01-01

    AIM: To construct a global “metabolic phenotype” of pancreatic ductal adenocarcinoma (PDAC) reflecting tumour-related metabolic enzyme expression. METHODS: A systematic review of the literature was performed using OvidSP and PubMed databases using keywords “pancreatic cancer” and individual glycolytic and mitochondrial oxidative phosphorylation (MOP) enzymes. Both human and animal studies investigating the oncological effect of enzyme expression changes and inhibitors in both an in vitro and in vivo setting were included in the review. Data reporting changes in enzyme expression and the effects on PDAC cells, such as survival and metastatic potential, were extracted to construct a metabolic phenotype. RESULTS: Seven hundred and ten papers were initially retrieved, and were screened to meet the review inclusion criteria. 107 unique articles were identified as reporting data involving glycolytic enzymes, and 28 articles involving MOP enzymes in PDAC. Data extraction followed a pre-defined protocol. There is consistent over-expression of glycolytic enzymes and lactate dehydrogenase in keeping with the Warburg effect to facilitate rapid adenosine-triphosphate production from glycolysis. Certain isoforms of these enzymes were over-expressed specifically in PDAC. Altering expression levels of HK, PGI, FBA, enolase, PK-M2 and LDA-A with metabolic inhibitors have shown a favourable effect on PDAC, thus identifying these as potential therapeutic targets. However, the Warburg effect on MOP enzymes is less clear, with different expression levels at different points in the Krebs cycle resulting in a fundamental change of metabolite levels, suggesting that other essential anabolic pathways are being stimulated. CONCLUSION: Further characterisation of the PDAC metabolic phenotype is necessary as currently there are few clinical studies and no successful clinical trials targeting metabolic enzymes. PMID:27022229

  12. Glucose regulates lipid metabolism in fasting king penguins.

    PubMed

    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.

  13. Overexpression of a Water-Forming NADH Oxidase Improves the Metabolism and Stress Tolerance of Saccharomyces cerevisiae in Aerobic Fermentation

    PubMed Central

    Shi, Xinchi; Zou, Yanan; Chen, Yong; Zheng, Cheng; Ying, Hanjie

    2016-01-01

    Redox homeostasis is fundamental to the maintenance of metabolism. Redox imbalance can cause oxidative stress, which affects metabolism and growth. Water-forming NADH oxidase regulates the redox balance by oxidizing cytosolic NADH to NAD+, which relieves cytosolic NADH accumulation through rapid glucose consumption in Saccharomyces cerevisiae, thus decreasing the production of the by product glycerol in industrial ethanol production. Here, we studied the effects of overexpression of a water-forming NADH oxidase from Lactococcus lactis on the stress response of S. cerevisiae in aerobic batch fermentation, and we constructed an interaction network of transcriptional regulation and metabolic networks to study the effects of and mechanisms underlying NADH oxidase regulation. The oxidase-overexpressing strain (NOX) showed increased glucose consumption, growth, and ethanol production, while glycerol production was remarkably lower. Glucose was exhausted by NOX at 26 h, while 18.92 ± 0.94 g/L residual glucose was left in the fermentation broth of the control strain (CON) at this time point. At 29.5 h, the ethanol concentration for NOX peaked at 35.25 ± 1.76 g/L, which was 14.37% higher than that for CON (30.82 ± 1.54 g/L). Gene expression involved in the synthesis of thiamine, which is associated with stress responses in various organisms, was increased in NOX. The transcription factor HAP4 was significantly upregulated in NOX at the late-exponential phase, indicating a diauxic shift in response to starvation. The apoptosis-inducing factor Nuc1 was downregulated while the transcription factor Sok2, which regulates the production of the small signaling molecule ammonia, was upregulated at the late-exponential phase, benefiting young cells on the rim. Reactive oxygen species production was decreased by 10% in NOX, supporting a decrease in apoptosis. The HOG pathway was not activated, although the osmotic stress was truly higher, indicating improved osmotolerance. Thus

  14. The influence of Angiostrongylus cantonensis (Nematoda, Metastrongylidae) infection on the aerobic metabolism of Biomphalaria straminea and Biomphalaria tenagophila (Mollusca, Gastropoda).

    PubMed

    Lima, Mariana G; Tunholi-Alves, Vinícius M; Gaudêncio, Fabrício N; Martins, Florence G; Castro, Rosane N; Thiengo, Silvana C; Garcia, Juberlan S; Maldonado, Arnaldo; Pinheiro, Jairo

    2016-12-01

    Angiostrongylus cantonensis is considered the main agent responsible for human eosinophilic meningoencephalitis. This parasite has low specificity for mollusk hosts and it can also use aquatic snails as auxiliary hosts. Studies based on the metabolic profile of Biomphalaria spp. infected by A. cantonensis have been conducted to observe parasite-host interactions. In the present study, the glucose content in the hemolymph and glycogen content in the digestive gland and cephalopedal mass of Biomphalaria tenagophila and Biomphalaria straminea experimentally infected by A. cantonensis were evaluated, along with the activity of LDH. The snails were dissected from 6 to 21days after infection to collect the hemolymph and separate the tissues. Decreases of 96% and 6.4% in the glucose content triggered a transition from aerobic to anaerobic metabolism in the two infected snail species, B. straminea and B. tenagophila, respectively. That finding was confirmed by high-performance liquid chromatography. These results indicate that when infected, these snails are able to change their metabolic profile, suggesting a strategy to maintain their homeostatic balance.

  15. Glycolysis-induced discordance between glucose metabolic rates measured with radiolabeled fluorodeoxyglucose and glucose

    SciTech Connect

    Ackermann, R.F.; Lear, J.L. )

    1989-12-01

    We have developed an autoradiographic method for estimating the oxidative and glycolytic components of local CMRglc (LCMRglc), using sequentially administered ({sup 18}F)fluorodeoxyglucose (FDG) and ({sup 14}C)-6-glucose (GLC). FDG-6-phosphate accumulation is proportional to the rate of glucose phosphorylation, which occurs before the divergence of glycolytic (GMg) and oxidative (GMo) glucose metabolism and is therefore related to total cerebral glucose metabolism GMt: GMg + GMo = GMt. With oxidative metabolism, the {sup 14}C label of GLC is temporarily retained in Krebs cycle-related substrate pools. We hypothesize that with glycolytic metabolism, however, a significant fraction of the {sup 14}C label is lost from the brain via lactate production and efflux from the brain. Thus, cerebral GLC metabolite concentration may be more closely related to GMo than to GMt. If true, the glycolytic metabolic rate will be related to the difference between FDG- and GLC-derived LCMRglc. Thus far, we have studied normal awake rats, rats with limbic activation induced by kainic acid (KA), and rats visually stimulated with 16-Hz flashes. In KA-treated rats, significant discordance between FDG and GLC accumulation, which we attribute to glycolysis, occurred only in activated limbic structures. In visually stimulated rats, significant discordance occurred only in the optic tectum.

  16. Enhanced hydrogen production from glucose by metabolically engineered Escherichia coli.

    PubMed

    Maeda, Toshinari; Sanchez-Torres, Viviana; Wood, Thomas K

    2007-12-01

    To utilize fermentative bacteria for producing the alternative fuel hydrogen, we performed successive rounds of P1 transduction from the Keio Escherichia coli K-12 library to introduce multiple, stable mutations into a single bacterium to direct the metabolic flux toward hydrogen production. E. coli cells convert glucose to various organic acids (such as succinate, pyruvate, lactate, formate, and acetate) to synthesize energy and hydrogen from formate by the formate hydrogen-lyase (FHL) system that consists of hydrogenase 3 and formate dehydrogenase-H. We altered the regulation of FHL by inactivating the repressor encoded by hycA and by overexpressing the activator encoded by fhlA, removed hydrogen uptake activity by deleting hyaB (hydrogenase 1) and hybC (hydrogenase 2), redirected glucose metabolism to formate by using the fdnG, fdoG, narG, focA, focB, poxB, and aceE mutations, and inactivated the succinate and lactate synthesis pathways by deleting frdC and ldhA, respectively. The best of the metabolically engineered strains, BW25113 hyaB hybC hycA fdoG frdC ldhA aceE, increased hydrogen production 4.6-fold from glucose and increased the hydrogen yield twofold from 0.65 to 1.3 mol H(2)/mol glucose (maximum, 2 mol H(2)/mol glucose).

  17. Within-Winter Flexibility in Muscle Masses, Myostatin, and Cellular Aerobic Metabolic Intensity in Passerine Birds.

    PubMed

    Swanson, David L; King, Marisa O; Culver, William; Zhang, Yufeng

    Metabolic rates of passerine birds are flexible traits that vary both seasonally and among and within winters. Seasonal variation in summit metabolic rates (Msum = maximum thermoregulatory metabolism) in birds is consistently correlated with changes in pectoralis muscle and heart masses and sometimes with variation in cellular aerobic metabolic intensity, so these traits might also be associated with shorter-term, within-winter variation in metabolic rates. To determine whether these mechanisms are associated with within-winter variation in Msum, we examined the effects of short-term (ST; 0-7 d), medium-term (MT; 14-30 d), and long-term (LT; 30-yr means) temperature variables on pectoralis muscle and heart masses, pectoralis expression of the muscle-growth inhibitor myostatin and its metalloproteinase activators TLL-1 and TLL-2, and pectoralis and heart citrate synthase (CS; an indicator of cellular aerobic metabolic intensity) activities for two temperate-zone resident passerines, house sparrows (Passer domesticus) and dark-eyed juncos (Junco hyemalis). For both species, pectoralis mass residuals were positively correlated with ST temperature variables, suggesting that cold temperatures resulted in increased turnover of pectoralis muscle, but heart mass showed little within-winter variation for either species. Pectoralis mRNA and protein expression of myostatin and the TLLs were only weakly correlated with ST and MT temperature variables, which is largely consistent with trends in muscle masses for both species. Pectoralis and heart CS activities showed weak and variable trends with ST temperature variables in both species, suggesting only minor effects of temperature variation on cellular aerobic metabolic intensity. Thus, neither muscle or heart masses, regulation by the myostatin system, nor cellular aerobic metabolic intensity varied consistently with winter temperature, suggesting that other factors regulate within-winter metabolic variation in these birds.

  18. Acclimation of aerobic-activated sludge degrading benzene derivatives and co-metabolic degradation activities of trichloroethylene by benzene derivative-grown aerobic sludge.

    PubMed

    Wang, Shizong; Yang, Qi; Bai, Zhiyong; Wang, Shidong; Wang, Yeyao; Nowak, Karolina M

    2015-01-01

    The acclimation of aerobic-activated sludge for degradation of benzene derivatives was investigated in batch experiments. Phenol, benzoic acid, toluene, aniline and chlorobenzene were concurrently added to five different bioreactors which contained the aerobic-activated sludge. After the acclimation process ended, the acclimated phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic-activated sludge were used to explore the co-metabolic degradation activities of trichloroethylene (TCE). Monod equation was employed to simulate the kinetics of co-metabolic degradation of TCE by benzene derivative-grown sludge. At the end of experiments, the mixed microbial communities grown under different conditions were identified. The results showed that the acclimation periods of microorganisms for different benzene derivatives varied. The maximum degradation rates of TCE for phenol-, benzoic acid-, toluene-, aniline- and chlorobenzene-grown aerobic sludge were 0.020, 0.017, 0.016, 0.0089 and 0.0047 mg g SS(-1) h(-1), respectively. The kinetic of TCE degradation in the absence of benzene derivative followed Monod equation well. Also, eight phyla were observed in the acclimated benzene derivative-grown aerobic sludge. Each of benzene derivative-grown aerobic sludge had different microbial community composition. This study can hopefully add new knowledge to the area of TCE co-metabolic by mixed microbial communities, and further the understanding on the function and applicability of aerobic-activated sludge.

  19. Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes

    PubMed Central

    Wopereis, Suzan; Rubingh, Carina M.; van Erk, Marjan J.; Verheij, Elwin R.; van Vliet, Trinette; Cnubben, Nicole H. P.; Smilde, Age K.; van der Greef, Jan; van Ommen, Ben; Hendriks, Henk F. J.

    2009-01-01

    Background The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on metabolism. Methodology To study the metabolic changes induced by a mild anti-inflammatory drug intervention, plasma metabolic profiling was applied in overweight human volunteers with elevated levels of the inflammatory plasma marker C-reactive protein. Liquid and gas chromatography mass spectrometric methods were used to detect high and low abundant plasma metabolites both in fasted conditions and during an oral glucose tolerance test. This is based on the concept that the resilience of the system can be assessed after perturbing a homeostatic situation. Conclusions Metabolic changes were subtle and were only detected using metabolic profiling in combination with an oral glucose tolerance test. The repeated measurements during the oral glucose tolerance test increased statistical power, but the metabolic perturbation also revealed metabolites that respond differentially to the oral glucose tolerance test. Specifically, multiple metabolic intermediates of the glutathione synthesis pathway showed time-dependent suppression in response to the glucose challenge test. The fact that this is an insulin sensitive pathway suggests that inflammatory modulation may alter insulin signaling in overweight men. PMID:19242536

  20. Education-Associated Cortical Glucose Metabolism during Sustained Attention

    PubMed Central

    Eisenberg, Daniel P.; London, Edythe D.; Matochik, John A.; Derbyshire, Stuart; Cohen, Lisa J.; Steinfeld, Matthew; Prosser, James; Galynker, Igor I.

    2007-01-01

    Despite research suggesting that education may mitigate cognitive sequelae of neural injury, little is known about interactions between education and regional brain function. We examined whether educational experience is associated with relative glucose metabolism in brain regions that are important for sustained attention and learning. Fourteen healthy adults, with twelve to eighteen years of schooling, underwent positron emission tomography (PET) scanning with 18F-fluorodeoxyglucose (FDG) during an auditory continuous discrimination task. Years of education correlated positively with relative glucose metabolism in the lingual gyri (bilaterally), left posterior cingulate gyrus, and left precuneus. Previously, these structures have shown early impairment in dementia. Further investigation should explore whether metabolic changes in these regions contribute to the possible protective effect of education on cognition. PMID:16110274

  1. A computer model simulating human glucose absorption and metabolism in health and metabolic disease states

    PubMed Central

    Naftalin, Richard J.

    2016-01-01

    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 implications on GLP

  2. Glucose Metabolism from Mouth to Muscle: A Student Experiment to Teach Glucose Metabolism during Exercise and Rest

    ERIC Educational Resources Information Center

    Engeroff, Tobias; Fleckenstein, Johannes; Banzer, Winfried

    2017-01-01

    We developed an experiment to help students understand basic regulation of postabsorptive and postprandial glucose metabolism and the availability of energy sources for physical activity in the fed and fasted state. Within a practical session, teams of two or three students (1 subject and 1 or 2 investigators) performed one of three different…

  3. Female rats selectively bred for high intrinsic aerobic fitness are protected from ovariectomy-associated metabolic dysfunction

    PubMed Central

    Padilla, Jaume; Park, Young-Min; Welly, Rebecca J.; Scroggins, Rebecca J.; Britton, Steven L.; Koch, Lauren G.; Jenkins, Nathan T.; Crissey, Jacqueline M.; Zidon, Terese; Morris, E. Matthew; Meers, Grace M. E.; Thyfault, John P.

    2015-01-01

    Ovariectomized rodents model human menopause in that they rapidly gain weight, reduce spontaneous physical activity (SPA), and develop metabolic dysfunction, including insulin resistance. How contrasting aerobic fitness levels impacts ovariectomy (OVX)-associated metabolic dysfunction is not known. Female rats selectively bred for high and low intrinsic aerobic fitness [high-capacity runners (HCR) and low-capacity runners (LCR), respectively] were maintained under sedentary conditions for 39 wk. Midway through the observation period, OVX or sham (SHM) operations were performed providing HCR-SHM, HCR-OVX, LCR-SHM, and LCR-OVX groups. Glucose tolerance, energy expenditure, and SPA were measured before and 4 wk after surgery, while body composition via dual-energy X-ray absorptiometry and adipose tissue distribution, brown adipose tissue (BAT), and skeletal muscle phenotype, hepatic lipid content, insulin resistance via homeostatic assessment model of insulin resistance and AdipoIR, and blood lipids were assessed at death. Remarkably, HCR were protected from OVX-associated increases in adiposity and insulin resistance, observed only in LCR. HCR rats were ∼30% smaller, had ∼70% greater spontaneous physical activity (SPA), consumed ∼10% more relative energy, had greater skeletal muscle proliferator-activated receptor coactivator 1-alpha, and ∼40% more BAT. OVX did not increase energy intake and reduced SPA to the same extent in both HCR and LCR. LCR were particularly affected by an OVX-associated reduction in resting energy expenditure and experienced a reduction in relative BAT; resting energy expenditure correlated positively with BAT across all animals (r = 0.6; P < 0.001). In conclusion, despite reduced SPA following OVX, high intrinsic aerobic fitness protects against OVX-associated increases in adiposity and insulin resistance. The mechanism may involve preservation of resting energy expenditure. PMID:25608751

  4. Aerobic fitness ecological validity in elite soccer players: a metabolic power approach.

    PubMed

    Manzi, Vincenzo; Impellizzeri, Franco; Castagna, Carlo

    2014-04-01

    The aim of this study was to examine the association between match metabolic power (MP) categories and aerobic fitness in elite-level male soccer players. Seventeen male professional soccer players were tested for VO2max, maximal aerobic speed (MAS), VO2 at ventilatory threshold (VO2VT and %VO2VT), and speed at a selected blood lactate concentration (4 mmol·L(-1), V(L4)). Aerobic fitness tests were performed at the end of preseason and after 12 and 24 weeks during the championship. Aerobic fitness and MP variables were considered as mean of all seasonal testing and of 16 Championship home matches for all the calculations, respectively. Results showed that VO2max (from 0.55 to 0.68), MAS (from 0.52 to 0.72), VO2VT (from 0.72 to 0.83), %VO2maxVT (from 0.62 to 0.65), and V(L4) (from 0.56 to 0.73) were significantly (p < 0.05 to 0.001) large to very large associated with MP variables. These results provide evidence to the ecological validity of aerobic fitness in male professional soccer. Strength and conditioning professionals should consider aerobic fitness in their training program when dealing with professional male soccer players. The MP method resulted an interesting approach for tracking external load in male professional soccer players.

  5. Temperature dependent growth, feeding, nutritional condition and aerobic metabolism of juvenile spiny lobster, Sagmariasus verreauxi.

    PubMed

    Fitzgibbon, Quinn P; Simon, Cedric J; Smith, Gregory G; Carter, Chris G; Battaglene, Stephen C

    2017-05-01

    We examined the effects of temperature on the growth, feeding, nutritional condition and aerobic metabolism of juvenile spiny lobster, Sagmariasus verreauxi, in order to determine if temperature acclimated aerobic scope correlates with optimum for growth and to establish the thermal tolerance window for this emerging aquaculture species. Juvenile lobsters (initial weight=10.95±0.47g) were reared (n=7) at temperatures from 11.0 to 28.5°C for 145days. All lobsters survived from 14.5 to 25.0°C while survival was reduced at 11.0°C (86%) and all lobsters died at 28.5°C. Lobster specific growth rate and specific feed consumption displayed a unimodal response with temperature, peaking at 21.5°C. Lobster standard, routine and maximum metabolic rates, and aerobic scope all increased exponentially up to maximum non-lethal temperature. Optimum temperature for growth did not correspond to that for maximum aerobic scope suggesting that aerobic scope is not an effective predictor of the thermal optimum of spiny lobsters. Plateauing of specific feed consumption beyond 21.5°C suggests that temperature dependent growth of lobsters is limited by capacity to ingest or digest sufficient food to meet increasing maintenance metabolic demands at high temperatures. The nutritional condition of lobsters was not influenced by temperature and feed conversion ratio was improved at lower temperatures. These findings add to a growing body of evidence questioning the generality of aerobic scope to describe the physiological thermal boundaries of aquatic ectotherms and suggest that feed intake plays a crucial role in regulating performance at thermal extremes.

  6. Linking neuronal brain activity to the glucose metabolism

    PubMed Central

    2013-01-01

    Background Energy homeostasis ensures the functionality of the entire organism. The human brain as a missing link in the global regulation of the complex whole body energy metabolism is subject to recent investigation. The goal of this study is to gain insight into the influence of neuronal brain activity on cerebral and peripheral energy metabolism. In particular, the tight link between brain energy supply and metabolic responses of the organism is of interest. We aim to identifying regulatory elements of the human brain in the whole body energy homeostasis. Methods First, we introduce a general mathematical model describing the human whole body energy metabolism. It takes into account the two central roles of the brain in terms of energy metabolism. The brain is considered as energy consumer as well as regulatory instance. Secondly, we validate our mathematical model by experimental data. Cerebral high-energy phosphate content and peripheral glucose metabolism are measured in healthy men upon neuronal activation induced by transcranial direct current stimulation versus sham stimulation. By parameter estimation we identify model parameters that provide insight into underlying neurophysiological processes. Identified parameters reveal effects of neuronal activity on regulatory mechanisms of systemic glucose metabolism. Results Our examinations support the view that the brain increases its glucose supply upon neuronal activation. The results indicate that the brain supplies itself with energy according to its needs, and preeminence of cerebral energy supply is reflected. This mechanism ensures balanced cerebral energy homeostasis. Conclusions The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported. PMID:23988084

  7. Glucose Metabolism of the Isolated Eccrine Sweat Gland

    PubMed Central

    Sato, Kenzo; Dobson, Richard L.

    1973-01-01

    This paper attempts to further clarify the characteristics of Mecholyl- or epinephrine-stimulated glucose metabolism in the isolated monkey eccrine sweat gland with special emphasis on its relationship to increased sodium transport. The Mecholyl- or epinephrine-stimulated glucose metabolism (as estimated by either lactate or 14CO2 production or both) is seen only in the secretory coil and not in the duct. It is markedly suppressed in the absence of glucose, Na+, or K+. It is inhibited by ouabain (10−3 M) and partially suppressed in a low-sodium (40 mM), high-potassium (100 mM) medium. 2,4-dinitrophenol (10−4 M) reverses ouabain-induced inhibition of lactate and 14CO2 production but only partially reverses inhibition induced by Na+ + K+ deprivation, indicating that metabolic inhibition by ouabain is secondary to the inhibition of sodium transport. There is no synergism between Mecholyl and epinephrine. The absence of any significant inhibitory effects by acetazolamide (Diamox) or HCO3−-free media suggests that H+ transport may not be important in sweat gland function. In contrast to a report by Wolfe et al., human eccrine sweat glands show considerable oxidative activity (14CO2 production of 0.42-0.72 nmol/gland/h). These observations are discussed in terms of the linkage between sweat gland energy metabolism and sodium transport. PMID:4269528

  8. Quantifying the contribution of the liver to glucose homeostasis: a detailed kinetic model of human hepatic glucose metabolism.

    PubMed

    König, Matthias; Bulik, Sascha; Holzhütter, Hermann-Georg

    2012-01-01

    Despite the crucial role of the liver in glucose homeostasis, a detailed mathematical model of human hepatic glucose metabolism is lacking so far. Here we present a detailed kinetic model of glycolysis, gluconeogenesis and glycogen metabolism in human hepatocytes integrated with the hormonal control of these pathways by insulin, glucagon and epinephrine. Model simulations are in good agreement with experimental data on (i) the quantitative contributions of glycolysis, gluconeogenesis, and glycogen metabolism to hepatic glucose production and hepatic glucose utilization under varying physiological states. (ii) the time courses of postprandial glycogen storage as well as glycogen depletion in overnight fasting and short term fasting (iii) the switch from net hepatic glucose production under hypoglycemia to net hepatic glucose utilization under hyperglycemia essential for glucose homeostasis (iv) hormone perturbations of hepatic glucose metabolism. Response analysis reveals an extra high capacity of the liver to counteract changes of plasma glucose level below 5 mM (hypoglycemia) and above 7.5 mM (hyperglycemia). Our model may serve as an important module of a whole-body model of human glucose metabolism and as a valuable tool for understanding the role of the liver in glucose homeostasis under normal conditions and in diseases like diabetes or glycogen storage diseases.

  9. Implications of Resveratrol on Glucose Uptake and Metabolism.

    PubMed

    León, David; Uribe, Elena; Zambrano, Angara; Salas, Mónica

    2017-03-07

    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.

  10. Glucose metabolism from mouth to muscle: a student experiment to teach glucose metabolism during exercise and rest.

    PubMed

    Engeroff, Tobias; Fleckenstein, Johannes; Banzer, Winfried

    2017-03-01

    We developed an experiment to help students understand basic regulation of postabsorptive and postprandial glucose metabolism and the availability of energy sources for physical activity in the fed and fasted state. Within a practical session, teams of two or three students (1 subject and 1 or 2 investigators) performed one of three different trials: 1) inactive, in which subjects ingested a glucose solution (75 g in 300 ml of water) and rested in the seated position until the end of the trial; 2) prior activity, in which the subject performed 15 min of walking before glucose ingestion and a subsequent resting phase; and 3) postactivity, in which the subject ingested glucose solution, walked (15 min), and rested afterwards. Glucose levels were drawn before trials (fasting value), immediately after glucose ingestion (0 min), and 5, 10, 15, 20, 25, 30, 40, 50, and 60 min thereafter. Students analyzed glucose values and worked on 12 tasks. Students evaluated the usefulness of the experiment; 54.2% of students found the experiment useful to enable them to gain a further understanding of the learning objectives and to clarify items, and 44.1% indicated that the experiment was necessary to enable them to understand the learning objectives. For 6.8% the experiment was not necessary but helpful to check what they had learned, and 3.4% found that the experiment was not necessary. The present article shows the great value of experiments within practical courses to help students gain knowledge of energy metabolism. Using an active learning strategy, students outworked complex physiological tasks and improved beneficial communication and interaction between students with different skill sets and problem-solving strategies.

  11. Cerebral metabolism of glucose in benign hereditary chorea

    SciTech Connect

    Suchowersky, O.; Hayden, M.R.; Martin, W.R.; Stoessl, A.J.; Hildebrand, A.M.; Pate, B.D.

    1986-01-01

    Benign hereditary chorea (BHC) is an autosomal dominant disorder characterized by chorea of early onset with little or no progression. There is marked clinical variability in this disease with some subjects having onset in infancy and others with onset in early adulthood. In contrast to Huntington's disease (HD), there is no dementia. Computed tomography is normal in all subjects with no evidence of caudate nucleus atrophy. We present the results of positron emission tomography using YF-2-fluorodeoxyglucose on three patients with this disorder from two families. Cerebral glucose metabolism in one patient was decreased in the caudate nucleus, as previously reported in HD. The other two persons from a second family showed a relative decrease in metabolic rates of glucose in the caudate when compared with the thalamus. It appears that caudate hypometabolism is not specific for HD. These findings suggest that the caudate nucleus may play a significant role in the pathophysiology of some persons with BHC.

  12. Rpl13a small nucleolar RNAs regulate systemic glucose metabolism

    PubMed Central

    Lee, Jiyeon; Harris, Alexis N.; Holley, Christopher L.; Mahadevan, Jana; Pyles, Kelly D.; Lavagnino, Zeno; Scherrer, David E.; Fujiwara, Hideji; Sidhu, Rohini; Zhang, Jessie; Huang, Stanley Ching-Cheng; Piston, David W.; Remedi, Maria S.; Urano, Fumihiko; Ory, Daniel S.

    2016-01-01

    Small nucleolar RNAs (snoRNAs) are non-coding RNAs that form ribonucleoproteins to guide covalent modifications of ribosomal and small nuclear RNAs in the nucleus. Recent studies have also uncovered additional non-canonical roles for snoRNAs. However, the physiological contributions of these small RNAs are largely unknown. Here, we selectively deleted four snoRNAs encoded within the introns of the ribosomal protein L13a (Rpl13a) locus in a mouse model. Loss of Rpl13a snoRNAs altered mitochondrial metabolism and lowered reactive oxygen species tone, leading to increased glucose-stimulated insulin secretion from pancreatic islets and enhanced systemic glucose tolerance. Islets from mice lacking Rpl13a snoRNAs demonstrated blunted oxidative stress responses. Furthermore, these mice were protected against diabetogenic stimuli that cause oxidative stress damage to islets. Our study illuminates a previously unrecognized role for snoRNAs in metabolic regulation. PMID:27820699

  13. Red blood cell glucose metabolism in human chronic fluoride toxicity

    SciTech Connect

    Saralakumari, D.; Rao, P.R. )

    1991-12-01

    Fluoride is a well known inhibitor of many enzyme systems in vitro. The most widely studied classic example of fluoride inhibition is its potent inhibition of glycolysis, specifically its action on the enzyme enolase. Despite the plethora of in vitro studies on the effects of fluoride on the enzyme activity, there is a paucity of information concerning the in vivo metabolic lesions caused by the chronic toxic doses of fluoride in humans. The present study has been undertaken with a view to assess the changes in glucose metabolism and related enzymes in erythrocytes of humans consuming toxic doses of fluoride for prolonged periods.

  14. [Gut microbiota may have influence on glucose and lipid metabolism].

    PubMed

    Hallundbæk Mikkelsen, Kristian; Nielsen, Morten Frost; Tvede, Michael; Hansen, Torben; Pedersen, Oluf Borbye; Holst, Jens Juul; Vilsbøll, Tina; Knop, Filip Krag

    2013-11-11

    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.

  15. Serum uromodulin is associated with impaired glucose metabolism

    PubMed Central

    Leiherer, Andreas; Muendlein, Axel; Saely, Christoph H.; Kinz, Elena; Brandtner, Eva M.; Fraunberger, Peter; Drexel, Heinz

    2017-01-01

    Abstract Uromodulin is the most abundant urine protein under physiological conditions. It has recently been described as a serum and plasma marker for kidney disease. Whether uromodulin is associated with impaired glucose metabolism is unknown. We therefore measured serum uromodulin and glucose traits in a cohort of 529 consecutively recruited patients. Serum uromodulin was significantly and inversely correlated with fasting plasma glucose (r = −0.161; P < 0.001), with plasma glucose 2 hours after an oral 75 g glucose challenge (r = −0.158; P = 0.001), and with HbA1c (r = −0.103; P = 0.018). A total of 146 (27.6%) of our patients had type 2 diabetes mellitus (T2DM). Analysis of covariance confirmed that T2DM was an independent determinant of serum uromodulin (F = 5.5, P = 0.020) after multivariate adjustment including hypertension and glomerular filtration rate. Prospectively, uromodulin was lowest in patients with T2DM at baseline, higher in initially nondiabetic subjects who developed diabetes during follow-up (FU) and highest among nondiabetic patients (147.7 ± 69.9 vs 164 ± 67 vs 179.9 ± 82.2 ng/mL, Ptrend < 0.001). Similar results were seen with respect to prediabetes (168.0 ± 81.2 vs 172.8 ± 66.3 vs 188.2 ± 74.0 ng/mL, P = 0.011). We conclude that serum uromodulin is significantly associated with impaired glucose metabolism and the development of prediabetes and diabetes. PMID:28151855

  16. The Lin28/let-7 axis regulates glucose metabolism

    PubMed Central

    Zhu, Hao; Shyh-Chang, Ng; Segrè, 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.

    2012-01-01

    SUMMARY The let-7 tumor suppressor microRNAs are known for their regulation of oncogenes, while the RNA-binding proteins Lin28a/b promote malignancy by blocking let-7 biogenesis. In studies of the Lin28/let-7 pathway, we discovered unexpected roles in regulating metabolism. When overexpressed in mice, both Lin28a and LIN28B promoted an insulin-sensitized state that resisted high fat diet-induced diabetes, whereas muscle-specific loss of Lin28a and overexpression of let-7 resulted in insulin resistance and impaired glucose tolerance. These phenomena occurred in part through let-7-mediated repression of multiple components of the insulin-PI3K-mTOR pathway, including IGF1R, INSR, and IRS2. The mTOR inhibitor rapamycin abrogated the enhanced glucose uptake and insulin-sensitivity conferred by Lin28a in vitro and in vivo. In addition, we found that let-7 targets were enriched for genes that contain SNPs associated with type 2 diabetes and fasting glucose in human genome-wide association studies. These data establish the Lin28/let-7 pathway as a central regulator of mammalian glucose metabolism. PMID:21962509

  17. Impact of salinity on the aerobic metabolism of phosphate-accumulating organisms.

    PubMed

    Welles, L; Lopez-Vazquez, C M; Hooijmans, C M; van Loosdrecht, M C M; Brdjanovic, D

    2015-04-01

    The use of saline water in urban areas for non-potable purposes to cope with fresh water scarcity, intrusion of saline water, and disposal of industrial saline wastewater into the sewerage lead to elevated salinity levels in wastewaters. Consequently, saline wastewater is generated, which needs to be treated before its discharge into surface water bodies. The objective of this research was to study the effects of salinity on the aerobic metabolism of phosphate-accumulating organisms (PAO), which belong to the microbial populations responsible for enhanced biological phosphorus removal (EBPR) in activated sludge systems. In this study, the short-term impact (hours) of salinity (as NaCl) was assessed on the aerobic metabolism of a PAO culture, enriched in a sequencing batch reactor (SBR). All aerobic PAO metabolic processes were drastically affected by elevated salinity concentrations. The aerobic maintenance energy requirement increased, when the salinity concentration rose up to a threshold concentration of 2 % salinity (on a W/V basis as NaCl), while above this concentration, the maintenance energy requirements seemed to decrease. All initial rates were affected by salinity, with the NH4- and PO4-uptake rates being the most sensitive. A salinity increase from 0 to 0.18 % caused a 25, 46, and 63 % inhibition of the O2, PO4, and NH4-uptake rates. The stoichiometric ratios of the aerobic conversions confirmed that growth was the process with the highest inhibition, followed by poly-P and glycogen formation. The study indicates that shock loads of 0.18 % salt, which corresponds to the use or intrusion of about 5 % seawater may severely affect the EBPR process already in wastewater treatment plants not exposed regularly to high salinity concentrations.

  18. Effects of intermittent fasting on glucose and lipid metabolism.

    PubMed

    Antoni, Rona; Johnston, Kelly L; Collins, Adam L; Robertson, M Denise

    2017-01-16

    Two intermittent fasting variants, intermittent energy restriction (IER) and time-restricted feeding (TRF), have received considerable interest as strategies for weight-management and/or improving metabolic health. With these strategies, the pattern of energy restriction and/or timing of food intake are altered so that individuals undergo frequently repeated periods of fasting. This review provides a commentary on the rodent and human literature, specifically focusing on the effects of IER and TRF on glucose and lipid metabolism. For IER, there is a growing evidence demonstrating its benefits on glucose and lipid homeostasis in the short-to-medium term; however, more long-term safety studies are required. Whilst the metabolic benefits of TRF appear quite profound in rodents, findings from the few human studies have been mixed. There is some suggestion that the metabolic changes elicited by these approaches can occur in the absence of energy restriction, and in the context of IER, may be distinct from those observed following similar weight-loss achieved via modest continuous energy restriction. Mechanistically, the frequently repeated prolonged fasting intervals may favour preferential reduction of ectopic fat, beneficially modulate aspects of adipose tissue physiology/morphology, and may also impinge on circadian clock regulation. However, mechanistic evidence is largely limited to findings from rodent studies, thus necessitating focused human studies, which also incorporate more dynamic assessments of glucose and lipid metabolism. Ultimately, much remains to be learned about intermittent fasting (in its various forms); however, the findings to date serve to highlight promising avenues for future research.

  19. Die aerobe Glykolyse der Tumorzelle

    NASA Astrophysics Data System (ADS)

    Schneider, Friedhelm

    1981-01-01

    A high aerobic glycolysis (aerobic lactate production) is the most significant feature of the energy metabolism of rapidly growing tumor cells. Several mechanisms, which may be different in different cell lines, seem to be involved in this characteristic of energy metabolism of the tumor cell. Changes in the cell membrane leading to increased uptake and utilization of glucose, a high level of fetal types of isoenzymes, a decreased number of mitochondria and a reduced capacity to metabolize pyruvate are some factors which must be taken into consideration. It is not possible to favour one of them at the present time.

  20. Metabolic and hormonal changes during aerobic exercise in distance runners.

    PubMed

    Fernández-Pastor, V J; Ruiz, M; Diego-Acosta, A M; Avila, C; García, J C; Pérez, F; Guirado, F; Noguer, N

    1999-03-01

    A group of long-distance runners is studied in order to clarify aspects concerning neuroendocrine mechanisms regulating organic adaptation to maximum effort, with special interest in the function of the growth hormone in fat metabolism and the possible use of ketone bodies as an alternative source of energy. A test is designed on a treadmill with a gradient of 3% and progressive increases in speed of 2 Km/h every 10 min, starting at 6 Km/h, and continuing until exhaustion. Masks are worn to enable the breath by breath measurement of expired gases and the subjects are monitored electrocardiographically using V5. For blood sample collection an antecubital vein is catheterized with a system enabling the replacement of the blood volume extracted by means of perfusion with physiological saline solution, and the increasing concentration of hormones in the blood is evaluated. The results obtained, indicate that epinephrine as well as GH hormones increase significatively from 20 min of exercise in runners promoting changes from carbohydrates to lipids as fuels to carry out exercise. The concomitant variations in energy substrates support the former hypothesis of work. Moreover, the muscle could employ acetylCoA originating from acetoacetate as an alternative metabolic source of fuel during maximum effort.

  1. Aerobic production of succinate from arabinose by metabolically engineered Corynebacterium glutamicum.

    PubMed

    Chen, Tao; Zhu, Nianqing; Xia, Huihua

    2014-01-01

    Arabinose is considered as an ideal feedstock for the microbial production of value-added chemicals due to its abundance in hemicellulosic wastes. In this study, the araBAD operon from Escherichia coli was introduced into succinate-producing Corynebacterium glutamicum, which enabled aerobic production of succinate using arabinose as sole carbon source. The engineered strain ZX1 (pXaraBAD, pEacsAgltA) produced 74.4 mM succinate with a yield of 0.58 mol (mol arabinose)(-1), which represented 69.9% of the theoretically maximal yield. Moreover, this strain produced 110.2 mM succinate using combined substrates of glucose and arabinose. To date, this is the highest succinate production under aerobic conditions in minimal medium.

  2. Glucose Metabolism in the Progression of Prostate Cancer

    PubMed Central

    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

  3. Seasonal Temperature Changes Do Not Affect Cardiac Glucose Metabolism

    PubMed Central

    Schildt, Jukka; Loimaala, Antti; Hippeläinen, Eero; Nikkinen, Päivi; Ahonen, Aapo

    2015-01-01

    FDG-PET/CT is widely used to diagnose cardiac inflammation such as cardiac sarcoidosis. Physiological myocardial FDG uptake often creates a problem when assessing the possible pathological glucose metabolism of the heart. Several factors, such as fasting, blood glucose, and hormone levels, influence normal myocardial glucose metabolism. The effect of outdoor temperature on myocardial FDG uptake has not been reported before. We retrospectively reviewed 29 cancer patients who underwent PET scans in warm summer months and again in cold winter months. We obtained myocardial, liver, and mediastinal standardized uptake values (SUVs) as well as quantitative cardiac heterogeneity and the myocardial FDG uptake pattern. We also compared age and body mass index to other variables. The mean myocardial FDG uptake showed no significant difference between summer and winter months. Average outdoor temperature did not correlate significantly with myocardial SUVmax in either summer or winter. The heterogeneity of myocardial FDG uptake did not differ significantly between seasons. Outdoor temperature seems to have no significant effect on myocardial FDG uptake or heterogeneity. Therefore, warming the patients prior to attending cardiac PET studies in order to reduce physiological myocardial FDG uptake seems to be unnecessary. PMID:26858844

  4. Osteoid osteoma is an osteocalcinoma affecting glucose metabolism.

    PubMed

    Confavreux, C B; Borel, O; Lee, F; Vaz, G; Guyard, M; Fadat, C; Carlier, M-C; Chapurlat, R; Karsenty, G

    2012-05-01

    Osteocalcin is a hormone secreted by osteoblasts, which regulates energy metabolism by increasing β-cell proliferation, insulin secretion, insulin sensitivity, and energy expenditure. This has been demonstrated in mice, but to date, the evidence implicating osteocalcin in the regulation of energy metabolism in humans are indirect. To address this question more directly, we asked whether a benign osteoblastic tumor, such as osteoma osteoid in young adults, may secrete osteocalcin. The study was designed to assess the effect of surgical resection of osteoid osteoma on osteocalcin and blood glucose levels in comparison with patients undergoing knee surgery and healthy volunteers. Blood collections were performed the day of surgery and the following morning after overnight fasting. Patients and controls were recruited in the orthopedic surgery department of New York Presbiterian Hospital, NY-USA and Hospices Civils de Lyon, France. Seven young males were included in the study: two had osteoid osteoma, two underwent knee surgery, and three were healthy volunteers. After resection of the osteoid osteomas, we observed a decrease of osteocalcin by 62% and 30% from the initial levels. Simultaneously, blood glucose increased respectively by 32% and 15%. Bone turnover markers were not affected. This case study shows for the first time that osteocalcin in humans affects blood glucose level. This study also suggests that ostoid osteoma may be considered, at least in part, as an osteocalcinoma.

  5. Towards creating a superstimulus to normalise glucose metabolism in the prediabetic: a case-study in the feast-famine and activity-rest cycle.

    PubMed

    Crowe, Louis; Caulfield, Brian

    2012-03-27

    We live in a time of plenty. During evolution, periods of hunger and simultaneously high activity levels would combine giving a stimulus which is absent from modern lifestyles. This is potentially connected with abnormal glucose metabolism. It was hypothesised that simultaneous fasting and aggressive aerobic neuromuscular electrical stimulation (NMES) exercise, until metabolic exhaustion, may be an acceptable modern equivalent. A healthy subject fasted for 44 h (water allowed) during which he undertook three aerobic NMES sessions at >50%VO(2max); heart rate >160 bpm. Metabolic gas analysis of a comparable session in the non-fasting state showed 100% carbohydrate substrate utilisation. With fasting the NMES exercise consumed mostly fat-up to 100% fat utilisation at 42 h. This clear shift away from using carbohydrate as a substrate and hypoglycaemia may indicate that carbohydrate stores are nearly depleted. The authors postulate that this may constitute a metabolic super stimulus mimicking the famine-activity periods of our ancestors.

  6. [Metabolism of labeled exogenous glucose in fiber flax tissues].

    PubMed

    Chikov, V I; Avvakumova, N Iu; Bakirova, G G; Khamidullina, L A

    2005-01-01

    A labeled glucose solution was introduced into cut fiber flax plants (45-50 cm high) using a special unit under a pressure of 0.1 atm for 30 min, 1, and 2 h. The highest quantities of labeled carbon were revealed in the woody tissue. Sucrose made up a considerable proportion in low molecular weight products of [ [2-14C]-glucose transformation (23.5%). Metabolism of labeled glucose in the leaves exposed to sunlight yielded a set of metabolites similar to products of 14CO2 photoassimilation. In the shade, the pattern of 14C distribution in labeled compounds of the water/alcohol soluble fraction remained similar in mature leaves, while in juvenile leaves, 14C content decreased in sucrose and increased in organic and amino acids. In the shade, the incorporation of 14C into starch and hot water soluble polysaccharides increased at the expense of the acetone fraction (lipids and pigments), water/salt soluble proteins, and cellulose. Low light conditions increased the radioactivity ratio of sparingly soluble (KOH and Triton X-100 soluble) proteins to albumins and globulins. We propose that the synthesis of components of the photosynthetic apparatus in juvenile leaves is directly powered by photosynthesis and the photosynthesis of glucose and the polymers compete for ATP energy. Appearance of sucrose in the woody tissue is due to its release from the phloem to the stem apoplast and the radial transfer to the xylem, where it is transported to the upper shoot with the transpiration flow.

  7. GSM mobile phone radiation suppresses brain glucose metabolism

    PubMed Central

    Kwon, Myoung Soo; Vorobyev, Victor; Kännälä, Sami; Laine, Matti; Rinne, Juha O; Toivonen, Tommi; Johansson, Jarkko; Teräs, Mika; Lindholm, Harri; Alanko, Tommi; Hämäläinen, Heikki

    2011-01-01

    We investigated the effects of mobile phone radiation on cerebral glucose metabolism using high-resolution positron emission tomography (PET) with the 18F-deoxyglucose (FDG) tracer. A long half-life (109 minutes) of the 18F isotope allowed a long, natural exposure condition outside the PET scanner. Thirteen young right-handed male subjects were exposed to a pulse-modulated 902.4 MHz Global System for Mobile Communications signal for 33 minutes, while performing a simple visual vigilance task. Temperature was also measured in the head region (forehead, eyes, cheeks, ear canals) during exposure. 18F-deoxyglucose PET images acquired after the exposure showed that relative cerebral metabolic rate of glucose was significantly reduced in the temporoparietal junction and anterior temporal lobe of the right hemisphere ipsilateral to the exposure. Temperature rise was also observed on the exposed side of the head, but the magnitude was very small. The exposure did not affect task performance (reaction time, error rate). Our results show that short-term mobile phone exposure can locally suppress brain energy metabolism in humans. PMID:21915135

  8. Fractional uptake value as a good indicator for glucose metabolism

    SciTech Connect

    Nishizawa, S.; Yonekura, Y.; Mukai, T. |

    1995-05-01

    In a previous paper, we demonstrated that hyperglycemia enhanced brain tumor detection in FDG-PET studies. However, the autoradiographic method underestimated cerebral glucose metabolism (CMRglc) in hyperglycemia, while dynamic PET scans are often not feasible due to patient`s condition. For such situations, we propose the use of the fractional uptake value (FUV) which is given by Ci(t)/{integral}Ca(t)dt where Ci(t) and Ca(t) are radio-activities in brain and plasma. In this study, we tested FUV as an indicator of the net clearance coefficient of FDG (K*) over a side range of plasma glucose levels. Seven patients with brain tumor underwent FDG-PET studies in normoglycemia (mean: 5.2 mM) and hyperglycemia (mean: 14.6 mM) on separate days. Dynamic PET scan was performed for 40 min with arterial sampling after an i.v. injection of 160-370 MBq of FDG. Data analysis was carried out on cortices contralateral of the tumor. The rate constants (K1*,k2*,k3*, and k4*) and cerebral blood volume of a 3 compartment model were estimated by non-linear least squared optimization. K* was defined as K*=K1*,k3*/(k2*+k3*). FUV was calculated using 4-min scan data from 36 to 40 min of the dynamic scan. The FUV demonstrated a good relationship with K value over a wide range of plasma glucose level (K*=2.0 10{sup -3} +1.02 FUV r=0.99), and proved to be a good indicator for cerebral glucose metabolism.

  9. Metabolic syndrome or glucose challenge in first episode of psychosis?

    PubMed

    Garcia-Rizo, C; Fernandez-Egea, E; Oliveira, C; Meseguer, A; Cabrera, B; Mezquida, G; Bioque, M; Penades, R; Parellada, E; Bernardo, M; Kirkpatrick, B

    2017-03-01

    Patients with schizophrenia exhibit a reduced life expectancy. Although unhealthy lifestyle or suicide risk plays a role, the main causes are diverse medical conditions such as cardiovascular diseases, type 2 diabetes mellitus and metabolic syndrome. Albeit pharmacological secondary side effects might also trigger previous conditions, studies in naïve patients reflect diverse anomalies at the onset. Patients with a first episode of psychosis, display a wide scope of metabolic abnormalities, ranging from normality till pathological values depending on the parameters studied. We attempted to evaluate the metabolic syndrome and glycemic homeostasis in a subset of antipsychotic-naïve patients with a first episode of non-affective psychosis. Patients (n=84) showed a similar prevalence of metabolic syndrome compared with a matched control sample (n=98) (6% vs 4%, P=0.562), while glucose homeostasis values differed significantly (14% vs. 5%, P=0.034). Our results suggest that metabolic syndrome is not a useful clinical condition to be evaluated in patients before pharmacological treatment. Abnormal glycemic homeostasis at the onset of the disease requires specific diagnostic tools and preventive measures in order to avoid future cardiovascular events. New strategies must be implemented in order to evaluate the cardiovascular risk and subsequent morbidity in patients at the onset of the disease.

  10. Posterior Cingulate Glucose Metabolism, Hippocampal Glucose Metabolism, and Hippocampal Volume in Cognitively Normal, Late-Middle-Aged Persons at 3 Levels of Genetic Risk for Alzheimer Disease

    PubMed Central

    Protas, Hillary D.; Chen, Kewei; Langbaum, Jessica B. S.; Fleisher, Adam S.; Alexander, Gene E.; Lee, Wendy; Bandy, Daniel; de Leon, Mony J.; Mosconi, Lisa; Buckley, Shannon; Truran-Sacrey, Diana; Schuff, Norbert; Weiner, Michael W.; Caselli, Richard J.; Reiman, Eric M.

    2013-01-01

    Objective To characterize and compare measurements of the posterior cingulate glucose metabolism, the hippocampal glucose metabolism, and hippocampal volume so as to distinguish cognitively normal, late-middle-aged persons with 2, 1, or 0 copies of the apolipoprotein E (APOE) ε4 allele, reflecting 3 levels of risk for late-onset Alzheimer disease. Design Cross-sectional comparison of measurements of cerebral glucose metabolism using 18F-fluorodeoxy-glucose positron emission tomography and measurements of brain volume using magnetic resonance imaging in cognitively normal ε4 homozygotes, ε4 heterozygotes, and noncarriers. Setting Academic medical center. Participants A total of 31 ε4 homozygotes, 42 ε4 heterozygotes, and 76 noncarriers, 49 to 67 years old, matched for sex, age, and educational level. Main Outcome Measures The measurements of posterior cingulate and hippocampal glucose metabolism were characterized using automated region-of-interest algorithms and normalized for whole-brain measurements. The hippocampal volume measurements were characterized using a semiautomated algorithm and normalized for total intracranial volume. Results Although there were no significant differences among the 3 groups of participants in their clinical ratings, neuropsychological test scores, hippocampal volumes (P=.60), or hippocampal glucose metabolism measurements (P = .12), there were significant group differences in their posterior cingulate glucose metabolism measurements (P=.001). The APOE ε4 gene dose was significantly associated with posterior cingulate glucose metabolism (r=0.29, P=.0003), and this association was significantly greater than those with hippocampal volume or hippocampal glucose metabolism (P<.05, determined by use of pairwise Fisher z tests). Conclusions Although our findings may depend in part on the analysis algorithms used, they suggest that a reduction in posterior cingulate glucose metabolism precedes a reduction in hippocampal volume or

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

    NASA Astrophysics Data System (ADS)

    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.

  12. Postprandial gut hormone responses and glucose metabolism in cholecystectomized patients.

    PubMed

    Sonne, David P; Hare, Kristine J; Martens, Pernille; Rehfeld, Jens F; Holst, Jens J; Vilsbøll, Tina; Knop, Filip K

    2013-02-15

    Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat-rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum bile acids were measured. We found similar basal glucose concentrations in the two groups, whereas cholecystectomized subjects had elevated postprandial glucose excursions. Cholecystectomized subjects had reduced postprandial concentrations of duodenal bile acids, but preserved postprandial plasma GLP-1 responses, compared with control subjects. Also, cholecystectomized patients exhibited augmented fasting glucagon. Basal plasma CCK concentrations were lower and peak concentrations were higher in cholecystectomized patients. The concentrations of GIP, GLP-2, and gastrin were similar in the two groups. In conclusion, cholecystectomized subjects had preserved postprandial GLP-1 responses in spite of decreased duodenal bile delivery, suggesting that gallbladder emptying is not a prerequisite for GLP-1 release. Cholecystectomized patients demonstrated a slight deterioration of postprandial glycemic control, probably because of metabolic changes unrelated to incretin secretion.

  13. Hindlimb muscle fibre size and glycogen stores in bank voles with increased aerobic exercise metabolism.

    PubMed

    Jaromin, Ewa; Wyszkowska, Julia; Labecka, Anna Maria; Sadowska, Edyta Teresa; Koteja, Paweł

    2016-02-01

    To test hypotheses concerning physiological factors limiting the rate of aerobic exercise metabolism, we used a unique experimental evolution model: lines of bank voles selected for high swim-induced aerobic metabolism (A) and unselected, control lines (C). We investigated putative adaptations that result in the increased performance of the hindlimb muscle (gastrocnemius joined with plantaris). The body mass-adjusted muscle mass was higher in A-lines (0.093 g) than in C-lines (0.083 g; P=0.01). However, selection did not affect mean muscle fibre cross-sectional area (P=0.34) or glycogen content assessed with a histochemical periodic acid-Schiff reaction (PAS; P=0.82). The results suggest that the increased aerobic performance is achieved by an increase of total muscle mass, without major qualitative changes in the muscle fibre architecture. However, such a conclusion should be treated with caution, because other modifications, such as increased density of capillaries or mitochondria, could occur.

  14. Rate limiting factors in trichloroethylene co-metabolic degradation by phenol-grown aerobic granules.

    PubMed

    Zhang, Yi; Tay, Joo Hwa

    2014-04-01

    The potential of aerobic granular sludge in co-metabolic removal of recalcitrant substances was evaluated using trichloroethylene (TCE) as the model compound. Aerobic granules cultivated in a sequencing batch reactor with phenol as the growth substrate exhibited TCE and phenol degradation activities lower than previously reported values. Depletion of reducing energy and diffusion limitation within the granules were investigated as the possible rate limiting factors. Sodium formate and citrate were supplied to the granules in batch studies as external electron sources. No significant enhancing effect was observed on the instant TCE transformation rates, but 10 mM formate could improve the ultimate transformation capacity by 26 %. Possible diffusion barrier was studied by sieving the biomass into five size fractions, and determining their specific TCE and phenol degradation rates and capacities. Biomass in the larger size fractions generally showed lower activities. Large granules of >700 μm diameter exhibited only 22 % of the flocs' TCE transformation capacity and 35 % of its phenol dependent SOUR, indicating the possible occurrence of diffusion limitation in larger biomass. However, the highest specific TCE transformation rate was observed with the fraction that mostly consisted of small granules (150-300 μm), suggesting an optimal size range while applying aerobic granules in TCE co-metabolic removal.

  15. Chidamide Inhibits Aerobic Metabolism to Induce Pancreatic Cancer Cell Growth Arrest by Promoting Mcl-1 Degradation

    PubMed Central

    Wang, Yanbing; Kuai, Qiyuan; Li, Changlan; Wang, Yu; Jiang, Xingwei; Wang, Xuanlin; Li, Weijing; He, Min; Ren, Suping; Yu, Qun

    2016-01-01

    Pancreatic cancer is a fatal malignancy worldwide and urgently requires valid therapies. Previous research showed that the HDAC inhibitor chidamide is a promising anti-cancer agent in pancreatic cancer cell lines. In this study, we elucidate a probable underlying anti-cancer mechanism of chidamide involving the degradation of Mcl-1. Mcl-1 is frequently upregulated in human cancers, which has been demonstrated to participate in oxidative phosphorylation, in addition to its anti-apoptotic actions as a Bcl-2 family member. The pancreatic cancer cell lines BxPC-3 and PANC-1 were treated with chidamide, resulting in Mcl-1 degradation accompanied by induction of Mcl-1 ubiquitination. Treatment with MG132, a proteasome inhibitor reduced Mcl-1 degradation stimulated by chidamide. Chidamide decreased O2 consumption and ATP production to inhibit aerobic metabolism in both pancreatic cancer cell lines and primary cells, similar to knockdown of Mcl-1, while overexpression of Mcl-1 in pancreatic cancer cells could restore the aerobic metabolism inhibited by chidamide. Furthermore, chidamide treatment or Mcl-1 knockdown significantly induced cell growth arrest in pancreatic cancer cell lines and primary cells, and Mcl-1 overexpression could reduce this cell growth inhibition. In conclusion, our results suggest that chidamide promotes Mcl-1 degradation through the ubiquitin-proteasome pathway, suppressing the maintenance of mitochondrial aerobic respiration by Mcl-1, and resulting in inhibition of pancreatic cancer cell proliferation. Our work supports the claim that chidamide has therapeutic potential for pancreatic cancer treatment. PMID:27875574

  16. Regulation of Lipid and Glucose Metabolism by Phosphatidylcholine Transfer Protein

    PubMed Central

    Kang, Hye Won; Wei, Jie; Cohen, David E.

    2010-01-01

    Phosphatidylcholine transfer protein (PC-TP, a.k.a. StARD2) binds phosphatidylcholines and catalyzes their intermembrane transfer and exchange in vitro. The structure of PC-TP comprises a hydrophobic pocket and a well-defined head-group binding site, and its gene expression is regulated by peroxisome proliferator activated receptor α. Recent studies have revealed key regulatory roles for PC-TP in lipid and glucose metabolism. Notably, Pctp−/− mice are sensitized to insulin action and exhibit more efficient brown fat-mediated thermogenesis. PC-TP appears to limit access of fatty acids to mitochondria by stimulating the activity of thioesterase superfamily member 2, a newly characterized long-chain fatty acyl-CoA thioesterase. Because PC-TP discriminates among phosphatidylcholines within lipid bilayers, it may function as a sensor that links metabolic regulation to membrane composition. PMID:20338778

  17. TRIM24 Links Glucose Metabolism with Transformation of Human Mammary Epithelial Cells

    PubMed Central

    Pathiraja, Thushangi N.; Thakkar, Kaushik N.; Jiang, Shiming; Stratton, Sabrina; Liu, Zhaoliang; Gagea, Mihai; Xi, Shi; Shah, Parantu K.; Phan, Liem; Lee, Mong-Hong; Andersen, Jannik; Stampfer, Martha; Barton, Michelle C.

    2015-01-01

    Tripartite motif 24 protein (TRIM24) is a plant homeodomain (PHD)/bromodomain histone reader, recently associated with poor overall survival of breast cancer patients. At a molecular level, TRIM24 is a negative regulator of p53 levels and a co-activator of estrogen receptor. However, the role of TRIM24 in breast tumorigenesis remains largely unknown. We used an isogenic human mammary epithelial cell (HMEC) culture model, derived from reduction mammoplasty tissue, and found that ectopic expression of TRIM24 in immortalized HMECs (TRIM24-iHMECs) greatly increased cellular proliferation and induced malignant transformation. Subcutaneous injection of TRIM24-iHMECs in nude mice led to growth of intermediate to high-grade tumors in 60-70% of mice. Molecular analysis of TRIM24-iHMECs revealed a glycolytic and tricarboxylic acid cycle gene signature, alongside increased glucose uptake and activated aerobic glycolysis. Collectively, these results identify a role for TRIM24 in breast tumorigenesis through reprogramming of glucose metabolism in HMECs, further supporting TRIM24 as a viable therapeutic target in breast cancers. PMID:25065590

  18. Metabolic reprogramming during neuronal differentiation from aerobic glycolysis to neuronal oxidative phosphorylation

    PubMed Central

    Zheng, Xinde; Boyer, Leah; Jin, Mingji; Mertens, Jerome; Kim, Yongsung; Ma, Li; Ma, Li; Hamm, Michael; Gage, Fred H; Hunter, Tony

    2016-01-01

    How metabolism is reprogrammed during neuronal differentiation is unknown. We found that the loss of hexokinase (HK2) and lactate dehydrogenase (LDHA) expression, together with a switch in pyruvate kinase gene splicing from PKM2 to PKM1, marks the transition from aerobic glycolysis in neural progenitor cells (NPC) to neuronal oxidative phosphorylation. The protein levels of c-MYC and N-MYC, transcriptional activators of the HK2 and LDHA genes, decrease dramatically. Constitutive expression of HK2 and LDHA during differentiation leads to neuronal cell death, indicating that the shut-off aerobic glycolysis is essential for neuronal survival. The metabolic regulators PGC-1α and ERRγ increase significantly upon neuronal differentiation to sustain the transcription of metabolic and mitochondrial genes, whose levels are unchanged compared to NPCs, revealing distinct transcriptional regulation of metabolic genes in the proliferation and post-mitotic differentiation states. Mitochondrial mass increases proportionally with neuronal mass growth, indicating an unknown mechanism linking mitochondrial biogenesis to cell size. DOI: http://dx.doi.org/10.7554/eLife.13374.001 PMID:27282387

  19. The low affinity glucose transporter HxtB is also involved in glucose signalling and metabolism in Aspergillus nidulans.

    PubMed

    Dos Reis, Thaila Fernanda; Nitsche, Benjamin M; de Lima, Pollyne Borborema Almeida; de Assis, Leandro José; Mellado, Laura; Harris, Steven D; Meyer, Vera; Dos Santos, Renato A Corrêa; Riaño-Pachón, Diego M; Ries, Laure Nicolas Annick; Goldman, Gustavo H

    2017-03-31

    One of the drawbacks during second-generation biofuel production from plant lignocellulosic biomass is the accumulation of glucose, the preferred carbon source of microorganisms, which causes the repression of hydrolytic enzyme secretion by industrially relevant filamentous fungi. Glucose sensing, subsequent transport and cellular signalling pathways have been barely elucidated in these organisms. This study therefore characterized the transcriptional response of the filamentous fungus Aspergillus nidulans to the presence of high and low glucose concentrations under continuous chemostat cultivation with the aim to identify novel factors involved in glucose sensing and signalling. Several transcription factor- and transporter-encoding genes were identified as being differentially regulated, including the previously characterized glucose and xylose transporter HxtB. HxtB was confirmed to be a low affinity glucose transporter, localizing to the plasma membrane under low- and high-glucose conditions. Furthermore, HxtB was shown to be involved in conidiation-related processes and may play a role in downstream glucose signalling. A gene predicted to encode the protein kinase PskA was also identified as being important for glucose metabolism. This study identified several proteins with predicted roles in glucose metabolic processes and provides a foundation for further investigation into the response of biotechnologically important filamentous fungi to glucose.

  20. The low affinity glucose transporter HxtB is also involved in glucose signalling and metabolism in Aspergillus nidulans

    PubMed Central

    dos Reis, Thaila Fernanda; Nitsche, Benjamin M.; de Lima, Pollyne Borborema Almeida; de Assis, Leandro José; Mellado, Laura; Harris, Steven D.; Meyer, Vera; dos Santos, Renato A. Corrêa; Riaño-Pachón, Diego M.; Ries, Laure Nicolas Annick; Goldman, Gustavo H.

    2017-01-01

    One of the drawbacks during second-generation biofuel production from plant lignocellulosic biomass is the accumulation of glucose, the preferred carbon source of microorganisms, which causes the repression of hydrolytic enzyme secretion by industrially relevant filamentous fungi. Glucose sensing, subsequent transport and cellular signalling pathways have been barely elucidated in these organisms. This study therefore characterized the transcriptional response of the filamentous fungus Aspergillus nidulans to the presence of high and low glucose concentrations under continuous chemostat cultivation with the aim to identify novel factors involved in glucose sensing and signalling. Several transcription factor- and transporter-encoding genes were identified as being differentially regulated, including the previously characterized glucose and xylose transporter HxtB. HxtB was confirmed to be a low affinity glucose transporter, localizing to the plasma membrane under low- and high-glucose conditions. Furthermore, HxtB was shown to be involved in conidiation-related processes and may play a role in downstream glucose signalling. A gene predicted to encode the protein kinase PskA was also identified as being important for glucose metabolism. This study identified several proteins with predicted roles in glucose metabolic processes and provides a foundation for further investigation into the response of biotechnologically important filamentous fungi to glucose. PMID:28361917

  1. Diminished brain glucose metabolism is a significant determinant for falling rates of systemic glucose utilization during sleep in normal humans.

    PubMed Central

    Boyle, P J; Scott, J C; Krentz, A J; Nagy, R J; Comstock, E; Hoffman, C

    1994-01-01

    Systemic glucose utilization declines during sleep in man. We tested the hypothesis that this decline in utilization is largely accounted for by reduced brain glucose metabolism. 10 normal subjects underwent internal jugular and radial artery cannulation to determine cerebral blood flow by N2O equilibrium technique and to quantitate cross-brain glucose and oxygen differences before and every 3 h during sleep. Sleep stage was graded by continuous electroencephalogram, and systemic glucose turnover was estimated by isotope dilution. Brain glucose metabolism fell from 33.6 +/- 2.2 mumol/100 g per min (mean +/- SE) before sleep (2300 h) to a mean nadir of 24.3 +/- 1.1 mumol/100 g per min at 0300 h during sleep (P = 0.001). Corresponding rates of systemic glucose utilization fell from 13.2 +/- 0.8 to 11.0 +/- 0.5 mumol/kg per min (P = 0.003). Diminished brain glucose metabolism was the product of a reduced arteriovenous glucose difference, 0.643 +/- 0.024 to 0.546 +/- 0.020 mmol/liter (P = 0.002), and cerebral blood flow, 50.3 +/- 2.8 to 44.6 +/- 1.4 cc/100 g per min (P = 0.021). Brain oxygen metabolism fell commensurately from 153.4 +/- 11.8 to 128.0 +/- 8.4 mumol/100 g per min (P = 0.045). The observed reduction in brain metabolism occurred independent of stage of central nervous system electrical activity (electroencephalographic data), and was more closely linked to duration of sleep. We conclude that a decline in brain glucose metabolism is a significant determinant of falling rates of systemic glucose utilization during sleep. Images PMID:8113391

  2. Dietary Iron Controls Circadian Hepatic Glucose Metabolism Through Heme Synthesis

    PubMed Central

    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

    2015-01-01

    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. PMID:25315005

  3. Polysaccharides from Enteromorpha prolifera Improve Glucose Metabolism in Diabetic Rats

    PubMed Central

    Lin, Wenting; Wang, Wenxiang; Liao, Dongdong; Chen, Damiao; Zhu, Pingping; Cai, Guoxi; Kiyoshi, Aoyagi

    2015-01-01

    This study investigated the effects of polysaccharides from Enteromorpha prolifera (PEP) on glucose metabolism in a rat model of diabetes mellitus (DM). PEP (0, 150, 300, and 600 mg/kg) was administered intragastrically to rats for four weeks. After treatment, fasting blood glucose (FBG) and insulin (INS) levels were measured, and the insulin sensitivity index (ISI) was calculated. The morphopathological changes in the pancreas were observed. Serum samples were collected to measure the oxidant-antioxidant status. The mRNA expression levels of glucokinase (GCK) and insulin receptor (InsR) in liver tissue and glucose transporter type 4 (GLUT-4) and adiponectin (APN) in adipose tissue were determined. Compared with the model group, the FBG and INS levels were lower, the ISI was higher, and the number of islet β-cells was significantly increased in all the PEP groups. In the medium- and high-dose PEP groups, MDA levels decreased, and the enzymatic activities of SOD and GSH-Px increased. The mRNA expression of InsR and GCK increased in all the PEP groups; APN mRNA expression increased in the high-dose PEP group, and GLUT-4 mRNA expression increased in adipose tissue. These findings suggest that PEP is a potential therapeutic agent that can be utilized to treat DM. PMID:26347892

  4. AKT1 G205T genotype influences obesity-related metabolic phenotypes and their responses to aerobic exercise training in older Caucasians.

    PubMed

    McKenzie, Jennifer A; Witkowski, Sarah; Ludlow, Andrew T; Roth, Stephen M; Hagberg, James M

    2011-03-01

    As part of the insulin signalling pathway, Akt influences growth and metabolism. The AKT1 gene G205T (rs1130214) polymorphism has potential functional effects. Thus, we determined whether the G205T polymorphism influences metabolic variables and their responses to aerobic exercise training. Following dietary stabilization, healthy, sedentary, 50- to 75-year-old Caucasian men (n = 51) and women (n = 58) underwent 6 months of aerobic exercise training. Before and after completing the intervention, dual-energy X-ray absorptiometry was used to measure percentage body fat, computed tomography to measure visceral and subcutaneous fat, and oral glucose tolerance testing to measure glucose total area under the curve (AUC), insulin AUC and insulin sensitivity. Taqman assay was used to determine AKT1 G205T genotypes. At baseline, men with the GG genotype (n = 29) had lower maximal oxygen consumption (VO2 max) values (P = 0.026) and higher percentage body fat (P = 0.046), subcutaneous fat (P = 0.021) and insulin AUC (P = 0.003) values than T allele carriers (n = 22). Despite their rather disadvantageous starting values, men with the GG genotype seemed to respond to exercise training more robustly than men with the T allele, highlighted by significantly greater fold change improvements in insulin AUC (P = 0.012) and glucose AUC (P = 0.035). Although the GG group also significantly improved VO2 max with training, the change in VO2 max was not as great as that of the T allele carriers (P = 0.037). In contrast, after accounting for hormone replacement therapy use, none of the variables differed in the women at baseline. As a result of exercise training, women with the T allele (n = 20) had greater fold change improvements in fasting glucose (P = 0.011), glucose AUC (P = 0.017) and insulin sensitivity (P = 0.044) than GG genotype women (n = 38). Our results suggest that the AKT1 G205T polymorphism influences metabolic variables and their responses to aerobic exercise training in

  5. Transcription of genes coding for metabolic key functions in Nitrosomonas europaea during aerobic and anaerobic growth.

    PubMed

    Beyer, Sonja; Gilch, Stefan; Meyer, Ortwin; Schmidt, Ingo

    2009-01-01

    Nitrosomonas europaea can grow under conditions of chemolithoautotrophic aerobic (oxygen as oxidant) as well as anaerobic [nitrogen dioxide (NO(2)) as oxidant] nitrification or chemoorganotrophic anaerobic pyruvate-dependent denitrification. In this study, the adaptation of the transcription (mRNA synthesis/concentration) of N. europaea to aerobic and anaerobic growth conditions was evaluated and the transcription of genes coding for metabolic key functions was analyzed: nitrogen and energy metabolism (amoA, hao, rh1, nirK, norB, nsc, aceE, ldhA, ppc, gltA, odhA, coxA), carbon dioxide fixation (cbbL), gluconeogenesis (ppsA), cell growth (ftsZ), and oxidative stress (sodB). During aerobic ammonia oxidation the specific activities of ammonia oxidation, nitrite reduction, and the growth rates correlated with the transcription level of the corresponding genes amoA/hao, nirK/norB/nsc, and cbbL/ftsZ. In anaerobically ammonia-oxidizing cells of N. europaea, the cellular mRNA concentrations of amoA, hao, rh1,coxA, cbbL, ftsZ, and sodB were reduced compared with aerobically nitrifying cells, but the mRNA levels of nirK, norB, and nsc were significantly increased. During anaerobic pyruvate-dependent denitrification, the mRNA abundance of nirK, norB, nsc, aceE, gltA, and odhA was increased, while the concentrations of amoA,hao, rh1, coxAcbbL, ftsZ, and sodB were significantly reduced. Temperature, pH value, and NH(4)(+), O(2), NO, and NO(2) concentrations had comparatively small effects on the transcription of the studied genes.

  6. Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.

    PubMed

    Panfoli, Isabella; Ravera, Silvia; Podestà, Marina; Cossu, Claudia; Santucci, Laura; Bartolucci, Martina; Bruschi, Maurizio; Calzia, Daniela; Sabatini, Federica; Bruschettini, Matteo; Ramenghi, Luca Antonio; Romantsik, Olga; Marimpietri, Danilo; Pistoia, Vito; Ghiggeri, Gianmarco; Frassoni, Francesco; Candiano, Giovanni

    2016-04-01

    Exosomes are secreted nanovesicles that are able to transfer RNA and proteins to target cells. The emerging role of mesenchymal stem cell (MSC) exosomes as promoters of aerobic ATP synthesis restoration in damaged cells, prompted us to assess whether they contain an extramitochondrial aerobic respiration capacity. Exosomes were isolated from culture medium of human MSCs from umbilical cord of ≥37-wk-old newborns or between 28- to 30-wk-old newborns (i.e.,term or preterm infants). Characterization of samples was conducted by cytofluorometry. Oxidative phosphorylation capacity was assessed by Western blot analysis, oximetry, and luminometric and fluorometric analyses. MSC exosomes express functional respiratory complexes I, IV, and V, consuming oxygen. ATP synthesis was only detectable in exosomes from term newborns, suggestive of a specific mechanism that is not completed at an early gestational age. Activities are outward facing and comparable to those detected in mitochondria isolated from term MSCs. MSC exosomes display an unsuspected aerobic respiratory ability independent of whole mitochondria. This may be relevant for their ability to rescue cell bioenergetics. The differential oxidative metabolism of pretermvs.term exosomes sheds new light on the preterm newborn's clinical vulnerability. A reduced ability to repair damaged tissue and an increased capability to cope with anoxic environment for preterm infants can be envisaged.-Panfoli, I., Ravera, S., Podestà, M., Cossu, C., Santucci, L., Bartolucci, M., Bruschi, M., Calzia, D., Sabatini, F., Bruschettini, M., Ramenghi, L. A., Romantsik, O., Marimpietri, D., Pistoia, V., Ghiggeri, G., Frassoni, F., Candiano, G. Exosomes from human mesenchymal stem cells conduct aerobic metabolism in term and preterm newborn infants.

  7. Transcriptional and metabolic effects of glucose on Streptococcus pneumoniae sugar metabolism

    PubMed Central

    Paixão, Laura; Caldas, José; Kloosterman, Tomas G.; Kuipers, Oscar P.; Vinga, Susana; Neves, Ana R.

    2015-01-01

    Streptococcus pneumoniae is a strictly fermentative human pathogen that relies on carbohydrate metabolism to generate energy for growth. The nasopharynx colonized by the bacterium is poor in free sugars, but mucosa lining glycans can provide a source of sugar. In blood and inflamed tissues glucose is the prevailing sugar. As a result during progression from colonization to disease S. pneumoniae has to cope with a pronounced shift in carbohydrate nature and availability. Thus, we set out to assess the pneumococcal response to sugars found in glycans and the influence of glucose (Glc) on this response at the transcriptional, physiological, and metabolic levels. Galactose (Gal), N-acetylglucosamine (GlcNAc), and mannose (Man) affected the expression of 8 to 14% of the genes covering cellular functions including central carbon metabolism and virulence. The pattern of end-products as monitored by in vivo 13C-NMR is in good agreement with the fermentation profiles during growth, while the pools of phosphorylated metabolites are consistent with the type of fermentation observed (homolactic vs. mixed) and regulation at the metabolic level. Furthermore, the accumulation of α-Gal6P and Man6P indicate metabolic bottlenecks in the metabolism of Gal and Man, respectively. Glc added to cells actively metabolizing other sugar(s) was readily consumed and elicited a metabolic shift toward a homolactic profile. The transcriptional response to Glc was large (over 5% of the genome). In central carbon metabolism (most represented category), Glc exerted mostly negative regulation. The smallest response to Glc was observed on a sugar mix, suggesting that exposure to varied sugars improves the fitness of S. pneumoniae. The expression of virulence factors was negatively controlled by Glc in a sugar-dependent manner. Overall, our results shed new light on the link between carbohydrate metabolism, adaptation to host niches and virulence. PMID:26500614

  8. Tumor suppressor WWOX regulates glucose metabolism via HIF1α modulation

    PubMed Central

    Abu-Remaileh, M; Aqeilan, R I

    2014-01-01

    The WW domain-containing oxidoreductase (WWOX) encodes a tumor suppressor that is frequently lost in many cancer types. Wwox-deficient mice develop normally but succumb to a lethal hypoglycemia early in life. Here, we identify WWOX as a tumor suppressor with emerging role in regulation of aerobic glycolysis. WWOX controls glycolytic genes' expression through hypoxia-inducible transcription factor 1α (HIF1α) regulation. Specifically, WWOX, via its first WW domain, physically interacts with HIF1α and modulates its levels and transactivation function. Consistent with this notion, Wwox-deficient cells exhibited increased HIF1α levels and activity and displayed increased glucose uptake. Remarkably, WWOX deficiency is associated with enhanced glycolysis and diminished mitochondrial respiration, conditions resembling the ‘Warburg effect'. Furthermore, Wwox-deficient cells are more tumorigenic and display increased levels of GLUT1 in vivo. Finally, WWOX expression is inversely correlated with GLUT1 levels in breast cancer samples highlighting WWOX as a modulator of cancer metabolism. Our studies uncover an unforeseen role for the tumor-suppressor WWOX in cancer metabolism. PMID:25012504

  9. Tumor suppressor WWOX regulates glucose metabolism via HIF1α modulation.

    PubMed

    Abu-Remaileh, M; Aqeilan, R I

    2014-11-01

    The WW domain-containing oxidoreductase (WWOX) encodes a tumor suppressor that is frequently lost in many cancer types. Wwox-deficient mice develop normally but succumb to a lethal hypoglycemia early in life. Here, we identify WWOX as a tumor suppressor with emerging role in regulation of aerobic glycolysis. WWOX controls glycolytic genes' expression through hypoxia-inducible transcription factor 1α (HIF1α) regulation. Specifically, WWOX, via its first WW domain, physically interacts with HIF1α and modulates its levels and transactivation function. Consistent with this notion, Wwox-deficient cells exhibited increased HIF1α levels and activity and displayed increased glucose uptake. Remarkably, WWOX deficiency is associated with enhanced glycolysis and diminished mitochondrial respiration, conditions resembling the 'Warburg effect'. Furthermore, Wwox-deficient cells are more tumorigenic and display increased levels of GLUT1 in vivo. Finally, WWOX expression is inversely correlated with GLUT1 levels in breast cancer samples highlighting WWOX as a modulator of cancer metabolism. Our studies uncover an unforeseen role for the tumor-suppressor WWOX in cancer metabolism.

  10. Glycogen metabolism protects against metabolic insult to preserve carotid body function during glucose deprivation.

    PubMed

    Holmes, Andrew P; Turner, Philip J; Carter, Paul; Leadbeater, Wendy; Ray, Clare J; Hauton, David; Buckler, Keith J; Kumar, Prem

    2014-10-15

    The view that the carotid body (CB) type I cells are direct physiological sensors of hypoglycaemia is challenged by the finding that the basal sensory neuronal outflow from the whole organ is unchanged in response to low glucose. The reason for this difference in viewpoint and how the whole CB maintains its metabolic integrity when exposed to low glucose is unknown. Here we show that, in the intact superfused rat CB, basal sensory neuronal activity was sustained during glucose deprivation for 29.1 ± 1.2 min, before irreversible failure following a brief period of excitation. Graded increases in the basal discharge induced by reducing the superfusate PO2 led to proportional decreases in the time to the pre-failure excitation during glucose deprivation which was dependent on a complete run-down in glycolysis and a fall in cellular energy status. A similar ability to withstand prolonged glucose deprivation was observed in isolated type I cells. Electron micrographs and immunofluorescence staining of rat CB sections revealed the presence of glycogen granules and the glycogen conversion enzymes glycogen synthase I and glycogen phosphorylase BB, dispersed throughout the type I cell cytoplasm. Furthermore, pharmacological attenuation of glycogenolysis and functional depletion of glycogen both significantly reduced the time to glycolytic run-down by ∼33 and 65%, respectively. These findings suggest that type I cell glycogen metabolism allows for the continuation of glycolysis and the maintenance of CB sensory neuronal output in periods of restricted glucose delivery and this may act as a key protective mechanism for the organ during hypoglycaemia. The ability, or otherwise, to preserve energetic status may thus account for variation in the reported capacity of the CB to sense physiological glucose concentrations and may even underlie its function during pathological states associated with augmented CB discharge.

  11. Integration of ChREBP-Mediated Glucose Sensing into Whole Body Metabolism.

    PubMed

    Baraille, Floriane; Planchais, Julien; Dentin, Renaud; Guilmeau, Sandra; Postic, Catherine

    2015-11-01

    Since glucose is the principal energy source for most cells, many organisms have evolved numerous and sophisticated mechanisms to sense glucose and respond to it appropriately. In this context, cloning of the carbohydrate responsive element binding protein has unraveled a critical molecular link between glucose metabolism and transcriptional reprogramming induced by glucose. In this review, we detail major findings that have advanced our knowledge of glucose sensing.

  12. Biodegradation of o-nitrophenol by aerobic granules with glucose as co-substrate.

    PubMed

    Basheer, Farrukh; Isa, M H; Farooqi, I H

    2012-01-01

    Aerobic granules to treat wastewater containing o-nitrophenol were successfully developed in a sequencing batch reactor (SBR) using activated sludge as inoculum. Stable aerobic granules were obtained with a clearly defined shape and diameters ranging from 2 to 6 mm after 122 days of operation. The integrity coefficient (IC) and granules density was found to be 98% and 1,054 kg m(-3) respectively. After development of aerobic granules, o-nitrophenols were successfully degraded to an efficiency of 78% at a concentration of 70 mg L(-1). GC-MS study revealed that the biodegradation of o-nitrophenol occurred via catechol via nitrobenzene pathway. Specific o-nitrophenol biodegradation rates followed the Haldane model and the associated kinetic parameters were found as follows: V(max) = 3.96 g o-nitrophenol g(-1)VSS(-1)d(-1), K(s) = 198.12 mg L(-1), and K(i) = 31.16 mg L(-1). The aerobic granules proved to be a feasible and effective way to degrade o-nitrophenol containing wastewater.

  13. Redox-sensing regulator Rex regulates aerobic metabolism, morphological differentiation, and avermectin production in Streptomyces avermitilis

    PubMed Central

    Liu, Xingchao; Cheng, Yaqing; Lyu, Mengya; Wen, Ying; Song, Yuan; Chen, Zhi; Li, Jilun

    2017-01-01

    The regulatory role of redox-sensing regulator Rex was investigated in Streptomyces avermitilis. Eleven genes/operons were demonstrated to be directly regulated by Rex; these genes/operons are involved in aerobic metabolism, morphological differentiation, and secondary metabolism. Rex represses transcription of target genes/operons by binding to Rex operator (ROP) sequences in the promoter regions. NADH reduces DNA-binding activity of Rex to target promoters, while NAD+ competitively binds to Rex and modulates its DNA-binding activity. Rex plays an essential regulatory role in aerobic metabolism by controlling expression of the respiratory genes atpIBEFHAGDC, cydA1B1CD, nuoA1-N1, rex-hemAC1DB, hppA, and ndh2. Rex also regulates morphological differentiation by repressing expression of wblE, which encodes a putative WhiB-family transcriptional regulator. A rex-deletion mutant (Drex) showed higher avermectin production than the wild-type strain ATCC31267, and was more tolerant of oxygen limitation conditions in regard to avermectin production. PMID:28303934

  14. WWOX loss activates aerobic glycolysis.

    PubMed

    Abu-Remaileh, Muhannad; Seewaldt, Victoria L; Aqeilan, Rami I

    2015-01-01

    Cancer cells undergo reprogramming of glucose metabolism to limit energy production to glycolysis-a state known as "aerobic glycolysis." Hypoxia-inducible factor 1 (HIF1α) is a transcription factor that regulates many genes responsible for this switch. As discussed here, new data suggest that the tumor suppressor WW domain-containing oxidoreductase (WWOX) modulates HIF1α, thereby regulating this metabolic state.

  15. WWOX loss activates aerobic glycolysis

    PubMed Central

    Abu-Remaileh, Muhannad; Seewaldt, Victoria L; Aqeilan, Rami I

    2015-01-01

    Cancer cells undergo reprogramming of glucose metabolism to limit energy production to glycolysis—a state known as “aerobic glycolysis.” Hypoxia-inducible factor 1 (HIF1α) is a transcription factor that regulates many genes responsible for this switch. As discussed here, new data suggest that the tumor suppressor WW domain-containing oxidoreductase (WWOX) modulates HIF1α, thereby regulating this metabolic state. PMID:27308416

  16. Intraspecific variation in aerobic metabolic rate of fish: relations with organ size and enzyme activity in brown trout.

    PubMed

    Norin, Tommy; Malte, Hans

    2012-01-01

    Highly active animals require a high aerobic capacity (i.e., a high maximum metabolic rate [MMR]) to sustain such activity, and it has been speculated that a greater capacity for aerobic performance is reflected in larger organs, which serve as energy processors but are also expensive to maintain and which increase the minimal cost of living (i.e., the basal or standard metabolic rate [SMR]). In this study, we assessed the extent of intraspecific variation in metabolic rate within a group of brown trout (Salmo trutta L.) and tested whether the observed variation in residual (body-mass-corrected) SMR, MMR, and absolute aerobic scope could be explained by variations in the residual size (mass) of metabolically active internal organs. Residual SMR was found to correlate positively with residual MMR, indicating a link between these two metabolic parameters, but no relationship between organ mass and metabolic rate was found for liver, heart, spleen, intestine, or stomach. Instead, activity in the liver of two aerobic mitochondrial enzymes, cytochrome c oxidase and, to a lesser extent, citrate synthase, was found to correlate with whole-animal metabolic rate, indicating that causes for intraspecific variation in the metabolic rate of fish can be found at a lower organizational level than organ size.

  17. Metabolism of 2-methylpropene (isobutylene) by the aerobic bacterium Mycobacterium sp. strain ELW1.

    PubMed

    Kottegoda, Samanthi; Waligora, Elizabeth; Hyman, Michael

    2015-03-01

    An aerobic bacterium (Mycobacterium sp. strain ELW1) that utilizes 2-methylpropene (isobutylene) as a sole source of carbon and energy was isolated and characterized. Strain ELW1 grew on 2-methylpropene (growth rate = 0.05 h(-1)) with a yield of 0.38 mg (dry weight) mg 2-methylpropene(-1). Strain ELW1 also grew more slowly on both cis- and trans-2-butene but did not grow on any other C2 to C5 straight-chain, branched, or chlorinated alkenes tested. Resting 2-methylpropene-grown cells consumed ethene, propene, and 1-butene without a lag phase. Epoxyethane accumulated as the only detected product of ethene oxidation. Both alkene consumption and epoxyethane production were fully inhibited in cells exposed to 1-octyne, suggesting that alkene oxidation is initiated by an alkyne-sensitive, epoxide-generating monooxygenase. Kinetic analyses indicated that 1,2-epoxy-2-methylpropane is rapidly consumed during 2-methylpropene degradation, while 2-methyl-2-propen-1-ol is not a significant metabolite of 2-methylpropene catabolism. Degradation of 1,2-epoxy-2-methylpropane by 2-methylpropene-grown cells led to the accumulation and further degradation of 2-methyl-1,2-propanediol and 2-hydroxyisobutyrate, two sequential metabolites previously identified in the aerobic microbial metabolism of methyl tert-butyl ether (MTBE) and tert-butyl alcohol (TBA). Growth of strain ELW1 on 2-methylpropene, 1,2-epoxy-2-methylpropane, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate was fully inhibited when cobalt ions were omitted from the growth medium, while growth on 3-hydroxybutyrate and other substrates was unaffected by the absence of added cobalt ions. Our results suggest that, like aerobic MTBE- and TBA-metabolizing bacteria, strain ELW1 utilizes a cobalt/cobalamin-dependent mutase to transform 2-hydroxyisobutyrate. Our results have been interpreted in terms of their impact on our understanding of the microbial metabolism of alkenes and ether oxygenates.

  18. Metabolism of 2-Methylpropene (Isobutylene) by the Aerobic Bacterium Mycobacterium sp. Strain ELW1

    PubMed Central

    Kottegoda, Samanthi; Waligora, Elizabeth

    2015-01-01

    An aerobic bacterium (Mycobacterium sp. strain ELW1) that utilizes 2-methylpropene (isobutylene) as a sole source of carbon and energy was isolated and characterized. Strain ELW1 grew on 2-methylpropene (growth rate = 0.05 h−1) with a yield of 0.38 mg (dry weight) mg 2-methylpropene−1. Strain ELW1 also grew more slowly on both cis- and trans-2-butene but did not grow on any other C2 to C5 straight-chain, branched, or chlorinated alkenes tested. Resting 2-methylpropene-grown cells consumed ethene, propene, and 1-butene without a lag phase. Epoxyethane accumulated as the only detected product of ethene oxidation. Both alkene consumption and epoxyethane production were fully inhibited in cells exposed to 1-octyne, suggesting that alkene oxidation is initiated by an alkyne-sensitive, epoxide-generating monooxygenase. Kinetic analyses indicated that 1,2-epoxy-2-methylpropane is rapidly consumed during 2-methylpropene degradation, while 2-methyl-2-propen-1-ol is not a significant metabolite of 2-methylpropene catabolism. Degradation of 1,2-epoxy-2-methylpropane by 2-methylpropene-grown cells led to the accumulation and further degradation of 2-methyl-1,2-propanediol and 2-hydroxyisobutyrate, two sequential metabolites previously identified in the aerobic microbial metabolism of methyl tert-butyl ether (MTBE) and tert-butyl alcohol (TBA). Growth of strain ELW1 on 2-methylpropene, 1,2-epoxy-2-methylpropane, 2-methyl-1,2-propanediol, and 2-hydroxyisobutyrate was fully inhibited when cobalt ions were omitted from the growth medium, while growth on 3-hydroxybutyrate and other substrates was unaffected by the absence of added cobalt ions. Our results suggest that, like aerobic MTBE- and TBA-metabolizing bacteria, strain ELW1 utilizes a cobalt/cobalamin-dependent mutase to transform 2-hydroxyisobutyrate. Our results have been interpreted in terms of their impact on our understanding of the microbial metabolism of alkenes and ether oxygenates. PMID:25576605

  19. Glucose starvation is required for insulin stimulation of glucose uptake and metabolism in cultured microvascular endothelial cells

    SciTech Connect

    Gerritsen, M.E.; Burke, T.M.; Allen, L.A.

    1988-03-01

    In the present study we determined the uptake and disposition of glucose in serum-deprived rabbit coronary microvessel endothelial (RCME) cells. RCME cells exhibited stereospecific hexose uptake inhibited by cytochalasin B. Pretreatment of the RCME cells with potassium cyanide or 2,4-dinitrophenol inhibited 2-deoxyglucose uptake but not 3-O-methylglucose transport. A major proportion (30-60%) of the 2-deoxyglucose present in the RCME cells was not phosphorylated. These two observations suggested that the rate-limiting step in the uptake of 2-deoxyglucose was not transport but rather the phosphorylation of 2-deoxyglucose to 2-deoxyglucose 6-phosphate. When glucose-deprived cells were incubated 2 hr with (U-14C)glucose the disposition of the label was as follows: glycogen 60%, acid-soluble fraction 30%, and lipid less than 5%. In contrast glucose-fed cells exhibited lower overall glucose incorporation, and a slightly different disposition: glycogen 45%, acid-soluble fraction 50%, and lipid 5%. Glucose-deprived RCME cells also exhibited greater basal levels of 2-deoxyglucose uptake compared to glucose-fed cells. RCME cells incubated in the absence of glucose and serum for 16 hr exhibited dose-dependent insulin stimulation of hexose uptake and subsequent metabolism to macromolecules (i.e., glycogen and the acid-soluble fraction). Significant effects of insulin were observed with concentrations as low as 2 x 10(-10) M, well within the physiological range. In contrast, cells preincubated in serum-free culture medium containing 5.5 mM glucose did not exhibit insulin-enhanced hexose uptake or glucose metabolism (even at doses as high as 10(-7) M). These studies indicate that the effects of insulin on rabbit coronary microvascular endothelial cell glucose uptake and metabolism require both serum and glucose deprivation.

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

    PubMed

    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.

  1. Glucose metabolic abnormality is associated with defective mineral homeostasis in skeletal disorder mouse model.

    PubMed

    Zou, JiangHuan; Xiong, XiWen; Lai, BeiBei; Sun, Min; Tu, Xin; Gao, Xiang

    2015-04-01

    Bone was reported as a crucial organ for regulating glucose homeostasis. In this study, we found that Phex mutant mice (PUG), a model of human X-linked hypophosphatemic rickets (XLH), displayed metabolic abnormality in addition to abnormal phosphate homeostasis, skeletal deformity and growth retardation. Glucose tolerance was elevated with enhanced insulin sensitivity in PUG, though circulating insulin level decreased. Interestingly, bone mineral density defects and glucose metabolic abnormality were both rescued by adding phosphorus- and calcium-enriched supplements in daily diet. Serum insulin level, glucose tolerance and insulin sensitivity showed no differences between PUG and wild-type mice with rescued osteocalcin (OCN) following treatment. Our study suggested that OCN is a potential mediator between mineral homeostasis and glucose metabolism. This investigation brings a new perspective on glucose metabolism regulation through skeleton triggered mineral homeostasis and provides new clues in clinical therapeutics of potential metabolic disorders in XLH patients.

  2. Importance of both fatness and aerobic fitness on metabolic syndrome risk in Japanese children.

    PubMed

    Sasayama, Kensaku; Ochi, Eisuke; Adachi, Minoru

    2015-01-01

    Associations between body mass index (BMI), peak oxygen consumption (VO(2peak)), and metabolic syndrome (MetS) risk factors have not been adequately studied in Japanese children. Here the relationships between these parameters and the threshold aerobic fitness level necessary for low MetS risk were determined. The participants (299 children; 140 boys and 159 girls, aged 9.1 ± 0.3 years) were divided into four groups using the medians of predicted VO(2peak) (pVO(2peak)) and BMI. MetS risk scores were calculated using z-scores. Receiver Operating Characteristic analysis was used to determine the threshold aerobic fitness level necessary for low MetS risk. The MetS risk score of the High BMI group was significantly higher than that of the Low BMI group for both sexes (p < 0.0001). However, the High BMI/High Fitness group had a significantly lower MetS risk score than the High BMI/Low Fitness group for both sexes. The (p)VO(2peak )cut-off values for low MetS risk were 47.9 and 44.9 ml/kg/min for boys and girls, respectively. Our results suggest that improvements in both fatness and aerobic fitness are important for decreasing MetS risk. We also confirmed the (p)VO(2peak) of cut-off values necessary for low MetS risk in Japanese children.

  3. Importance of Both Fatness and Aerobic Fitness on Metabolic Syndrome Risk in Japanese Children

    PubMed Central

    Sasayama, Kensaku; Ochi, Eisuke; Adachi, Minoru

    2015-01-01

    Associations between body mass index (BMI), peak oxygen consumption (VO2peak), and metabolic syndrome (MetS) risk factors have not been adequately studied in Japanese children. Here the relationships between these parameters and the threshold aerobic fitness level necessary for low MetS risk were determined. The participants (299 children; 140 boys and 159 girls, aged 9.1 ± 0.3 years) were divided into four groups using the medians of predicted VO2peak (pVO2peak) and BMI. MetS risk scores were calculated using z-scores. Receiver Operating Characteristic analysis was used to determine the threshold aerobic fitness level necessary for low MetS risk. The MetS risk score of the High BMI group was significantly higher than that of the Low BMI group for both sexes (p < 0.0001). However, the High BMI/High Fitness group had a significantly lower MetS risk score than the High BMI/Low Fitness group for both sexes. The pVO2peak cut-off values for low MetS risk were 47.9 and 44.9 ml/kg/min for boys and girls, respectively. Our results suggest that improvements in both fatness and aerobic fitness are important for decreasing MetS risk. We also confirmed the pVO2peak of cut-off values necessary for low MetS risk in Japanese children. PMID:25993528

  4. Aerobic degradation of trichloroethylene by co-metabolism using phenol and gasoline as growth substrates.

    PubMed

    Li, Yan; Li, Bing; Wang, Cui-Ping; Fan, Jun-Zhao; Sun, Hong-Wen

    2014-05-22

    Trichloroethylene (TCE) is a common groundwater contaminant of toxic and carcinogenic concern. Aerobic co-metabolic processes are the predominant pathways for TCE complete degradation. In this study, Pseudomonas fluorescens was studied as the active microorganism to degrade TCE under aerobic condition by co-metabolic degradation using phenol and gasoline as growth substrates. Operating conditions influencing TCE degradation efficiency were optimized. TCE co-metabolic degradation rate reached the maximum of 80% under the optimized conditions of degradation time of 3 days, initial OD600 of microorganism culture of 0.14 (1.26×10⁷ cell/mL), initial phenol concentration of 100 mg/L, initial TCE concentration of 0.1 mg/L, pH of 6.0, and salinity of 0.1%. The modified transformation capacity and transformation yield were 20 μg (TCE)/mg (biomass) and 5.1 μg (TCE)/mg (phenol), respectively. Addition of nutrient broth promoted TCE degradation with phenol as growth substrate. It was revealed that catechol 1,2-dioxygenase played an important role in TCE co-metabolism. The dechlorination of TCE was complete, and less chlorinated products were not detected at the end of the experiment. TCE could also be co-metabolized in the presence of gasoline; however, the degradation rate was not high (28%). When phenol was introduced into the system of TCE and gasoline, TCE and gasoline could be removed at substantial rates (up to 59% and 69%, respectively). This study provides a promising approach for the removal of combined pollution of TCE and gasoline.

  5. Aerobic Degradation of Trichloroethylene by Co-Metabolism Using Phenol and Gasoline as Growth Substrates

    PubMed Central

    Li, Yan; Li, Bing; Wang, Cui-Ping; Fan, Jun-Zhao; Sun, Hong-Wen

    2014-01-01

    Trichloroethylene (TCE) is a common groundwater contaminant of toxic and carcinogenic concern. Aerobic co-metabolic processes are the predominant pathways for TCE complete degradation. In this study, Pseudomonas fluorescens was studied as the active microorganism to degrade TCE under aerobic condition by co-metabolic degradation using phenol and gasoline as growth substrates. Operating conditions influencing TCE degradation efficiency were optimized. TCE co-metabolic degradation rate reached the maximum of 80% under the optimized conditions of degradation time of 3 days, initial OD600 of microorganism culture of 0.14 (1.26 × 107 cell/mL), initial phenol concentration of 100 mg/L, initial TCE concentration of 0.1 mg/L, pH of 6.0, and salinity of 0.1%. The modified transformation capacity and transformation yield were 20 μg (TCE)/mg (biomass) and 5.1 μg (TCE)/mg (phenol), respectively. Addition of nutrient broth promoted TCE degradation with phenol as growth substrate. It was revealed that catechol 1,2-dioxygenase played an important role in TCE co-metabolism. The dechlorination of TCE was complete, and less chlorinated products were not detected at the end of the experiment. TCE could also be co-metabolized in the presence of gasoline; however, the degradation rate was not high (28%). When phenol was introduced into the system of TCE and gasoline, TCE and gasoline could be removed at substantial rates (up to 59% and 69%, respectively). This study provides a promising approach for the removal of combined pollution of TCE and gasoline. PMID:24857922

  6. Eight-Week Training Cessation Suppresses Physiological Stress but Rapidly Impairs Health Metabolic Profiles and Aerobic Capacity in Elite Taekwondo Athletes

    PubMed Central

    Liao, Yi-Hung; Sung, Yu-Chi

    2016-01-01

    Changes in an athlete’s physiological and health metabolic profiles after detraining have not been studied in elite Taekwondo (TKD) athletes. To enable a better understanding of these physiological changes to training cessation, this study examined the effects of 8-weeks detraining on the aerobic capacity, body composition, inflammatory status and health metabolic profile in elite TKD athletes. Sixteen elite TKD athletes (age: 21.0 ± 0.8 yrs, BMI: 22.4 ± 3.9 kg/m2; Mean ± SD; 11 males and 5 females) participated in this study. Physical activity level assessment using computerized physical activity logs was performed during the competitive preparation season (i.e. one-week before national competition) and at two week intervals throughout the detraining period. Participant aerobic capacity, body fat, and blood biomarkers were measured before and after detraining, and the blood biomarker analyses included leukocyte subpopulations, blood glucose, insulin, dehydroepiandrosterone-sulfate (DHEA-S), and cortisol. Eight-week detraining increased DHEA-S/cortisol ratio (+57.3%, p = 0.004), increased insulin/cortisol ratio (+59.9%, p = 0.004), reduced aerobic power (–2.43%, p = 0.043), increased body fat accumulation (body fat%: +21.3%, p < 0.001), decreased muscle mass (muscle mass%: –4.04%, p < 0.001), and elevated HOMA-IR (the biomarker of systemic insulin resistance; +34.2%, p = 0.006). The neutrophil-to-lymphocyte ratio (NLR), a systemic inflammatory index, increased by 48.2% (p = 0.005). The change in aerobic capacity was correlated with the increased fat mass (r = –0.429, p = 0.049) but not with muscle loss. An increase in the NLR was correlated to the changes in HOMA-IR (r = 0.44, p = 0.044) and aerobic capacity (r = –0.439, p = 0.045). We demonstrate that 8-week detraining suppresses physiological stress but rapidly results in declines in athletic performance and health metabolic profiles, including reduced aerobic capacity, increased body fat, muscle

  7. Emerging role of the brain in the homeostatic regulation of energy and glucose metabolism

    PubMed Central

    Roh, Eun; Song, Do Kyeong; Kim, Min-Seon

    2016-01-01

    Accumulated evidence from genetic animal models suggests that the brain, particularly the hypothalamus, has a key role in the homeostatic regulation of energy and glucose metabolism. The brain integrates multiple metabolic inputs from the periphery through nutrients, gut-derived satiety signals and adiposity-related hormones. The brain modulates various aspects of metabolism, such as food intake, energy expenditure, insulin secretion, hepatic glucose production and glucose/fatty acid metabolism in adipose tissue and skeletal muscle. Highly coordinated interactions between the brain and peripheral metabolic organs are critical for the maintenance of energy and glucose homeostasis. Defective crosstalk between the brain and peripheral organs contributes to the development of obesity and type 2 diabetes. Here we comprehensively review the above topics, discussing the main findings related to the role of the brain in the homeostatic regulation of energy and glucose metabolism. PMID:26964832

  8. Saccharomyces cerevisiae engineered for xylose metabolism requires gluconeogenesis and the oxidative branch of the pentose phosphate pathway for aerobic xylose assimilation.

    PubMed

    Hector, Ronald E; Mertens, Jeffrey A; Bowman, Michael J; Nichols, Nancy N; Cotta, Michael A; Hughes, Stephen R

    2011-09-01

    Saccharomyces strains engineered to ferment xylose using Scheffersomyces stipitis xylose reductase (XR) and xylitol dehydrogenase (XDH) genes appear to be limited by metabolic imbalances, due to differing cofactor specificities of XR and XDH. The S. stipitis XR, which uses both NADH and NADPH, is hypothesized to reduce the cofactor imbalance, allowing xylose fermentation in this yeast. However, unadapted S. cerevisiae strains expressing this XR grow poorly on xylose, suggesting that metabolism is still imbalanced, even under aerobic conditions. In this study, we investigated the possible reasons for this imbalance by deleting genes required for NADPH production and gluconeogenesis in S. cerevisiae. S. cerevisiae cells expressing the XR-XDH, but not a xylose isomerase, pathway required the oxidative branch of the pentose phosphate pathway (PPP) and gluconeogenic production of glucose-6-P for xylose assimilation. The requirement for generating glucose-6-P from xylose was also shown for Kluyveromyces lactis. When grown in xylose medium, both K. lactis and S. stipitis showed increases in enzyme activity required for producing glucose-6-P. Thus, natural xylose-assimilating yeast respond to xylose, in part, by upregulating enzymes required for recycling xylose back to glucose-6-P for the production of NADPH via the oxidative branch of the PPP. Finally, we show that induction of these enzymes correlated with increased tolerance to the NADPH-depleting compound diamide and the fermentation inhibitors furfural and hydroxymethyl furfural; S. cerevisiae was not able to increase enzyme activity for glucose-6-P production when grown in xylose medium and was more sensitive to these inhibitors in xylose medium compared to glucose.

  9. ATP6AP2/(Pro)renin Receptor Contributes to Glucose Metabolism via Stabilizing the Pyruvate Dehydrogenase E1 β Subunit*

    PubMed Central

    Kanda, Atsuhiro; Noda, Kousuke; Ishida, Susumu

    2015-01-01

    Aerobic glucose metabolism is indispensable for metabolically active cells; however, the regulatory mechanism of efficient energy generation in the highly evolved mammalian retina remains incompletely understood. Here, we revealed an unsuspected role for (pro)renin receptor, also known as ATP6AP2, in energy metabolism. Immunoprecipitation and mass spectrometry analyses identified the pyruvate dehydrogenase (PDH) complex as Atp6ap2-interacting proteins in the mouse retina. Yeast two-hybrid assays demonstrated direct molecular binding between ATP6AP2 and the PDH E1 β subunit (PDHB). Pdhb immunoreactivity co-localized with Atp6ap2 in multiple retinal layers including the retinal pigment epithelium (RPE). ATP6AP2 knockdown in RPE cells reduced PDH activity, showing a predilection to anaerobic glycolysis. ATP6AP2 protected PDHB from phosphorylation, thus controlling its protein stability. Down-regulated PDH activity due to ATP6AP2 knockdown inhibited glucose-stimulated oxidative stress in RPE cells. Our present data unraveled the novel function of ATP6AP2/(P)RR as a PDHB stabilizer, contributing to aerobic glucose metabolism together with oxidative stress. PMID:25720494

  10. Heterogeneous cerebral glucose metabolism in normal pressure hydrocephalus.

    PubMed Central

    Tedeschi, E; Hasselbalch, S G; Waldemar, G; Juhler, M; Høgh, P; Holm, S; Garde, L; Knudsen, L L; Klinken, L; Gjerris, F

    1995-01-01

    The regional cerebral metabolic rate for glucose (rCMRglu) has never been investigated in large consecutive groups of patients with normal pressure hydrocephalus (NPH), a potentially treatable form of dementia with an unpredictable outcome after shunt surgery. Using PET and 18F-2-fluorodeoxyglucose, rCMRglu was studied in 18 patients who fulfilled hydrodynamic criteria for NPH and in whom a biopsy of the frontal cortex was obtained. When compared with an age matched group of 11 healthy subjects, the patients with NPH showed a significant rCMRglu reduction in all cortical and subcortical regions of interest. Individual metabolic patterns, however, disclosed a large topographical heterogeneity. Furthermore, histopathological examination identified Alzheimer's disease or cerebrovascular disease in six cases, and no parenchymal disease or non-specific degenerative processes in the remaining 12. After separating the patients according to the histological diagnosis, the rCMRglu patterns were still heterogeneous, the abnormalities ranging from focal to diffuse in both subgroups. After shunt operation, 11 patients did not improve or worsened clinically. Six patients improved; of those, two had Alzheimer changes and two cerebrovascular changes in their biopsy. The metabolic pattern of these six patients did not differ from the rest of the NPH group. The results indicate that the NPH syndrome may be non-specifically associated with different degenerative disorders. The metabolic heterogeneity, together with the heterogeneous histopathological findings, indicate the necessity of reevaluating the pathogenesis of the NPH syndrome, and may account for the high variability in the success rate of shunt surgery series. Images PMID:7500099

  11. The interplay between aerobic metabolism and antipredator performance: vigilance is related to recovery rate after exercise.

    PubMed

    Killen, Shaun S; Reid, Donald; Marras, Stefano; Domenici, Paolo

    2015-01-01

    When attacked by a predator, fish respond with a sudden fast-start motion away from the threat. Although this anaerobically-powered swimming necessitates a recovery phase which is fueled aerobically, little is known about links between escape performance and aerobic traits such as aerobic scope (AS) or recovery time after exhaustive exercise. Slower recovery ability or a reduced AS could make some individuals less likely to engage in a fast-start response or display reduced performance. Conversely, increased vigilance in some individuals could permit faster responses to an attack but also increase energy demand and prolong recovery after anaerobic exercise. We examined how AS and the ability to recover from anaerobic exercise relates to differences in fast-start escape performance in juvenile golden gray mullet at different acclimation temperatures. Individuals were acclimated to either 18, 22, or 26°C, then measured for standard and maximal metabolic rates and AS using intermittent flow respirometry. Anaerobic capacity and the time taken to recover after exercise were also assessed. Each fish was also filmed during a simulated attack to determine response latency, maximum speed and acceleration, and turning rate displayed during the escape response. Across temperatures, individuals with shorter response latencies during a simulated attack are those with the longest recovery time after exhaustive anaerobic exercise. Because a short response latency implies high preparedness to escape, these results highlight the trade-off between the increased vigilance and metabolic demand, which leads to longer recovery times in fast reactors. These results improve our understanding of the intrinsic physiological traits that generate inter-individual variability in escape ability, and emphasize that a full appreciation of trade-offs associated with predator avoidance and energy balance must include energetic costs associated with vigilance and recovery from anaerobic exercise.

  12. The interplay between aerobic metabolism and antipredator performance: vigilance is related to recovery rate after exercise

    PubMed Central

    Killen, Shaun S.; Reid, Donald; Marras, Stefano; Domenici, Paolo

    2015-01-01

    When attacked by a predator, fish respond with a sudden fast-start motion away from the threat. Although this anaerobically-powered swimming necessitates a recovery phase which is fueled aerobically, little is known about links between escape performance and aerobic traits such as aerobic scope (AS) or recovery time after exhaustive exercise. Slower recovery ability or a reduced AS could make some individuals less likely to engage in a fast-start response or display reduced performance. Conversely, increased vigilance in some individuals could permit faster responses to an attack but also increase energy demand and prolong recovery after anaerobic exercise. We examined how AS and the ability to recover from anaerobic exercise relates to differences in fast-start escape performance in juvenile golden gray mullet at different acclimation temperatures. Individuals were acclimated to either 18, 22, or 26°C, then measured for standard and maximal metabolic rates and AS using intermittent flow respirometry. Anaerobic capacity and the time taken to recover after exercise were also assessed. Each fish was also filmed during a simulated attack to determine response latency, maximum speed and acceleration, and turning rate displayed during the escape response. Across temperatures, individuals with shorter response latencies during a simulated attack are those with the longest recovery time after exhaustive anaerobic exercise. Because a short response latency implies high preparedness to escape, these results highlight the trade-off between the increased vigilance and metabolic demand, which leads to longer recovery times in fast reactors. These results improve our understanding of the intrinsic physiological traits that generate inter-individual variability in escape ability, and emphasize that a full appreciation of trade-offs associated with predator avoidance and energy balance must include energetic costs associated with vigilance and recovery from anaerobic exercise

  13. Effect of supplemental protein source during the winter on pre- and postpartum glucose metabolism

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Circulating serum glucose concentrations as well as glucose utilization have been shown to be affected by forage quality. Supplemental protein provided to grazing range cows while consuming low quality forage may improve glucose metabolism. The objective of our study was to determine the effects of ...

  14. Phylloquinone intake is associated with glucose metabolism in middle- and older-aged men and women

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Animal and metabolic studies suggest that vitamin K may have a beneficial role in glucose homeostasis. The aim of this study was to examine the association between vitamin K intake and measures of glucose metabolism in a community-based sample of healthy adults. We assessed the cross-sectional assoc...

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

    PubMed

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

    PubMed Central

    Pichette, Jennifer

    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. PMID:27478532

  17. Impaired glucose tolerance and metabolic syndrome in idiopathic neuropathy.

    PubMed

    Smith, A Gordon

    2012-05-01

    Idiopathic neuropathy is one of the most common clinical problems encountered in general medical and neurological practices, accounting for up to 40% of all neuropathies in referral series. Several groups have reported an elevated prevalence of impaired glucose tolerance (IGT) in idiopathic neuropathy subjects, although the only carefully conducted case-control study suggested hypertriglyceridemia was a more important risk factor. The nature of the relationship between IGT and neuropathy is a subject of active debate. An evolving literature suggests metabolic syndrome, particularly dyslipidemia and obesity, are potent neuropathy risk factors for both idiopathic and diabetic neuropathy patients. Once established, diabetic neuropathy is likely to be very difficult to reverse. IGT-associated neuropathy, however, may be more amenable to therapy and could represent an ideal population in which to examine potential therapies for diabetes and obesity related neuropathies. Further research is needed to better define the epidemiological relation between IGT, metabolic syndrome, and neuropathy, its underlying pathophysiology, and to develop appropriate surrogate measures and clinical trials strategies.

  18. Excess glucose induces hypoxia-inducible factor-1α in pancreatic cancer cells and stimulates glucose metabolism and cell migration

    PubMed Central

    Liu, Zhiwen; Jia, Xiaohui; Duan, Yijie; Xiao, Huijie; Sundqvist, Karl-Gösta; Permert, Johan; Wang, Feng

    2013-01-01

    Pancreatic cancer patients frequently show hyperglycemia, but it is uncertain whether hyperglycemia stimulates pancreatic cancer cells. We have investigated whether excess glucose induces hypoxia-inducible factor-1α (HIF-1α) and stimulates glucose metabolism and cell migration in pancreatic cancer cells. We studied wild-type (wt) MiaPaCa2 pancreatic cancer cells and a MiaPaCa2 subline (namely si-MiaPaCa2) that had HIF-1α-specific small interfering RNA. Wt-MiaPaCa2 cells are known to be HIF-1α-positive in hypoxia and HIF-1α-negative in normoxia, whereas si-MiaPaCa2 cells are devoid of HIF-1α in both normoxia and hypoxia. We incubated these cells with different amounts of glucose and determined HIF-1α mRNA and protein by real-time polymerase chain reaction and western blotting. We determined glucose consumption, lactate production and intracellular hexokinase-II and ATP to assess glucose metabolisms and determined pyruvate dehydrogenase kinase-1, reactive oxygen species and fumarate to assess mitochondrial activities. Further, we studied cell migration using a Boyden chamber. Excess glucose (16.7−22.2mM) increased HIF-1α in hypoxic wt-MiaPaCa2 cells. HIF-1α expression increased ATP contents and inhibited mitochondrial activities. Extracellular glucose and hypoxia stimulated glucose metabolisms independent of HIF-1α. Excess glucose stimulated the migration of wt- and si-MiaPaCa2 cells in both normoxia and hypoxia. Thus, glucose stimulated cell migration independent of HIF-1α. Nevertheless, hypoxic wt-MiaPaCa2 cells showed greater migrating ability than their si-MiaPaCa2 counterparts. We conclude that (1) excess glucose increases HIF-1α and ATP in hypoxic wt-MiaPaCa2 cells, (2) extracellular glucose and hypoxia regulate glucose metabolisms independent of HIF-1α and (3) glucose stimulates cell migration by mechanisms that are both dependent on HIF-1α and independent of it. PMID:23377827

  19. D-Glucose and D-mannose-based metabolic probes. Part 3: Synthesis of specifically deuterated D-glucose, D-mannose, and 2-deoxy-D-glucose.

    PubMed

    Fokt, Izabela; Skora, Stanislaw; Conrad, Charles; Madden, Timothy; Emmett, Mark; Priebe, Waldemar

    2013-03-07

    Altered carbohydrate metabolism in cancer cells was first noted by Otto Warburg more than 80 years ago. Upregulation of genes controlling the glycolytic pathway under normoxia, known as the Warburg effect, clearly differentiates malignant from non-malignant cells. The resurgence of interest in cancer metabolism aims at a better understanding of the metabolic differences between malignant and non-malignant cells and the creation of novel therapeutic and diagnostic agents exploiting these differences. Modified d-glucose and d-mannose analogs were shown to interfere with the metabolism of their respective monosaccharide parent molecules and are potentially clinically useful anticancer and diagnostic agents. One such agent, 2-deoxy-d-glucose (2-DG), has been extensively studied in vitro and in vivo and also clinically evaluated. Studies clearly indicate that 2-DG has a pleiotropic mechanism of action. In addition to effectively inhibiting glycolysis, 2-DG has also been shown to affect protein glycosylation. In order to better understand its molecular mechanism of action, we have designed and synthesized deuterated molecular probes to study 2-DG interference with d-glucose and d-mannose metabolism using mass spectrometry. We present here the synthesis of all desired probes: 2-deutero-d-glucose, 2-deutero-d-mannose, 6-deutero-d-glucose, 6-deutero-d-mannose, and 2-deutero-2-deoxy-d-glucose as well as their complete chemical characterization.

  20. Amperometric enzyme electrodes for aerobic and anaerobic glucose monitoring prepared by glucose oxidase immobilized in mixed ferrocene-cobaltocenium dendrimers.

    PubMed

    Alonso, Beatriz; Armada, Pilar García; Losada, José; Cuadrado, Isabel; González, Blanca; Casado, Carmen M

    2004-07-15

    The enzyme glucose oxidase (GOx) has been immobilized electrostatically onto carbon and platinum electrodes modified with mixed ferrocene-cobaltocenium dendrimers. The ferrocene units have been used successfully as mediators between the GOx and the electrode under anaerobic conditions. In experiments carried out in the presence of oxygen, the cobaltocenium moieties act as electrocatalysts in the reduction of the oxygen in the solution, thus making possible the determination of the oxygen variation due to the enzymatic reaction, with high sensitivity. The current response of the electrode was determined by measuring steady-state current values obtained applying a constant potential. The effect of the substrate concentration, the dendrimer generation, the thickness of the dendrimer layer, interferences, and storage on the response of the sensors were investigated.

  1. Resistance to glucose starvation as metabolic trait of platinum-resistant human epithelial ovarian cancer cells

    PubMed Central

    Pastò, Anna; Pagotto, Anna; Pilotto, Giorgia; De Paoli, Angela; De Salvo, Gian Luca; Baldoni, Alessandra; Nicoletto, Maria Ornella; Ricci, Francesca; Damia, Giovanna; Bellio, Chiara

    2017-01-01

    Deregulated glucose metabolism is observed in cancer but whether this metabolic trait influences response to or is modulated by cytotoxic drugs is unknown. We show here that tumor cells from epithelial ovarian cancer (EOC) patients can be categorized, according to their in vitro viability under glucose starvation, into glucose deprivation-sensitive (glucose-addicted, GA) and glucose deprivation-resistant (glucose non-addicted, GNA). When EOC cells were cultured in the absence of glucose, all samples from platinum (PLT)-sensitive patients felt into the GA group; they disclosed higher expression of glucose metabolism enzymes, higher proliferation rates and in vitro sensitivity to PLT. Moreover, GA patients showed reduced multi-drug resistance pump expression and autophagy, compared to GNA samples. The close association between PLT sensitivity and glucose metabolic profile was confirmed in a xenograft model, where a stringent parallelism between PLT sensitivity/resistance and glucose metabolism was identified. Finally, in a cohort of naïve EOC patients categorized as GA or GNA at diagnosis, Kaplan Meier curves showed that the GA phenotype was associated with significantly better progression-free survival, compared to GNA patients. PMID:28031535

  2. The effect of chlorpyrifos on thermogenic capacity of bank voles selected for increased aerobic exercise metabolism.

    PubMed

    Dheyongera, Geoffrey; Grzebyk, Katherine; Rudolf, Agata M; Sadowska, Edyta T; Koteja, Paweł

    2016-04-01

    Agro-chemicals potentially cause adverse effects in non-target organisms. The rate of animal energy metabolism can influence their susceptibility to pesticides by influencing food consumption, biotransformation and elimination rates of toxicants. We used experimental evolution to study the effects of inherent differences in energy metabolism rate and exposure to the organophosphate insecticide, chlorpyrifos (CPF) on thermogenic capacity in a wild rodent, the bank vole (Myodes = Clethrionomys glareolus). The voles were sampled from four replicate lines selected for high swim-induced aerobic metabolism (A) and four unselected control (C) lines. Thermogenic capacity, measured as the maximum cold-induced rate of oxygen consumption (VO2cold), was higher in the A - than C lines, and it decreased after continuous exposure to CPF via food or after a single dose administered via oral gavage, but only when measured shortly after exposure. VO2cold measured 24 h after repeated exposure was not affected. In addition, gavage with a single dose led to decreased food consumption and loss in body mass. Importantly, the adverse effects of CPF did not differ between the selected and control lines. Therefore, exposure to CPF has adverse effects on thermoregulatory performance and energy balance in this species. The effects are short-lived and their magnitude is not associated with the inherent level of energy metabolism. Even without severe symptoms of poisoning, fitness can be compromised under harsh environmental conditions, such as cold and wet weather.

  3. Peritoneal Dialysate Glucose Load and Systemic Glucose Metabolism in Non-Diabetics: Results from the GLOBAL Fluid Cohort Study

    PubMed Central

    Chess, James; Do, Jun-Young; Noh, Hyunjin; Lee, Hi-Bahl; Kim, Yong-Lim; Summers, Angela; Williams, Paul Ford; Davison, Sara; Dorval, Marc

    2016-01-01

    Background and Objectives Glucose control is a significant predictor of mortality in diabetic peritoneal dialysis (PD) patients. During PD, the local toxic effects of intra-peritoneal glucose are well recognized, but despite large amounts of glucose being absorbed, the systemic effects of this in non-diabetic patients are not clear. We sought to clarify whether dialysate glucose has an effect upon systemic glucose metabolism. Methods and Materials We analysed the Global Fluid Study cohort, a prospective, observational cohort study initiated in 2002. A subset of 10 centres from 3 countries with high data quality were selected (368 incident and 272 prevalent non-diabetic patients), with multilevel, multivariable analysis of the reciprocal of random glucose levels, and a stratified-by-centre Cox survival analysis. Results The median follow up was 5.6 and 6.4 years respectively in incident and prevalent patients. On multivariate analysis, serum glucose increased with age (β = -0.007, 95%CI -0.010, -0.004) and decreased with higher serum sodium (β = 0.002, 95%CI 0.0005, 0.003) in incident patients and increased with dialysate glucose (β = -0.0002, 95%CI -0.0004, -0.00006) in prevalent patients. Levels suggested undiagnosed diabetes in 5.4% of prevalent patients. Glucose levels predicted death in unadjusted analyses of both incident and prevalent groups but in an adjusted survival analysis they did not (for random glucose 6–10 compared with <6, Incident group HR 0.92, 95%CI 0.58, 1.46, Prevalent group HR 1.42, 95%CI 0.86, 2.34). Conclusions In prevalent non-diabetic patients, random glucose levels at a diabetic level are under-recognised and increase with dialysate glucose load. Random glucose levels predict mortality in unadjusted analyses, but this association has not been proven in adjusted analyses. PMID:27249020

  4. Effects of Exhaustive Aerobic Exercise on Tryptophan-Kynurenine Metabolism in Trained Athletes.

    PubMed

    Strasser, Barbara; Geiger, Daniela; Schauer, Markus; Gatterer, Hannes; Burtscher, Martin; Fuchs, Dietmar

    2016-01-01

    Exhaustive exercise can cause a transient depression of immune function. Data indicate significant effects of immune activation cascades on the biochemistry of monoamines and amino acids such as tryptophan. Tryptophan can be metabolized through different pathways, a major route being the kynurenine pathway, which is often systemically up-regulated when the immune response is activated. The present study was undertaken to examine the effect of exhaustive aerobic exercise on biomarkers of immune activation and tryptophan metabolism in trained athletes. After a standardized breakfast 2 h prior to exercise, 33 trained athletes (17 women, 16 men) performed an incremental cycle ergometer exercise test at 60 rpm until exhaustion. After a 20 min rest phase, the participants performed a 20 min maximal time-trial on a cycle ergometer (RBM Cyclus 2, Germany). During the test, cyclists were strongly encouraged to choose a maximal pedalling rate that could be maintained for the respective test duration. Serum concentrations of amino acids tryptophan, kynurenine, phenylalanine, and tyrosine were determined by HPLC and immune system biomarker neopterin by ELISA at rest and immediately post exercise. Intense exercise was associated with a strong increase in neopterin concentrations (p<0.001), indicating increased immune activation following intense exercise. Exhaustive exercise significantly reduced tryptophan concentrations by 12% (p<0.001) and increased kynurenine levels by 6% (p = 0.022). Also phenylalanine to tyrosine ratios were lower after exercise as compared with baseline (p<0.001). The kynurenine to tryptophan ratio correlated with neopterin (r = 0.560, p<0.01). Thus, increased tryptophan catabolism by indoleamine 2,3-dioxygenase appears likely. Peak oxygen uptake correlated with baseline tryptophan and kynurenine concentrations (r = 0.562 and r = 0.511, respectively, both p<0.01). Findings demonstrate that exhaustive aerobic exercise is associated with increased immune

  5. Targeting protein kinase CK2 suppresses bladder cancer cell survival via the glucose metabolic pathway

    PubMed Central

    Li, Peng; Yuan, Wenbo; Deng, Xiaheng; Cheng, Yidong; Li, Pengchao; Yang, Haiwei; Tao, Jun; Lu, Qiang

    2016-01-01

    Casein kinase 2 (CK2) is a constitutively active serine/threonine kinase that promotes cell proliferation and resists apoptosis. Elevated CK2 expression has been demonstrated in several solid tumors. The expression of CK2α in bladder cancer was elevated in tumor tissues compared with that in adjacent normal tissues. Amplified expression of CK2α was highly correlated with histological grade in bladder cancer(P = 0.024). Knockdown of CK2α in bladder cancer cell lines resulted in a reduction in tumor aerobic glycolysis, accompanied with lower phosphorylated AKT. Moreover, low CK2α levels suppressed cell growth, and similar results could be reproduced after treatment with CX-4945 with a dose-dependent response. CX-4945 inhibited migration and induced apoptosis. Furthermore, knockdown of CK2α decreased the tumorigenicity of bladder cancer cells in vivo. This study is the first to report that CK2 increases glucose metabolism in human bladder cancer. Blocking CK2 function may provide novel diagnostic and potential therapeutic. PMID:27888634

  6. Cattle temperament influences metabolism: metabolic response to glucose tolerance and insulin sensitivity tests in beef steers.

    PubMed

    Burdick Sanchez, N C; Carroll, J A; Broadway, P R; Hughes, H D; Roberts, S L; Richeson, J T; Schmidt, T B; Vann, R C

    2016-07-01

    Cattle temperament, defined as the reactivity of cattle to humans or novel environments, can greatly influence several physiological systems in the body, including immunity, stress, and most recently discovered, metabolism. Greater circulating concentrations of nonesterified fatty acids (NEFAs) found in temperamental cattle suggest that temperamental cattle are metabolically different than calm cattle. Further, elevated NEFA concentrations have been reported to influence insulin sensitivity. Therefore, the objective of this study was to determine whether cattle temperament would influence the metabolic response to a glucose tolerance test (GTT) and insulin sensitivity test (IST). Angus-cross steers (16 calm and 15 temperamental; 216 ± 6 kg BW) were selected based on temperament score measured at weaning. On day 1, steers were moved into indoor stanchions to allow measurement of individual ad libitum feed intake. On day 6, steers were fitted with indwelling rectal temperature probes and jugular catheters. At 9 AM on day 7, steers received the GTT (0.5-mL/kg BW of a 50% dextrose solution), and at 2 PM on day 7, steers received the IST (2.5 IU bovine insulin/kg BW). Blood samples were collected and serum isolated at -60, -45, -30, -15, 0, 10, 20, 30, 45, 60, 90, 120, and 150 min relative to each challenge. Serum was stored at -80°C until analyzed for cortisol, glucose, NEFA, and blood urea nitrogen concentrations. All variables changed over time (P < 0.01). For the duration of the study, temperamental steers maintained greater (P < 0.01) serum NEFA and less (P ≤ 0.01) serum blood urea nitrogen and insulin sensitivity (calculated using Revised Quantitative Insulin Sensitivity Check Index) compared with calm steers. During the GTT, temperamental steers had greater (P < 0.01) serum glucose, yet decreased (P = 0.03) serum insulin and (P < 0.01) serum insulin: serum glucose compared to calm cattle. During the IST, temperamental steers had greater (P < 0.01) serum

  7. Aerobic interval exercise improves parameters of nonalcoholic fatty liver disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

    PubMed

    Kapravelou, Garyfallia; Martínez, Rosario; Andrade, Ana M; Nebot, Elena; Camiletti-Moirón, Daniel; Aparicio, Virginia A; Lopez-Jurado, Maria; Aranda, Pilar; Arrebola, Francisco; Fernandez-Segura, Eduardo; Bermano, Giovanna; Goua, Marie; Galisteo, Milagros; Porres, Jesus M

    2015-12-01

    Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P < 0.0001) and suffered significant alterations in plasma lipid profile, area under the curve after oral glucose overload (P < 0.0001), liver histology and functionality, and antioxidant status. The AIT protocol reduced the severity of alterations related to glucose and lipid metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS.

  8. Black and White race differences in aerobic capacity, muscle fiber type, and their influence on metabolic processes.

    PubMed

    Ceaser, Tyrone; Hunter, Gary

    2015-05-01

    Obesity is a known risk factor for cardiometabolic disease. Increasing aerobic capacity (VO2max) reduces adiposity, maintains weight, and reduces the risk of developing obesity and cardiometabolic disease. Two major determinants of aerobic capacity are the metabolic properties specific to a particular muscle fiber type and the capacity of the cardiorespiratory system to deliver nutrient-rich content to the muscle. Recent research suggests that some race/ethnic groups, particularly non-Hispanic Black subjects, are predisposed to a reduced VO2max by way of muscle fiber type. Combined with insufficient physical activity, these characteristics place non-Hispanic Black subjects at an increased risk for obesity and other adverse health outcomes when compared with other race/ethnic groups. The purpose of this review was to suggest a model for explaining how skeletal muscle fiber type may contribute to reduced aerobic capacity and obesity among non-Hispanic Black subjects. Our review indicates that metabolic properties of type II skeletal muscle (e.g. reduced oxidative capacity, capillary density) are related to various cardiometabolic diseases. Based on the review, non-Hispanic Black subjects appear to have a lower maximal aerobic capacity and a greater percentage of type II skeletal muscle fibers. Combined with reduced energy expenditure and reduced hemoglobin concentration, non-Hispanic Black subjects may be inherently predisposed to a reduced maximal aerobic capacity compared with non-Hispanic White subjects, thereby increasing the risk for obesity and related metabolic diseases.

  9. Decreased Insulin Receptors but Normal Glucose Metabolism in Duchenne Muscular Dystrophy

    NASA Astrophysics Data System (ADS)

    de Pirro, Roberto; Lauro, Renato; Testa, Ivano; Ferretti, Ginofabrizio; de Martinis, Carlo; Dellantonio, Renzo

    1982-04-01

    Compared to matched controls, 17 patients with Duchenne muscular dystrophy showed decreased insulin binding to monocytes due to decreased receptor concentration. These patients showed no signs of altered glucose metabolism and retrospective analysis of the clinical records of a further 56 such patients revealed no modification in carbohydrate metabolism. These data suggest that reduced insulin receptor number does not produce overt modifications of glucose metabolism in Duchenne muscular dystrophy.

  10. Calorespirometry reveals that goldfish prioritize aerobic metabolism over metabolic rate depression in all but near-anoxic environments.

    PubMed

    Regan, Matthew D; Gill, Ivan S; Richards, Jeffrey G

    2017-02-15

    Metabolic rate depression (MRD) has long been proposed as the key metabolic strategy of hypoxic survival, but surprisingly, the effects of changes in hypoxic O2 tensions (PwO2 ) on MRD are largely unexplored. We simultaneously measured the O2 consumption rate (ṀO2 ) and metabolic heat of goldfish using calorespirometry to test the hypothesis that MRD is employed at hypoxic PwO2  values and initiated just below Pcrit, the PwO2 below which ṀO2  is forced to progressively decline as the fish oxyconforms to decreasing PwO2 Specifically, we used closed-chamber and flow-through calorespirometry together with terminal sampling experiments to examine the effects of PwO2  and time on ṀO2 , metabolic heat and anaerobic metabolism (lactate and ethanol production). The closed-chamber and flow-through experiments yielded slightly different results. Under closed-chamber conditions with a continually decreasing PwO2 , goldfish showed a Pcrit of 3.0±0.3 kPa and metabolic heat production was only depressed at PwO2  between 0 and 0.67 kPa. Under flow-through conditions with PwO2  held at a variety of oxygen tensions for 1 and 4 h, goldfish also initiated MRD between 0 and 0.67 kPa but maintained ṀO2  to 0.67 kPa, indicating that Pcrit is at or below this PwO2 Anaerobic metabolism was strongly activated at PwO2 ≤1.3 kPa, but only used within the first hour at 1.3 and 0.67 kPa, as anaerobic end-products did not accumulate between 1 and 4 h exposure. Taken together, it appears that goldfish reserve MRD for near-anoxia, supporting routine metabolic rate at sub-PcritPwO2  values with the help of anaerobic glycolysis in the closed-chamber experiments, and aerobically after an initial (<1 h) activation of anaerobic metabolism in the flow-through experiments, even at 0.67 kPa PwO2.

  11. Dynamic in vivo (31)P nuclear magnetic resonance study of Saccharomyces cerevisiae in glucose-limited chemostat culture during the aerobic-anaerobic shift.

    PubMed

    Gonzalez, B; de Graaf, A; Renaud, M; Sahm, H

    2000-04-01

    The purpose of this work was to analyse in vivo the influence of sudden oxygen depletion on Saccharomyces cerevisiae, grown in glucose-limited chemostat culture, using a recently developed cyclone reactor coupled with (31)P NMR spectroscopy. Before, during and after the transition, intracellular and extracellular phosphorylated metabolites as well as the pHs in the different cellular compartments were monitored with a time resolution of 2.5 min. The employed integrated NMR bioreactor system allowed the defined glucose-limited continuous cultivation of yeast at a density of 75 g DW/l and a p(O(2)) of 30% air saturation. A purely oxidative metabolism was maintained at all times. In vivo (31)P NMR spectra obtained were of excellent quality and even allowed the detection of phosphoenolpyruvate (PEP). During the switch from aerobic to anaerobic conditions, a rapid, significant decrease of intracellular ATP and PEP levels was observed and the cytoplasmic pH decreased from 7.5 to 6.8. This change, which was accompanied by a transient influx of extracellular inorganic phosphate (P(i)), appeared to correlate linearly with the decrease of the ATP concentration, suggesting that the cause of the partial collapse of the plasma membrane pH gradient was a reduced availability of ATP. The complete phosphorous balance established from our measurement data showed that polyphosphate was not the source of the increased intracellular P(i). The derived intracellular P(i), ATP and ADP concentration data confirmed that the glycolytic flux at the level of glyceraldehyde-3-phosphate dehydrogenase, 3-phosphoglycerate kinase and enolase enzymes is mainly controlled by thermodynamic constraints.

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

    PubMed Central

    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

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

    PubMed

    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.

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

    SciTech Connect

    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.

  15. Restriction of Aerobic Metabolism by Acquired or Innate Arylsulfatase B Deficiency: A New Approach to the Warburg Effect

    PubMed Central

    Bhattacharyya, Sumit; Feferman, Leo; Tobacman, Joanne K.

    2016-01-01

    Aerobic respiration is required for optimal efficiency of metabolism in mammalian cells. Under circumstances when oxygen utilization is impaired, cells survive by anerobic metabolism. The malignant cell has cultivated the use of anerobic metabolism in an aerobic environment, the Warburg effect, but the explanation for this preference is not clear. This paper presents evidence that deficiency of the enzyme arylsulfatase B (ARSB; N-acetylgalactosamine 4-sulfatase), either innate or acquired, helps to explain the Warburg phenomenon. ARSB is the enzyme that removes 4-sulfate groups from the non-reducing end of chondroitin 4-sulfate and dermatan sulfate. Previous reports indicated reduced ARSB activity in malignancy and replication of the effects of hypoxia by decline in ARSB. Hypoxia reduced ARSB activity, since molecular oxygen is needed for post-translational modification of ARSB. In this report, studies were performed in human HepG2 cells and in hepatocytes from ARSB-deficient and normal C57BL/6J control mice. Decline of ARSB, in the presence of oxygen, profoundly reduced the oxygen consumption rate and increased the extracellular acidification rate, indicating preference for aerobic glycolysis. Specific study findings indicate that decline in ARSB activity enhanced aerobic glycolysis and impaired normal redox processes, consistent with a critical role of ARSB and sulfate reduction in mammalian metabolism. PMID:27605497

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

    PubMed Central

    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 < 0.001) 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. PMID:28230765

  17. Effect of selected monoterpenes on methane oxidation, denitrification, and aerobic metabolism by bacteria in pure culture.

    PubMed

    Amaral, J A; Ekins, A; Richards, S R; Knowles, R

    1998-02-01

    Selected monoterpenes inhibited methane oxidation by methanotrophs (Methylosinus trichosporium OB3b, Methylobacter luteus), denitrification by environmental isolates, and aerobic metabolism by several heterotrophic pure cultures. Inhibition occurred to various extents and was transient. Complete inhibition of methane oxidation by Methylosinus trichosporium OB3b with 1.1 mM (-)-alpha-pinene lasted for more than 2 days with a culture of optical density of 0.05 before activity resumed. Inhibition was greater under conditions under which particulate methane monooxygenase was expressed. No apparent consumption or conversion of monoterpenes by methanotrophs was detected by gas chromatography, and the reason that transient inhibition occurs is not clear. Aerobic metabolism by several heterotrophs was much less sensitive than methanotrophy was; Escherichia coli (optical density, 0.01), for example, was not affected by up to 7.3 mM (-)-alpha-pinene. The degree of inhibition was monoterpene and species dependent. Denitrification by isolates from a polluted sediment was not inhibited by 3.7 mM (-)-alpha-pinene, gamma-terpinene, or beta-myrcene, whereas 50 to 100% inhibition was observed for isolates from a temperate swamp soil. The inhibitory effect of monoterpenes on methane oxidation was greatest with unsaturated, cyclic hydrocarbon forms [e.g., (-)-alpha-pinene, (S)-(-)-limonene, (R)-(+)-limonene, and gamma-terpinene]. Lower levels of inhibition occurred with oxide and alcohol derivatives [(R)-(+)-limonene oxide, alpha-pinene oxide, linalool, alpha-terpineol] and a noncyclic hydrocarbon (beta-myrcene). Isomers of pinene inhibited activity to different extents. Given their natural sources, monoterpenes may be significant factors affecting bacterial activities in nature.

  18. MKR mice have increased dynamic glucose disposal despite metabolic inflexibility, and hepatic and peripheral insulin insensitivity

    PubMed Central

    Vaitheesvaran, B.; LeRoith, D.

    2014-01-01

    Aims/hypothesis Recent work has shown that there can be significant differences when glucose disposal is assessed for high-fat induced insulin resistance by static clamp methods vs dynamic assessment during a stable isotope i.p. glucose tolerance test. MKR mice, though lean, have severe insulin resistance and decreased muscle fatty acid oxidation. Our goal was to assess dynamic vs static glucose disposal in MKR mice, and to correlate glucose disposal and muscle–adipose–liver flux interactions with metabolic flexibility (indirect calorimetry) and muscle characteristics. Methods Stable isotope flux phenotyping was performed using [6,6-2H2]glucose, [U-13C6]glucose and [2-13C]glycerol. Muscle triacylglycerol (TAG) and diacylglycerol (DAG) content was assessed by thin layer chromatography, and histological determination of fibre type and cytochrome c activity performed. Metabolic flexibility was assessed by indirect calorimetry. Results Indirect calorimetry showed that MKR mice used more glucose than FVB/N mice during fasting (respiratory exchange ratio [RER] 0.88 vs 0.77, respectively). Compared with FVB/N mice, MKR mice had faster dynamic glucose disposal, despite increased whole-muscle DAG and TAG, and similar hepatic glucose production with higher fasting insulin and unchanged basal glucose. Fed MKR muscle had more glycogen, and increased levels of GLUT1 and GLUT4 than FVB/N muscle. Histology indicated that MKR soleus had mildly decreased cytochrome c activity overall and more type II (glycolytic) fibres compared with that in FVB/N mice. Conclusions/interpretation MKR muscle adapts to using glucose, with more type II fibres present in red muscle. Fasting RER is elevated and glucose disposal during an i.p. glucose tolerance test is accelerated despite increased muscle DAG and TAG. Metabolic inflexibility may result from the compensatory use of fuel that can be best utilised for energy requirements; static vs dynamic glucose disposal assessments may measure

  19. Aerobic glucose fermentation by Trypanosoma cruzi axenic culture amastigote-like forms during growth and differentiation to epimastigotes.

    PubMed

    Engel, J C; Franke de Cazzulo, B M; Stoppani, A O; Cannata, J J; Cazzulo, J J

    1987-11-01

    Axenic culture amastigote-like forms of Trypanosoma cruzi, grown at 28 degrees C, reach a stationary phase after two generations, and differentiate to epimastigotes, which then resume growth. Axenic culture amastigotes readily ferment glucose to succinate and acetate, and do not excrete NH3; they have high activities of hexokinase and phosphoenolpyruvate carboxykinase, and very low citrate synthase activity; cytochrome o is absent, and cytochrome b-like is present at a very low level. Epimastigotes catabolize glucose and produce succinate and acetate at a considerably lower rate; they exhibit lower levels of hexokinase and carboxykinase, and much higher levels of citrate synthase and cytochromes o and b-like. They catabolize amino acids, as shown by excretion of NH3 to the medium. The results suggest that axenic culture amastigotes have an essentially glycolytic metabolism, and they acquire the ability to oxidize substrates such as amino acids only after differentiation to epimastigotes.

  20. Glucose, glycolysis and lymphocyte responses.

    PubMed

    Donnelly, Raymond P; Finlay, David K

    2015-12-01

    Activated lymphocytes engage in robust growth and rapid proliferation. To achieve this, they tend to adopt a form of glucose metabolism termed aerobic glycolysis. This type of metabolism allows for the use of large amounts of glucose to generate energy, but also to support biosynthetic processes. This review article will discuss how aerobic glycolysis supports the biosynthetic demands of activated T cells, B cells and Natural Killer cells, and the emerging concept that glycolysis is integrally linked to the differentiation and function of these lymphocyte populations.

  1. Metabolic correlates of selection on aerobic capacity in laboratory mice: a test of the model for the evolution of endothermy.

    PubMed

    Gebczyński, Andrzej K; Konarzewski, Marek

    2009-09-01

    According to the aerobic capacity model of the evolution of endothermy, high levels of basal/resting metabolic rate (BMR/RMR) underlying endothermy have evolved as a correlated response to selection for high rates of aerobic metabolism (V(O(2)max)). To test the model we studied metabolic, behavioural and morphological correlates of replicated selection on maximum body mass-corrected metabolism elicited by swimming (V(O(2)swim)) in male laboratory mice. While 10 generations of selection did not change body mass, it resulted in a 12% difference in V(O(2)swim) between mice of selected and control line types and significant, correlated responses in maximum metabolic rates elicited by exposure to cold in a helium-oxygen atmosphere (V(O(2)He)), and during forced running on a motorized treadmill (V(O(2)run)). Selected and control lines also significantly differed with respect to duration of running (a measure of stamina, t(run)), and the distance run to exhaustion (d(e)). However, the selection protocol did not result in elevated BMR and voluntary activity. Higher V(O(2)max) in selected animals was positively correlated with higher masses of gastrocnemius muscles and heart but not of other visceral organs (intestine, stomach, liver and kidneys). These findings provide a mechanistic explanation for the lack of correlation between basal and maximal metabolic rates in selected mice. Overall, our study does not support the assumptions of the aerobic capacity model for the evolution of endothermy.

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

    PubMed

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

    2016-12-13

    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.

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

    PubMed Central

    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

  4. Inactivation of the Kluyveromyces lactis KlPDA1 gene leads to loss of pyruvate dehydrogenase activity, impairs growth on glucose and triggers aerobic alcoholic fermentation.

    PubMed

    Zeeman, A M; Luttik, M A; Thiele, C; van Dijken, J P; Pronk, J T; Steensma, H Y

    1998-12-01

    The KlPDA1 gene, encoding the E1alpha subunit of the mitochondrial pyruvate-dehydrogenase (PDH) complex was isolated from a Kluyveromyces lactis genomic library by screening with a 1.1 kb internal fragment of the Saccharomyces cerevisiae PDA1 gene. The predicted amino acid sequence encoded by KlPDA1 showed 87% similarity and 79% identity to its S. cerevisiae counterpart. Disruption of KIPDA1 resulted in complete absence of PDH activity in cell extracts. The maximum specific growth rate on glucose of null mutants was 3.5-fold lower than that of the wild-type, whereas growth on ethanol was unaffected. Wild-type K. lactis CBS 2359 exhibits a Crabtree-negative phenotype, i.e. no ethanol was produced in aerobic batch cultures grown on glucose. In contrast, substantial amounts of ethanol and acetaldehyde were produced in aerobic cultures of an isogenic Klpda1 null mutant. A wild-type specific growth rate was restored after introduction of an intact KlPDA1 gene but not, as previously found for S. cerevisiae pda1 mutants, by cultivation in the presence of leucine. The occurrence of aerobic fermentation and slow growth of the Klpda1 null mutant indicate that, although present, the enzymes of the PDH bypass (pyruvate decarboxylase, acetaldehyde dehydrogenase and acetyl-CoA synthetase) could not efficiently replace the PDH complex during batch cultivation on glucose. Only at relatively low growth rates (D = 0.10 h(-1)) in aerobic, glucose-limited chemostat cultures, could the PDH bypass completely replace the PDH complex, thus allowing fully respiratory growth. This resulted in a lower biomass yield [g biomass (g glucose)-1] than in the wild-type due to a higher consumption of ATP in the PDH bypass compared to the formation of acetyl-CoA via the PDH complex.

  5. Insulin effect on glucose transport in thymocytes and splenocytes from rats with metabolic syndrome

    PubMed Central

    2010-01-01

    Metabolic syndrome (MS) may comprise several clinical conditions such as obesity, diabetes and inflammatory disorders, which are characterized by metabolic imbalances. The study of glucose transport and regulation by insulin in lymphocytes is important, since the way they increase inflammation and susceptibility to infections are common in MS. We studied glucose internalization in isolated thymocytes and splenocytes, its regulation by insulin, and the role of three glucose transporters (Gluts) in control and in MS rats. Control glucose internalization and insulin responses were lower in splenocytes than in thymocytes. Control and insulin-induced glucose internalization in thymocytes declined with age, while transport by splenocyte continued to respond to insulin. Control thymocyte glucose internalization was blocked by antibodies against Glut 1 and 4, while the insulin response also was blocked by an anti-Glut 3 antibody. On four month old control and insulin-induced response, splenocyte transport was only blocked by Glut 1 and 4 antibodies. At six months splenocyte glucose internalization depended on Glut 1 and was less sensitive to the effects of an anti-Glut 4 antibody. In MS splenocytes the capacity of anti-Glut 1 antibodies to inhibit control and insulin-dependent glucose transport was less significant, and we found that in MS rats, glucose internalization was dependent on Glut 3 and Glut 4. In summary, the altered metabolic state present in MS rats shows signs of modulation of glucose internalization by the Glut1, Glut 3 and Glut 4 transporters, compared with its own age control. PMID:21044347

  6. Glucose metabolism provide distinct prosurvival benefits to non-small cell lung carcinomas.

    PubMed

    Wu, Rongrong; Galan-Acosta, Lorena; Norberg, Erik

    2015-05-08

    Heterogeneity within the same tumor type has been described to be complex and occur at multiple levels. Less is known about the heterogeneity at the level of metabolism, within a tumor set, yet metabolic pathways are highly relevant to survival signaling in tumors. In this study, we profiled the glucose metabolism of several non-small cell lung carcinoma (NSCLC) cell lines and could show that, NSCLC display distinct glycolytic metabolism. Genetic and pharmacological perturbation of glycolysis was selectively toxic to NSCLCs with high rates of glycolysis. Furthermore, high expression of hexokinase-2, localized at the mitochondria, was a feature of the NSCLCs dependent on glucose catabolism. Our study provides evidence for quantitative metabolic diversity in NSCLCs and indicates that glucose metabolism provide differential prosurvival benefits to NSCLCs.

  7. The role of osteocalcin in human glucose metabolism: marker or mediator?

    PubMed Central

    Booth, Sarah L.; Centi, Amanda; Smith, Steven R.; Gundberg, Caren

    2015-01-01

    Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bone matrix protein that regulates hydroxyapatite size and shape through its vitamin-K-dependent γ-carboxylated form. In circulation, the concentration of osteocalcin is a measure of bone formation. The undercarboxylated form of osteocalcin is reported to be active in glucose metabolism in mice. Total serum osteocalcin concentrations in humans are inversely associated with measures of glucose metabolism; however, human data are inconclusive with regard to the role of uncarboxylated osteocalcin in glucose metabolism because most studies do not account for the influence of vitamin K on the proportion of undercarboxylated osteocalcin or differentiate between the total and uncarboxylated forms of osteocalcin. Furthermore, most human studies do not concomitantly measure other bone turnover markers to isolate the role of osteocalcin as a measure of bone formation from its effect on glucose metabolism. Carefully designed studies are required to define the role of osteocalcin and its carboxylated or undercarboxylated forms in the regulation of glucose metabolism in humans. PMID:23147574

  8. Generating short-term kinetic responses of primary metabolism of Penicillium chrysogenum through glucose perturbation in the bioscope mini reactor.

    PubMed

    Nasution, U; van Gulik, W M; Proell, A; van Winden, W A; Heijnen, J J

    2006-09-01

    A first study of the in vivo kinetic properties of primary metabolism of Penicillium chrysogenum is presented. Dynamic metabolite data have been generated by rapidly increasing the extracellular glucose concentration of cells cultivated under well-defined conditions in an aerobic glucose-limited chemostat followed by measurement of the fast dynamic response of the primary metabolite levels (glucose pulse experiment). These experiments were carried out directly in the chemostat as well as in a mini plug flow reactor (BioScope) outside the chemostat. The results of the glucose pulse experiments carried out in the chemostat and the Bioscope were highly similar. During the 90 s time window of the pulse experiment, the glucose consumption rate increased to a value twice as high as in the steady state, a much lower increase than observed for the fermenting yeast Saccharomyces cerevisiae under similar conditions. Although the observed metabolite patterns in P. chrysogenum were comparable to S. cerevisiae large differences in the magnitude of the dynamic behavior were observed between both organisms. During the pulse experiment the level of glycolytic and TCA cycle intermediates, and adenine nucleotides changed between two- and five-fold. Furthermore, a highly similar five-fold increase in the cytocolic NADH/NAD ratio could be calculated from two independent equilibrium assumptions (fructose 1,6 bis-phosphate to the pool of 2 and 3PG and oxaloacetate to fumarate with glutamate transaminase). It was also found that the C4 pool (aspartate, fumarate, and malate) became much more reduced due to this increase in NADH/NAD ratio. Equilibrium conditions were confirmed to exist in the hexose-P pool, the glycolysis between F16bP and 2+3PG and in the C4 pool of the TCA cycle (fumarate, malate, oxaloacetate and aspartate).

  9. Glucose and fatty acid metabolism in normal and diabetic rabbit cerebral microvessels

    SciTech Connect

    Hingorani, V.; Brecher, P.

    1987-05-01

    Rabbit cerebral microvessels were used to study fatty acid metabolism and its utilization relative to glucose. Microvessels were incubated with either (6-/sup 14/C)glucose or (1-/sup 14/C)oleic acid and the incorporation of radioactivity into /sup 14/CO/sub 2/, lactate, triglyceride, cholesterol ester, and phospholipid was determined. The inclusion of 5.5 mM glucose in the incubation mixture reduced oleate oxidation by 50% and increased esterification into both phospholipid and triglyceride. Glucose oxidation to CO/sub 2/ was reduced by oleate addition, whereas lactate production was unaffected. 2'-Tetradecylglycidic acid, an inhibitor of carnitine acyltransferase I, blocked oleic acid oxidation in the presence and absence of glucose. It did not effect fatty acid esterification when glucose was absent and eliminated the inhibition of oleate on glucose oxidation. Glucose oxidation to /sup 14/CO/sub 2/ was markedly suppressed in microvessels from alloxan-treated diabetic rabbits but lactate formation was unchanged. Fatty acid oxidation to CO/sub 2/ and incorporation into triglyceride, phospholipid, and cholesterol ester remained unchanged in the diabetic state. The experiments show that both fatty acid and glucose can be used as a fuel source by the cerebral microvessels, and the interactions found between fatty acid and glucose metabolism are similar to the fatty acid-glucose cycle, described previously.

  10. Silvering and swimming effects on aerobic metabolism and reactive oxygen species in the European eel.

    PubMed

    Amérand, Aline; Mortelette, Hélène; Belhomme, Marc; Moisan, Christine

    2017-01-01

    Silvering, the last metamorphosis in the eel life cycle induces morphological and physiological modifications in yellow eels (sedentary stage). It pre-adapts them to cope with the extreme conditions they will encounter during their 6000-km spawning migration. A previous study showed that silver eels are able to cope with reactive oxygen species (ROS) over-production linked to an increase in aerobic metabolism during sustained swimming, but the question remains as to whether this mechanism is associated with silvering. A sustained swimming session decreased red muscle in vitro mitochondrial oxygen consumption (MO2) but increased ROS production in both eel stages. The swimming exercise used here was perhaps too intense to induce a stimulation of mitochondrial function or biogenesis even when antioxidant enzyme activities were unchanged. Pro-oxidant/antioxidant imbalance by lipid peroxidation increased in yellow but significantly decreased in silver eels. The silvering process therefore appears to allow a pre-adaptation of red muscle radical metabolism to the demands of spawning migration.

  11. Insulin secretion and cellular glucose metabolism after prolonged low-grade intralipid infusion in young men.

    PubMed

    Jensen, Christine B; Storgaard, Heidi; Holst, Jens J; Dela, Flemming; Madsbad, Sten; Vaag, Allan A

    2003-06-01

    We examined the simultaneous effects of a 24-h low-grade Intralipid infusion on peripheral glucose disposal, intracellular glucose partitioning and insulin secretion rates in twenty young men, by 2-step hyperinsulinemic euglycemic clamp [low insulin clamp (LI), 10 mU/m(2) x min; high insulin clamp (HI), 40 mU/m(2) x min], 3-(3)H-glucose, indirect calorimetry, and iv glucose tolerance test. Free fatty acid concentrations were similar during basal steady state but 3.7- to 13-fold higher during clamps. P-glucagon increased and the insulin/glucagon ratio decreased at both LI and HI during Intralipid infusion. At LI, glucose oxidation decreased by 10%, whereas glucose disposal, glycolytic flux, glucose storage, and glucose production were not significantly altered. At HI, glucose disposal, and glucose oxidation decreased by 12% and 24%, respectively, during Intralipid infusion. Glycolytic flux, glucose storage, and glucose production were unchanged. Insulin secretion rates increased in response to Intralipid infusion, but disposition indices (DI = insulin action.insulin secretion) were unchanged. In conclusion, a 24-h low-grade Intralipid infusion caused insulin resistance in the oxidative (but not in the nonoxidative) glucose metabolism in young healthy men. Moreover, insulin hypersecretion perfectly countered the free-fatty acid-induced insulin resistance. Future studies are needed to determine the role of a prolonged moderate lipid load in subjects at increased risk of developing diabetes.

  12. Metabolic network analysis of DB1 melanoma cells: how much energy is derived from aerobic glycolysis?

    PubMed

    Shestov, A A; Mancuso, A; Leeper, D B; Glickson, J D

    2013-01-01

    A network model has been developed for analysis of tumor glucose metabolism from (13)C MRS isotope exchange kinetic data. Data were obtained from DB1 melanoma cells grown on polystyrene microcarrier beads contained in a 20-mm diameter perfusion chamber in a 9.4 T Varian NMR spectrometer; the cells were perfused with 26 mM [1,6-(13)C(2)]glucose under normoxic conditions and 37°C and monitored by (13)C NMR spectroscopy for 6 h. The model consists of ∼150 differential equations in the cumomer formalism describing glucose and lactate transport, glycolysis, TCA cycle, pyruvate cycling, the pentose shunt, lactate dehydrogenase, the malate-aspartate and glycerophosphate shuttles, and various anaplerotic pathways. The rate of oxygen consumption (CMRO(2)) was measured polarographically by monitoring differences in pO(2). The model was validated by excellent agreement between model predicted and experimentally measured values of CMRO(2) and glutamate pool size. Assuming a P/O ratio of 2.5 for NADH and 1.5 for FADH2, ATP production was estimated as 46% glycolytic and 54% mitochondrial based on average values of CMRO(2) and glycolytic flux (two experiments).

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

    SciTech Connect

    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)

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

    PubMed Central

    Meng, Shengxi; Cao, Jianmei; Feng, Qin; Peng, Jinghua; Hu, Yiyang

    2013-01-01

    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. PMID:24062792

  15. High- and moderate-intensity aerobic exercise and excess post-exercise oxygen consumption in men with metabolic syndrome.

    PubMed

    Larsen, I; Welde, B; Martins, C; Tjønna, A E

    2014-06-01

    Physical activity is central in prevention and treatment of metabolic syndrome. High-intensity aerobic exercise can induce larger energy expenditure per unit of time compared with moderate-intensity exercise. Furthermore, it may induce larger energy expenditure at post-exercise recovery. The aim of this study is to compare the excess post-exercise oxygen consumption (EPOC) in three different aerobic exercise sessions in men with metabolic syndrome. Seven men (age: 56.7 ± 10.8) with metabolic syndrome participated in this crossover study. The sessions consisted of one aerobic interval (1-AIT), four aerobic intervals (4-AIT), and 47-min continuous moderate exercise (CME) on separate days, with at least 48 h between each test day. Resting metabolic rate (RMR) was measured pre-exercise and used as baseline value. EPOC was measured until baseline metabolic rate was re-established. An increase in O2 uptake lasting for 70.4 ± 24.8 min (4-AIT), 35.9 ± 17.3 min (1-AIT), and 45.6 ± 17.3 min (CME) was observed. EPOC were 2.9 ± 1.7 L O2 (4-AIT), 1.3 ±  .1 L O2 (1-AIT), and 1.4 ± 1.1 L O2 (CME). There were significant differences (P < 0.001) between 4-AIT, CME, and 1-AIT. Total EPOC was highest after 4-AIT. These data suggest that exercise intensity has a significant positive effect on EPOC in men with metabolic syndrome.

  16. Regulation and Function of Versatile Aerobic and Anaerobic Respiratory Metabolism in Pseudomonas aeruginosa

    PubMed Central

    Arai, Hiroyuki

    2011-01-01

    Pseudomonas aeruginosa is a ubiquitously distributed opportunistic pathogen that inhabits soil and water as well as animal-, human-, and plant-host-associated environments. The ubiquity would be attributed to its very versatile energy metabolism. P. aeruginosa has a highly branched respiratory chain terminated by multiple terminal oxidases and denitrification enzymes. Five terminal oxidases for aerobic respiration have been identified in the P. aeruginosa cells. Three of them, the cbb3-1 oxidase, the cbb3-2 oxidase, and the aa3 oxidase, are cytochrome c oxidases and the other two, the bo3 oxidase and the cyanide-insensitive oxidase, are quinol oxidases. Each oxidase has a specific affinity for oxygen, efficiency of energy coupling, and tolerance to various stresses such as cyanide and reactive nitrogen species. These terminal oxidases are used differentially according to the environmental conditions. P. aeruginosa also has a complete set of the denitrification enzymes that reduce nitrate to molecular nitrogen via nitrite, nitric oxide (NO), and nitrous oxide. These nitrogen oxides function as alternative electron acceptors and enable P. aeruginosa to grow under anaerobic conditions. One of the denitrification enzymes, NO reductase, is also expected to function for detoxification of NO produced by the host immune defense system. The control of the expression of these aerobic and anaerobic respiratory enzymes would contribute to the adaptation of P. aeruginosa to a wide range of environmental conditions including in the infected hosts. Characteristics of these respiratory enzymes and the regulatory system that controls the expression of the respiratory genes in the P. aeruginosa cells are overviewed in this article. PMID:21833336

  17. Glucose metabolism and gene expression in juvenile zebrafish (Danio rerio) challenged with a high carbohydrate diet: effects of an acute glucose stimulus during late embryonic life.

    PubMed

    Rocha, Filipa; Dias, Jorge; Engrola, Sofia; Gavaia, Paulo; Geurden, Inge; Dinis, Maria Teresa; Panserat, Stephane

    2015-02-14

    Knowledge on the role of early nutritional stimuli as triggers of metabolic pathways in fish is extremely scarce. The objective of the present study was to assess the long-term effects of glucose injection in the yolk (early stimulus) on carbohydrate metabolism and gene regulation in zebrafish juveniles challenged with a high-carbohydrate low-protein (HC) diet. Eggs were microinjected at 1 d post-fertilisation (dpf) with either glucose (2 M) or saline solutions. Up to 25 dpf, fish were fed a low-carbohydrate high-protein (LC) control diet, which was followed by a challenge with the HC diet. Survival and growth of 35 dpf juveniles were not affected by injection or the HC diet. Glucose stimulus induced some long-term metabolic changes in the juveniles, as shown by the altered expression of genes involved in glucose metabolism. On glycolysis, the expression levels of hexokinase 1 (HK1) and phosphofructokinase-6 (6PFK) were up-regulated in the visceral and muscle tissues, respectively, of juveniles exposed to the glucose stimulus, indicating a possible improvement in glucose oxidation. On gluconeogenesis, the inhibition of the expression levels of PEPCK in fish injected with glucose suggested lower production of hepatic glucose. Unexpectedly, fructose-1,6-bisphosphatase (FBP) expression was induced and 6PFK expression reduced by glucose stimulus, leaving the possibility of a specific regulation of the FBP-6PFK metabolic cycle. Glucose metabolism in juveniles was estimated using a [¹⁴C]glucose tracer; fish previously exposed to the stimulus showed lower retention of [¹⁴C]glucose in visceral tissue (but not in muscle tissue) and, accordingly, higher glucose catabolism, in comparison with the saline group. Globally, our data suggest that glucose stimulus at embryo stage has the potential to alter particular steps of glucose metabolism in zebrafish juveniles.

  18. Preparation and Catalytic Activity for Aerobic Glucose Oxidation of Crown Jewel Structured Pt/Au Bimetallic Nanoclusters

    PubMed Central

    Zhang, Haijun; Wang, Liqiong; Lu, Lilin; Toshima, Naoki

    2016-01-01

    Understanding of the “structure-activity” relations for catalysts at an atomic level has been regarded as one of the most important objectives in catalysis studies. Bimetallic nanoclusters (NCs) in its many types, such as core/shell, random alloy, cluster-in-cluster, bi-hemisphere, and crown jewel (one kind of atom locating at the top position of another kind of NC), attract significant attention owing to their excellent optical, electronic, and catalytic properties. PVP-protected crown jewel-structured Pt/Au (CJ-Pt/Au) bimetallic nanoclusters (BNCs) with Au atoms located at active top sites were synthesized via a replacement reaction using 1.4-nm Pt NCs as mother clusters even considering the fact that the replacement reaction between Pt and Au3+ ions is difficult to be occurred. The prepared CJ-Pt/Au colloidal catalysts characterized by UV-Vis, TEM, HR-TEM and HAADF-STEM-EELS showed a high catalytic activity for aerobic glucose oxidation, and the top Au atoms decorating the Pt NCs were about 15 times more active than the Au atoms of Au NCs with similar particle size. PMID:27476577

  19. Preparation and Catalytic Activity for Aerobic Glucose Oxidation of Crown Jewel Structured Pt/Au Bimetallic Nanoclusters.

    PubMed

    Zhang, Haijun; Wang, Liqiong; Lu, Lilin; Toshima, Naoki

    2016-08-01

    Understanding of the "structure-activity" relations for catalysts at an atomic level has been regarded as one of the most important objectives in catalysis studies. Bimetallic nanoclusters (NCs) in its many types, such as core/shell, random alloy, cluster-in-cluster, bi-hemisphere, and crown jewel (one kind of atom locating at the top position of another kind of NC), attract significant attention owing to their excellent optical, electronic, and catalytic properties. PVP-protected crown jewel-structured Pt/Au (CJ-Pt/Au) bimetallic nanoclusters (BNCs) with Au atoms located at active top sites were synthesized via a replacement reaction using 1.4-nm Pt NCs as mother clusters even considering the fact that the replacement reaction between Pt and Au(3+) ions is difficult to be occurred. The prepared CJ-Pt/Au colloidal catalysts characterized by UV-Vis, TEM, HR-TEM and HAADF-STEM-EELS showed a high catalytic activity for aerobic glucose oxidation, and the top Au atoms decorating the Pt NCs were about 15 times more active than the Au atoms of Au NCs with similar particle size.

  20. Preparation and Catalytic Activity for Aerobic Glucose Oxidation of Crown Jewel Structured Pt/Au Bimetallic Nanoclusters

    NASA Astrophysics Data System (ADS)

    Zhang, Haijun; Wang, Liqiong; Lu, Lilin; Toshima, Naoki

    2016-08-01

    Understanding of the “structure-activity” relations for catalysts at an atomic level has been regarded as one of the most important objectives in catalysis studies. Bimetallic nanoclusters (NCs) in its many types, such as core/shell, random alloy, cluster-in-cluster, bi-hemisphere, and crown jewel (one kind of atom locating at the top position of another kind of NC), attract significant attention owing to their excellent optical, electronic, and catalytic properties. PVP-protected crown jewel-structured Pt/Au (CJ-Pt/Au) bimetallic nanoclusters (BNCs) with Au atoms located at active top sites were synthesized via a replacement reaction using 1.4-nm Pt NCs as mother clusters even considering the fact that the replacement reaction between Pt and Au3+ ions is difficult to be occurred. The prepared CJ-Pt/Au colloidal catalysts characterized by UV-Vis, TEM, HR-TEM and HAADF-STEM-EELS showed a high catalytic activity for aerobic glucose oxidation, and the top Au atoms decorating the Pt NCs were about 15 times more active than the Au atoms of Au NCs with similar particle size.

  1. Bypasses in intracellular glucose metabolism in iron-limited Pseudomonas putida.

    PubMed

    Sasnow, Samantha S; Wei, Hua; Aristilde, Ludmilla

    2016-02-01

    Decreased biomass growth in iron (Fe)-limited Pseudomonas is generally attributed to downregulated expression of Fe-requiring proteins accompanied by an increase in siderophore biosynthesis. Here, we applied a stable isotope-assisted metabolomics approach to explore the underlying carbon metabolism in glucose-grown Pseudomonas putida KT2440. Compared to Fe-replete cells, Fe-limited cells exhibited a sixfold reduction in growth rate but the glucose uptake rate was only halved, implying an imbalance between glucose uptake and biomass growth. This imbalance could not be explained by carbon loss via siderophore production, which accounted for only 10% of the carbon-equivalent glucose uptake. In lieu of the classic glycolytic pathway, the Entner-Doudoroff (ED) pathway in Pseudomonas is the principal route for glucose catabolism following glucose oxidation to gluconate. Remarkably, gluconate secretion represented 44% of the glucose uptake in Fe-limited cells but only 2% in Fe-replete cells. Metabolic (13) C flux analysis and intracellular metabolite levels under Fe limitation indicated a decrease in carbon fluxes through the ED pathway and through Fe-containing metabolic enzymes. The secreted siderophore was found to promote dissolution of Fe-bearing minerals to a greater extent than the high extracellular gluconate. In sum, bypasses in the Fe-limited glucose metabolism were achieved to promote Fe availability via siderophore secretion and to reroute excess carbon influx via enhanced gluconate secretion.

  2. High concentrations of glucose reduce the oxidative metabolism of dog neutrophils in vitro

    PubMed Central

    2013-01-01

    Background Dogs are commonly affected by hyperglycemic conditions. Hyperglycemia compromises the immune response and favors bacterial infections; however, reports on the effects of glucose on neutrophil oxidative metabolism and apoptosis are conflicting in humans and rare in dogs. Considering the many complex factors that affect neutrophil oxidative metabolism in vivo, we investigated in vitro the specific effect of high concentrations of glucose on superoxide production and apoptosis rate in neutrophils from healthy dogs. Results The capacity of the neutrophils to reduce tetrazolium nitroblue decreased significantly in the higher concentration of glucose (15.13 ± 9.73% (8 mmol/L) versus 8.93 ± 5.71% (16 mmol/L)). However, there were no changes in tetrazolium nitroblue reduction at different glucose concentrations when the neutrophils were first activated with phorbol myristate acetate. High concentrations of glucose did not affect the viability and apoptosis rate of canine neutrophils either with or without prior camptothecin stimulation. This study provides the first evidence that high concentrations of glucose inhibit the oxidative metabolism of canine neutrophils in vitro in a manner similar to that which occurs in humans, and that the decrease in superoxide production did not increase the apoptosis rate. Conclusions A high concentration of glucose reduces the oxidative metabolism of canine neutrophils in vitro. It is likely that glucose at high concentrations rapidly affects membrane receptors responsible for the activation of NADPH oxidase in neutrophils; therefore, the nonspecific immune response can be compromised in dogs with acute and chronic hyperglycemic conditions. PMID:23388121

  3. Effects of dehydroepiandrosterone (DHEA) on glucose metabolism in isolated hepatocytes from Zucker rats

    SciTech Connect

    Finan, A.; Cleary, M.P.

    1986-03-05

    DHEA has been shown to competitively inhibit the pentose phosphate shunt (PPS) enzyme glucose-6-phosphate dehydrogenase (G6PD) when added in vitro to supernatants or homogenates prepared from mammalian tissues. However, no consistent effect on G6PD activity has been determined in tissue removed from DHEA-treated rats. To explore the effects of DHEA on PPS, glucose utilization was measured in hepatocytes from lean and obese male Zucker rats (8 wks of age) following 1 wk of DHEA treatment (0.6% in diet). Incubation of isolated hepatocytes from treated lean Zucker rats with either (1-/sup 14/C) glucose or (6-/sup 14/C) glucose resulted in significant decreases in CO/sub 2/ production and total glucose utilization. DHEA-lean rats also had lowered fat pad weights. In obese rats, there was no effect of 1 wk of treatment on either glucose metabolism or fat pad weight. The calculated percent contribution of the PPS to glucose metabolism in hepatocytes was not changed for either DHEA-lean or obese rats when compared to control rats. In conclusion, 1 wk of DHEA treatment lowered overall glucose metabolism in hepatocytes of lean Zucker rats, but did not selectively affect the PPS. The lack of an effect of short-term treatment in obese rats may be due to differences in their metabolism or storage/release of DHEA in tissues in comparison to lean rats.

  4. A new intra-aerobic metabolism in the nitrite-dependent anaerobic methane-oxidizing bacterium Candidatus 'Methylomirabilis oxyfera'.

    PubMed

    Wu, Ming L; Ettwig, Katharina F; Jetten, Mike S M; Strous, Marc; Keltjens, Jan T; van Niftrik, Laura

    2011-01-01

    Biological methane oxidation proceeds either through aerobic or anaerobic pathways. The newly discovered bacterium Candidatus 'Methylomirabilis oxyfera' challenges this dichotomy. This bacterium performs anaerobic methane oxidation coupled to denitrification, but does so in a peculiar way. Instead of scavenging oxygen from the environment, like the aerobic methanotrophs, or driving methane oxidation by reverse methanogenesis, like the methanogenic archaea in sulfate-reducing systems, it produces its own supply of oxygen by metabolizing nitrite via nitric oxide into oxygen and dinitrogen gas. The intracellularly produced oxygen is then used for the oxidation of methane by the classical aerobic methane oxidation pathway involving methane mono-oxygenase. The present mini-review summarizes the current knowledge about this process and the micro-organism responsible for it.

  5. AICAR administration affects glucose metabolism by upregulating the novel glucose transporter, GLUT8, in equine skeletal muscle.

    PubMed

    de Laat, M A; Robinson, M A; Gruntmeir, K J; Liu, Y; Soma, L R; Lacombe, V A

    2015-09-01

    Equine metabolic syndrome is characterized by obesity and insulin resistance (IR). Currently, there is no effective pharmacological treatment for this insidious disease. Glucose uptake is mediated by a family of glucose transporters (GLUT), and is regulated by insulin-dependent and -independent pathways, including 5-AMP-activated protein kinase (AMPK). Importantly, the activation of AMPK, by 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR) stimulates glucose uptake in both healthy and diabetic humans. However, whether AICAR promotes glucose uptake in horses has not been established. It is hypothesized that AICAR administration would enhance glucose transport in equine skeletal muscle through AMPK activation. In this study, the effect of an intravenous AICAR infusion on blood glucose and insulin concentrations, as well as on GLUT expression and AMPK activation in equine skeletal muscle (quantified by Western blotting) was examined. Upon administration, plasma AICAR rapidly reached peak concentration. Treatment with AICAR resulted in a decrease (P <0.05) in blood glucose and an increase (P <0.05) in insulin concentration without a change in lactate concentration. The ratio of phosphorylated to total AMPK was increased (P <0.05) in skeletal muscle. While GLUT4 and GLUT1 protein expression remained unchanged, GLUT8 was increased (P <0.05) following AICAR treatment. Up-regulation of GLUT8 protein expression by AICAR suggests that this novel GLUT isoform plays an important role in equine muscle glucose transport. In addition, the data suggest that AMPK activation enhances pancreatic insulin secretion. Collectively, the findings suggest that AICAR acutely promotes muscle glucose uptake in healthy horses and thus its therapeutic potential for managing IR requires investigation.

  6. Immune system and glucose metabolism interaction in schizophrenia: a chicken-egg dilemma.

    PubMed

    Steiner, Johann; Bernstein, Hans-Gert; Schiltz, Kolja; Müller, Ulf J; Westphal, Sabine; Drexhage, Hemmo A; Bogerts, Bernhard

    2014-01-03

    Impaired glucose metabolism and the development of metabolic syndrome contribute to a reduction in the average life expectancy of individuals with schizophrenia. It is unclear whether this association simply reflects an unhealthy lifestyle or whether weight gain and impaired glucose tolerance in patients with schizophrenia are directly attributable to the side effects of atypical antipsychotic medications or disease-inherent derangements. In addition, numerous previous studies have highlighted alterations in the immune system of patients with schizophrenia. Increased concentrations of interleukin (IL)-1, IL-6, and transforming growth factor-beta (TGF-β) appear to be state markers, whereas IL-12, interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and soluble IL-2 receptor (sIL-2R) appear to be trait markers of schizophrenia. Moreover, the mononuclear phagocyte system (MPS) and microglial activation are involved in the early course of the disease. This review illustrates a "chicken-egg dilemma", as it is currently unclear whether impaired cerebral glucose utilization leads to secondary disturbances in peripheral glucose metabolism, an increased risk of cardiovascular complications, and accompanying pro-inflammatory changes in patients with schizophrenia or whether immune mechanisms may be involved in the initial pathogenesis of schizophrenia, which leads to disturbances in glucose metabolism such as metabolic syndrome. Alternatively, shared underlying factors may be responsible for the co-occurrence of immune system and glucose metabolism disturbances in schizophrenia.

  7. Cerebral glucose metabolism after portacaval shunting in the rat. Patterns of metabolism and implications for the pathogenesis of hepatic encephalopathy.

    PubMed Central

    Lockwood, A H; Ginsberg, M D; Rhoades, H M; Gutierrez, M T

    1986-01-01

    The regional cerebral metabolic rate for glucose was measured in normal and portacaval shunted rats and the effects of unilateral carotid infusions of "threshold" amounts of ammonia were assessed. 8 wk after shunting the glucose metabolic rate was increased in all 20 brain regions sampled. Effects on subcortical and phylogenetically older regions of the brain were most pronounced with a 74% increase observed in the reticular formation at the collicular level. Increases in the cerebral cortex ranged from 12 to 18%. Unilateral infusions of ammonia did not affect behavior but altered the electroencephalogram and selectively increased the glucose metabolic rate in the thalamus, hypothalamus, and substantia nigra in half of the animals, a pattern similar to that seen after a portacaval shunt, suggesting hyperammonemia as the cause of postshunt increases in glucose metabolism. Visual inspection of autoradiograms, computed correlation coefficients relating interregional metabolism, and principal component analysis suggest that normal cerebral metabolic and functional interrelationships are altered by shunting. Ammonia stimulation of the hypothalamic satiety centers may suppress appetite and lead to cachexia. Reductions in the ammonia detoxification capacity of skeletal muscle may increase the probability of developing future episodes of hyperammonemia, perpetuating the process. Direct effects of ammonia on specific brain centers such as the dorsomedial hypothalamus and reticular activating system may combine with global disruptions of cerebral metabolic-functional relationships to produce the protean manifestations of portal-systemic encephalopathy. Images PMID:3722388

  8. Cerebral glucose metabolism in childhood-onset obsessive-compulsive disorder

    SciTech Connect

    Swedo, S.E.; Schapiro, M.B.; Grady, C.L.; Cheslow, D.L.; Leonard, H.L.; Kumar, A.; Friedland, R.; Rapoport, S.I.; Rapoport, J.L.

    1989-06-01

    The cerebral metabolic rate for glucose was studied in 18 adults with childhood-onset obsessive-compulsive disorder (OCD) and in age- and sex-matched controls using positron emission tomography and fludeoxyglucose F 18. Both groups were scanned during rest, with reduced auditory and visual stimulation. The group with OCD showed an increased glucose metabolism in the left orbital frontal, right sensorimotor, and bilateral prefrontal and anterior cingulate regions as compared with controls. Ratios of regional activity to mean cortical gray matter metabolism were increased for the right prefrontal and left anterior cingulate regions in the group with OCD as a whole. Correlations between glucose metabolism and clinical assessment measures showed a significant relationship between metabolic activity and both state and trait measurements of OCD and anxiety as well as the response to clomipramine hydrochloride therapy. These results are consistent with the suggestion that OCD may result from a functional disturbance in the frontal-limbic-basal ganglia system.

  9. Daily rhythms in glucose metabolism: suprachiasmatic nucleus output to peripheral tissue.

    PubMed

    La Fleur, S E

    2003-03-01

    The body has developed several control mechanisms to maintain plasma glucose concentrations within strict boundaries. Within those physiological boundaries, a clear daily rhythm in plasma glucose concentrations is present; this rhythm depends on the biological clock, which is located in the hypothalamic suprachiasmatic nucleus (SCN), and is independent of the daily rhythm in food intake. Interestingly, there is also a daily rhythm in glucose uptake, which also depends on the SCN and follows the same pattern as the daily rhythm in plasma glucose concentrations; both rise before the onset of activity. Thus, the SCN prepares the individual for the upcoming activity period in two different ways: by increasing plasma glucose concentrations and by facilitating tissue glucose uptake. In addition to this anticipation of glucose metabolism to expected glucose demands, the SCN also influences, depending on the time of the day, the responses of pancreas and liver to abrupt glucose changes (such as a glucose rise after a meal or hypoglycaemia). This review presents the view that the SCN uses different routes to (i) maintain daily glucose balance and (ii) set the level of the endocrine response to abrupt blood glucose changes.

  10. Effects of pulp and paper mill effluent extracts on liver anaerobic and aerobic metabolic enzymes in rainbow trout.

    PubMed

    Orrego, Rodrigo; Pandelides, Zacharias; Guchardi, John; Holdway, Douglas

    2011-05-01

    This study investigates whether pulse exposure to Chilean pulp and paper mill effluent solid phase extracted (SPE) extracts via intraperitoneal injection (IP), would result in changes in the activities of the respiratory metabolic enzymes citrate synthase (CS) and lactate dehydrogenase (LDH) in rainbow trout livers. It also investigated if an alteration in liver metabolic capacity influenced the liver detoxification processes and estrogenic effects previously reported. Besides, a comparison of those enzymatic activities with fish IP injected with SPE extracts of two model effluents coming from industries that process 100% different type of feedstock (softwood, SW and hardwood, HW) was also evaluated. An initial induction of the anaerobic metabolism (increase in LDH enzymatic activity) was detected in all Chilean pulp mill effluent extracts evaluated, contrary to the initial unaltered aerobic metabolism (CS enzymatic activity) observed. A compensatory relationship in energy metabolism (Pasteur effect) was observed when comparing both enzymatic activities of fish exposed to those effluent extracts. LDH and CS activities observed in fish injected with Chilean extracts seem to be related to the effects observed in fish injected with SW extracts. This study showed that intraperitoneal injection of pulp and paper mill effluent extracts affected the anaerobic and aerobic metabolic capacities in rainbow trout livers, but this metabolic alteration did not affect detoxification capability or estrogenic effect previously reported.

  11. Global Metabolic Stress of Isoeffort Continuous and High Intensity Interval Aerobic Exercise: A Comparative (1)H NMR Metabonomic Study.

    PubMed

    Zafeiridis, Andreas; Chatziioannou, Anastasia Chrysovalantou; Sarivasiliou, Haralambos; Kyparos, Antonios; Nikolaidis, Michalis G; Vrabas, Ioannis S; Pechlivanis, Alexandros; Zoumpoulakis, Panagiotis; Baskakis, Constantinos; Dipla, Konstantina; Theodoridis, Georgios A

    2016-12-02

    The overall metabolic/energetic stress that occurs during an acute bout of exercise is proposed to be the main driving force for long-term training adaptations. Continuous and high-intensity interval exercise protocols (HIIE) are currently prescribed to acquire the muscular and metabolic benefits of aerobic training. We applied (1)H NMR-based metabonomics to compare the overall metabolic perturbation and activation of individual bioenergetic pathways of three popular aerobic exercises matched for effort/strain. Nine men performed continuous, long-interval (3 min), and short-interval (30 s) bouts of exercise under isoeffort conditions. Blood was collected before and after exercise. The multivariate PCA and OPLS-DA models showed a distinct separation of pre- and postexercise samples in three protocols. The two models did not discriminate the postexercise overall metabolic profiles of the three exercise types. Analysis focused on muscle bioenergetic pathways revealed an extensive upregulation of carbohydrate-lipid metabolism and the TCA cycle in all three protocols; there were only a few differences among protocols in the postexercise abundance of molecules when long-interval bouts were performed. In conclusion, continuous and HIIE exercise protocols, when performed with similar effort/strain, induce comparable global metabolic response/stress despite their marked differences in work-bout intensities. This study highlights the importance of NMR metabonomics in comprehensive monitoring of metabolic consequences of exercise training in the blood of athletes and exercising individuals.

  12. Effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness of female patients with metabolic syndrome

    PubMed Central

    Kang, Seol-Jung; Kim,, Eon-ho; Ko, Kwang-Jun

    2016-01-01

    [Purpose] The purpose of this study was to investigate the effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness or female patients with metabolic syndrome. [Subjects and Methods] Subjects were randomly assigned to an exercise group (n=12) or a control group (n=11). Subjects in the exercise group performed aerobic exercise at 60–80% of maximum heart rate for 40 min 5 times a week for 12 weeks. The changes in metabolic syndrome risk factors, resting heart rate, physical fitness, and arterial stiffness were measured and analyzed before and after initiation of the exercise program to determine the effect of exercise. Arterial stiffness was assessed based on brachial-ankle pulse wave velocity (ba-PWV). [Results] Compared to the control group; The metabolic syndrome risk factors (weight, % body fat, waist circumference, systolic blood pressure, diastolic blood pressure, and HDL-Cholesterol) were significantly improved in the exercise: resting heart rate was significantly decreased; VO2max, muscle strength and muscle endurance were significantly increased; and ba-PWV was significantly decreased. [Conclusion] Aerobic exercise had beneficial effects on the resting heart rate, physical fitness, and arterial stiffness of patients with metabolic syndrome. PMID:27390411

  13. Effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness of female patients with metabolic syndrome.

    PubMed

    Kang, Seol-Jung; Kim, Eon-Ho; Ko, Kwang-Jun

    2016-06-01

    [Purpose] The purpose of this study was to investigate the effects of aerobic exercise on the resting heart rate, physical fitness, and arterial stiffness or female patients with metabolic syndrome. [Subjects and Methods] Subjects were randomly assigned to an exercise group (n=12) or a control group (n=11). Subjects in the exercise group performed aerobic exercise at 60-80% of maximum heart rate for 40 min 5 times a week for 12 weeks. The changes in metabolic syndrome risk factors, resting heart rate, physical fitness, and arterial stiffness were measured and analyzed before and after initiation of the exercise program to determine the effect of exercise. Arterial stiffness was assessed based on brachial-ankle pulse wave velocity (ba-PWV). [Results] Compared to the control group; The metabolic syndrome risk factors (weight, % body fat, waist circumference, systolic blood pressure, diastolic blood pressure, and HDL-Cholesterol) were significantly improved in the exercise: resting heart rate was significantly decreased; VO2max, muscle strength and muscle endurance were significantly increased; and ba-PWV was significantly decreased. [Conclusion] Aerobic exercise had beneficial effects on the resting heart rate, physical fitness, and arterial stiffness of patients with metabolic syndrome.

  14. Aerobic exercise increases peripheral and hepatic insulin sensitivity in sedentary adolescents

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Data are limited on the effects of controlled aerobic exercise programs (without weight loss) on insulin sensitivity and glucose metabolism in children and adolescents. To determine whether a controlled aerobic exercise program (without weight loss) improves peripheral and hepatic insulin sensitivi...

  15. Effects of berberine on glucose metabolism in vitro.

    PubMed

    Yin, Jun; Hu, Renming; Chen, Mingdao; Tang, Jinfeng; Li, Fengying; Yang, Ying; Chen, Jialun

    2002-11-01

    The action of berberine was compared with metformin and troglitazone (TZD) with regard to the glucose-lowering action in vitro. HepG2 cell line, phenotypically similar to human hepatocytes, was used for glucose consumption (GC) studies. Cell proliferation was measured by methylthiotetrazole (MTT) assay. In moderate high glucose concentration (11.1 mmol/L), GC of HepG2 cells was increased by 32% to 60% (P <.001 to P <.0001) with 5 x 10(-6) mol/L to 1 x 10(-4) mol/L berberine, which was comparable to that with 1 x 10(-3) mol/L metformin. The glucose-lowering effect of berberine decreased as the glucose concentration increased. The maximal potency was reached in the presence of 5.5 mmol/L glucose, and it was abolished when the glucose concentration increased to 22.2 mmol/L. The effect was not dependent on insulin concentration, which was similar to that of metformin and was different from that of TZD, whose glucose-lowering effect is insulin dependent. TZD had a better antihyperglycemic potency than metformin when insulin was added (P <.001). In the meantime, a significant toxicity of the drug to HepG2 cells was also observed. The betaTC3 cell line was used for insulin release testing, and no secretogogue effect of berberine was observed. These observations suggest that berberine is able to exert a glucose-lowering effect in hepatocytes, which is insulin independent and similar to that of metformin, but has no effect on insulin secretion.

  16. PHLPP regulates hexokinase 2-dependent glucose metabolism in colon cancer cells

    PubMed Central

    Xiong, Xiaopeng; Wen, Yang-An; Mitov, Mihail I; C Oaks, Mary; Miyamoto, Shigeki; Gao, Tianyan

    2017-01-01

    Increased glucose metabolism is considered as one of the most important metabolic alterations adapted by cancer cells in order to generate energy as well as high levels of glycolytic intermediates to support rapid proliferation. PH domain leucine-rich repeat protein phosphatase (PHLPP) belongs to a novel family of Ser/Thr protein phosphatases that function as tumor suppressors in various types of human cancer. Here we determined the role of PHLPP in regulating glucose metabolism in colon cancer cells. Knockdown of PHLPP increased the rate of glucose consumption and lactate production, whereas overexpression of PHLPP had the opposite effect. Bioenergetic analysis using Seahorse Extracelluar Flux Analyzer revealed that silencing PHLPP expression induced a glycolytic shift in colon cancer cells. Mechanistically, we found that PHLPP formed a complex with Akt and hexokinase 2 (HK2) in the mitochondrial fraction of colon cancer cells and knockdown of PHLPP enhanced Akt-mediated phosphorylation and mitochondrial localization of HK2. Depletion of HK2 expression or treating cells with Akt and HK2 inhibitors reversed PHLPP loss-induced increase in glycolysis. Furthermore, PHLPP knockdown cells became addicted to glucose as a major energy source in that glucose starvation significantly decreased cancer cell survival. As HK2 is the key enzyme that determines the direction and magnitude of glucose flux, our study identified PHLPP as a novel regulator of glucose metabolism by controlling HK2 activity in colon cancer cells. PMID:28179998

  17. Succinate is a preferential metabolic stimulus-coupling signal for glucose-induced proinsulin biosynthesis translation.

    PubMed

    Alarcon, Cristina; Wicksteed, Barton; Prentki, Marc; Corkey, Barbara E; Rhodes, Christopher J

    2002-08-01

    The secondary signals emanating from increased glucose metabolism, which lead to specific increases in proinsulin biosynthesis translation, remain elusive. It is known that signals for glucose-stimulated insulin secretion and proinsulin biosynthesis diverge downstream of glycolysis. Consequently, the mitochondrial products ATP, Krebs cycle intermediates, glutamate, and acetoacetate were investigated as candidate stimulus-coupling signals specific for glucose-induced proinsulin biosynthesis in rat islets. Decreasing ATP levels by oxidative phosphorylation inhibitors showed comparable effects on proinsulin biosynthesis and total protein synthesis. Although it is a cofactor, ATP is unlikely to be a metabolic stimulus-coupling signal specific for glucose-induced proinsulin biosynthesis. Neither glutamic acid methyl ester nor acetoacetic acid methyl ester showed a specific effect on glucose-stimulated proinsulin biosynthesis. Interestingly, among Krebs cycle intermediates, only succinic acid monomethyl ester specifically stimulated proinsulin biosynthesis. Malonic acid methyl ester, an inhibitor of succinate dehydrogenase, also specifically increased glucose-induced proinsulin biosynthesis without affecting islet ATP levels or insulin secretion. Glucose caused a 40% increase in islet intracellular succinate levels, but malonic acid methyl ester showed no further effect, probably due to efficient conversion of succinate to succinyl-CoA. In this regard, a GTP-dependent succinyl-CoA synthetase activity was found in cytosolic fractions of pancreatic islets. Thus, succinate and/or succinyl-CoA appear to be preferential metabolic stimulus-coupling factors for glucose-induced proinsulin biosynthesis translation.

  18. Brain glucose sensing, glucokinase and neural control of metabolism and islet function.

    PubMed

    Ogunnowo-Bada, E O; Heeley, N; Brochard, L; Evans, M L

    2014-09-01

    It is increasingly apparent that the brain plays a central role in metabolic homeostasis, including the maintenance of blood glucose. This is achieved by various efferent pathways from the brain to periphery, which help control hepatic glucose flux and perhaps insulin-stimulated insulin secretion. Also, critically important for the brain given its dependence on a constant supply of glucose as a fuel--emergency counter-regulatory responses are triggered by the brain if blood glucose starts to fall. To exert these control functions, the brain needs to detect rapidly and accurately changes in blood glucose. In this review, we summarize some of the mechanisms postulated to play a role in this and examine the potential role of the low-affinity hexokinase, glucokinase, in the brain as a key part of some of this sensing. We also discuss how these processes may become altered in diabetes and related metabolic diseases.

  19. The role of osteocalcin in human glucose metabolism: marker or mediator?

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Increasing evidence supports an association between the skeleton and energy metabolism. These interactions are mediated by a variety of hormones, cytokines, and nutrients. Here, the evidence for a role of osteocalcin in the regulation of glucose metabolism in humans is reviewed. Osteocalcin is a bon...

  20. Heritability of metabolic response to the intravenous glucose tolerance test in German Holstein Friesian bulls.

    PubMed

    Pieper, Laura; Staufenbiel, Rudolf; Christ, Jana; Panicke, Lothar; Müller, Uwe; Brockmann, Gudrun A

    2016-09-01

    Selection for improved health and welfare in farm animals is of increasing interest worldwide. Peripartum energy balance is a key factor for pathogenesis of diseases in dairy cows. The intravenous glucose tolerance test (ivGTT) can be used to study the metabolic response to a glucose stimulus. The aim of this study was to estimate heritability of ivGTT traits in German Holstein bulls. A total of 541 Holstein bulls aged 7 to 17 mo from 2 breeding stations were subjected to the ivGTT. Serum glucose concentrations were measured at 0, 7, 14, 21, 28, 35, 42, 49, 56, and 63 min relative to glucose infusion. The maximum increase in blood glucose concentration, glucose area equivalent, and blood glucose half-life period were calculated. Heritabilities were estimated using a univariate animal model including station-year-season and age as fixed effects, and animal additive genetic and residual as random effects. The estimated heritabilities were 0.19 for fasting glucose concentration, 0.43 for glucose area equivalent, 0.40 for glucose half-life period, 0.14 for the peak glucose concentration, and 0.12 for the maximum increase of blood glucose concentration. Correlations between ivGTT traits and breeding values for milk yield and composition were not found. The results indicate that heritability for response to glucose is high, which warrants further investigation of this trait for genetic improvement of metabolic disorders. Research is necessary to determine the target levels of ivGTT traits and potential associations between ivGTT traits in breeding bulls and periparturient diseases in their offspring.

  1. Impaired glucose and lipid metabolism in ageing aryl hydrocarbon receptor deficient mice

    PubMed Central

    Biljes, Daniel; Hammerschmidt-Kamper, Christiane; Kadow, Stephanie; Diel, Patrick; Weigt, Carmen; Burkart, Volker; Esser, Charlotte

    2015-01-01

    Disturbed homeostasis of glucose and lipid metabolism are dominant features of the so-called metabolic syndrome (MetS) and can increase the risk for the development of type 2 diabetes (T2D), a severe metabolic disease. T2D prevalence increases with age. The aryl hydrocarbon receptor (AHR) is a sensor of small molecules including dietary components. AHR has been identified as potential regulator of glucose homeostasis and lipid metabolism. Epidemiologically, exposure to xenobiotic AHR ligands such as polycyclic aromatic hydrocarbons is linked to T2D. We assess here the potential role of the AHR in disturbances of glucose and lipid metabolism in young (age 2-5 months) and old (age > 1,5 years) AHR-deficient (AHR KO) mice. Fasted young wildtype (WT) and AHR-KO mice displayed similar blood glucose kinetics after challenge with intra-peritoneal glucose injection. However, old AHR-KO mice showed lower tolerance than WT to i.p. administered glucose, i.e. glucose levels rose higher and returned more slowly to normal levels. Old mice had overall higher insulin levels than young mice, and old AHR-KO had a somewhat disturbed insulin kinetic in the serum after glucose challenge. Surprisingly, young AHR-KO mice had significantly lower triglycerides, cholesterol, high density lipoprotein values than WT, i.e., a dyslipidemic profile. With ageing, AHR-KO and WT mice did not differ in these lipid levels, except for slightly reduced levels of triglycerides and cholesterol. In conclusion, our findings in AHR KO mice suggest that AHR expression is relevant for the maintenance of glucose and lipid homeostasis in old mice. PMID:26664351

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

    PubMed Central

    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

  3. Microbial metabolism of pyridine, quinoline, acridine, and their derivatives under aerobic and anaerobic conditions.

    PubMed Central

    Kaiser, J P; Feng, Y; Bollag, J M

    1996-01-01

    Our review of the metabolic pathways of pyridines and aza-arenes showed that biodegradation of heterocyclic aromatic compounds occurs under both aerobic and anaerobic conditions. Depending upon the environmental conditions, different types of bacteria, fungi, and enzymes are involved in the degradation process of these compounds. Our review indicated that different organisms are using different pathways to biotransform a substrate. Our review also showed that the transformation rate of the pyridine derivatives is dependent on the substituents. For example, pyridine carboxylic acids have the highest transformation rate followed by mono-hydroxypyridines, methylpyridines, aminopyridines, and halogenated pyridines. Through the isolation of metabolites, it was possible to demonstrate the mineralization pathway of various heterocyclic aromatic compounds. By using 14C-labeled substrates, it was possible to show that ring fission of a specific heterocyclic compound occurs at a specific position of the ring. Furthermore, many researchers have been able to isolate and characterize the microorganisms or even the enzymes involved in the transformation of these compounds or their derivatives. In studies involving 18O labeling as well as the use of cofactors and coenzymes, it was possible to prove that specific enzymes (e.g., mono- or dioxygenases) are involved in a particular degradation step. By using H2 18O, it could be shown that in certain transformation reactions, the oxygen was derived from water and that therefore these reactions might also occur under anaerobic conditions. PMID:8840783

  4. Aerobic glycolysis and lymphocyte transformation

    PubMed Central

    Hume, David A.; Radik, Judith L.; Ferber, Ernst; Weidemann, Maurice J.

    1978-01-01

    1. The role of enhanced aerobic glycolysis in the transformation of rat thymocytes by concanavalin A has been investigated. Concanavalin A addition doubled [U-14C]glucose uptake by rat thymocytes over 3h and caused an equivalent increased incorporation into protein, lipids and RNA. A disproportionately large percentage of the extra glucose taken up was converted into lactate, but concanavalin A also caused a specific increase in pyruvate oxidation, leading to an increase in the percentage contribution of glucose to the respiratory fuel. 2. Acetoacetate metabolism, which was not affected by concanavalin A, strongly suppressed pyruvate oxidation in the presence of [U-14C]glucose, but did not prevent the concanavalin A-induced stimulation of this process. Glucose uptake was not affected by acetoacetate in the presence or absence of concanavalin A, but in each case acetoacetate increased the percentage of glucose uptake accounted for by lactate production. 3. [3H]Thymidine incorporation into DNA in concanavalin A-treated thymocyte cultures was sensitive to the glucose concentration in the medium in a biphasic manner. Very low concentrations of glucose (25μm) stimulated DNA synthesis half-maximally, but maximum [3H]thymidine incorporation was observed only when the glucose concentration was raised to 1mm. Lactate addition did not alter the sensitivity of [3H]-thymidine uptake to glucose, but inosine blocked the effect of added glucose and strongly inhibited DNA synthesis. 4. It is suggested that the major function of enhanced aerobic glycolysis in transforming lymphocytes is to maintain higher steady-state amounts of glycolytic intermediates to act as precursors for macromolecule synthesis. PMID:310305

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

    PubMed

    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.

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

    PubMed

    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.

  7. Age differences in intercorrelations between regional cerebral metabolic rates for glucose

    SciTech Connect

    Horwitz, B.; Duara, R.; Rapoport, S.I.

    1986-01-01

    Patterns of cerebral metabolic intercorrelations were compared in the resting state in 15 healthy young men (ages 20 to 32 years) and 15 healthy elderly men (ages 64 to 83 years). Controlling for whole-brain glucose metabolism, partial correlation coefficients were determined between pairs of regional cerebral metabolic rates for glucose determined by positron emission tomography using (18F)fluorodeoxyglucose and obtained in 59 brain regions. Compared with the young men, the elderly men had fewer statistically significant correlations, with the most notable reductions observed between the parietal lobe regions, and between the parietal and frontal lobe regions. These results suggest that cerebral functional interactions are reduced in healthy elderly men.

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

    SciTech Connect

    Phillips, R.L.; London, E.D.; Links, J.M.; Cascella, N.G. )

    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.

  9. Brain metabolism in autism. Resting cerebral glucose utilization rates as measured with positron emission tomography

    SciTech Connect

    Rumsey, J.M.; Duara, R.; Grady, C.; Rapoport, J.L.; Margolin, R.A.; Rapoport, S.I.; Cutler, N.R.

    1985-05-01

    The cerebral metabolic rate for glucose was studied in ten men (mean age = 26 years) with well-documented histories of infantile autism and in 15 age-matched normal male controls using positron emission tomography and (F-18) 2-fluoro-2-deoxy-D-glucose. Positron emission tomography was completed during rest, with reduced visual and auditory stimulation. While the autistic group as a whole showed significantly elevated glucose utilization in widespread regions of the brain, there was considerable overlap between the two groups. No brain region showed a reduced metabolic rate in the autistic group. Significantly more autistic, as compared with control, subjects showed extreme relative metabolic rates (ratios of regional metabolic rates to whole brain rates and asymmetries) in one or more brain regions.

  10. CNS Control of Glucose Metabolism: Response to Environmental Challenges

    PubMed Central

    Arble, Deanna M.; Sandoval, Darleen A.

    2013-01-01

    Over the last 15 years, considerable work has accumulated to support the role of the CNS in regulating postprandial glucose levels. As discussed in the first section of this review, the CNS receives and integrates information from afferent neurons, circulating hormones, and postprandially generated nutrients to subsequently direct changes in glucose output by the liver and glucose uptake by peripheral tissues. The second major component of this review focuses on the effects of external pressures, including high fat diet and changes to the light:dark cycle on CNS-regulating glucose homeostasis. We also discuss the interaction between these different pressures and how they contribute to the multifaceted mechanisms that we hypothesize contribute to the dysregulation of glucose in type 2 diabetes mellitus (T2DM). We argue that while current peripheral therapies serve to delay the progression of T2DM, generating combined obesity and T2DM therapies targeted at the CNS, the primary site of dysfunction for both diseases, would lead to a more profound impact on the progression of both diseases. PMID:23550218

  11. CNS control of glucose metabolism: response to environmental challenges.

    PubMed

    Arble, Deanna M; Sandoval, Darleen A

    2013-01-01

    Over the last 15 years, considerable work has accumulated to support the role of the CNS in regulating postprandial glucose levels. As discussed in the first section of this review, the CNS receives and integrates information from afferent neurons, circulating hormones, and postprandially generated nutrients to subsequently direct changes in glucose output by the liver and glucose uptake by peripheral tissues. The second major component of this review focuses on the effects of external pressures, including high fat diet and changes to the light:dark cycle on CNS-regulating glucose homeostasis. We also discuss the interaction between these different pressures and how they contribute to the multifaceted mechanisms that we hypothesize contribute to the dysregulation of glucose in type 2 diabetes mellitus (T2DM). We argue that while current peripheral therapies serve to delay the progression of T2DM, generating combined obesity and T2DM therapies targeted at the CNS, the primary site of dysfunction for both diseases, would lead to a more profound impact on the progression of both diseases.

  12. Metabolic phenotyping guidelines: assessing glucose homeostasis in rodent models.

    PubMed

    Bowe, James E; Franklin, Zara J; Hauge-Evans, Astrid C; King, Aileen J; Persaud, Shanta J; Jones, Peter M

    2014-09-01

    The pathophysiology of diabetes as a disease is characterised by an inability to maintain normal glucose homeostasis. In type 1 diabetes, this is due to autoimmune destruction of the pancreatic β-cells and subsequent lack of insulin production, and in type 2 diabetes it is due to a combination of both insulin resistance and an inability of the β-cells to compensate adequately with increased insulin release. Animal models, in particular genetically modified mice, are increasingly being used to elucidate the mechanisms underlying both type 1 and type 2 diabetes, and as such the ability to study glucose homeostasis in vivo has become an essential tool. Several techniques exist for measuring different aspects of glucose tolerance and each of these methods has distinct advantages and disadvantages. Thus the appropriate methodology may vary from study to study depending on the desired end-points, the animal model, and other practical considerations. This review outlines the most commonly used techniques for assessing glucose tolerance in rodents and details the factors that should be taken into account in their use. Representative scenarios illustrating some of the practical considerations of designing in vivo experiments for the measurement of glucose homeostasis are also discussed.

  13. The role of the pancreatic endocannabinoid system in glucose metabolism.

    PubMed

    Bermúdez-Silva, Francisco J; Suárez Pérez, Juan; Nadal, Angel; Rodríguez de Fonseca, Fernando

    2009-02-01

    The endogenous cannabinoid system participates in the regulation of energy homeostasis, and this fact led to the identification of a new group of therapeutic agents for complicated obesity and diabetes. Cannabinoid receptor antagonists are now realities in clinical practice. The use of such antagonists for reducing body weight gain, lowering cholesterol and improving glucose homeostasis is based on the ability of the endocannabinoids to coordinately regulate energy homeostasis by interacting with central and peripheral targets, including adipose tissue, muscle, liver and endocrine pancreas. In this review we will analyse the presence of this system in the main cell types of the islets of Langerhans, as well as the physiological relevance of the endocannabinoids and parent acylethanolamides in hormone secretion and glucose homeostasis. We will also analyse the impact that these findings may have in clinical practice and the potential outcome of new therapeutic strategies for modulating glucose homeostasis and insulin/glucagon secretion.

  14. Glutamine and glucose metabolism in rat splenocytes and mesenteric lymph node lymphocytes.

    PubMed

    Wu, G Y; Field, C J; Marliss, E B

    1991-01-01

    The metabolism of glutamine (2 mM) and glucose (5 mM) was studied in splenocytes and mesenteric lymph node lymphocytes of Wistar-Furth rats to assess their relative importance as energy substrates. The major products from glutamine were ammonia, glutamate, aspartate, and CO2, whereas those from glucose were lactate, pyruvate, and CO2 in cells from both lymphoid organs. The individual rates of glutamine and glucose metabolism were decreased in the presence of both substrates, compared with the rates when present separately. The rates of glucose and some (but not all) aspects of glutamine metabolism were higher (P less than 0.01) in splenocytes than in mesenteric lymphocytes. In cells from both lymphoid organs, glutamine and glucose could potentially contribute almost equal amounts of ATP in the presence of both substrates. Glutamine and glucose individually were able to provide sufficient amounts of ATP to maintain its concentrations in the cells throughout a 2-h incubation period at the same levels as with both substrates present. We also found that splenocyte concentration (3.3-100 x 10(6) cells/ml) in the incubations is an important determinant of rates of metabolite formation from glutamine when expressed per 10(6) cells. We conclude that glucose is not the only quantitatively significant energy substrate or even the major one for lymphocytes, because glutamine at near-physiological concentration can be readily utilized by these cells.

  15. Retinal lipid and glucose metabolism dictates angiogenesis through lipid sensor Ffar1

    PubMed Central

    Joyal, Jean-Sébastien; Sun, Ye; Gantner, Marin L.; Shao, Zhuo; Evans, Lucy P.; Saba, Nicholas; Fredrick, Thomas; Burnim, Samuel; Kim, Jin Sung; Patel, Gauri; Juan, Aimee M.; Hurst, Christian G.; Hatton, Colman J.; Cui, Zhenghao; Pierce, Kerry A.; Bherer, Patrick; Aguilar, Edith; Powner, Michael B.; Vevis, Kristis; Boisvert, Michel; Fu, Zhongjie; Levy, Emile; Fruttiger, Marcus; Packard, Alan; Rezende, Flavio A.; Maranda, Bruno; Sapieha, Przemyslaw; Chen, Jing; Friedlander, Martin; Clish, Clary B.; Smith, Lois E.H.

    2016-01-01

    Tissues with high metabolic rates often use lipid as well as glucose for energy, conferring a survival advantage during feast and famine.1 Current dogma suggests that high-energy consuming photoreceptors depend on glucose.2,3 Here we show that retina also uses fatty acids (FA) β-oxidation for energy. Moreover, we identify a lipid sensor Ffar1 that curbs glucose uptake when FA are available. Very low-density lipoprotein receptor (VLDLR), expressed in tissues with a high metabolic rate, facilitates the uptake of triglyceride-derived FA.4,5 Vldlr is present in photoreceptors.6 In Vldlr−/− retinas, Ffar1, sensing high circulating lipid levels despite decreased FA uptake5, suppresses glucose transporter Glut1. This impaired glucose entry into photoreceptors results in a dual lipid/glucose fuel shortage and reduction in the Krebs cycle intermediate α-ketoglutarate (KG). Low α-KG levels promote hypoxia-induced factor-1α (Hif1a) stabilization and vascular endothelial growth factor (Vegfa) secretion by starved Vldlr−/− photoreceptors, attracting neovessels to supply fuel. These aberrant vessels invading normally avascular photoreceptors in Vldlr−/− retinas are reminiscent of retinal angiomatous proliferation (RAP), a subset of neovascular age-related macular degeneration (AMD)7, associated with high vitreous VEGF levels in humans. Dysregulated lipid and glucose photoreceptor energy metabolism may therefore be a driving force in neovascular AMD and other retinal diseases. PMID:26974308

  16. Dietary substitution of medium-chain triglycerides improves insulin-mediated glucose metabolism in NIDDM subjects.

    PubMed

    Eckel, R H; Hanson, A S; Chen, A Y; Berman, J N; Yost, T J; Brass, E P

    1992-05-01

    Dietary medium-chain triglycerides (MCT) may improve insulin-mediated glucose metabolism. To examine this possibility, 10 non-insulin-dependent diabetes mellitus (NIDDM) patients, 4 hypertriglyceridemic, and 6 normotriglyceridemic nondiabetic control subjects were examined with a 5-day cross-over design, in which the short-term metabolic effects of a 40% fat diet containing 77.5% of fat calories as MCT were compared with an isocaloric long-chain triglyceride-containing diet. In diabetic patients, MCT failed to alter fasting serum glucose concentrations but reduced preprandial glycemic excursions by 45% (F = 7.9, P less than 0.01). On MCT, the amount of glucose needed to maintain euglycemia during an intravenous insulin infusion was increased in diabetic subjects by 30%, in hypertriglyceridemic subjects by 30%, and in normotriglyceridemic control subjects by 17%. MCT increased mean +/- SE insulin-mediated glucose disposal (4.52 +/- 0.56 vs. 2.89 +/- 0.21 mg.kg-1.min-1; n = 3, P less than 0.05) but failed to alter basal glucose metabolism or insulin-mediated suppression of hepatic glucose output. Metabolic responses to MCT were observed independent of sulfonylurea therapy or severity of fasting hyperglycemia. No change in fasting serum insulin or triglyceride concentrations were seen with MCT administration. Although MCT increased mean fasting serum beta-hydroxybutyrate levels from 0.10 +/- 0.03 to 0.26 +/- 0.06 mM (P less than 0.05) in normotriglyceridemic nondiabetic subjects, no change was seen in diabetic patients. Thus, MCT-containing diets increased insulin-mediated glucose metabolism in both diabetic patients and nondiabetic subjects. In diabetic subjects, this effect appears to be mediated by increases in insulin-mediated glucose disposal.(ABSTRACT TRUNCATED AT 250 WORDS)

  17. Early decline in glucose transport and metabolism precedes shift to ketogenic system in female aging and Alzheimer's mouse brain: implication for bioenergetic intervention.

    PubMed

    Ding, Fan; Yao, Jia; Rettberg, Jamaica R; Chen, Shuhua; Brinton, Roberta Diaz

    2013-01-01

    We previously demonstrated that mitochondrial bioenergetic deficits in the female brain accompanied reproductive senescence and was accompanied by a shift from an aerobic glycolytic to a ketogenic phenotype. Herein, we investigated the relationship between systems of fuel supply, transport and mitochondrial metabolic enzyme expression/activity during aging (3-15 months) in the hippocampus of nontransgenic (nonTg) background and 3xTgAD female mice. Results indicate that during female brain aging, both nonTg and 3xTgAD brains undergo significant decline in glucose transport, as detected by FDG-microPET, between 6-9 months of age just prior to the transition into reproductive senescence. The deficit in brain metabolism was sustained thereafter. Decline in glucose transport coincided with significant decline in neuronal glucose transporter expression and hexokinase activity with a concomitant rise in phosphorylated/inactivated pyruvate dehydrogenase. Lactate utilization declined in parallel to the decline in glucose transport suggesting lactate did not serve as an alternative fuel. An adaptive response in the nonTg hippocampus was a shift to transport and utilization of ketone bodies as an alternative fuel. In the 3xTgAD brain, utilization of ketone bodies as an alternative fuel was evident at the earliest age investigated and declined thereafter. The 3xTgAD adaptive response was to substantially increase monocarboxylate transporters in neurons while decreasing their expression at the BBB and in astrocytes. Collectively, these data indicate that the earliest change in the metabolic system of the aging female brain is the decline in neuronal glucose transport and metabolism followed by decline in mitochondrial function. The adaptive shift to the ketogenic system as an alternative fuel coincided with decline in mitochondrial function. Translationally, these data provide insights into the earliest events in bioenergetic aging of the female brain and provide potential

  18. Olanzapine and aripiprazole differentially affect glucose uptake and energy metabolism in human mononuclear blood cells.

    PubMed

    Stapel, Britta; Kotsiari, Alexandra; Scherr, Michaela; Hilfiker-Kleiner, Denise; Bleich, Stefan; Frieling, Helge; Kahl, Kai G

    2017-05-01

    The use of antipsychotics carries the risk of metabolic side effects, such as weight gain and new onset type-2 diabetes mellitus. The mechanisms of the observed metabolic alterations are not fully understood. We compared the effects of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (aripiprazole), on glucose metabolism. Primary human peripheral blood mononuclear cells (PBMC) were isolated and stimulated with olanzapine or aripiprazole for 72 h. Cellular glucose uptake was analyzed in vitro by 18F-FDG uptake. Further measurements comprised mRNA expression of glucose transporter (GLUT) 1 and 3, GLUT1 protein expression, DNA methylation of GLUT1 promoter region, and proteins involved in downstream glucometabolic processes. We observed a 2-fold increase in glucose uptake after stimulation with aripiprazole. In contrast, olanzapine stimulation decreased glucose uptake by 40%, accompanied by downregulation of the cellular energy sensor AMP activated protein kinase (AMPK). GLUT1 protein expression increased, GLUT1 mRNA expression decreased, and GLUT1 promoter was hypermethylated with both antipsychotics. Pyruvat-dehydrogenase (PDH) complex activity decreased with olanzapine only. Our findings suggest that the atypical antipsychotics olanzapine and aripiprazole differentially affect energy metabolism in PBMC. The observed decrease in glucose uptake in olanzapine stimulated PBMC, accompanied by decreased PDH point to a worsening in cellular energy metabolism not compensated by AMKP upregulation. In contrast, aripiprazole stimulation lead to increased glucose uptake, while not affecting PDH complex expression. The observed differences may be involved in the different metabolic profiles observed in aripiprazole and olanzapine treated patients.

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

    PubMed

    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.

  20. D-glucose metabolism in BRIN-BD11 islet cells.

    PubMed

    Rasschaert, J; Flatt, P R; Barnett, C R; McClenaghan, N H; Malaisse, W J

    1996-04-01

    A novel insulin-secreting cell line, BRIN-BD11, was recently established following electrofusion of RINm5F cells with NEDH rat pancreatic islet cells. In the present study, D-glucose metabolism was compared in BRIN-BD11 and RINm5F cells. The concentration dependency of D[5-3H]glucose utilization displayed a comparable pattern in the two cell lines, but the absolute values were lower in BRIN-BD11 than RINm5F cells. Except in the case of D-[1-14C]glucose, the ratio between 14C labeled D-glucose oxidation and D-[5-3H]glucose utilization was higher, however, in BRIN-BD11 than RINm5F cells. Moreover, BRIN-BD11 cells were less affected than RINm5F cells by a rise in D-glucose concentration, in terms of the inhibitory action of the hexose upon oxidative variables, such as oxidative glycolysis, pyruvate decarboxylation, and oxidation of glucose-derived acetyl residues in the Krebs cycle. The total energy yield from D-glucose catabolism appeared similar, however, in BRIN-BD11 and RINm5F cells. These findings extend the knowledge that BRIN-BD11 cells display an improved metabolic and secretory behavior, when considering the difference otherwise found between normal and tumoral islet cells.

  1. Fuel metabolism in Canada geese: effects of glucagon on glucose kinetics

    PubMed Central

    Weber, Jean-Michel

    2015-01-01

    During prolonged fasting, birds must rely on glucose mobilization to maintain normoglycemia. Glucagon is known to modulate avian energy metabolism during prolonged fasting, but the metabolic effects of this hormone on long-distance migrant birds have never been investigated. Our goal was to determine whether glucagon regulates the mobilization of the main lipid and carbohydrate fuels in migrant birds. Using the Canada goose (Branta canadensis) as a model species, we looked for evidence of fuel mobilization via changes in metabolite concentrations. No changes could be found for any lipid fraction, but glucagon elicited a strong increase in glucose concentration. Therefore, we aimed to quantify the effects of this hormone on glucose kinetics using continuous infusion of 6-[3H]-d-glucose. Glucagon was found to cause a 50% increase in glucose mobilization (from 22.2 ± 2.4 μmol·kg−1·min−1 to 33.5 ± 3.3 μmol·kg−1·min−1) and, together with an unchanged rate of carbohydrate oxidation, led to a 90% increase in plasma glucose concentration. This hormone also led to a twofold increase in plasma lactate concentration. No changes in plasma lipid concentration or composition were observed. This study is the first to demonstrate how glucagon modulates glucose kinetics in a long-distance migrant bird and to quantify its rates of glucose mobilization. PMID:26108869

  2. Physiologic action of glucagon on liver glucose metabolism

    PubMed Central

    Ramnanan, C. J.; Edgerton, D. S.; Kraft, G.; Cherrington, A. D.

    2017-01-01

    Glucagon is a primary regulator of hepatic glucose production (HGP) in vivo during fasting, exercise and hypoglycaemia. Glucagon also plays a role in limiting hepatic glucose uptake and producing the hyperglycaemic phenotype associated with insulin deficiency and insulin resistance. In response to a physiological rise in glucagon, HGP is rapidly stimulated. This increase in HGP is entirely attributable to an enhancement of glycogenolysis, with little to no acute effect on gluconeogenesis. This dramatic rise in glycogenolysis in response to hyperglucagonemia wanes with time. A component of this waning effect is known to be independent of hyperglycemia, though the molecular basis for this tachyphylaxis is not fully understood. In the overnight fasted state, the presence of basal glucagon secretion is essential in countering the suppressive effects of basal insulin, resulting in the maintenance of appropriate levels of glycogenolysis, fasting HGP and blood glucose. The enhancement of glycogenolysis in response to elevated glucagon is critical in the life-preserving counterregulatory response to hypoglycaemia, as well as a key factor in providing adequate circulating glucose for working muscle during exercise. Finally, glucagon has a key role in promoting the catabolic consequences associated with states of deficient insulin action, which supports the therapeutic potential in developing glucagon receptor antagonists or inhibitors of glucagon secretion. PMID:21824265

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

    PubMed

    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.

  4. A Physiology-Based Model Describing Heterogeneity in Glucose Metabolism

    PubMed Central

    Maas, Anne H.; Rozendaal, Yvonne J. W.; van Pul, Carola; Hilbers, Peter A. J.; Cottaar, Ward J.; Haak, Harm R.; van Riel, Natal A. W.

    2014-01-01

    Background: Current diabetes education methods are costly, time-consuming, and do not actively engage the patient. Here, we describe the development and verification of the physiological model for healthy subjects that forms the basis of the Eindhoven Diabetes Education Simulator (E-DES). E-DES shall provide diabetes patients with an individualized virtual practice environment incorporating the main factors that influence glycemic control: food, exercise, and medication. Method: The physiological model consists of 4 compartments for which the inflow and outflow of glucose and insulin are calculated using 6 nonlinear coupled differential equations and 14 parameters. These parameters are estimated on 12 sets of oral glucose tolerance test (OGTT) data (226 healthy subjects) obtained from literature. The resulting parameter set is verified on 8 separate literature OGTT data sets (229 subjects). The model is considered verified if 95% of the glucose data points lie within an acceptance range of ±20% of the corresponding model value. Results: All glucose data points of the verification data sets lie within the predefined acceptance range. Physiological processes represented in the model include insulin resistance and β-cell function. Adjusting the corresponding parameters allows to describe heterogeneity in the data and shows the capabilities of this model for individualization. Conclusion: We have verified the physiological model of the E-DES for healthy subjects. Heterogeneity of the data has successfully been modeled by adjusting the 4 parameters describing insulin resistance and β-cell function. Our model will form the basis of a simulator providing individualized education on glucose control. PMID:25526760

  5. HexR Controls Glucose-Responsive Genes and Central Carbon Metabolism in Neisseria meningitidis

    PubMed Central

    Antunes, Ana; Golfieri, Giacomo; Ferlicca, Francesca; Giuliani, Marzia M.; Scarlato, Vincenzo

    2015-01-01

    ABSTRACT Neisseria meningitidis, an exclusively human pathogen and the leading cause of bacterial meningitis, must adapt to different host niches during human infection. N. meningitidis can utilize a restricted range of carbon sources, including lactate, glucose, and pyruvate, whose concentrations vary in host niches. Microarray analysis of N. meningitidis grown in a chemically defined medium in the presence or absence of glucose allowed us to identify genes regulated by carbon source availability. Most such genes are implicated in energy metabolism and transport, and some are implicated in virulence. In particular, genes involved in glucose catabolism were upregulated, whereas genes involved in the tricarboxylic acid cycle were downregulated. Several genes encoding surface-exposed proteins, including the MafA adhesins and Neisseria surface protein A, were upregulated in the presence of glucose. Our microarray analysis led to the identification of a glucose-responsive hexR-like transcriptional regulator that controls genes of the central carbon metabolism of N. meningitidis in response to glucose. We characterized the HexR regulon and showed that the hexR gene is accountable for some of the glucose-responsive regulation; in vitro assays with the purified protein showed that HexR binds to the promoters of the central metabolic operons of the bacterium. Based on DNA sequence alignment of the target sites, we propose a 17-bp pseudopalindromic consensus HexR binding motif. Furthermore, N. meningitidis strains lacking hexR expression were deficient in establishing successful bacteremia in an infant rat model of infection, indicating the importance of this regulator for the survival of this pathogen in vivo. IMPORTANCE Neisseria meningitidis grows on a limited range of nutrients during infection. We analyzed the gene expression of N. meningitidis in response to glucose, the main energy source available in human blood, and we found that glucose regulates many genes

  6. Diabetes, insulin-mediated glucose metabolism and Sertoli/blood-testis barrier function

    PubMed Central

    Alves, Marco G.; Martins, Ana D.; Cavaco, José E.; Socorro, Sílvia; Oliveira, Pedro F.

    2013-01-01

    Blood testis barrier (BTB) is one of the tightest blood-barriers controlling the entry of substances into the intratubular fluid. Diabetes Mellitus (DM) is an epidemic metabolic disease concurrent with falling fertility rates, which provokes severe detrimental BTB alterations. It induces testicular alterations, disrupting the metabolic cooperation between the cellular constituents of BTB, with dramatic consequences on sperm quality and fertility. As Sertoli cells are involved in the regulation of spermatogenesis, providing nutritional support for germ cells, any metabolic alteration in these cells derived from DM may be responsible for spermatogenesis disruption, playing a crucial role in fertility/subfertility associated with this pathology. These cells have a glucose sensing machinery that reacts to hormonal fluctuations and several mechanisms to counteract hyper/hypoglycemic events. The role of DM on Sertoli/BTB glucose metabolism dynamics and the metabolic molecular mechanisms through which DM and insulin deregulation alter its functioning, affecting male reproductive potential will be discussed. PMID:24665384

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

    PubMed

    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.

  8. Dynamical modeling of liver Aquaporin-9 expression and glycerol permeability in hepatic glucose metabolism.

    PubMed

    Gena, Patrizia; Buono, Nicoletta Del; D'Abbicco, Marcello; Mastrodonato, Maria; Berardi, Marco; Svelto, Maria; Lopez, Luciano; Calamita, Giuseppe

    2017-01-01

    Liver is crucial in the homeostasis of glycerol, an important metabolic intermediate. Plasma glycerol is imported by hepatocytes mainly through Aquaporin-9 (AQP9), an aquaglyceroporin channel negatively regulated by insulin in rodents. AQP9 is of critical importance in glycerol metabolism since hepatic glycerol utilization is rate-limited at the hepatocyte membrane permeation step. Glycerol kinase catalyzes the initial step for the conversion of the imported glycerol into glycerol-3-phosphate, a major substrate for de novo synthesis of glucose (gluconeogenesis) and/or triacyglycerols (lipogenesis). A model addressing the glucose-insulin system to describe the hepatic glycerol import and metabolism and the correlation with the glucose homeostasis is lacking so far. Here we consider a system of first-order ordinary differential equations delineating the relevance of hepatocyte AQP9 in liver glycerol permeability. Assuming the hepatic glycerol permeability as depending on the protein levels of AQP9, a mathematical function is designed describing the time course of the involvement of AQP9 in mouse hepatic glycerol metabolism in different nutritional states. The resulting theoretical relationship is derived fitting experimental data obtained with murine models at the fed, fasted or re-fed condition. While providing useful insights into the dynamics of liver AQP9 involvement in male rodent glycerol homeostasis our model may be adapted to the human liver serving as an important module of a whole body-model of the glucose metabolism both in health and metabolic diseases.

  9. High diving metabolism results in a short aerobic dive limit for Steller sea lions (Eumetopias jubatus).

    PubMed

    Gerlinsky, Carling D; Rosen, David A S; Trites, Andrew W

    2013-07-01

    The diving capacity of marine mammals is typically defined by the aerobic dive limit (ADL) which, in lieu of direct measurements, can be calculated (cADL) from total body oxygen stores (TBO) and diving metabolic rate (DMR). To estimate cADL, we measured blood oxygen stores, and combined this with diving oxygen consumption rates (VO2) recorded from 4 trained Steller sea lions diving in the open ocean to depths of 10 or 40 m. We also examined the effect of diving exercise on O2 stores by comparing blood O2 stores of our diving animals to non-diving individuals at an aquarium. Mass-specific blood volume of the non-diving individuals was higher in the winter than in summer, but there was no overall difference in blood O2 stores between the diving and non-diving groups. Estimated TBO (35.9 ml O2 kg(-1)) was slightly lower than previously reported for Steller sea lions and other Otariids. Calculated ADL was 3.0 min (based on an average DMR of 2.24 L O2 min(-1)) and was significantly shorter than the average 4.4 min dives our study animals performed when making single long dives-but was similar to the times recorded during diving bouts (a series of 4 dives followed by a recovery period on the surface), as well as the dive times of wild animals. Our study is the first to estimate cADL based on direct measures of VO2 and blood oxygen stores for an Otariid and indicates they have a much shorter ADL than previously thought.

  10. Metabolic response of different high-intensity aerobic interval exercise protocols.

    PubMed

    Gosselin, Luc E; Kozlowski, Karl F; DeVinney-Boymel, Lee; Hambridge, Caitlin

    2012-10-01

    Although high-intensity sprint interval training (SIT) employing the Wingate protocol results in significant physiological adaptations, it is conducted at supramaximal intensity and is potentially unsafe for sedentary middle-aged adults. We therefore evaluated the metabolic and cardiovascular response in healthy young individuals performing 4 high-intensity (~90% VO2max) aerobic interval training (HIT) protocols with similar total work output but different work-to-rest ratio. Eight young physically active subjects participated in 5 different bouts of exercise over a 3-week period. Protocol 1 consisted of 20-minute continuous exercise at approximately 70% of VO2max, whereas protocols 2-5 were interval based with a work-active rest duration (in seconds) of 30/30, 60/30, 90/30, and 60/60, respectively. Each interval protocol resulted in approximately 10 minutes of exercise at a workload corresponding to approximately 90% VO2max, but differed in the total rest duration. The 90/30 HIT protocol resulted in the highest VO2, HR, rating of perceived exertion, and blood lactate, whereas the 30/30 protocol resulted in the lowest of these parameters. The total caloric energy expenditure was lowest in the 90/30 and 60/30 protocols (~150 kcal), whereas the other 3 protocols did not differ (~195 kcal) from one another. The immediate postexercise blood pressure response was similar across all the protocols. These finding indicate that HIT performed at approximately 90% of VO2max is no more physiologically taxing than is steady-state exercise conducted at 70% VO2max, but the response during HIT is influenced by the work-to-rest ratio. This interval protocol may be used as an alternative approach to steady-state exercise training but with less time commitment.

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

    PubMed Central

    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

  12. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate.

    PubMed Central

    Tsacopoulos, M; Evêquoz-Mercier, V; Perrottet, P; Buchner, E

    1988-01-01

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy[3H]glucose convert this glucose analogue to 2-deoxy[3H]glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O2 and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system. Images PMID:3186756

  13. Honeybee retinal glial cells transform glucose and supply the neurons with metabolic substrate

    SciTech Connect

    Tsacopoulos, M.; Evequoz-Mercier, V.; Perrottet, P.; Buchner, E.

    1988-11-01

    The retina of the honeybee drone is a nervous tissue in which glial cells and photoreceptor cells (sensory neurons) constitute two distinct metabolic compartments. Retinal slices incubated with 2-deoxy(/sup 3/H)glucose convert this glucose analogue to 2-deoxy(/sup 3/H)glucose 6-phosphate, but this conversion is made only in the glial cells. Hence, glycolysis occurs only in glial cells. In contrast, the neurons consume O/sub 2/ and this consumption is sustained by the hydrolysis of glycogen, which is contained in large amounts in the glia. During photostimulation the increased oxidative metabolism of the neurons is sustained by a higher supply of carbohydrates from the glia. This clear case of metabolic interaction between neurons and glial cells supports Golgi's original hypothesis, proposed nearly 100 years ago, about the nutritive function of glial cells in the nervous system.

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

    PubMed Central

    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

  15. Energizing eukaryotic cell-free protein synthesis with glucose metabolism.

    PubMed

    Anderson, Mark J; Stark, Jessica C; Hodgman, C Eric; Jewett, Michael C

    2015-07-08

    Eukaryotic cell-free protein synthesis (CFPS) is limited by the dependence on costly high-energy phosphate compounds and exogenous enzymes to power protein synthesis (e.g., creatine phosphate and creatine kinase, CrP/CrK). Here, we report the ability to use glucose as a secondary energy substrate to regenerate ATP in a Saccharomyces cerevisiae crude extract CFPS platform. We observed synthesis of 3.64±0.35 μg mL(-1) active luciferase in batch reactions with 16 mM glucose and 25 mM phosphate, resulting in a 16% increase in relative protein yield (μg protein/$ reagents) compared to the CrP/CrK system. Our demonstration provides the foundation for development of cost-effective eukaryotic CFPS platforms.

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

    NASA Astrophysics Data System (ADS)

    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.

  17. In vitro metabolic engineering of bioelectricity generation by the complete oxidation of glucose.

    PubMed

    Zhu, Zhiguang; Zhang, Y-H Percival

    2017-01-01

    The direct generation of electricity from the most abundant renewable sugar, glucose, is an appealing alternative to the production of liquid biofuels and biohydrogen. However, enzyme-catalyzed bioelectricity generation from glucose suffers from low yields due to the incomplete oxidation of the six-carbon compound glucose via one or few enzymes. Here, we demonstrate a synthetic ATP- and CoA-free 12-enzyme pathway to implement the complete oxidation of glucose in vitro. This pathway is comprised of glucose phosphorylation via polyphosphate glucokinase, NADH generation catalyzed by glucose 6-phosphate dehydrogenase (G6PDH) and 6-phosphogluconate dehydrogenase (6PGDH), electron transfer from NADH to the anode, and glucose 6-phosphate regeneration via the non-oxidative pentose phosphate pathway and gluconeogenesis. The faraday efficiency from glucose to electrons via this pathway was as high as 98.8%, suggesting the generation of nearly 24 electrons per molecule of glucose. The generated current density was greatly increased from 2.8 to 6.9mAcm(-2) by replacing a low-activity G6PDH with a high-activity G6PDH and introducing a new enzyme, 6-phosphogluconolactonase, between G6PDH and 6PGDH. These results suggest the great potential of high-yield bioelectricity generation through in vitro metabolic engineering.

  18. Aerobic and anaerobic metabolism in oxygen minimum layer fishes: the role of alcohol dehydrogenase.

    PubMed

    Torres, Joseph J; Grigsby, Michelle D; Clarke, M Elizabeth

    2012-06-01

    Zones of minimum oxygen form at intermediate depth in all the world's oceans as a result of global circulation patterns that keep the water at oceanic mid-depths out of contact with the atmosphere for hundreds of years. In areas where primary production is very high, the microbial oxidation of sinking organic matter results in very low oxygen concentrations at mid-depths. Such is the case with the Arabian Sea, with O(2) concentrations reaching zero at 200 m and remaining very low (<0.1 ml O(2)l(-1)) for hundreds of meters below this depth, and in the California borderland, where oxygen levels reach 0.2 ml O(2)l(-1) at 700 m with severely hypoxic (<1.0 ml O(2)l(-1)) waters at depths 300 m above and below that. Despite the very low oxygen, mesopelagic fishes (primarily lanternfishes: Mytophidae) inhabiting the Arabian Sea and California borderland perform a daily vertical migration into the low-oxygen layer, spending daylight hours in the oxygen minimum zone and migrating upward into normoxic waters at night. To find out how fishes were able to survive their daily sojourns into the minimum zone, we tested the activity of four enzymes, one (lactate dehydrogenase, LDH) that served as a proxy for anaerobic glycolysis with a conventional lactate endpoint, a second (citrate synthase, CS) that is indicative of aerobic metabolism, a third (malate dehydrogenase) that functions in the Krebs' cycle and as a bridge linking mitochondrion and cytosol, and a fourth (alcohol dehydrogenase, ADH) that catalyzes the final reaction in a pathway where pyruvate is reduced to ethanol. Ethanol is a metabolic product easily excreted by fish, preventing lactate accumulation. The ADH pathway is rarely very active in vertebrate muscle; activity has previously been seen only in goldfish and other cyprinids capable of prolonged anaerobiosis. Activity of the enzyme suite in Arabian Sea and California fishes was compared with that of ecological analogs in the same family and with the same

  19. [Recombinant Escherichia coli strains deficient in mixed acid fermentation pathways and capable of rapid aerobic growth on glucose with a reduced Crabtree effect].

    PubMed

    Morzhakova, A A; Skorokhodova, A Iu; Gulevich, A Iu; Debabov, V G

    2013-01-01

    In this study, we constructed and characterized Escherichia coli strains deficient for mixed acid fermentation pathways, which are capable of rapid aerobic growth on glucose without pronounced bacterial Crabtree effect. The main pathways of production of acetic and lactic acids and ethanol in these strains were inactivated by a deletion of the ackA, pta, poxB, IdhA, and adhEgenes. The phosphoenolpyruvate-dependent phosphotransferase system of glucose transport and phosphorylation was inactivated in the strains by a deletion of the ptsG gene. The possibility of alternative transport and phosphorylation of the carbohydrate substrate was ensured in recombinants by constitutive expression of the galP and glk genes, which encode the low-affinity H+-symporter of D-galactose and glucokinase, respectively. SGMI.0DeltaptsG PtacgalP and SG M1.0DeltaptsG PIglk PtacgalP strains were capable of rapid aerobic growth in a minimal medium containing 2.0 and 10.0 g/l of glucose and secreted only small amounts of acetic acid and trace amounts of pyruvic acid.

  20. Preparation and catalytic activity of poly(N-vinyl-2-pyrrolidone)-protected Au nanoparticles for the aerobic oxidation of glucose.

    PubMed

    Zhang, Haijun; Li, Wenqi; Gu, Yajun; Zhang, Shaowei

    2014-08-01

    PVP-protected Au nanoparticles (NPs) for the aerobic oxidation of glucose were prepared by using NaBH4 reduction method. The effects of processing parameters such as Au3+ ion concentration, reaction temperature, ratio of NaBH4 or PVP to Au3+, and solvent composition on their particle sizes and catalytic activities were studied in detail and the synthesis conditions optimized. As-prepared Au NPs possessed a FCC structure, with an average size varying from about 100 to 2.6 nm depending on their preparation conditions. The size changes affected their catalytic activities in the aerobic oxidation of glucose. The Au NPs with the average size of 2.6 nm prepared under the optimal conditions showed a high instantaneous catalytic activity as well as a high long-time stability. Based on the kinetic study on the glucose oxidation over the PVP-protected Au NPs, the corresponding apparent activation energy was determined as 82 kJ mol(-1).

  1. Changes induced by sucrose administration on glucose metabolism in pancreatic islets in normal hamsters.

    PubMed

    Massa, M L; Borelli, M I; Del Zotto, H; Gagliardino, J J

    2001-12-01

    We correlated the changes in glucose-induced insulin secretion with those observed in glucose metabolism and hexokinase/glucokinase activity in islets from normal sucrose-fed hamsters. Blood glucose and insulin levels were measured in normal male hamsters fed with (S5) or without (C5) 10% sucrose in the drinking water for 5 weeks. Isolated islets (collagenase digestion) from both groups of animals were used to study insulin secretion, (14)CO(2) and (3)H(2)O production from D-[U-(14)C]-glucose and D-[5-(3)H]-glucose respectively, with 3.3 or 16.7 mM glucose in the medium, and hexokinase/glucokinase activity (fluorometric assay) in islet homogenates. Whereas S5 and C5 animals had comparable normal blood glucose levels, S5 showed higher insulin levels than C5 hamsters (2.3+/-0.1 vs 0.6+/-0.03 ng/ml, P<0.001). Islets from S5 hamsters released significantly more insulin than C5 islets in the presence of low and high glucose (3.3 mM glucose: 0.77+/-0.04 vs 0.20+/-0.06 pg/ng DNA/min, P<0.001; 16.7 mM glucose: 2.77+/-0.12 vs 0.85+/-0.06 pg/ng DNA/min, P<0.001) and produced significantly higher amounts of (14)CO(2) and (3)H(2)O at both glucose concentrations ((14)CO(2): 3.3 mM glucose: 0.27+/-0.01 vs 0.18+/-0.01, P<0.001; 16.7 mM glucose: 1.44+/-0.15 vs 0.96+/-0.08, P<0.02; (3)H(2)O: 3.3 mM glucose: 0.31+/-0.02 vs 0.15+/-0.01, P<0.001; 16.7 mM glucose: 1.46+/-0.20 vs 0.76+/-0.05 pmol glucose/ng DNA/min, P<0.005). The hexokinase K(m) and V(max) values from S5 animals were significantly higher than those from C5 ones (K(m): 100.14+/-7.01 vs 59.90+/- 3.95 microM, P<0.001; V(max): 0.010+/-0.0005 vs 0.008+/- 0.0006 pmol glucose/ng DNA/min, P<0.02). Conversely, the glucokinase K(m) value from S5 animals was significantly lower than in C5 animals (K(m): 15.31+/-2.64 vs 35.01+/-1.65 mM, P<0.001), whereas V(max) figures were within a comparable range in both groups (V(max): 0.048+/-0.009 vs 0.094+/-0.035 pmol glucose/ng DNA/min, not significant). The glucose phosphorylation ratio

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

    PubMed

    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.

  3. Effects of Mangifera indica (Careless) on Microcirculation and Glucose Metabolism in Healthy Volunteers.

    PubMed

    Buchwald-Werner, Sybille; Schön, Christiane; Frank, Sonja; Reule, Claudia

    2017-02-10

    A commercial Mangifera indica fruit powder (Careless) showed beneficial acute effects on microcirculation in a randomized, double-blind, crossover pilot study. Here, long-term effects on microcirculation and glucose metabolism were investigated in a double-blind, randomized, placebo-controlled, 3-arm parallel-design study in healthy individuals. A daily dose of 100 mg or 300 mg of the fruit powder was compared to placebo after supplementation for 4 weeks. Microcirculation and endothelial function were assessed by the Oxygen-to-see System and pulse amplitude tonometry, respectively. Glucose metabolism was assessed under fasting and postprandial conditions by capillary glucose and HbA1c values.Microcirculatory reactive hyperemia flow increased, especially in the 100 mg group (p = 0.025). The 300 mg of the M. indica fruit preparation reduced postprandial glucose levels by trend if compared to placebo (p = 0.0535) accompanied by significantly lower HbA1c values compared to baseline. Furthermore, 300 mg intake significantly improved postprandial endothelial function in individuals with decreased endothelial function after high-dose glucose intake (p = 0.0408; n = 11).In conclusion, the study suggests moderate beneficial effects of M. indica fruit preparation on microcirculation, endothelial function, and glucose metabolism.

  4. Adrenalectomy fails to stimulate brown adipose tissue metabolism in ob/ob mice fed glucose.

    PubMed

    Kim, H K; Romsos, D R

    1988-11-01

    Adrenalectomy arrests the development of obesity in ob/ob mice fed nonpurified high-starch diets partly by stimulating the low thermogenic activity of brown adipose tissue (BAT). However, adrenalectomy fails to suppress the development of obesity in ob/ob mice fed a purified high-glucose diet. Effects of adrenalectomy on BAT metabolism in ob/ob mice fed purified high-starch or high-glucose diets were therefore examined. Adrenalectomy markedly decreased the efficiency of energy retention and increased BAT metabolism (as assessed by GDP binding to BAT mitochondria, GDP-inhibitable acetate- or chloride-induced mitochondrial swelling, and by rates of norepinephrine turnover in BAT) in ob/ob mice fed a high-starch purified diet but had only minimal effects on energy efficiency or BAT metabolism in ob/ob mice fed a high-glucose purified diet. Plasma insulin concentrations decreased and thyroxine concentrations increased in adrenalectomized ob/ob mice fed the high-starch diet; changes in these hormones were less pronounced in adrenalectomized ob/ob mice fed the high-glucose diet. Consumption of glucose mimics effects of adrenal secretions on BAT metabolism in ob/ob mice.

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

    PubMed Central

    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

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

    PubMed Central

    2010-01-01

    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 metabolism during Aedes

  7. Keratin 8/18 regulation of glucose metabolism in normal versus cancerous hepatic cells through differential modulation of hexokinase status and insulin signaling

    SciTech Connect

    Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane; Faure, Robert; Marceau, Normand

    2013-02-15

    As differentiated cells, hepatocytes primarily metabolize glucose for ATP production through oxidative phosphorylation of glycolytic pyruvate, whereas proliferative hepatocellular carcinoma (HCC) cells undergo a metabolic shift to aerobic glycolysis despite oxygen availability. Keratins, the intermediate filament (IF) proteins of epithelial cells, are expressed as pairs in a lineage/differentiation manner. Hepatocyte and HCC (hepatoma) cell IFs are made solely of keratins 8/18 (K8/K18), thus providing models of choice to address K8/K18 IF functions in normal and cancerous epithelial cells. Here, we demonstrate distinctive increases in glucose uptake, glucose-6-phosphate formation, lactate release, and glycogen formation in K8/K18 IF-lacking hepatocytes and/or hepatoma cells versus their respective IF-containing counterparts. We also show that the K8/K18-dependent glucose uptake/G6P formation is linked to alterations in hexokinase I/II/IV content and localization at mitochondria, with little effect on GLUT1 status. In addition, we find that the insulin-stimulated glycogen formation in normal hepatocytes involves the main PI-3 kinase-dependent signaling pathway and that the K8/K18 IF loss makes them more efficient glycogen producers. In comparison, the higher insulin-dependent glycogen formation in K8/K18 IF-lacking hepatoma cells is associated with a signaling occurring through a mTOR-dependent pathway, along with an augmentation in cell proliferative activity. Together, the results uncover a key K8/K18 regulation of glucose metabolism in normal and cancerous hepatic cells through differential modulations of mitochondrial HK status and insulin-mediated signaling.

  8. Alterations of hippocampal glucose metabolism by even versus uneven medium chain triglycerides

    PubMed Central

    McDonald, Tanya S; Tan, Kah Ni; Hodson, Mark P; Borges, Karin

    2014-01-01

    Medium chain triglycerides (MCTs) are used to treat neurologic disorders with metabolic impairments, including childhood epilepsy and early Alzheimer's disease. However, the metabolic effects of MCTs in the brain are still unclear. Here, we studied the effects of feeding even and uneven MCTs on brain glucose metabolism in the mouse. Adult mice were fed 35% (calories) of trioctanoin or triheptanoin (the triglycerides of octanoate or heptanoate, respectively) or a matching control diet for 3 weeks. Enzymatic assays and targeted metabolomics by liquid chromatography tandem mass spectrometry were used to quantify metabolites in extracts from the hippocampal formations (HFs). Both oils increased the levels of β-hydroxybutyrate, but no other significant metabolic alterations were observed after triheptanoin feeding. The levels of glucose 6-phosphate and fructose 6-phosphate were increased in the HF of mice fed trioctanoin, whereas levels of metabolites further downstream in the glycolytic pathway and the pentose phosphate pathway were reduced. This indicates that trioctanoin reduces glucose utilization because of a decrease in phosphofructokinase activity. Trioctanoin and triheptanoin showed similar anticonvulsant effects in the 6 Hz seizure model, but it remains unknown to what extent the anticonvulsant mechanism(s) are shared. In conclusion, triheptanoin unlike trioctanoin appears to not alter glucose metabolism in the healthy brain. PMID:24169853

  9. MicroRNA-26a regulates insulin sensitivity and metabolism of glucose and lipids

    PubMed Central

    Fu, Xianghui; Dong, Bingning; Tian, Yan; Lefebvre, Philippe; Meng, Zhipeng; Wang, Xichun; Pattou, François; Han, Weidong; Wang, Xiaoqiong; Lou, Fang; Jove, Richard; Staels, Bart; Moore, David D.; Huang, Wendong

    2015-01-01

    Type 2 diabetes (T2D) is characterized by insulin resistance and increased hepatic glucose production, yet the molecular mechanisms underlying these abnormalities are poorly understood. MicroRNAs (miRs) are a class of small, noncoding RNAs that have been implicated in the regulation of human diseases, including T2D. miR-26a is known to play a critical role in tumorigenesis; however, its function in cellular metabolism remains unknown. Here, we determined that miR-26a regulates insulin signaling and metabolism of glucose and lipids. Compared with lean individuals, overweight humans had decreased expression of miR-26a in the liver. Moreover, miR-26 was downregulated in 2 obese mouse models compared with control animals. Global or liver-specific overexpression of miR-26a in mice fed a high-fat diet improved insulin sensitivity, decreased hepatic glucose production, and decreased fatty acid synthesis, thereby preventing obesity-induced metabolic complications. Conversely, silencing of endogenous miR-26a in conventional diet–fed mice impaired insulin sensitivity, enhanced glucose production, and increased fatty acid synthesis. miR-26a targeted several key regulators of hepatic metabolism and insulin signaling. These findings reveal miR-26a as a regulator of liver metabolism and suggest miR-26a should be further explored as a potential target for the treatment of T2D. PMID:25961460

  10. Measuring maximum and standard metabolic rates using intermittent-flow respirometry: a student laboratory investigation of aerobic metabolic scope and environmental hypoxia in aquatic breathers.

    PubMed

    Rosewarne, P J; Wilson, J M; Svendsen, J C

    2016-01-01

    Metabolic rate is one of the most widely measured physiological traits in animals and may be influenced by both endogenous (e.g. body mass) and exogenous factors (e.g. oxygen availability and temperature). Standard metabolic rate (SMR) and maximum metabolic rate (MMR) are two fundamental physiological variables providing the floor and ceiling in aerobic energy metabolism. The total amount of energy available between these two variables constitutes the aerobic metabolic scope (AMS). A laboratory exercise aimed at an undergraduate level physiology class, which details the appropriate data acquisition methods and calculations to measure oxygen consumption rates in rainbow trout Oncorhynchus mykiss, is presented here. Specifically, the teaching exercise employs intermittent flow respirometry to measure SMR and MMR, derives AMS from the measurements and demonstrates how AMS is affected by environmental oxygen. Students' results typically reveal a decline in AMS in response to environmental hypoxia. The same techniques can be applied to investigate the influence of other key factors on metabolic rate (e.g. temperature and body mass). Discussion of the results develops students' understanding of the mechanisms underlying these fundamental physiological traits and the influence of exogenous factors. More generally, the teaching exercise outlines essential laboratory concepts in addition to metabolic rate calculations, data acquisition and unit conversions that enhance competency in quantitative analysis and reasoning. Finally, the described procedures are generally applicable to other fish species or aquatic breathers such as crustaceans (e.g. crayfish) and provide an alternative to using higher (or more derived) animals to investigate questions related to metabolic physiology.

  11. [Bone diseases caused by impaired glucose and lipid metabolism].

    PubMed

    Kanazawa, Ippei; Sugimoto, Toshitsugu

    2013-11-01

    The number of patients with lifestyle-related diseases is rapidly increasing in Japan. Metabolic syndrome caused by abdominal fat accumulation induces diabetes mellitus, dyslipidemia, and hypertension, resulting in an increase in cardiovascular diseases. On the other hand, recent studies have shown that the lifestyle-related diseases are risk factors of osteoporotic fractures. Although it remains still unclear how metabolic disorders affect bone tissue, oxidative stress and/or glycation stress might directly have negative impacts on bone tissue and increase the risk of fractures. In this review, we describe the association of diabetes mellitus and dyslipidemia with the fracture risk through oxidative stress and glycation stress.

  12. Regional cerebral glucose metabolic rate in human sleep assessed by positron emission tomography

    SciTech Connect

    Buchsbaum, M.S.; Wu, J.; Hazlett, E.; Sicotte, N.; Bunney, W.E. Jr. ); Gillin, J.C. )

    1989-01-01

    The cerebral metabolic rate of glucose was measured during nighttime sleep in 36 normal volunteers using positron emission tomography and fluorine-18-labeled 2-deoxyglucose (FDG). In comparison to waking controls, subjects given FDG during non-rapid eye movement (NREM) sleep showed about a 23% reduction in metabolic rate across the entire brain. This decrease was greater for the frontal than temporal or occipital lobes, and greater for basal ganglia and thalamus than cortex. Subjects in rapid eye movement (REM) sleep tended to have higher cortical metabolic rates than walking subjects. The cingulate gyrus was the only cortical structure to show a significant increase in glucose metabolic rate in REM sleep in comparison to waking. The basal ganglia were relatively more active on the right in REM sleep and symmetrical in NREM sleep.

  13. The Sedoheptulose Kinase CARKL Directs Macrophage Polarization through Control of Glucose Metabolism

    PubMed Central

    Haschemi, Arvand; Kosma, Paul; Gille, Lars; Evans, Charles R.; Burant, Charles F.; Starkl, Philipp; Knapp, Bernhard; Haas, Robert; Schmid, Johannes A.; Jandl, Christoph; Amir, Shahzada; Lubec, Gert; Park, Jaehong; Esterbauer, Harald; Bilban, Martin; Brizuela, Leonardo; Pospisilik, J. Andrew; Otterbein, Leo E.; Wagner, Oswald

    2012-01-01

    Summary Immune cells are somewhat unique in that activation responses can alter quantitative phenotypes upwards of 100,000-fold. To date little is known about the metabolic adaptations necessary to mount such dramatic phenotypic shifts. Screening for novel regulators of macrophage activation, we found nonprotein kinases of glucose metabolism among the most enriched classes of candidate immune modulators. We find that one of these, the carbohydrate kinase-like protein CARKL, is rapidly downregulated in vitro and in vivo upon LPS stimulation in both mice and humans. Interestingly, CARKL catalyzes an orphan reaction in the pentose phosphate pathway, refocusing cellular metabolism to a high-redox state upon physiological or artificial downregulation. We find that CARKL-dependent metabolic reprogramming is required for proper M1- and M2-like macrophage polarization and uncover a rate-limiting requirement for appropriate glucose flux in macrophage polarization. PMID:22682222

  14. DMH1 increases glucose metabolism through activating Akt in L6 rat skeletal muscle cells.

    PubMed

    Xie, Xin; Xu, Xiao-Ming; Li, Na; Zhang, Yong-Hui; Zhao, Yu; Ma, Chun-Yan; Dong, De-Li

    2014-01-01

    DMH1(4-[6-(4-Isopropoxyphenyl)pyrazolo [1,5-a]pyrimidin-3-yl] quinoline) is a compound C analogue with the structural modifications at the 3- and 6-positions in pyrazolo[1,5-a]pyrimidine backbone. Compound C was reported to inhibit both AMPK and Akt. Our preliminary work found that DMH1 activated Akt. Since Akt was involved in glucose metabolism, we aimed to identify the effects of DMH1 on glucose metabolism in L6 rat muscle cells and the potential mechanism. Results showed that DMH1 increased lactic acid release and glucose consumption in L6 rat muscle cells in a dose-dependent manner. DMH1 activated Akt in L6 cells. Akt inhibitor inhibited DMH1-induced Akt activation and DMH1-induced increases of glucose uptake and consumption. DMH1 had no cytotoxicity in L6 cells, but inhibited mitochondrial function and reduced ATP production. DMH1 showed no effect on AMPK, but in the presence of Akt inhibitor, DMH1 significantly activated AMPK. Compound C inhibited DMH1-induced Akt activation in L6 cells. Compound C inhibited DMH1-induced increase of glucose uptake, consumption and lactic acid release in L6 cells. DMH1 inhibited PP2A activity, and PP2A activator forskolin reversed DMH1-induced Akt activation. We concluded that DMH1 increased glucose metabolism through activating Akt and DMH1 activated Akt through inhibiting PP2A activity in L6 rat muscle cells. In view of the analogue structure of DMH1 and compound C and the contrasting effects of DMH1 and compound C on Akt, the present study provides a novel leading chemical structure targeting Akt with potential use for regulating glucose metabolism.

  15. Evidence for impaired glucose metabolism in the striatum, obtained postmortem, from some subjects with schizophrenia

    PubMed Central

    Dean, B; Thomas, N; Scarr, E; Udawela, M

    2016-01-01

    Studies using central nervous system tissue obtained postmortem suggest pathways involved in energy and metabolism contribute to the pathophysiology of schizophrenia; neuroimaging studies suggesting glucose metabolism is particularly affected in the striatum. To gain information on the status of pathways involved in glucose metabolism in the striatum, we measured levels of glucose, pyruvate, acetyl-CoA and lactate as well as the β subunit of pyruvate dehydrogenase, a rate limiting enzyme, in the postmortem tissue from subjects with schizophrenia and age/sex-matched controls. The subjects with schizophrenia were made up of two subgroups, which could be divided because they either had (muscarinic receptor deficit schizophrenia (MRDS)), or did not have (non-MRDS), a marked deficit in cortical muscarinic receptors. Compared to controls, levels of β subunit of pyruvate dehydrogenase were lower (Δ mean=−20%) and levels of pyruvate (Δ mean=+47%) and lactate (Δ mean=+15%) were significantly higher in the striatum from subjects with schizophrenia. Notably, in subjects with non-MRDS, striatal levels of β subunit of pyruvate dehydrogenase were lower (Δ mean=−29%), whereas levels of pyruvate (Δ mean=−66%), acetyl-CoA (Δ mean=−28%) and glucose (Δ mean=-27%) were higher, whereas levels of lactate (Δ mean=+17%) were higher in MRDS. Finally, discriminate analyses using levels the β subunit of pyruvate dehydrogenase and glucose, or better still, β subunit of pyruvate dehydrogenase and glucose in combination with pyruvate, lactate or acetyl-CoA could separate subjects with non-MRDS from controls with high levels of specificity (up to 93%) and selectivity (up to 91%). Our data show the benefit of being able to study defined subgroups within the syndrome of schizophrenia as such an approach has revealed that changes in glucose metabolism may be a significant contributor to the pathophysiology of non-MRDS. PMID:27845781

  16. Carbohydrate and Amino Acid Metabolism in the Ectomycorrhizal Ascomycete Sphaerosporella brunnea during Glucose Utilization 1

    PubMed Central

    Martin, Francis; Ramstedt, Mauritz; Söderhäll, Kenneth; Canet, Daniel

    1988-01-01

    Nuclear magnetic resonance spectroscopy was utilized to study the metabolism of [1-13C]glucose in mycelia of the ectomycorrhizal ascomycete Sphaerosporella brunnea. The main purpose was to assess the biochemical pathways for the assimilation of glucose and to identify the compounds accumulated during glucose assimilation. The majority of the 13C label was incorporated into mannitol, while glycogen, trehalose and free amino acids were labeled to a much lesser extent. The high enrichment of the C1/C6 position of mannitol indicated that the polyol was formed via a direct route from absorbed glucose. Randomization of the 13C label was observed to occur in glucose and trehalose leading to the accumulation of [1,6-13C]trehalose and [1,6-13C]glucose. This suggests that the majority of the glucose carbon used to form trehalose was cycled through the metabolically active mannitol pool. The proportion of label entering the free amino acids represented 38% of the soluble 13C after 6 hours of continuous glucose labeling. Therefore, amino acid biosynthesis is an important sink of assimilated carbon. Carbon-13 was incorporated into [3-13C]alanine and [2-13C]-, [3-13C]-, and [4-13C]glutamate and glutamine. From the analysis of the intramolecular 13C enrichment of these amino acids, it is concluded that [3-13C]pyruvate, arising from [1-13C]glucose catabolism, was used by alanine aminotransferase, pyruvate dehydrogenase, and pyruvate carboxylase (or phosphoenolpyruvate carboxykinase). Intramolecular 13C labeling patterns of glutamate and glutamine were similar and are consistent with the operation of the Krebs cycle. There is strong evidence for (a) randomization of the label on C2 and C3 positions of oxaloacetate via malate dehydrogenase and fumarase, and (b) the dual biosynthetic and respiratory role of the citrate synthase, aconitase, and isocitrate dehydrogenase reactions. The high flux of carbon through the carboxylation (presumably pyruvate carboxylase) step indicates that CO

  17. Sex-specific effects of prenatal stress on glucose homoeostasis and peripheral metabolism in rats.

    PubMed

    Brunton, Paula J; Sullivan, Katie M; Kerrigan, David; Russell, John A; Seckl, Jonathan R; Drake, Amanda J

    2013-05-01

    Glucocorticoid overexposure during pregnancy programmes offspring physiology and predisposes to later disease. However, any impact of ethologically relevant maternal stress is less clear, yet of physiological importance. Here, we investigated in rats the short- and long-term effects in adult offspring of repeated social stress (exposure to an aggressive lactating female) during late pregnancy on glucose regulation following stress, glucose-insulin homoeostasis and peripheral expression of genes important in regulating glucose and lipid metabolism and glucocorticoid action. Prenatal stress (PNS) was associated with reduced birth weight in female, but not male, offspring. The increase in blood glucose with restraint was exaggerated in adult PNS males compared with controls, but not in females. Oral glucose tolerance testing showed no effects on plasma glucose or insulin concentrations in either sex at 3 months; however, at 6 months, PNS females were hyperinsulinaemic following an oral glucose load. In PNS males, plasma triglyceride concentrations were increased, with reduced hepatic mRNA expression of 5α-reductase and peroxisome proliferator-activated receptor α (Pparα (Ppara)) and a strong trend towards reduced peroxisome proliferator-activated receptor gamma coactivator 1α (Pgc1α (Ppargc1a)) and Pparγ (Pparg) expression, whereas only Pgc1α mRNA was affected in PNS females. Conversely, in subcutaneous fat, PNS reduced mRNA expression of 11β-hydroxysteroid dehydrogenase type 1 (11βhsd1), phosphoenolpyruvate carboxykinase (Pepck (Pck1)), adipose triglyceride lipase (Atgl) and diglyceride acyltransferase 2 (Dgat2) in females, but only Pepck mRNA expression was reduced in PNS males. Thus, prenatal social stress differentially programmes glucose homoeostasis and peripheral metabolism in male and female offspring. These long-term alterations in physiology may increase susceptibility to metabolic disease.

  18. Reprogramming of glucose metabolism in hepatocellular carcinoma: Progress and prospects

    PubMed Central

    Shang, Run-Ze; Qu, Shi-Bin; Wang, De-Sheng

    2016-01-01

    Hepatocellular carcinoma (HCC) is one of the most lethal cancers, and its rate of incidence is rising annually. Despite the progress in diagnosis and treatment, the overall prognoses of HCC patients remain dismal due to the difficulties in early diagnosis and the high level of tumor invasion, metastasis and recurrence. It is urgent to explore the underlying mechanism of HCC carcinogenesis and progression to find out the specific biomarkers for HCC early diagnosis and the promising target for HCC chemotherapy. Recently, the reprogramming of cancer metabolism has been identified as a hallmark of cancer. The shift from the oxidative phosphorylation metabolic pathway to the glycolysis pathway in HCC meets the demands of rapid cell proliferation and offers a favorable microenvironment for tumor progression. Such metabolic reprogramming could be considered as a critical link between the different HCC genotypes and phenotypes. The regulation of metabolic reprogramming in cancer is complex and may occur via genetic mutations and epigenetic modulations including oncogenes, tumor suppressor genes, signaling pathways, noncoding RNAs, and glycolytic enzymes etc. Understanding the regulatory mechanisms of glycolysis in HCC may enrich our knowledge of hepatocellular carcinogenesis and provide important foundations in the search for novel diagnostic biomarkers and promising therapeutic targets for HCC. PMID:28018100

  19. Effects of insulin infusion on glucose homeostasis and glucose metabolism in rainbow trout fed a high-carbohydrate diet.

    PubMed

    Polakof, S; Moon, T W; Aguirre, P; Skiba-Cassy, S; Panserat, S

    2010-12-15

    The origin for the poor glucose utilization in carnivorous fish species fed high carbohydrate diets remains under debate. In the present study, we have fed rainbow trout a diet containing 30% carbohydrate for 1 or 5 days. In both cases, fish were implanted with mini-osmotic pumps releasing 0.7 i.u. kg(-1) day(-1) bovine insulin, and mRNA transcripts and the protein phosphorylation status of proteins controlling glycemia and glucose-related metabolism were studied in fish killed 6 h after the last meal. We demonstrate that when the exposure occurs over a short term (30 h), insulin exerts beneficial actions on trout glucose homeostasis, including a lowered glycemia and increased hepatic lipogenic and glycogenic potentials. However, when trout were fed for 5 days, these beneficial actions of insulin infusion were no longer observed. Thus, the increased lipogenic potential observed after one single meal was not present, and this together with the increased glycogenesis and the decreased glucose exported to the blood from the liver explains the lack of hypoglycemic action of insulin. The fact that insulin improved glucose homeostasis when administrated over a short time period implies that endogenous insulin secretion is inadequate in trout to deal with this amount of dietary carbohydrates. Moreover, the fact that a longer exposure to insulin resulted in a reduced response indicates that the rainbow trout is sensitive to insulin, re-enforcing the hypothesis that the hyperglycemia observed following a high carbohydrate meal is an insulin secretion issue rather an insulin action issue.

  20. Metabolic Glucose Status and Pituitary Pathology Portend Therapeutic Outcomes in Acromegaly

    PubMed Central

    Cheng, Sonia; Serri, Omar; L. Asa, Sylvia; Ezzat, Shereen

    2013-01-01

    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. PMID:24039977

  1. The hypothalamus and metabolism: integrating signals to control energy and glucose homeostasis.

    PubMed

    Coll, Anthony P; Yeo, Giles S H

    2013-12-01

    Molecules acting in the central nervous system play a critical role in the control of both energy and glucose homeostasis. The hypothalamus consists of a highly diverse collection of interconnected neurons and supporting glial cells that allow this region of the brain to sense and respond to a diverse range of hormonal and metabolic signals. We review recent advances in our understanding of the anatomical architecture and molecular mechanisms within the hypothalamus and how these facilitate the orchestration of systemic metabolic processes.

  2. Noninvasive measurement of regional myocardial glucose metabolism by positron emission computed tomography. [Dogs

    SciTech Connect

    Schelbert, H.R.; Phelps, M.E.

    1980-06-01

    While the results of regional myocardial glucose metabolism measurements using positron emission computed tomography (/sup 13/N-ammonia) are promising, their utility and value remains to be determined in man. If this technique can be applied to patients with acute myocardial ischemia or infarction it may permit delineation of regional myocardial segments with altered, yet still active metabolism. Further, it may become possible to evaluate the effects of interventions designed to salvage reversibly injured myocardium by this technique.

  3. Cerebral energy metabolism, glucose transport and blood flow: changes with maturation and adaptation to hypoglycaemia.

    PubMed

    Nehlig, A

    1997-02-01

    Brain maturation is characterized by a peak of cerebral energy metabolism and blood flow occurring between 3 and 8 years of age in humans and around 14-17 days of postnatal life in rats. This high activity coincides with the period of active brain growth. The human brain is dependent on glucose alone during that period, whereas rat brain uses both glucose and ketone bodies to cover its energetic and biosynthetic needs. The maturation of the density of glucose transporter sites-GLUT1 located at the blood-brain barrier and GLUT3 at the neuronal membrane-parallels the development of cerebral glucose utilization. During moderate acute hypoglycaemia, there are no changes in cerebral functional activity; cerebral glucose utilization decreases and blood flow increases only when hypoglycaemia is severe (lower than 2 mumol/ml). During chronic hypoglycaemia, the brain adapts to the low circulating levels of glucose: the number of glucose transporter sites is increased, and cerebral glucose utilization and function are maintained at normal levels while cerebral blood flow is more moderately increased than during acute hypoglycaemia. Neuronal damage consecutive to severe and prolonged hypoglycaemia occurs mainly in the cerebral cortex, hippocampus and caudate-putamen as a result of active release of excitatory amino acids.

  4. Accumulation of d-Glucose from Pentoses by Metabolically Engineered Escherichia coli

    PubMed Central

    Xia, Tian; Han, Qi; Costanzo, William V.; Zhu, Yixuan; Urbauer, Jeffrey L.

    2015-01-01

    Escherichia coli that is unable to metabolize d-glucose (with knockouts in ptsG, manZ, and glk) accumulates a small amount of d-glucose (yield of about 0.01 g/g) during growth on the pentoses d-xylose or l-arabinose as a sole carbon source. Additional knockouts in the zwf and pfkA genes, encoding, respectively, d-glucose-6-phosphate 1-dehydrogenase and 6-phosphofructokinase I (E. coli MEC143), increased accumulation to greater than 1 g/liter d-glucose and 100 mg/liter d-mannose from 5 g/liter d-xylose or l-arabinose. Knockouts of other genes associated with interconversions of d-glucose-phosphates demonstrate that d-glucose is formed primarily by the dephosphorylation of d-glucose-6-phosphate. Under controlled batch conditions with 20 g/liter d-xylose, MEC143 generated 4.4 g/liter d-glucose and 0.6 g/liter d-mannose. The results establish a direct link between pentoses and hexoses and provide a novel strategy to increase carbon backbone length from five to six carbons by directing flux through the pentose phosphate pathway. PMID:25746993

  5. Therapeutic vaccine against DPP4 improves glucose metabolism in mice.

    PubMed

    Pang, Zhengda; Nakagami, Hironori; Osako, Mariana K; Koriyama, Hiroshi; Nakagami, Futoshi; Tomioka, Hideki; Shimamura, Munehisa; Kurinami, Hitomi; Takami, Yoichi; Morishita, Ryuichi; Rakugi, Hiromi

    2014-04-01

    The increasing prevalence of type 2 diabetes mellitus is associated with a significant economic burden. We developed a dipeptidyl peptidase 4 (DPP4)-targeted immune therapy to increase glucagon-like peptide 1 hormone levels and improve insulin sensitivity for the prevention and treatment of type 2 diabetes mellitus. Immunization with the DPP4 vaccine in C57BL/6J mice successfully increased DPP4 titer, inhibited plasma DPP4 activity, and induced an increase in the plasma glucagon-like peptide 1 level. Moreover, this elevated titer was sustained for 3 mo. In mice fed a high-fat diet, DPP4 vaccination resulted in improved postprandial glucose excursions and insulin sensitivity and, in the diabetic KK-A(y) and db/db mice strains, DPP4 vaccination significantly reduced glucose excursions and increased both plasma insulin and pancreatic insulin content. Importantly, T cells were not activated following challenge with DPP4 itself, which suggests that this vaccine does not induce cell-mediated autoimmunity. Additionally, no significant immune-mediated damage was detected in cells and tissues where DPP4 is expressed. Thus, this DPP4 vaccine may provide a therapeutic alternative for patients with diabetes.

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

    PubMed

    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.

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

    PubMed Central

    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

  8. Metabolic responses to prolonged consumption of glucose- and fructose-sweetened beverages are not associated with postprandial or 24-hour glucose and insulin excursions

    Technology Transfer Automated Retrieval System (TEKTRAN)

    It has been proposed that the adverse metabolic effects of chronic consumption of sugar-sweetened beverages which contain both glucose and fructose are a consequence of increased circulating glucose and insulin excursions, i.e dietary glycemic index (GI). Objective: We determined if the greater adv...

  9. The Causes and Consequences of Altered Glucose Metabolism in Cancer

    DTIC Science & Technology

    2007-10-05

    Allalunis-Turner J, Haromy A, Beaulieu C, Thompson R, Lee CT, Lopaschuk GD, Puttagunta L, Bonnet S, Harry G, Hashimoto K, Porter CJ, Andrade MA, Thebaud B ...diagram). B . Diagram of the Warburg Effect. Even in the presence of normal oxygen conditions, many cancer cells convert pyruvate to lactate. The...mitochondria of these cells often appear to be functional, so it remains uncertain why this altered metabolism occurs. A. B . 5 conditions. Based on

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

    PubMed

    Xia, Xuan; Yan, Jinhua; Shen, Yunfeng; Tang, Kuanxiao; Yin, Jun; Zhang, Yanhua; Yang, Dongjie; Liang, Hua; Ye, Jianping; Weng, Jianping

    2011-02-03

    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.

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

    PubMed Central

    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

  12. Studies of fatty liver and kidney syndrome in chickens: dynamics of glucose metabolism.

    PubMed

    Balnave, D; Wolfenden, J; Ball, F M; Cumming, R B; Leng, R A

    1977-11-01

    1. Fatty liver and kidney syndrome (FLKS) was induced in a proportion of a group of 4-week-old chickens by giving a diet of meat meal and wheat; inclusion in the diet of animal tallow for 54 h substantially reduced the occurrence of FLKS. 2. Measurements of dynamic aspects of glucose metabolism were made with single injections of [2-3H]glucose which indicated that birds given the 'FLKS-inducing' diet and showing physical symptoms of FLKS had significantly lower rates of synthesis of glucose than birds given either the same diet supplemented with tallow or a commercial diet. 3. In a second series of experiments glucose metabolism was studied in birds (1) with or without physical symptoms that were given the 'FLKS-inducing' diet and (2) birds given the same diet supplemented with tallow or biotin. Affected birds fed the 'FLKS-inducing' diet had significantly lower plasma glucose concentrations, pool sizes and synthesis rates than birds fed the same diet and not showing symptoms, or birds fed the supplemented diets. 4. It is suggested that the cause of death in birds with FLKS is a low rate of gluconeogenesis during periods without feed which results in a lack of glucose to meet essential functions.

  13. Increased response to insulin of glucose metabolism in the 6-day unloaded rat soleus muscle

    NASA Technical Reports Server (NTRS)

    Henriksen, Erik J.; Tischler, Marc E.; Johnson, David G.

    1986-01-01

    Hind leg muscles of female rats were unloaded by tail cast suspension for 6 days. In the fresh-frozen unloaded soleus, the significantly greater concentration of glycogen correlated with a lower activity ratio of glycogen phosphorylase (p less than 0.02). The activity ratio of glycogen synthase also was lower (p less than 0.001), possibly due to the higher concentration of glycogen. In isolated unloaded soleus, insulin (0.1 milliunit/ml) increased the oxidation of D(U-C-14) glucose, release of lactate and pyruvate, incorporation of D-(U-C-14) glucose into glycogen, and the concentration of glucose 6-phosphate more (p less than 0.05) than in the weight-bearing soleus. At physiological doses of insulin, the percent of maximal uptake of 2-deoxy-D-(1,2-H-3) glucose/muscle also was greater in the unloaded soleus. Unloading of the soleus increased, by 50 percent the concentration of insuling receptors, due to no decrease in total receptor number during muscle atrophy. This increase may account for the greater response of glucose metabolism to insulin in this muscle. The extensor digitorum longus, which generally shows little response to unloading, displayed no differential response of glucose metabolism to insulin.

  14. Computational modeling of glucose transport in pancreatic β-cells identifies metabolic thresholds and therapeutic targets in diabetes.

    PubMed

    Luni, Camilla; Marth, Jamey D; Doyle, Francis J

    2012-01-01

    Pancreatic β-cell dysfunction is a diagnostic criterion of Type 2 diabetes and includes defects in glucose transport and insulin secretion. In healthy individuals, β-cells maintain plasma glucose concentrations within a narrow range in concert with insulin action among multiple tissues. Postprandial elevations in blood glucose facilitate glucose uptake into β-cells by diffusion through glucose transporters residing at the plasma membrane. Glucose transport is essential for glycolysis and glucose-stimulated insulin secretion. In human Type 2 diabetes and in the mouse model of obesity-associated diabetes, a marked deficiency of β-cell glucose transporters and glucose uptake occurs with the loss of glucose-stimulated insulin secretion. Recent studies have shown that the preservation of glucose transport in β-cells maintains normal insulin secretion and blocks the development of obesity-associated diabetes. To further elucidate the underlying mechanisms, we have constructed a computational model of human β-cell glucose transport in health and in Type 2 diabetes, and present a systems analysis based on experimental results from human and animal studies. Our findings identify a metabolic threshold or "tipping point" whereby diminished glucose transport across the plasma membrane of β-cells limits intracellular glucose-6-phosphate production by glucokinase. This metabolic threshold is crossed in Type 2 diabetes and results in β-cell dysfunction including the loss of glucose stimulated insulin secretion. Our model further discriminates among molecular control points in this pathway wherein maximal therapeutic intervention is achieved.

  15. The effect of aerobic exercise and starvation on growth performance and postprandial metabolic response in juvenile southern catfish (Silurus meridionalis).

    PubMed

    Li, Xiu-Ming; Liu, Li; Yuan, Jian-Ming; Xiao, Yuan-Yuan; Fu, Shi-Jian; Zhang, Yao-Guang

    2016-03-01

    To investigate the effects of aerobic exercise and starvation on growth performance, postprandial metabolic response and their interaction in a sedentary fish species, either satiation-fed or starved juvenile southern catfish (Silurus meridionalis) were exercised at 25 °C under three water velocities, i.e., nearly still water (control), 1 body length (bl) s(-1) and 2 bl s(-1), for eight weeks. Then, the feed intake (FI), food conversion efficiency (FCE), specific growth rate (SGR), morphological parameters, resting ṀO2 (ṀO2rest) and postprandial ṀO2 responses of the experimental fish were measured. Exercise at a low velocity (1 bl s(-1)) showed no effect on any growth performance parameter, whereas exercise at a high velocity (2 bl s(-1)) exhibited higher FI but similar SGR due to the extra energy expenditure from swimming and consequent decreased FCE. Starvation led to a significant body mass loss, whereas the effect intensified in both exercise groups. Exercise resulted in improved cardio-respiratory capacity, as indicated by increased gill and heart indexes, whereas it exhibited no effect on resting and postprandial metabolism in S. meridionalis. The starved fish displayed significantly larger heart, gill and digestive tract indexes compared with the feeding fish, suggesting selective maintenance of cardio-respiratory and digestive function in this fish species during starvation. However, starved fish still exhibited impaired digestive performance, as evidenced by the prolonged duration and low postprandial metabolic increase, and this effect was further exacerbated in both the 1 and 2 bl s(-1) exercise groups. These data suggest the following: (1) aerobic exercise produced no improvement in growth performance but may have led to the impairment of growth under insufficient food conditions; (2) the mass of different organs and tissues responded differently to aerobic exercise and starvation due to the different physiological roles they play; and (3

  16. Matching Meals to Body Clocks—Impact on Weight and Glucose Metabolism

    PubMed Central

    Hutchison, Amy T.; Wittert, Gary A.; Heilbronn, Leonie K.

    2017-01-01

    The prevalence of type 2 diabetes continues to rise worldwide and is reaching pandemic proportions. The notion that this is due to obesity, resulting from excessive energy consumption and reduced physical activity, is overly simplistic. Circadian de-synchrony, which occurs when physiological processes are at odds with timing imposed by internal clocks, also promotes obesity and impairs glucose tolerance in mouse models, and is a feature of modern human lifestyles. The purpose of this review is to highlight what is known about glucose metabolism in animal and human models of circadian de-synchrony and examine the evidence as to whether shifts in meal timing contribute to impairments in glucose metabolism, gut hormone secretion and the risk of type 2 diabetes. Lastly, we examine whether restricting food intake to discrete time periods, will prevent or reverse abnormalities in glucose metabolism with the view to improving metabolic health in shift workers and in those more generally at risk of chronic diseases such as type 2 diabetes and cardiovascular disease. PMID:28257081

  17. A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism

    PubMed Central

    Amoasii, Leonela; Holland, William; Sanchez-Ortiz, Efrain; Baskin, Kedryn K.; Pearson, Mackenzie; Burgess, Shawn C.; Nelson, Benjamin R.; Bassel-Duby, Rhonda; Olson, Eric N.

    2016-01-01

    The Mediator complex governs gene expression by linking upstream signaling pathways with the basal transcriptional machinery. However, how individual Mediator subunits may function in different tissues remains to be investigated. Through skeletal muscle-specific deletion of the Mediator subunit MED13 in mice, we discovered a gene regulatory mechanism by which skeletal muscle modulates the response of the liver to a high-fat diet. Skeletal muscle-specific deletion of MED13 in mice conferred resistance to hepatic steatosis by activating a metabolic gene program that enhances muscle glucose uptake and storage as glycogen. The consequent insulin-sensitizing effect within skeletal muscle lowered systemic glucose and insulin levels independently of weight gain and adiposity and prevented hepatic lipid accumulation. MED13 suppressed the expression of genes involved in glucose uptake and metabolism in skeletal muscle by inhibiting the nuclear receptor NURR1 and the MEF2 transcription factor. These findings reveal a fundamental molecular mechanism for the governance of glucose metabolism and the control of hepatic lipid accumulation by skeletal muscle. Intriguingly, MED13 exerts opposing metabolic actions in skeletal muscle and the heart, highlighting the customized, tissue-specific functions of the Mediator complex. PMID:26883362

  18. Chromium supplementation alters the glucose and lipid metabolism of feedlot cattle during the receiving period

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crossbreed steers (n = 20; 235 ± 4 kg) were fed 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brand Chromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (C...

  19. Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Crossbred steers (n = 20; 235 +/- 4 kg) were fed 53 days during a receiving period to determine if supplementing chromium (Cr; KemTRACE®brandChromium Propionate 0.04%, Kemin Industries) would alter the glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0...

  20. Intelligence and Changes in Regional Cerebral Glucose Metabolic Rate Following Learning.

    ERIC Educational Resources Information Center

    Haier, Richard J.; And Others

    1992-01-01

    A study of eight normal right-handed men demonstrates widespread significant decreases in brain glucose metabolic rate (GMR) following learning a complex computer task, a computer game. Correlations between magnitude of GMR change and intelligence scores are also demonstrated. (SLD)

  1. Insulin resistance for glucose metabolism in disused soleus muscle of mice

    NASA Technical Reports Server (NTRS)

    Seider, M. J.; Nicholson, W. F.; Booth, F. W.

    1981-01-01

    Results of this study on mice provide the first direct evidence of insulin resistance for glucose metabolism in skeletal muscle that has undergone a previous period of reduced muscle usage. This lack of responsiveness to insulin developed in one day and in the presence of hypoinsulinemia. Future studies will utilize the model of hindlimb immobilization to determine the causes of these changes.

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

    PubMed

    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.

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

    PubMed Central

    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

  4. Oolong tea does not improve glucose metabolism in non-diabetic adults

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Studies of the influence of tea on glucose metabolism have produced inconsistent results, possibly due to lack of dietary control and/or unclear characterization of tea products. Therefore, a double-blind crossover study was conducted in which healthy males (n=19) consumed each of three oolong tea ...

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

    PubMed Central

    Fuse, Yuji; Tamaoki, Junya; Akiyama, Shin-ichi; Muratani, Masafumi

    2016-01-01

    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. PMID:28116036

  6. A MED13-dependent skeletal muscle gene program controls systemic glucose homeostasis and hepatic metabolism.

    PubMed

    Amoasii, Leonela; Holland, William; Sanchez-Ortiz, Efrain; Baskin, Kedryn K; Pearson, Mackenzie; Burgess, Shawn C; Nelson, Benjamin R; Bassel-Duby, Rhonda; Olson, Eric N

    2016-02-15

    The Mediator complex governs gene expression by linking upstream signaling pathways with the basal transcriptional machinery. However, how individual Mediator subunits may function in different tissues remains to be investigated. Through skeletal muscle-specific deletion of the Mediator subunit MED13 in mice, we discovered a gene regulatory mechanism by which skeletal muscle modulates the response of the liver to a high-fat diet. Skeletal muscle-specific deletion of MED13 in mice conferred resistance to hepatic steatosis by activating a metabolic gene program that enhances muscle glucose uptake and storage as glycogen. The consequent insulin-sensitizing effect within skeletal muscle lowered systemic glucose and insulin levels independently of weight gain and adiposity and prevented hepatic lipid accumulation. MED13 suppressed the expression of genes involved in glucose uptake and metabolism in skeletal muscle by inhibiting the nuclear receptor NURR1 and the MEF2 transcription factor. These findings reveal a fundamental molecular mechanism for the governance of glucose metabolism and the control of hepatic lipid accumulation by skeletal muscle. Intriguingly, MED13 exerts opposing metabolic actions in skeletal muscle and the heart, highlighting the customized, tissue-specific functions of the Mediator complex.

  7. Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver

    EPA Science Inventory

    Pulmonary Ozone Exposure Alters Essential Metabolic Pathways involved in Glucose Homeostasis in the Liver D.B. Johnson, 1 W.O. Ward, 2 V.L. Bass, 2 M.C.J. Schladweiler, 2A.D. Ledbetter, 2 D. Andrews, and U.P. Kodavanti 2 1 Curriculum in Toxicology, UNC School of Medicine, Cha...

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

    ERIC Educational Resources Information Center

    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)

  9. Impaired kisspeptin signaling decreases metabolism and promotes glucose intolerance and obesity.

    PubMed

    Tolson, Kristen P; Garcia, Christian; Yen, Stephanie; Simonds, Stephanie; Stefanidis, Aneta; Lawrence, Alison; Smith, Jeremy T; Kauffman, Alexander S

    2014-07-01

    The neuropeptide kisspeptin regulates reproduction by stimulating gonadotropin-releasing hormone (GnRH) neurons via the kisspeptin receptor KISS1R. In addition to GnRH neurons, KISS1R is expressed in other brain areas and peripheral tissues, which suggests that kisspeptin has additional functions beyond reproduction. Here, we studied the energetic and metabolic phenotype in mice lacking kisspeptin signaling (Kiss1r KO mice). Compared with WT littermates, adult Kiss1r KO females displayed dramatically higher BW, leptin levels, and adiposity, along with strikingly impaired glucose tolerance. Conversely, male Kiss1r KO mice had normal BW and glucose regulation. Surprisingly, despite their obesity, Kiss1r KO females ate less than WT females; however, Kiss1r KO females displayed markedly reduced locomotor activity, respiratory rate, and energy expenditure, which were not due to impaired thyroid hormone secretion. The BW and metabolic phenotype in Kiss1r KO females was not solely reflective of absent gonadal estrogen, as chronically ovariectomized Kiss1r KO females developed obesity, hyperleptinemia, reduced metabolism, and glucose intolerance compared with ovariectomized WT females. Our findings demonstrate that in addition to reproduction, kisspeptin signaling influences BW, energy expenditure, and glucose homeostasis in a sexually dimorphic and partially sex steroid-independent manner; therefore, alterations in kisspeptin signaling might contribute, directly or indirectly, to some facets of human obesity, diabetes, or metabolic dysfunction.

  10. NFκB up-regulation of glucose transporter 3 is essential for hyperactive mammalian target of rapamycin-induced aerobic glycolysis and tumor growth.

    PubMed

    Zha, Xiaojun; Hu, Zhongdong; Ji, Shuang; Jin, Fuquan; Jiang, Keguo; Li, Chunjia; Zhao, Pan; Tu, Zhenzhen; Chen, Xianguo; Di, Lijun; Zhou, Haisheng; Zhang, Hongbing

    2015-04-01

    Accumulating evidence indicates that mammalian target of rapamycin (mTOR) exerts a crucial role in aerobic glycolysis and tumorigenesis, but the underlying mechanisms remain largely obscure. Results from Tsc1- or Tsc2-null mouse embryonic fibroblasts (MEFs) and human cancer cell lines consistently indicate that the expression of glucose transporter 3 (Glut3) is dramatically up-regulated by mTOR. The rapamycin-sensitive mTOR complex 1 (mTORC1), but not the rapamycin-insensitive mTOR complex 2 (mTORC2), was involved in the regulation of Glut3 expression. Moreover, mTORC1 enhances Glut3 expression through the activation of the IKK/NFκB pathway. Depletion of Glut3 led to the suppression of aerobic glycolysis, the inhibition of cell proliferation and colony formation, and the attenuation of the tumorigenic potential of the cells with aberrantly hyper-activated mTORC1 signaling in nude mice. We conclude that Glut3 is a downstream target of mTORC1, and it is critical for oncogenic mTORC1-mediated aerobic glycolysis and tumorigenesis. Hence Glut3 may be a potential target for therapy against cancers caused by the aberrantly activated mTORC1 signaling.

  11. Glycolysis inhibitor 2-deoxy-D-glucose suppresses carcinogen-induced rat hepatocarcinogenesis by restricting cancer cell metabolism.

    PubMed

    Wang, Zhaofa; Zhang, Liming; Zhang, Dong; Sun, Rongsheng; Wang, Qingyan; Liu, Xinyi

    2015-03-01

    The abnormal metabolism of cancer cells is a crucial feature of tumors and provides promising therapeutic targets for cancer treatments. Aerobic glycolysis in cancer cells, termed the Warburg effect, is a highlighted characteristic of cancer‑specific metabolism. However, the effect of glycolysis inhibition on hepatocarcinogenesis remains to be elucidated. In the present study, the effects of the glycolysis inhibitor 2‑deoxy‑D‑glucose (2‑DG) on the N‑diethylnitrosamine (DEN)‑induced rat hepatocarcinoma model and its underlying mechanisms were investigated. It was observed that 2‑DG significantly delayed hepatocarcinogenesis and effectively prolonged survival time in the DEN‑treated rats. The glycolysis inhibitor, 2‑DG prominently decreased cell proliferation and increased cell apoptosis in the DEN‑induced rat hepatoma and had no evident impact on the pericarcinomatous liver tissues. Further investigation revealed that 2‑DG resulted in a reduction of glycolysis products, the compensatory increase of hexokinase 2 expression and a decrease in 6‑phosphofructo‑2‑kinase, pyruvate kinase M2 and lactate dehydrogenase A expression in the hepatoma tissues. The inhibition of glycolysis further suppressed the tricarboxylic acid cycle, fatty acid and cholesterol biosynthesis and ATP production, while it promoted autophagic activation. In addition, the in vitro study demonstrated that hypoxia, an important factor in the tumor microenvironment, may assist in increasing 2‑DG‑induced inhibition of cell viability, cell cycle retardation and the decrease of colony formation ability in hepatoma cells. Taken together, the present results suggested that 2‑DG may inhibit hepatocarcinogenesis in the DEN‑treated rats via restricting cancer cell metabolism. This finding provides a promising measure in the prevention and treatment of hepatoma.

  12. Changes in structure, activity and metabolism of aerobic granules as a microbial response to high phenol loading.

    PubMed

    Jiang, H-L; Tay, J-H; Tay, S T-L

    2004-02-01

    Four column-type sequential aerobic sludge blanket reactors were fed with phenol as the sole carbon and energy source and operated at loading rates of 1.0, 1.5, 2.0 and 2.5 kg phenol m(-3) day(-1). The results indicated that phenol loading exerted a profound influence on the structure, activity and metabolism of the aerobic granules. Compact granules with good settling ability were maintained at loadings up to 2.0 kg phenol m(-3) day(-1), and structurally weakened granules with enhanced production of extracellular polymers and proteins and significantly lower hydrophobicities were observed at the highest loading of 2.5 kg phenol m(-3) day(-1). Specific oxygen uptake rate, catechol 2,3-dioxygenase (C23O) and catechol 1,2-dioxygenase (C12O) activities peaked at a loading of 2.0 kg phenol m(-3) day(-1), and declined thereafter. Granules degraded phenol completely in all four reactors, mainly through the meta cleavage pathway as C23O activities were significantly higher than C12O activities. At the highest loading applied, the anabolism and catabolism of microorganisms were regulated such that phenol degradation proceeded exclusively via the meta pathway, apparently to produce more energy for overstimulation of protein production against phenol toxicity. This work contributes to a better understanding of the ability of aerobic granules to handle high-strength industrial wastewaters containing chemicals that are normally inhibitory to microbial growth.

  13. Exploration and comparison of inborn capacity of aerobic and anaerobic metabolisms of Saccharomyces cerevisiae for microbial electrical current production.

    PubMed

    Mao, Longfei; Verwoerd, Wynand S

    2013-01-01

    Saccharomyces cerevisiae possesses numerous advantageous biological features, such as being robust, easily handled, mostly non-pathogenic and having high catabolic rates, etc., which can be considered as merits for being used as a promising biocatalyst in microbial fuel cells (MFCs) for electricity generation. Previous studies have developed efficient MFC configurations to convert metabolic electron shuttles, such as cytoplasmic NADH, into usable electric current. However, no studies have elucidated the maximum potential of S. cerevisiae for current output and the underlying metabolic pathways, resulting from the interaction of thousands of reactions inside the cell during MFC operation. To address these two key issues, this study used in silico metabolic engineering techniques, flux balance analysis (FBA), and flux variability analysis with target flux minimization (FATMIN), to model the metabolic perturbation of S. cerevisiae under the MFC-energy extraction. The FBA results showed that, in the cytoplasmic NADH-dependent mediated electron transfer (MET) mode, S. cerevisiae had a potential to produce currents at up to 5.781 A/gDW for the anaerobic and 6.193 A/gDW for the aerobic environments. The FATMIN results showed that the aerobic and anaerobic metabolisms are resilient, relying on six and five contributing reactions respectively for high current production. Two reactions, catalyzed by glutamate dehydrogenase (NAD) (EC 1.4.1.3) and methylene tetrahydrofolate dehydrogenase (NAD) (EC 1.5.1.5), were shared in both current-production modes and contributed to over 80% of the identified maximum current outputs. It is also shown that the NADH regeneration was much less energy costly than biomass production rate. Taken together, our finding suggests that S. cerevisiae should receive more research effort for MFC electricity production.

  14. Pseudomonas aeruginosa strain MA01 aerobically metabolizes the aminodinitrotoluenes produced by 2,4,6-trinitrotoluene nitro group reduction.

    PubMed

    Alvarez, M A; Kitts, C L; Botsford, J L; Unkefer, P J

    1995-11-01

    Many microbes reduce the nitro substituents of 2,4,6-trinitrotoluene (TNT), producing aminodinitrotoluenes (ADNTs). These compounds are recalcitrant to further breakdown and are acutely toxic. In a search for organisms capable of metabolizing ADNTs, a bacterial strain was isolated for the ability to use 2-aminobenzoate (anthranilate) as sole C-source. This isolate, Pseudomonas aeruginosa MA01, metabolized TNT by first reducing one nitro group to form either 2-amino-4,6-dinitrotoluene (2ADNT) or 4-amino-2,6-dinitrotoluene (4ADNT). However, strain MA01 was distinct from other TNT-reducing organisms in that it transformed these compounds into highly polar metabolites through an O2-dependent process. Strain MA01 was able to cometabolize TNT, 2ADNT, and 4ADNT in the presence of a variety of carbon and energy sources. During aerobic cometabolism with succinate, 45% of uniformly ring-labeled [14C]TNT was transformed to highly polar compounds. Aerobic cometabolism of purified [14C]2ADNT and [14C]4ADNT with succinate as C-source produced similar amounts of these polar metabolites. During O2-limited cometabolism with succinate as C-source and nitrate as electron acceptor, less than 8% of the [14C]TNT was transformed to polar metabolites. Purified 2,6-diamino-4-nitrotoluene was not metabolized, and while 2,4-diamino-6-nitrotoluene was acetylated, the product (N-acetyl-2,4-diamino-6-nitrotoluene) was not further metabolized. Therefore, strain MA01 metabolized TNT by oxidation of the ADNTs and not by reduction the remaining nitro groups on the ADNTs.

  15. Exploration and comparison of inborn capacity of aerobic and anaerobic metabolisms of Saccharomyces cerevisiae for microbial electrical current production

    PubMed Central

    Mao, Longfei; Verwoerd, Wynand S

    2013-01-01

    Saccharomyces cerevisiae possesses numerous advantageous biological features, such as being robust, easily handled, mostly non-pathogenic and having high catabolic rates, etc., which can be considered as merits for being used as a promising biocatalyst in microbial fuel cells (MFCs) for electricity generation. Previous studies have developed efficient MFC configurations to convert metabolic electron shuttles, such as cytoplasmic NADH, into usable electric current. However, no studies have elucidated the maximum potential of S. cerevisiae for current output and the underlying metabolic pathways, resulting from the interaction of thousands of reactions inside the cell during MFC operation. To address these two key issues, this study used in silico metabolic engineering techniques, flux balance analysis (FBA), and flux variability analysis with target flux minimization (FATMIN), to model the metabolic perturbation of S. cerevisiae under the MFC-energy extraction. The FBA results showed that, in the cytoplasmic NADH-dependent mediated electron transfer (MET) mode, S. cerevisiae had a potential to produce currents at up to 5.781 A/gDW for the anaerobic and 6.193 A/gDW for the aerobic environments. The FATMIN results showed that the aerobic and anaerobic metabolisms are resilient, relying on six and five contributing reactions respectively for high current production. Two reactions, catalyzed by glutamate dehydrogenase (NAD) (EC 1.4.1.3) and methylene tetrahydrofolate dehydrogenase (NAD) (EC 1.5.1.5), were shared in both current-production modes and contributed to over 80% of the identified maximum current outputs. It is also shown that the NADH regeneration was much less energy costly than biomass production rate. Taken together, our finding suggests that S. cerevisiae should receive more research effort for MFC electricity production. PMID:23969939

  16. A new application of electrical impedance spectroscopy for measuring glucose metabolism: a phantom study

    NASA Astrophysics Data System (ADS)

    Dhurjaty, Sreeram; Qiu, Yuchen; Tan, Maxine; Liu, Hong; Zheng, Bin

    2015-03-01

    Glucose metabolism relates to biochemical processes in living organisms and plays an important role in diabetes and cancer-metastasis. Although many methods are available for measuring glucose metabolism-activities, from simple blood tests to positron emission tomography, currently there is no robust and affordable device that enables monitoring of glucose levels in real-time. In this study we tested feasibility of applying a unique resonance-frequency based electronic impedance spectroscopy (REIS) device that has been, recently developed to measure and monitor glucose metabolism levels using a phantom study. In this new testing model, a multi-frequency electrical signal sequence is applied and scanned through the subject. When the positive reactance of an inductor inside the device cancels out the negative reactance of the capacitance of the subject, the electrical impedance reaches a minimum value and this frequency is defined as the resonance frequency. The REIS system has a 24-bit analog-to-digital signal convertor and a frequency-resolution of 100Hz. In the experiment, two probes are placed inside a 100cc container initially filled with distilled water. As we gradually added liquid-glucose in increments of 1cc (250mg), we measured resonance frequencies and minimum electrical signal values (where A/D was normalized to a full scale of 1V). The results showed that resonance frequencies monotonously decreased from 243kHz to 178kHz, while the minimum voltages increased from 405mV to 793mV as the added amount of glucose increased from 0 to 5cc. The study demonstrated the feasibility of applying this new REIS technology to measure and/or monitor glucose levels in real-time in future.

  17. Deletion of Cyclophilin D Impairs β-Oxidation and Promotes Glucose Metabolism

    PubMed Central

    Tavecchio, Michele; Lisanti, Sofia; Bennett, Michael J.; Languino, Lucia R.; Altieri, Dario C.

    2015-01-01

    Cyclophilin D (CypD) is a mitochondrial matrix protein implicated in cell death, but a potential role in bioenergetics is not understood. Here, we show that loss or depletion of CypD in cell lines and mice induces defects in mitochondrial bioenergetics due to impaired fatty acid β-oxidation. In turn, CypD loss triggers a global compensatory shift towards glycolysis, with transcriptional upregulation of effectors of glucose metabolism, increased glucose consumption and higher ATP production. In vivo, the glycolytic shift secondary to CypD deletion is associated with expansion of insulin-producing β-cells, mild hyperinsulinemia, improved glucose tolerance, and resistance to high fat diet-induced liver damage and weight gain. Therefore, CypD is a novel regulator of mitochondrial bioenergetics, and unexpectedly controls glucose homeostasis, in vivo. PMID:26515038

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

    PubMed Central

    Chung, Soo Im; Ryu, Su Noh; Kang, Mi Young

    2016-01-01

    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. PMID:27775654

  19. The effects of cisplatin and other divalent platinum compounds on glucose metabolism and pancreatic endocrine function.

    PubMed

    Goldstein, R S; Mayor, G H; Gingerich, R L; Hook, J B; Rosenbaum, R W; Bond, J T

    1983-07-01

    Three divalent platinum compounds, cis-dichlorodiammineplatinum (cis-DDP), trans-dichlorodiammineplatinum (trans-DDP), and ammonium tetrachloroplatinate, were examined for their effects on glucose metabolism in male F-344 rats. Rats were treated with a single iv dose of cis-DDP (0, 2.5, or 5 mg/kg), trans-DDP (0, 5, 7.5, or 15 mg/kg) or tetrachloroplatinate (0, 6, or 18 mg/kg). Glucose tolerance was evaluated 2, 4, 7, and 14 days following platinum treatment by serially measuring plasma glucose before and following an ip glucose load. Administration of 5 mg/kg cis-DDP impaired glucose tolerance on Days 2 and 4, but not on Days 7 and 14. Plasma immunoreactive glucagon (IRG) was elevated at all times following cis-DDP treatment and thus was not correlated with the transient impairment in glucose tolerance. Plasma immunoreactive insulin (IRI) response to a glucose load was deficient relative to the degree of hyperglycemia in cis-DDP-treated (5 mg/kg) animals on Days 2 and 4. However, neither histopathological damage of the pancreas nor pancreatic stores of IRI were affected by cis-DDP treatment. In contrast to cis-DDP, equimolar or greater than equimolar doses of trans-DDP or tetrachloroplatinate did not significantly affect glucose tolerance at any time examined. These results indicate that cis-DDP-mediated glucose intolerance is unique to the geometry of the complex and is related to properties other than the presence of a divalent platinum atom. Furthermore, glucose intolerance following cis-DDP treatment appears to be related to a relative deficiency in insulin secretion.

  20. UCP2 mRNA expression is dependent on glucose metabolism in pancreatic islets

    SciTech Connect

    Dalgaard, Louise T.

    2012-01-06

    Highlights: Black-Right-Pointing-Pointer UCP2 mRNA levels are decreased in islets of Langerhans from glucokinase deficient mice. Black-Right-Pointing-Pointer UCP2 mRNA up-regulation by glucose is dependent on glucokinase. Black-Right-Pointing-Pointer Absence of UCP2 increases GSIS of glucokinase heterozygous pancreatic islets. Black-Right-Pointing-Pointer This may protect glucokinase deficient mice from hyperglycemic damages. -- Abstract: Uncoupling Protein 2 (UCP2) is expressed in the pancreatic {beta}-cell, where it partially uncouples the mitochondrial proton gradient, decreasing both ATP-production and glucose-stimulated insulin secretion (GSIS). Increased glucose levels up-regulate UCP2 mRNA and protein levels, but the mechanism for UCP2 up-regulation in response to increased glucose is unknown. The aim was to examine the effects of glucokinase (GK) deficiency on UCP2 mRNA levels and to characterize the interaction between UCP2 and GK with regard to glucose-stimulated insulin secretion in pancreatic islets. UCP2 mRNA expression was reduced in GK+/- islets and GK heterozygosity prevented glucose-induced up-regulation of islet UCP2 mRNA. In contrast to UCP2 protein function UCP2 mRNA regulation was not dependent on superoxide generation, but rather on products of glucose metabolism, because MnTBAP, a superoxide dismutase mimetic, did not prevent the glucose-induced up-regulation of UCP2. Glucose-stimulated insulin secretion was increased in UCP2-/- and GK+/- islets compared with GK+/- islets and UCP2 deficiency improved glucose tolerance of GK+/- mice. Accordingly, UCP2 deficiency increased ATP-levels of GK+/- mice. Thus, the compensatory down-regulation of UCP2 is involved in preserving the insulin secretory capacity of GK mutant mice and might also be implicated in limiting disease progression in MODY2 patients.

  1. Similarities of cerebral glucose metabolism in Alzheimer's and Parkinsonian dementia

    SciTech Connect

    Kuhl, D.E.; Metter, E.J.; Benson, D.F.; Ashford, J.W.; Riege, W.H.; Fujikawa, D.G.; Markham, C.H.; Maltese, A.

    1985-05-01

    In the dementia of probable Alzheimer's Disease (AD), there is a decrease in the metabolic ratio of parietal cortex/caudate-thalamus which relates measures in the most and in the least severely affected locations. Since some demented patients with Parkinson's Disease (PDD) are known to share pathological and neurochemical features with AD patients, the authors evaluated if the distribution of cerebral hypometabolism in PDD and AD were the same. Local cerebral metabolic rates were determined using the FDG method and positron tomography in subjects with AD (N=23), and PDD (N=7), multiple infarct dementia (MID)(N=6), and controls (N=10). In MID, the mean par/caudthal ratio was normal (0.79 +- 0.9, N=6). In AD and PDD patients, this ratio correlated negatively with both the severity (r=-0.624, rho=0.001) and duration (r=-0.657, rho=0.001) of dementia. The ratio was markedly decreased in subjects with mild to severe dementia (0.46 +- 0.09, N=21) and with dementia duration greater than two years (0.44 +- 0.08, N=18), but the ratio was also significantly decreased in patients with less advanced disease, i.e., when dementia was only questionable (0.64 +- 0.14, N=9) (t=2.27, rho<0.037) and when duration was two years or less (0.62 +- 0.13, N=12)(t=2.88, rho<0.009). This similarity of hypometabolism in AD and PDD is additional evidence that a common mechanism may operate in both disorders. The par/caud-thal metabolic ratio may be an index useful in the differential diagnosis of early dementia.

  2. Carbohydrate and the regulation of blood glucose and metabolism.

    PubMed

    Wolever, Thomas M S

    2003-05-01

    Classifying the glycemic responses of carbohydrate foods using the glycemic index (GI) requires standardized methodology for valid results. Dietary carbohydrates influence metabolism by at least four mechanisms: nature of the monosaccharides absorbed, amount of carbohydrate consumed, rate of absorption, and colonic fermentation. Reducing glycemic responses by reducing carbohydrate intake increases postprandial serum free-fatty acids (FFA) and does not improve overall glycemic control in diabetic subjects. By contrast, low-GI diets reduce serum FFA and improve glycemic control. Thus, current evidence supports FAO/WHO recommendations to maintain a high-carbohydrate diet and choose low-GI starchy foods.

  3. Association of Insulin Resistance with Glucose and Lipid Metabolism: Ethnic Heterogeneity in Far Western China

    PubMed Central

    Yan, Yi-Zhong; Ma, Ru-Lin; Zhang, Jing-Yu; He, Jia; Ma, Jiao-Long; Pang, Hong-Rui; Mu, La-Ti; Ding, Yu-Song; Guo, Heng; Zhang, Mei; Liu, Jia-Ming; Rui, Dong-Sheng; Wang, Kui

    2016-01-01

    Objective. To study the relationships between IR and glucose and lipid metabolism in far western China and these relationships' ethnic heterogeneity. Methods. From the baseline survey, 419 Uygur cases, 331 Kazak cases, and 220 Han cases were randomly selected, resulting in a total of 970 cases for study. FINS concentration was measured by radioimmunoassay. Results. (1) In the Kazak population, IR was correlated with hyperglycemia; high levels of TC, TG, and LDL-C; and low levels of HDL-C and abdominal obesity (all P < 0.05). (2) In the Uygur population, the influence of IR on hyperglycemia and abdominal obesity was the greatest. In the Kazak population, IR was associated with hyperglycemia most closely. In the Han population, IR may have had an impact on the incidence of low HDL-C levels. (3) After adjusting for sex, age, smoking status, and alcohol consumption, IR was still associated with anomalies in the metabolism of the Uygur, Kazak, and Han populations. Conclusion. IR was involved in the process of glucose and lipid metabolism, and its degree of involvement differed among the ethnicities studied. We could consider reducing the occurrence of abnormal glucose and lipid metabolism by controlling IR and aiming to reduce the prevalence of metabolic syndrome and related diseases. PMID:28100934

  4. Glucose metabolic flux distribution of Lactobacillus amylophilus during lactic acid production using kitchen waste saccharified solution.

    PubMed

    Liu, Jianguo; Wang, Qunhui; Zou, Hui; Liu, Yingying; Wang, Juan; Gan, Kemin; Xiang, Juan

    2013-11-01

    The (13) C isotope tracer method was used to investigate the glucose metabolic flux distribution and regulation in Lactobacillus amylophilus to improve lactic acid production using kitchen waste saccharified solution (KWSS). The results demonstrate that L. amylophilus is a homofermentative bacterium. In synthetic medium, 60.6% of the glucose entered the Embden-Meyerhof-Parnas (EMP) to produce lactic acid, whereas 36.4% of the glucose entered the pentose phosphate metabolic pathway (HMP). After solid-liquid separation of the KWSS, the addition of Fe(3+) during fermentation enhanced the NADPH production efficiency and increased the NADH content. The flux to the EMP was also effectively increased. Compared with the control (60.6% flux to EMP without Fe(3+) addition), the flux to the EMP with the addition of Fe(3+) (74.3%) increased by 23.8%. In the subsequent pyruvate metabolism, Fe(3+) also increased lactate dehydrogenase activity, and inhibited alcohol dehydrogenase, pyruvate dehydrogenase and pyruvate carboxylase, thereby increasing the lactic acid production to 9.03 g l(-1) , an increase of 8% compared with the control. All other organic acid by-products were lower than in the control. However, the addition of Zn(2+) showed an opposite effect, decreasing the lactic acid production. In conclusion it is feasible and effective means using GC-MS, isotope experiment and MATLAB software to integrate research the metabolic flux distribution of lactic acid bacteria, and the results provide the theoretical foundation for similar metabolic flux distribution.

  5. Regional Cerebral Glucose Metabolism in Novelty Seeking and Antisocial Personality: A Positron Emission Tomography Study

    PubMed Central

    Park, So Hyeon; Park, Hyun Soo

    2016-01-01

    Novelty seeking (NS) and antisocial personality (ASP) are commonly exhibited by those who suffer from addictions, such as substance abuse. NS has been suggested to be a fundamental aspect of ASP. To investigate the neurobiological substrate of NS and ASP, we tested the relationship between regional cerebral glucose metabolism and the level of NS, determining the differences between individuals with and without ASP. Seventy-two healthy adults (43 males, mean age±SD=38.8±16.6 years, range=20~70 years; 29 females, 44.2±20.1 years, range=19~72 years) underwent resting-state brain positron emission tomography (PET) 40 minutes after 18F-fluorodeoxyglucose (FDG) injection. Within 10 days of the FDG PET study, participants completed Cloninger's 240-item Temperament and Character Inventory (TCI) to determine NS scores. Participants with and without ASP were grouped according to their TCI profiles. Statistical parametric mapping analysis was performed using the FDG PET and TCI profile data. NS scores positively correlated with metabolism in the left anterior cingulate gyrus and the insula on both sides of the brain and negatively correlated with metabolism in the right pallidum and putamen. Participants with ASP showed differences in cerebral glucose metabolism across various cortical and subcortical regions, mainly in the frontal and prefrontal areas. These data demonstrate altered regional cerebral glucose metabolism in individuals with NS and ASP and inform our understanding of the neurobiological substrates of problematic behaviors and personality disorders. PMID:27574485

  6. Quantitative analysis of drug effects at the whole-body level: a case study for glucose metabolism in malaria patients.

    PubMed

    Snoep, Jacky L; Green, Kathleen; Eicher, Johann; Palm, Daniel C; Penkler, Gerald; du Toit, Francois; Walters, Nicolas; Burger, Robert; Westerhoff, Hans V; van Niekerk, David D

    2015-12-01

    We propose a hierarchical modelling approach to construct models for disease states at the whole-body level. Such models can simulate effects of drug-induced inhibition of reaction steps on the whole-body physiology. We illustrate the approach for glucose metabolism in malaria patients, by merging two detailed kinetic models for glucose metabolism in the parasite Plasmodium falciparum and the human red blood cell with a coarse-grained model for whole-body glucose metabolism. In addition we use a genome-scale metabolic model for the parasite to predict amino acid production profiles by the malaria parasite that can be used as a complex biomarker.

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

    SciTech Connect

    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.

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

    SciTech Connect

    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.

  9. Chromium supplementation alters both glucose and lipid metabolism in feedlot cattle during the receiving period.

    PubMed

    Bernhard, B C; Burdick, N C; Rathmann, R J; Carroll, J A; Finck, D N; Jennings, M A; Young, T R; Johnson, B J

    2012-12-01

    Crossbred steers (n = 20; 235 ± 4 kg) were fed for 53 d during a receiving period to determine if supplementing chromium (Cr; KemTRACE Chromium Propionate 0.04%, Kemin Industries, Des Moines, IA) would alter glucose or lipid metabolism of newly received cattle. Chromium premixes were supplemented to add 0 (Con) or 0.2 mg/kg of Cr to the total diet on a DM basis. Cattle were fitted with jugular catheters on d 52. A glucose tolerance test (GTT) and an insulin sensitivity test (IST) were conducted on d 53. Blood samples were collected from -60 to 150 min relative to each infusion. Serum was isolated to determine glucose, insulin, and NEFA concentrations. Throughout GTT, no differences were detected in glucose concentrations, glucose clearance rates (k), or preinfusion insulin concentrations (P > 0.50), but insulin concentrations postinfusion tended (P = 0.06) to be greater for the Cr-supplemented steers. This caused an increase in the insulin to glucose ratio (I:G) from 0 to 150 min postinfusion for the Cr-supplemented steers (P = 0.03). In addition, NEFA concentrations during GTT were lower (P ≤ 0.01) for Cr-supplemented steers both preinfusion and postinfusion. During IST, there was no treatment effect on glucose concentrations preinfusion (P = 0.38), but postinfusion glucose concentrations were greater (P< 0.01) in the Cr-supplemented steers. The k of Cr-supplemented steers tended (P = 0.06) to be faster than Con steers from 30 to 45 min postinfusion. During the same test, there was no treatment effect detected for insulin concentrations (P > 0.33). The I:G were not affected by treatment (P > 0.40).Concentrations of NEFA were reduced (P < 0.01) both preinfusion and postinfusion during IST for Cr-supplemented steers. Results of this study indicate that supplementation of Cr can significantly alter lipid metabolism. This suggests that these steers had less dependence on lipid metabolism for energy or sensitivity of adipose tissue to antilipolytic signals was

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

    PubMed Central

    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

  11. Aerobic fitness does not modulate protein metabolism in response to increased exercise: a controlled trial

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Purpose: This study examined how a sudden increase in exercise energy expenditure affected whole body protein turnover and nitrogen balance in people of differing aerobic fitness. We hypothesized that whole-body protein turnover would be attenuated, and nitrogen balance would be preserved, in aerobi...

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

    SciTech Connect

    Bass, V.; Gordon, C.J.; Jarema, K.A.; MacPhail, R.C.; Cascio, W.E.; Phillips, P.M.; Ledbetter, A.D.; Schladweiler, M.C.; Andrews, D.; Miller, D.; Doerfler, D.L.; Kodavanti, U.P.

    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

  13. Assessment of metabolic status in young Japanese females using postprandial glucose and insulin levels

    PubMed Central

    Sakuma, Masae; Sasaki, Megumi; Katsuda, Sayaka; Kobayashi, Kana; Takaya, Chiaki; Umeda, Minako; Arai, Hidekazu

    2014-01-01

    Lifestyle-related diseases develop through the accumulation of undesirable lifestyle habits both prior to the onset of disease as well as during normal healthy life. Accordingly, early detection of, and intervention in, metabolic disorders is desirable, but is hampered by the lack of an established evaluation index for young individuals. The purpose of this study was to investigate the utility of a biomarker of health in young female subjects. The subjects were young healthy Japanese females in whom energy expenditure was measured for a period of 210 min after a test meal. In addition, Δplasma glucose and Δserum insulin were calculated from the fasting and 30 min values. ΔPlasma glucose and Δserum insulin levels varied widely compared to fasting levels. Both the area under the curve of carbohydrate oxidation rate and serum free fatty acid levels were higher in individuals in the high Δplasma glucose group. Moreover, Δplasma glucose was higher in individuals in the high Δserum insulin group than in the low Δserum insulin group. We conclude that nutritional balanced liquid loading test using Δplasma glucose and Δserum insulin as the evaluation index is useful for the detection of primary metabolic disorders in young females. PMID:24895484

  14. [Anthropometry at birth of the child of a mother with a change in glucose metabolism].

    PubMed

    Moreno-Ruiz, M E; Espinosa de los Monteros, A E; Peñuela-Olaya, M A

    1991-05-01

    The study compares 156 newborns whose mothers had an endocrinological diagnosis of various glucose metabolism disorders, and a control group of 42 newborn whose mothers had no glucose metabolism disorder. The entire sample including the control group had 98 males and 100 females. The study group with 156 newborns was divided into 4 groups, depending on the degree of the mother's disorder. In group 1, the baby's mothers suffered diabetes mellitus type 1; group 2, diabetes type 2; group 3, gestational diabetes; and group 4, pregnancy disorders of glucose. We observed that there were no differences among the groups in the weight/height ratio. Nevertheless there was great variability in the correlation between height and weight among the study groups. Multiplex box and whisker plots conform that intergroup dispersions in the weight height ratio was greater for the experimental group than for the control group. The pattern results was similar for the weight-head circumference ratio. We concluded that adequate control of glucose metabolism disorder during pregnancy results in product with normal growth indices.

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

    PubMed

    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.

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

    PubMed Central

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

    2015-01-01

    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. PMID:26375250

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

    PubMed

    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.

  18. Ozone induces glucose intolerance and systemic metabolic effects in young and aged Brown Norway rats.

    PubMed

    Bass, V; Gordon, C J; Jarema, K A; MacPhail, R C; Cascio, W E; Phillips, P M; Ledbetter, A D; Schladweiler, M C; Andrews, D; Miller, D; Doerfler, D L; Kodavanti, U P

    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 α2-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.

  19. Obesity-Related Hormones and Metabolic Risk Factors: A Randomized Trial of Diet plus Either Strength or Aerobic Training versus Diet Alone in Overweight Participants

    PubMed Central

    Geliebter, Allan; Ochner, Christopher N; Dambkowski, Carl L; Hashim, Sami A

    2014-01-01

    There is debate about the additive effects of exercise in conjunction with diet to treat obesity, and not much is known about the differential effects of strength versus aerobic training. This randomized controlled trial examined the effects of diet plus strength training, diet plus aerobic training, or diet only on metabolic risk factors associated with obesity. Eighty-one overweight and obese participants completed the 8-week intervention. All participants received an energy-restrictive formula diet with an energy content based on 70% of measured resting metabolic rate (RMR). Participants assigned to an exercise group trained 3 days/week under supervision. Anthropometrics and fasting hormones were assessed pre- and post-intervention. Mean weight loss (8.5 ± 4.3kg SD) did not differ between groups nor did reductions in BMI or body fat, although the diet plus strength training group showed marginally greater lean mass retention. There were significant improvements in the values and number of metabolic syndrome risk factors, and decreases in insulin concentrations and insulin resistance, which did not vary between groups. For men, testosterone increased significantly more in the diet plus aerobic training as compared to the other groups. As compared to diet alone, the addition of strength or aerobic training did not improve changes in BMI, body fat or metabolic risk factors although the diet plus strength training group showed a trend toward preservation of lean mass, and the diet plus aerobic group in men resulted in increased testosterone concentrations. PMID:25599089

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

    PubMed

    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.

  1. Impact of in vivo fatty acid oxidation blockade on glucose turnover and muscle glucose metabolism during low-dose AICAR infusion.

    PubMed

    Christopher, Michael; Rantzau, Christian; Chen, Zhi-Ping; Snow, Rodney; Kemp, Bruce; Alford, Frank P

    2006-11-01

    AMPK plays a central role in influencing fuel usage and selection. The aim of this study was to analyze the impact of low-dose AMP analog 5-aminoimidazole-4-carboxamide-1-beta-d-ribosyl monophosphate (ZMP) on whole body glucose turnover and skeletal muscle (SkM) glucose metabolism. Dogs were restudied after prior 48-h fatty acid oxidation (FA(OX)) blockade by methylpalmoxirate (MP; 5 x 12 hourly 10 mg/kg doses). During the basal equilibrium period (0-150 min), fasting dogs (n = 8) were infused with [3-(3)H]glucose followed by either 2-h saline or AICAR (1.5-2.0 mg x kg(-1) x min(-1)) infusions. SkM was biopsied at completion of each study. On a separate day, the same protocol was undertaken after 48-h in vivo FA(OX) blockade. The AICAR and AICAR + MP studies were repeated in three chronic alloxan-diabetic dogs. AICAR produced a transient fall in plasma glucose and increase in insulin and a small decline in free fatty acid (FFA). Parallel increases in hepatic glucose production (HGP), glucose disappearance (R(d tissue)), and glycolytic flux (GF) occurred, whereas metabolic clearance rate of glucose (MCR(g)) did not change significantly. Intracellular SkM glucose, glucose 6-phosphate, and glycogen were unchanged. Acetyl-CoA carboxylase (ACC approximately pSer(221)) increased by 50%. In the AICAR + MP studies, the metabolic responses were modified: the glucose was lower over 120 min, only minor changes occurred with insulin and FFA, and HGP and R(d tissue) responses were markedly attenuated, but MCR(g) and GF increased significantly. SkM substrates were unchanged, but ACC approximately pSer(221) rose by 80%. Thus low-dose AICAR leads to increases in HGP and SkM glucose uptake, which are modified by prior FA(ox) blockade.

  2. A Kinetic Model of Whole-Body Glucose Metabolism with Reference to the Domestic Dog (Canis lupus familiaris)

    PubMed Central

    McKnight, Leslie L.; Shoveller, Anna K.; Lopez, Secundino

    2015-01-01

    A new two-pool model to describe glucose kinetics in the steady state is presented. The pools are plasma glucose, Q1, and tissue glucose, Q2 (both µmol). The flows (all µmol/min) into the plasma pool (Pool 1) are absorbed glucose entry from dietary sources, labelled glucose infusion, and hepatic glucose production. There is one flow out of Pool 1, glucose uptake by the tissues. Inflows to the tissues pool (Pool 2) are from plasma and glycogenolysis. Outflows from Pool 2 are to plasma, glucose oxidation, and glycogenesis and other metabolism. Application of the model was illustrated using experimental data derived from healthy adult Labrador Retrievers in the fasted and fed (repeated meal feeding) states. In general, model derived estimates of glucose kinetics were representative of normal glucose metabolism, where rates of glucose production and uptake are similar and act to maintain blood glucose concentrations. Furthermore, estimates of within tissue glucose cycling indicated glycogenolysis in fasting and glycogenesis when fed. In the fasted state, model outputs were consistent with those reported in the canine literature derived using a single pool model. PMID:27347515

  3. A Kinetic Model of Whole-Body Glucose Metabolism with Reference to the Domestic Dog (Canis lupus familiaris).

    PubMed

    McKnight, Leslie L; Shoveller, Anna K; Lopez, Secundino; France, James

    2015-01-01

    A new two-pool model to describe glucose kinetics in the steady state is presented. The pools are plasma glucose, Q 1, and tissue glucose, Q 2 (both µmol). The flows (all µmol/min) into the plasma pool (Pool 1) are absorbed glucose entry from dietary sources, labelled glucose infusion, and hepatic glucose production. There is one flow out of Pool 1, glucose uptake by the tissues. Inflows to the tissues pool (Pool 2) are from plasma and glycogenolysis. Outflows from Pool 2 are to plasma, glucose oxidation, and glycogenesis and other metabolism. Application of the model was illustrated using experimental data derived from healthy adult Labrador Retrievers in the fasted and fed (repeated meal feeding) states. In general, model derived estimates of glucose kinetics were representative of normal glucose metabolism, where rates of glucose production and uptake are similar and act to maintain blood glucose concentrations. Furthermore, estimates of within tissue glucose cycling indicated glycogenolysis in fasting and glycogenesis when fed. In the fasted state, model outputs were consistent with those reported in the canine literature derived using a single pool model.

  4. Prenatal Exposures to Multiple Thyroid Hormone Disruptors: Effects on Glucose and Lipid Metabolism

    PubMed Central

    Molehin, Deborah

    2016-01-01

    Background. Thyroid hormones (THs) are essential for normal human fetal development and play a major role in the regulation of glucose and lipid metabolism. Delivery of TH to target tissues is dependent on processes including TH synthesis, transport, and metabolism. Thyroid hormone endocrine disruptors (TH-EDCs) are chemical substances that interfere with these processes, potentially leading to adverse pregnancy outcomes. Objectives. This review focuses on the effects of prenatal exposures to combinations of TH-EDCs on fetal and neonatal glucose and lipid metabolism and also discusses the various mechanisms by which TH-EDCs interfere with other hormonal pathways. Methods. We conducted a comprehensive narrative review on the effects of TH-EDCs with particular emphasis on exposure during pregnancy. Discussion. TH imbalance has been linked to many metabolic processes and the effects of TH imbalance are particularly pronounced in early fetal development due to fetal dependence on maternal TH for proper growth and development. The pervasive presence of EDCs in the environment results in ubiquitous exposure to either single or mixtures of EDCs with deleterious effects on metabolism. Conclusions. Further evaluation of combined effects of TH-EDCs on fetal metabolic endpoints could improve advice provided to expectant mothers. PMID:26989557

  5. Sleep Disturbances and Glucose Metabolism in Older Adults: The Cardiovascular Health Study

    PubMed Central

    Carnethon, Mercedes; Biggs, Mary Lou; Djoussé, Luc; Kaplan, Robert C.; Siscovick, David S.; 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 1989–1994. In 1989–1990, participants underwent an oral glucose tolerance test, from which insulin secretion and insulin sensitivity were estimated. Fasting glucose levels were measured in 1989–1990 and again in 1992–1993, 1994–1995, 1996–1997, and 1998–1999, and medication use was ascertained yearly. We determined the cross-sectional associations of sleep symptoms with fasting glucose levels, 2-h glucose levels, insulin sensitivity, and insulin secretion using generalized estimated equations and linear regression models. We determined the associations of updated and averaged sleep symptoms with incident diabetes in Cox proportional hazards models. We adjusted for sociodemographics, lifestyle factors, and medical history. RESULTS Observed apnea, snoring, and daytime sleepiness were associated with higher fasting glucose levels, higher 2-h glucose levels, lower insulin sensitivity, and higher insulin secretion. The risk of the development of type 2 diabetes was positively associated with observed apnea (hazard ratio [HR] 1.84 [95% CI 1.19–2.86]), snoring (HR 1.27 [95% CI 0.95–1.71]), and daytime sleepiness (HR 1.54 [95% CI 1.13–2.12]). In contrast, we did not find consistent associations between insomnia symptoms and glucose metabolism or incident type 2 diabetes. CONCLUSIONS Easily collected symptoms of SDB are strongly associated with insulin resistance and the incidence of type 2 diabetes in older adults. Monitoring glucose metabolism in such patients may

  6. Preserved pontine glucose metabolism in Alzheimer disease: A reference region for functional brain image (PET) analysis

    SciTech Connect

    Minoshima, Satoshi; Frey, K.A.; Foster, N.L.; Kuhl, D.W.

    1995-07-01

    Our goal was to examine regional preservation of energy metabolism in Alzheimer disease (AD) and to evaluate effects of PET data normalization to reference regions. Regional metabolic rates in the pons, thalamus, putamen, sensorimotor cortex, visual cortex, and cerebellum (reference regions) were determined stereotaxically and examined in 37 patients with probable AD and 22 normal controls based on quantitative {sup 18}FDG-PET measurements. Following normalization of metabolic rates of the parietotemporal association cortex and whole brain to each reference region, distinctions of the two groups were assessed. The pons showed the best preservation of glucose metabolism in AD. Other reference regions showed relatively preserved metabolism compared with the parietotemporal association cortex and whole brain, but had significant metabolic reduction. Data normalization to the pons not only enhanced statistical significance of metabolic reduction in the parietotemporal association cortex, but also preserved the presence of global cerebral metabolic reduction indicated in analysis of the quantitative data. Energy metabolism in the pons in probable AD is well preserved. The pons is a reliable reference for data normalization and will enhance diagnostic accuracy and efficiency of quantitative and nonquantitative functional brain imaging. 39 refs., 2 figs., 3 tabs.

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

    PubMed Central

    Nakagawa, Gen; Kouzuma, Atsushi; Hirose, Atsumi; Kasai, Takuya; Yoshida, Gen; Watanabe, Kazuya

    2015-01-01

    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. PMID:26394222

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

    PubMed

    Nakagawa, Gen; Kouzuma, Atsushi; Hirose, Atsumi; Kasai, Takuya; Yoshida, Gen; Watanabe, Kazuya

    2015-01-01

    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.

  9. Profiling human gut bacterial metabolism and its kinetics using [U-13C]glucose and NMR.

    PubMed

    de Graaf, Albert A; Maathuis, Annet; de Waard, Pieter; Deutz, Nicolaas E P; Dijkema, Cor; de Vos, Willem M; Venema, Koen

    2010-01-01

    This study introduces a stable-isotope metabolic approach employing [U-(13)C]glucose that, as a novelty, allows selective profiling of the human intestinal microbial metabolic products of carbohydrate food components, as well as the measurement of the kinetics of their formation pathways, in a single experiment. A well-established, validated in vitro model of human intestinal fermentation was inoculated with standardized gastrointestinal microbiota from volunteers. After culture stabilization, [U-(13)C]glucose was added as an isotopically labeled metabolic precursor. System lumen and dialysate samples were taken at regular intervals. Metabolite concentrations and isotopic labeling were determined by NMR, GC, and enzymatic methods. The main microbial metabolites were lactate, acetate, butyrate, formate, ethanol, and glycerol. They together accounted for a (13)C recovery rate as high as 91.2%. Using an NMR chemical shift prediction approach, several minor products that showed (13)C incorporation were identified as organic acids, amino acids, and various alcohols. Using computer modeling of the (12)C contents and (13)C labeling kinetics, the metabolic fluxes in the gut microbial pathways for synthesis of lactate, formate, acetate, and butyrate were determined separately for glucose and unlabeled background substrates. This novel approach enables the study of the modulation of human intestinal function by single nutrients, providing a new rational basis for achieving control of the short-chain fatty acids profile by manipulating substrate and microbiota composition in a purposeful manner.

  10. Exercise effects on postprandial glucose metabolism in type 1 diabetes: a triple-tracer approach.

    PubMed

    Mallad, Ashwini; Hinshaw, Ling; Schiavon, Michele; Dalla Man, Chiara; Dadlani, Vikash; Basu, Rita; Lingineni, Ravi; Cobelli, Claudio; Johnson, Matthew L; Carter, Rickey; Kudva, Yogish C; Basu, Ananda

    2015-06-15

    To determine the effects of exercise on postprandial glucose metabolism and insulin action in type 1 diabetes (T1D), we applied the triple tracer technique to study 16 T1D subjects on insulin pump therapy before, during, and after 75 min of moderate-intensity exercise (50% V̇o2max) that started 120 min after a mixed meal containing 75 g of labeled glucose. Prandial insulin bolus was administered as per each subject's customary insulin/carbohydrate ratio adjusted for meal time meter glucose and the level of physical activity. Basal insulin infusion rates were not altered. There were no episodes of hypoglycemia during the study. Plasma dopamine and norepinephrine concentrations rose during exercise. During exercise, rates of endogenous glucose production rose rapidly to baseline levels despite high circulating insulin and glucose concentrations. Interestingly, plasma insulin concentrations increased during exercise despite no changes in insulin pump infusion rates, implying increased mobilization of insulin from subcutaneous depots. Glucagon concentrations rose before and during exercise. Therapeutic approaches for T1D management during exercise will need to account for its effects on glucose turnover, insulin mobilization, glucagon, and sympathetic response and possibly other blood-borne feedback and afferent reflex mechanisms to improve both hypoglycemia and hyperglycemia.

  11. New data and concepts on glutamine and glucose metabolism in the gut.

    PubMed

    Mithieux, G

    2001-07-01

    Both glutamine and glucose are highly utilized by the small intestine in various animal species. They are, however, very partially oxidized, the major known fate of glucose being lactate and alanine, and that of glutamine being citrulline or proline. At variance with the current view that only the liver and kidney are gluconeogenic organs, because both are the only tissues to express the glucose-6 phosphatase gene, this gene is also expressed in the small intestine in rats and humans, and is strongly induced in insulinopenic states, such as fasting and diabetes. Under the latter conditions, the small intestine contributes 20-25% of whole-body endogenous glucose production. The main small intestine gluconeogenic substrate is glutamine and, to a lesser extent, glycerol. Accounting for these fluxes, the phosphoenolpyruvate carboxykinase gene is strongly induced in insulinopenia and, although up to now it had been considered absent from this tissue, the glycerokinase gene is expressed in the small intestine. The production of glucose by the small intestine may be acutely blunted upon insulin infusion. These new data also emphasize the central role of alanine aminotransferase in the coupling of glutamine and glucose metabolisms in the small intestine.

  12. Effect of a deacyl gymnemic acid on glucose homeostasis & metabolic parameters in a rat model of metabolic syndrome

    PubMed Central

    Bhansali, Shobhit; Shafiq, Nusrat; Pandhi, Promila; Singh, Amrit Pal; Singh, Inderjeet; Singh, Pawan Kumar; Sharma, Sadhna; Malhotra, Samir

    2013-01-01

    Background & objectives: Metabolic syndrome (MS) comprises several cardio-metabolic risk factors, which include obesity, hypertension, hyperglycaemia, hypertriglyceridaemia and decreased HDL cholesterol. Leaf extract of Gymnema sylvestre has been shown to possess glucose lowering activity in animal models. This study was carried out to evaluate the efficacy of deacyl gymnemic acid (DAGA), active constituent of G. sylvestre, in a rat model of MS. Methods: Six groups consisting of six wistar rats in each, were studied. Group I received the normal diet, while the remaining five groups received high fructose diet (HFD) for 20 days to induce MS. HFD was continued in these five groups for the next 20 days along with group II received vehicle solution, group III received pioglitazone and groups IV- VI received DAGA in variable doses. Systolic blood pressure (SBP) was measured using tail-cuff method. Oral glucose tolerance test (OGTT) was done at baseline and at days 20 and 40. Blood samples were collected for glucose, insulin and lipid profile. Results: Administration of HFD for 20 days resulted in weight gain (>10%), increase in SBP, fasting plasma glucose (FPG) and triglycerides fulfilling the criteria for MS. Administration of DAGA (200 mg/kg) reduced SBP and significantly improved the FPG and HOMA-IR (homeostatis model assessment-insulin resistance) with modest improvement in lipid profile without decrease in body weight similar to pioglitazone. Interpretation & conclusions: Our findings show that DAGA decreases SBP and improves parameters of glucose-insulin homeostasis in a rat model of MS induced by HFD. Further studies are required to elucidate the mechanism of action. PMID:23852298

  13. Metabolic fate of glucose and candidate signaling and excess-fuel detoxification pathways in pancreatic β-cells.

    PubMed

    Mugabo, Yves; Zhao, Shangang; Lamontagne, Julien; Al-Mass, Anfal; Peyot, Marie-Line; Corkey, Barbara E; Joly, Erik; Madiraju, S R Murthy; Prentki, Marc

    2017-03-09

    Glucose metabolism promotes insulin secretion in β-cells via metabolic coupling factors that are incompletely defined. Moreover, chronically elevated glucose causes β-cell dysfunction, but little is known about how cells handle excess fuels to avoid toxicity. Here we sought to determine which among the candidate pathways and coupling factors best correlates with glucose-stimulated insulin secretion (GSIS), define the fate of glucose in the β-cell, and identify pathways possibly involved in excess-fuel detoxification. We exposed isolated rat islets for 1 h to increasing glucose concentrations and measured various pathways and metabolites. Glucose oxidation, oxygen consumption, and ATP production correlated well with GSIS and saturated at 16 mM glucose. However, glucose utilization, glycerol release, triglyceride and glycogen contents, free fatty acid (FFA) content and release, and cholesterol and cholesterol esters increased linearly up to 25 mM glucose. Besides being oxidized, glucose was mainly metabolized via glycerol production and release and lipid synthesis (particularly FFA, triglycerides, and cholesterol), whereas glycogen production was comparatively low. Using targeted metabolomics in INS-1(832/13) cells, we found that several metabolites correlated well with GSIS, in particular, some Krebs cycle intermediates, malonyl-CoA, and lower ADP levels. Glucose dose dependently increased the dihydroxyacetone phosphate/glycerol 3-phosphate ratio in INS1(832/13) cells, indicating a more oxidized state of NAD in the cytosol upon glucose stimulation. Overall, the data support a role for accelerated oxidative mitochondrial metabolism, anaplerosis, and malonyl-CoA/lipid signaling in β-cell metabolic signaling and suggest that a decrease in ADP levels is important in GSIS. The results also suggest that excess-fuel detoxification pathways in β-cells possibly comprise glycerol and FFA formation and release extracellularly and the diversion of glucose carbons to

  14. Association between Glucose Metabolism and Sleep-disordered Breathing during REM Sleep

    PubMed Central

    Gottlieb, Daniel J.; Redline, Susan; Punjabi, Naresh M.

    2015-01-01

    Rationale: Sleep-disordered breathing (SDB) has been associated with impaired glucose metabolism. It is possible that the association between SDB and glucose metabolism is distinct for non-REM versus REM sleep because of differences in sleep-state–dependent sympathetic activation and/or degree of hypoxemia. Objectives: To characterize the association between REM-related SDB, glucose intolerance, and insulin resistance in a community-based sample. Methods: A cross-sectional analysis that included 3,310 participants from the Sleep Heart Health Study was undertaken (53% female; mean age, 66.1 yr). Full montage home-polysomnography and fasting glucose were available on all participants. SDB severity during REM and non-REM sleep was quantified using the apnea–hypopnea index in REM (AHIREM) and non-REM sleep (AHINREM), respectively. Fasting and 2-hour post-challenge glucose levels were assessed during a glucose tolerance test (n = 2,264). The homeostatic model assessment index for insulin resistance (HOMA-IR) was calculated (n = 1,543). Linear regression was used to assess the associations of AHIREM and AHINREM with fasting and post-prandial glucose levels and HOMA-IR. Measurements and Main Results: AHIREM and AHINREM were associated with fasting glycemia, post-prandial glucose levels, and HOMA-IR in models that adjusted for age, sex, race, and site. However, with additional adjustment for body mass index, waist circumference, and sleep duration, AHIREM was only associated with HOMA-IR (β = 0.04; 95% CI, 0.1–0.07; P = 0.01), whereas AHINREM was only associated with fasting (β = 0.93; 95% CI, 0.14–1.72; P = 0.02) and post-prandial glucose levels (β = 3.0; 95% CI, 0.5–5.5; P = 0.02). Conclusions: AHIREM is associated with insulin resistance but not with fasting glycemia or glucose intolerance. PMID:26200994

  15. Effect of dietary chromium-L-methionine on glucose metabolism of beef steers.

    PubMed

    Kegley, E B; Galloway, D L; Fakler, T M

    2000-12-01

    Thirty-six crossbred steers (288 +/- 3.7 kg initial BW) were used to determine the effect of Cr, as chromium-L-methionine, on glucose tolerance and insulin sensitivity in beef calves. Calves were fed a control diet or the diet supplemented with 400 or 800 microg Cr/kg of diet as chromium-L-methionine. Calves were kept in drylots (six calves/pen; two pens/dietary treatment). Steers were caught twice a day in locking headgates and individually fed their respective diets for a period of 22, 23, or 24 d prior to the metabolic challenges. Calves received a totally mixed diet containing 54% corn, 38% cottonseed hulls, and 5% soybean meal. On d 21, 22, and 23, four calves/dietary treatment were fitted with an indwelling jugular catheter. Approximately 24 h after catheterization, an intravenous glucose tolerance test (500 mg glucose/kg of BW), followed 5 h later by an intravenous insulin challenge test (0.1 IU insulin/kg of BW), was conducted. There was no effect (P > 0.10) of dietary treatment on ADG or ADFI. During the intravenous glucose tolerance test, serum insulin concentrations were increased by supplemental chromium-L-methionine (linear effect of Cr, P < 0.05). There was a time x treatment interaction (P < 0.05) on plasma glucose concentrations after the glucose infusion. Plasma glucose concentrations of calves fed 400 microg Cr/kg of diet were lower than those of controls and calves supplemented with 800 microg Cr/kg of diet (quadratic effect of Cr, P < 0.05) 5 and 10 min after the glucose infusion. Supplemental chromium-L-methionine increased the glucose clearance rate from 5 to 10 min after the insulin challenge test (linear effect of Cr, P < 0.05). Glucose half-life from 5 to 10 min after the insulin infusion was also decreased by supplemental chromium-L-methionine (linear effect of Cr, P < 0.10). These data indicate that supplemental Cr, as chromium-L-methionine, increased glucose clearance rate after an insulin infusion and increased the insulin response to

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

    PubMed Central

    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

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

    PubMed

    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.

  18. Acute effect of antidiabetic 1,4-dihydropyridine compound cerebrocrast on cardiac function and glucose metabolism in the isolated, perfused normal rat heart.

    PubMed

    Briede, Janina; Stivrina, Mara; Vigante, Brigita; Stoldere, Dzintra; Duburs, Gunars

    2008-01-01

    Diabetes mellitus (DM) is an important cardiovascular risk factor and is associated with abnormalities in endothelial and vascular smooth muscle cell function, evoked by chronic hyperglycemia and hyperlipidemia. Chronic insulin deficiency or resistance is marked by decreases in the intensity of glucose transport, glucose phosphorylation, and glucose oxidation, plus decreases in ATP levels in cardiac myocytes. It is important to search for new agents that promote glucose consumption in the heart and partially inhibit extensive fatty acid beta-oxidation observed in diabetic, ischemia. When the oxygen supply for myocardium is decreased, the heart accumulates potentially toxic intermediates of fatty acid beta-oxidation, that is, long-chain acylcarnitine and long-chain acyl-CoA metabolites. Exogenous glucose and heart glycogen become an important compensatory source of energy. Therefore we studied the effect of the antidiabetic 1,4-dihydropyridine compound cerebrocrast at concentrations from 10(-10) M to 10(-7) M on isolated rat hearts using the method of Langendorff, on physiological parameters and energy metabolism. Cerebrocrast at concentrations from 10(-10) M to 10(-7) M has a negative inotropic effect on the rat heart. It inhibits L-type Ca(2+)channels thereby diminishing the cellular Ca(2+) supply, reducing contractile activity, and oxygen consumption, that normally favors enhanced glucose uptake, metabolism, and production of high-energy phosphates (ATP content) in myocardium. Cerebrocrast decreases heart rate and left ventricular (LV) systolic pressure; at concentrations of 10(-10) M and 10(-9) M it evokes short-term vasodilatation of coronary arteries. Increase of ATP content in the myocytes induced by cerebrocrast has a ubiquitous role. It can preserve the integrity of the cell plasma membranes, maintain normal cellular function, and inhibit release of lactate dehydrogenase (LDH) from cells that is associated with diabetes and heart ischemia. Administration of

  19. Sudachitin, a polymethoxylated flavone, improves glucose and lipid metabolism by increasing mitochondrial biogenesis in skeletal muscle

    PubMed Central

    2014-01-01

    Background Obesity is a major risk factor for insulin resistance, type 2 diabetes, and stroke. Flavonoids are effective antioxidants that protect against these chronic diseases. In this study, we evaluated the effects of sudachitin, a polymethoxylated flavonoid found in the skin of the Citrus sudachi fruit, on glucose, lipid, and energy metabolism in mice with high-fat diet-induced obesity and db/db diabetic mice. In our current study, we show that sudachitin improves metabolism and stimulates mitochondrial biogenesis, thereby increasing energy expenditure and reducing weight gain. Methods C57BL/6 J mice fed a high-fat diet (40% fat) and db/db mice fed a normal diet were treated orally with 5 mg/kg sudachitin or vehicle for 12 weeks. Following treatment, oxygen expenditure was assessed using indirect calorimetry, while glucose tolerance, insulin sensitivity, and indices of dyslipidemia were assessed by serum biochemistry. Quantitative polymerase chain reaction was used to determine the effect of sudachitin on the transcription of key metabolism-regulating genes in the skeletal muscle, liver, and white and brown adipose tissues. Primary myocytes were also prepared to examine the signaling mechanisms targeted by sudachitin in vitro. Results Sudachitin improved dyslipidemia, as evidenced by reduction in triglyceride and free fatty acid levels, and improved glucose tolerance and insulin resistance. It also enhanced energy expenditure and fatty acid β-oxidation by increasing mitochondrial biogenesis and function. The in vitro assay results suggest that sudachitin increased Sirt1 and PGC-1α expression in the skeletal muscle. Conclusions Sudachitin may improve dyslipidemia and metabolic syndrome by improving energy metabolism. Furthermore, it also induces mitochondrial biogenesis to protect against metabolic disorders. PMID:25114710

  20. Muscle-specific deletion of carnitine acetyltransferase compromises glucose tolerance and metabolic flexibility.

    PubMed

    Muoio, Deborah M; Noland, Robert C; Kovalik, Jean-Paul; Seiler, Sarah E; Davies, Michael N; DeBalsi, Karen L; Ilkayeva, Olga R; Stevens, Robert D; Kheterpal, Indu; Zhang, Jingying; Covington, Jeffrey D; Bajpeyi, Sudip; Ravussin, Eric; Kraus, William; Koves, Timothy R; Mynatt, Randall L

    2012-05-02

    The concept of "metabolic inflexibility" was first introduced to describe the failure of insulin-resistant human subjects to appropriately adjust mitochondrial fuel selection in response to nutritional cues. This phenomenon has since gained increasing recognition as a core component of the metabolic syndrome, but the underlying mechanisms have remained elusive. Here, we identify an essential role for the mitochondrial matrix enzyme, carnitine acetyltransferase (CrAT), in regulating substrate switching and glucose tolerance. By converting acetyl-CoA to its membrane permeant acetylcarnitine ester, CrAT regulates mitochondrial and intracellular carbon trafficking. Studies in muscle-specific Crat knockout mice, primary human skeletal myocytes, and human subjects undergoing L-carnitine supplementation support a model wherein CrAT combats nutrient stress, promotes metabolic flexibility, and enhances insulin action by permitting mitochondrial efflux of excess acetyl moieties that otherwise inhibit key regulatory enzymes such as pyruvate dehydrogenase. These findings offer therapeutically relevant insights into the molecular basis of metabolic inflexibility.

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

    NASA Astrophysics Data System (ADS)

    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.

  2. Molybdate and tungstate act like vanadate on glucose metabolism in isolated hepatocytes.

    PubMed Central

    Fillat, C; Rodríguez-Gil, J E; Guinovart, J J

    1992-01-01

    In rat hepatocytes, molybdate and tungstate inactivate glycogen synthase by a mechanism independent of Ca2+ and activate glycogen phosphorylase by a Ca(2+)-dependent mechanism. On the other hand, both molybdate and tungstate increase fructose 2,6-bisphosphate levels and counteract the decrease in this metabolite induced by glucagon. These effectors do not directly modify 6-phosphofructo-2-kinase activity, even though they partially counteract the inactivation of this enzyme induced by glucagon. These effects are related to an increase on the glycolytic flux, as indicated by the increase in L-lactate and CO2 production and the decrease in glucose 6-phosphate levels in the presence of glucose. All these effects are similar to those previously reported for vanadate, although molybdate and tungstate are less effective than vanadate. These results could indicate that molybdate, tungstate and vanadate act on glucose metabolism in isolated hepatocytes by a similar mechanism of action. PMID:1313228

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

    PubMed

    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.

  4. Selective and Efficient Elimination of Vibrio cholerae with a Chemical Modulator that Targets Glucose Metabolism

    PubMed Central

    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

  5. [The synergistic effect of FGF-21 and insulin on regulating glucose metabolism and its mechanism].

    PubMed

    Yu, Dan; Sun, Cui-Yu; Sun, Guo-Peng; Ren, Gui-Ping; Ye, Xian-Long; Zhu, Sheng-Long; Wang, Wen-Fei; Xu, Peng-Fei; Li, Shu-Jie; Wu, Qiang; Niu, Ze-Shan; Sun, Tian; Liu, Ming-Yao; Li, De-Shan

    2014-07-01

    Previous studies proposed that the synergistic effect of fibroblast growth factor-21 (FGF-21) and insulin may be due to the improvement of insulin sensitivity by FGF-21. However, there is no experimental evidence to support this. This study was designed to elucidate the mechanism of synergistic effect of FGF-21 and insulin in the regulation of glucose metabolism. The synergistic effect of FGF-21 and insulin on regulating glucose metabolism was demonstrated by investigating the glucose absorption rate by insulin resistance HepG2 cell model and the blood glucose chances in type 2 diabetic db/db mice after treatments with different concentrations of FGF-21 or/and insulin; The synergistic metabolism was revealed through detecting GLUT1 and GLUT4 transcription levels in the liver by real-time PCR method. The experimental results showed that FGF-21 and insulin have a synergistic effect on the regulation of glucose metabolism. The results of real-time PCR showed that the effective dose of FGF-21 could up-regulate the transcription level of GLUT1 in a dose-dependent manner, but had no effect on the transcription level of GLUT4. Insulin (4 u) alone could up-regulate the transcription level of GLUT4, yet had no effect on that of GLUT1. Ineffective dose 0.1 mg kg(-1) FGF-21 alone could not change the transcription level of GLUT1 or GLUT4. However, when the ineffective dose 0.1 mg x kg(-1) FGF-21 was used in combination with insulin (4 u) significantly increased the transcription levels of both GLUT1 and GLUT4, the transcription level of GLUT1 was similar to that treated with 5 time concentration of FGF-21 alone; the transcription level of GLUT4 is higher than that treated with insulin (4 u) alone. In summary, in the presence of FGF-21, insulin increases the sensitivity of FGF-21 through enhancing GLUT1 transcription. Vice versa, FGF-21 increases the sensitivity of insulin by stimulating GLUT4 transcription in the presence of insulin. FGF-21 and insulin exert a synergistic

  6. [The evolutionary anthropometric profile of the child of a mother with a change in glucose metabolism].

    PubMed

    Moreno-Ruiz, M E; Espinoza de los Monteros, A E; Peñuela-Olaya, M A

    1991-05-01

    There is not sufficient information about the follow up of children belonging to mothers with some degree of glucose metabolism disorder. At The National Institute of Perinatology were studied 151 newborn. The babies were divided into four groups. The group 1 consisting of babies born from mothers with diabetes mellitus type I; group 2 of babies born from mothers with diabetes mellitus type II; group 3 including babies from mother with gestational diabetes and group 4 babies from mothers who presented alteration in glucose metabolism during pregnancy. After the evaluation of the somatic indicator we found an harmonic behavior in group 3 in weight, height and head circumference again. The most important finding was the low correlation in anthropometry at birth and one year of age. Finally we conclude that a strict control on the follow-up of the somatic growth of children, must be achieved because the hypertrophy during the first year of age depends on sociocultural and economic patterns.

  7. [Comparative characteristics of glucose metabolism in the liver of rats under acute alcohol and morphine intoxication].

    PubMed

    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.

  8. [Study of regional cerebral glucose metabolism, in man, while awake or asleep, by positron emission tomography].

    PubMed

    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.

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

    PubMed

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

    2015-12-01

    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.

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

    PubMed Central

    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

  11. Type 2 Diabetes and Breast Cancer: The Interplay between Impaired Glucose Metabolism and Oxidant Stress

    PubMed Central

    Ferroni, Patrizia; Riondino, Silvia; Buonomo, Oreste; Palmirotta, Raffaele; Guadagni, Fiorella; Roselli, Mario

    2015-01-01

    Metabolic disorders, especially type 2 diabetes and its associated complications, represent a growing public health problem. Epidemiological findings indicate a close relationship between diabetes and many types of cancer (including breast cancer risk), which regards not only the dysmetabolic condition, but also its underlying risk factors and therapeutic interventions. This review discusses the advances in understanding of the mechanisms linking metabolic disorders and breast cancer. Among the proposed mechanisms to explain such an association, a major role is played by the dysregulated glucose metabolism, which concurs with a chronic proinflammatory condition and an associated oxidative stress to promote tumour initiation and progression. As regards the altered glucose metabolism, hyperinsulinaemia, both endogenous due to insulin-resistance and drug-induced, appears to promote tumour cell growth through the involvement of innate immune activation, platelet activation, increased reactive oxygen species, exposure to protumorigenic and proangiogenic cytokines, and increased substrate availability to neoplastic cells. In this context, understanding the relationship between metabolic disorders and cancer is becoming imperative, and an accurate analysis of these associations could be used to identify biomarkers able to predict disease risk and/or prognosis and to help in the choice of proper evidence-based diagnostic and therapeutic protocols. PMID:26171112

  12. Bed Rest Worsens Impairments in Fat and Glucose Metabolism in Older, Overweight Adults

    PubMed Central

    2014-01-01

    Background. The effects of bed rest on the dysregulation of fatty acid and glucose metabolism have not been addressed in the older population. Objective. We examined the effect of 10 days of bed rest on fatty acid kinetics and hepatic and peripheral insulin resistance in aging. Methods. We utilized an octreotide, basal glucagon replacement, multistage insulin infusion, and the concomitant infusion of [6,6 2H2]glucose to derive insulin-mediated suppression of glucose production and insulin-stimulated glucose disposal in nine older, overweight individuals (body mass index 28.1 ± 1.7 kg m−2; 39.9% ± 1.9% fat). During the multistage insulin infusion, we also infused [1-13C]palmitate to examine free fatty acid rate of appearance (R a). Results. Body weight, % body fat, and energy metabolism did not change with bed rest. There was a significant decrease (−2291 ± 316cm3) in visceral fat, and no change in abdominal subcutaneous fat with bed rest. Insulin-mediated suppression of glucose production was modest prior to bed rest and was further reduced (>15% ± 2%) by bed rest. There was also a minor decrease in the insulin-mediated suppression of free fatty acid R a after bed rest and, as a consequence, a small variation in plasma free fatty acid from pre- to post-bed rest in the first stage of the multistage insulin infusion. There was also a significant bed rest–induced decline (>2.0 ± 0.6 mg kg FFM−1 min− 1) in insulin-stimulated glucose disposal. Conclusions. Preexisting impairments in insulin sensitivity are worsened by bed rest and seem linked to alterations in the regulation of free fatty acid in older, overweight individuals. PMID:23902932

  13. Ameliorating effect of chromium administration on hepatic glucose metabolism in streptozotocin-induced experimental diabetes.

    PubMed

    Sundaram, Bhuvaneshwari; Singhal, Kirti; Sandhir, Rajat

    2012-01-01

    Chromium has been recognized as an essential trace element that plays an important role in carbohydrate metabolism. However, the molecular mechanisms involved in its action are not clear. This study was undertaken to understand the mechanism of chromium action in experimental diabetes. Streptozotocin-induced diabetic animals were administered chromium as chromium picolinate (CrP) at a daily dose of 1 mg/kg body weight for a period of 4 weeks. It was observed that chromium complexed with picolinate was effective in lowering plasma glucose levels as well as was able to alleviate polyphagia, polydipsia, and weight loss in diabetic animals. Administration of chromium was also found to normalize glycogen content in liver of diabetic animals to near control levels. The reduction in plasma glucose levels by chromium was accompanied by increase in activity of glycolytic enzymes (e.g., glucokinase, phosphofructokinase, and pyruvate kinase) and by suppression in activity of gluconeogenic enzymes (e.g., glucose-6-phosphatase and phosphoenolpyruvate carboxykinase) in liver. Hepatic glucose uptake was found to be increased by chromium supplementation as demonstrated by decrease in Km and increase in Vmax values in diabetic animals. Chromium levels were lower in the liver of diabetic rats when compared with that of control rats. A negative correlation was observed between plasma glucose and chromium concentration in patients with diabetes. The data suggests that chromium supplementation as CrP is beneficial in correcting hyperglycemia, implying that the modulation of the glucose metabolism by chromium may be therapeutically beneficial in the treatment of diabetes.

  14. Glycogen storage disease type Ia: linkage of glucose, glycogen, lactic acid, triglyceride, and uric acid metabolism.

    PubMed

    Sever, Sakine; Weinstein, David A; Wolfsdorf, Joseph I; Gedik, Reyhan; Schaefer, Ernst J

    2012-01-01

    A female presented in infancy with hypotonia, undetectable serum glucose, lactic acidosis, and triglycerides >5000 mg/dL. The diagnosis of type 1A glycogen storage disease was made via the result of a liver biopsy, which showed increased glycogen and absent glucose-6-phosphatase enzyme activity. The patient was treated with dextrose administered orally, which was replaced by frequent feedings of cornstarch, which resulted in an improvement of her metabolic parameters. At age 18 years of age, she had marked hypertriglyceridemia (3860 mg/dL) and eruptive xanthomas and was treated with fenofibrate, atorvastatin, and fish oil. At age 29 years she was noted to have multiple liver adenomas, severe anemia, and hyperuricemia. Aggressive cornstarch therapy was commenced with a goal of maintaining her blood glucose levels >75 mg/dL and lactate levels <2 mmol/L. After 15 months on this regimen, her lipids levels (measured in mg/dL) off all medications were as follows: total cholesterol 222, triglycerides 179, high-density lipoprotein cholesterol 32, and calculated low-density lipoprotein cholesterol 154. Her weight was stable with a body mass index of 24.8 kg/m(2). Her liver adenomas had decreased in size, and her anemia and hyperuricemia had improved. She was homozygous for the R83C missense mutation in G6PC. Our data indicate that optimized metabolic control to maintain blood glucose levels >75 mg/dL is critical in the management of this disease.

  15. Effects of chronic noise on glucose metabolism and gut microbiota–host inflammatory homeostasis in rats

    PubMed Central

    Cui, Bo; Gai, Zhihui; She, Xiaojun; Wang, Rui; Xi, Zhuge

    2016-01-01

    Chronic noise exposure has been implicated in increased risk of diabetes. However, there is limited experimental evidence of the mechanisms linking chronic noise stress and glucose metabolism. We addressed this in the present study by examining glucose metabolism, immune response, and changes in gut microbiota/host inflammatory homeostasis in rats exposed to noise for 30 consecutive days. Chronic noise exposure increased blood glucose and corticosterone levels for at least 14 days after cessation of noise. Stressed rats also exhibited elevated levels of glycogen and triglyceride in the liver and impaired hepatic insulin production via insulin-induced insulin receptor/insulin receptor substrate 1/glycogen synthase kinase 3β signalling, which persisted for 3–14 days after cessation of noise exposure. Chronic noise altered the percentage of Proteobacteria and Actinobacteria in the gut, increasing Roseburia but decreasing Faecalibacterium levels in the cecum relative to controls. Immunoglobulin A, interleukin 1β, and tumor necrosis factor α levels were also elevated in the intestine of these animals, corresponding to noise-induced abnormalities in glucose regulation and insulin sensitivity. These results suggest that lifelong environmental noise exposure could have cumulative effects on diabetes onset and development resulting from alterations in gut microbiota composition and intestinal inflammation. PMID:27811997

  16. Microglia, Amyloid, and Glucose Metabolism in Parkinson's Disease with and without Dementia

    PubMed Central

    Edison, Paul; Ahmed, Imtiaz; Fan, Zhen; Hinz, Rainer; Gelosa, Giorgio; Ray Chaudhuri, K; Walker, Zuzana; Turkheimer, Federico E; Brooks, David J

    2013-01-01

    [11C](R)PK11195-PET measures upregulation of translocator protein, which is associated with microglial activation, [11C]PIB-PET is a marker of amyloid, while [18F]FDG-PET measures cerebral glucose metabolism (rCMRGlc). We hypothesize that microglial activation is an early event in the Parkinson's disease (PD) spectrum and is independent of the amyloid pathology. The aim of this study is to evaluate in vivo the relationship between microglial activation, amyloid deposition, and glucose metabolism in Parkinson's disease dementia (PDD) and PD subjects without dementia. Here, we evaluated 11 PDD subjects, 8 PD subjects without dementia, and 24 control subjects. Subjects underwent T1 and T2 MRI, [11C](R)PK11195, [18F]FDG, and [11C]PIB PET scans. Parametric maps of [11C](R)PK11195 binding potential, rCMRGlc, and [11C]PIB uptake were interrogated using region of interest and SPM (statistical parametric mapping) analysis. The PDD patients showed a significant increase of microglial activation in anterior and posterior cingulate, striatum, frontal, temporal, parietal, and occipital cortical regions compared with the controls. The PD subjects also showed a statistically significant increase in microglial activation in temporal, parietal, and occipital regions. [11C]PIB uptake was marginally increased in PDD and PD. There was a significant reduction in glucose metabolism in PDD and PD. We have also demonstrated pixel-by-pixel correlation between mini-mental state examination (MMSE) score and microglial activation, and MMSE score and rCMRGlc. In conclusion, we have demonstrated that cortical microglial activation and reduced glucose metabolism can be detected early on in this disease spectrum. Significant microglial activation may be a factor in driving the disease process in PDD. Given this, agents that affect microglial activation could have an influence on disease progression. PMID:23303049

  17. Global Loss of Bmal1 Expression Alters Adipose Tissue Hormones, Gene Expression and Glucose Metabolism

    PubMed Central

    Kennaway, David John; Varcoe, Tamara Jayne; Voultsios, Athena; Boden, Michael James

    2013-01-01

    The close relationship between circadian rhythm disruption and poor metabolic status is becoming increasingly evident, but role of adipokines is poorly understood. Here we investigated adipocyte function and the metabolic status of mice with a global loss of the core clock gene Bmal1 fed either a normal or a high fat diet (22% by weight). Bmal1 null mice aged 2 months were killed across 24 hours and plasma adiponectin and leptin, and adipose tissue expression of Adipoq, Lep, Retn and Nampt mRNA measured. Glucose, insulin and pyruvate tolerance tests were conducted and the expression of liver glycolytic and gluconeogenic enzyme mRNA determined. Bmal1 null mice displayed a pattern of increased plasma adiponectin and plasma leptin concentrations on both control and high fat diets. Bmal1 null male and female mice displayed increased adiposity (1.8 fold and 2.3 fold respectively) on the normal diet, but the high fat diet did not exaggerate these differences. Despite normal glucose and insulin tolerance, Bmal1 null mice had increased production of glucose from pyruvate, implying increased liver gluconeogenesis. The Bmal1 null mice had arrhythmic clock gene expression in epigonadal fat and liver, and loss of rhythmic transcription of a range of metabolic genes. Furthermore, the expression of epigonadal fat Adipoq, Retn, Nampt, AdipoR1 and AdipoR2 and liver Pfkfb3 mRNA were down-regulated. These results show for the first time that global loss of Bmal1, and the consequent arrhythmicity, results in compensatory changes in adipokines involved in the cellular control of glucose metabolism. PMID:23750248

  18. Microglia, amyloid, and glucose metabolism in Parkinson's disease with and without dementia.

    PubMed

    Edison, Paul; Ahmed, Imtiaz; Fan, Zhen; Hinz, Rainer; Gelosa, Giorgio; Ray Chaudhuri, K; Walker, Zuzana; Turkheimer, Federico E; Brooks, David J

    2013-05-01

    [(11)C](R)PK11195-PET measures upregulation of translocator protein, which is associated with microglial activation, [(11)C]PIB-PET is a marker of amyloid, while [(18)F]FDG-PET measures cerebral glucose metabolism (rCMRGlc). We hypothesize that microglial activation is an early event in the Parkinson's disease (PD) spectrum and is independent of the amyloid pathology. The aim of this study is to evaluate in vivo the relationship between microglial activation, amyloid deposition, and glucose metabolism in Parkinson's disease dementia (PDD) and PD subjects without dementia. Here, we evaluated 11 PDD subjects, 8 PD subjects without dementia, and 24 control subjects. Subjects underwent T1 and T2 MRI, [(11)C](R)PK11195, [(18)F]FDG, and [(11)C]PIB PET scans. Parametric maps of [(11)C](R)PK11195 binding potential, rCMRGlc, and [(11)C]PIB uptake were interrogated using region of interest and SPM (statistical parametric mapping) analysis. The PDD patients showed a significant increase of microglial activation in anterior and posterior cingulate, striatum, frontal, temporal, parietal, and occipital cortical regions compared with the controls. The PD subjects also showed a statistically significant increase in microglial activation in temporal, parietal, and occipital regions. [(11)C]PIB uptake was marginally increased in PDD and PD. There was a significant reduction in glucose metabolism in PDD and PD. We have also demonstrated pixel-by-pixel correlation between mini-mental state examination (MMSE) score and microglial activation, and MMSE score and rCMRGlc. In conclusion, we have demonstrated that cortical microglial activation and reduced glucose metabolism can be detected early on in this disease spectrum. Significant microglial activation may be a factor in driving the disease process in PDD. Given this, agents that affect microglial activation could have an influence on disease progression.

  19. High-fat/low-carbohydrate diets regulate glucose metabolism via a long-term transcriptional loop.

    PubMed

    Sparks, Lauren M; Xie, Hui; Koza, Robert A; Mynatt, Randall; Bray, George A; Smith, Steven R

    2006-11-01

    Insulin sensitivity is characterized by insulin-stimulated glucose metabolism in skeletal muscle. We hypothesized that carbohydrate metabolism and storage might be under transcriptional control. To test this hypothesis, we fed insulin-sensitive males (glucose disposal rate, 14.7 +/- 4.1 mg/kg fat-free mass [FFM] per minute) an isoenergetic high-fat/low-carbohydrate diet (HF/LCD) for 3 days with muscle biopsies before and after intervention. Oligonucleotide microarrays revealed a total of 369 genes of 18861 genes on the arrays were differentially regulated in response to diet (Bonferonni adjusted P < .01). A similar experiment was conducted in mice with a 3-week intervention using a control group and an HF/LCD group to offset the lack of a control group within the human cohort. As part of an analysis of results previously published from this data set, 7 genes in the carbohydrate metabolism pathway changed in response to the HF/LCD, and 3 genes were confirmed by quantitative reverse transcriptase-polymerase chain reaction: fructose-2,6-biphosphatase 3 (PFKFB3), pyruvate dehydrogenase kinase, isoenzyme 4 (PDK4), and glycogen synthase 1 (muscle). In a separate experiment, we fed C57Bl/6J mice an HF/LCD for 3 weeks and found that the same glucose metabolism genes were changed by approximately 70% on average. Fructose-2,6-biphosphatase 3 and pyruvate dehydrogenase kinase, isoenzyme 4 increased and glycogen synthase 1 (muscle) decreased. Combined, these results suggest a mechanism whereby HF/LCD regulates the genes necessary for glucose utilization and storage vis-á-vis transcriptional control.

  20. Effects of Systemic Metabolic Fuels on Glucose and Lactate Levels in the Brain Extracellular Compartment of the Mouse

    PubMed Central

    Béland-Millar, Alexandria; Larcher, Jeremy; Courtemanche, Justine; Yuan, Tina; Messier, Claude

    2017-01-01

    Classic neuroenergetic research has emphasized the role of glucose, its transport and its metabolism in sustaining normal neural function leading to the textbook statement that it is the necessary and sole metabolic fuel of the mammalian brain. New evidence, including the Astrocyte-to-Neuron Lactate Shuttle hypothesis, suggests that the brain can use other metabolic substrates. To further study that possibility, we examined the effect of intraperitoneally administered metabolic fuels (glucose, fructose, lactate, pyruvate, ß-hydroxybutyrate, and galactose), and insulin, on blood, and extracellular brain levels of glucose and lactate in the adult male CD1 mouse. Primary motor cortex extracellular levels of glucose and lactate were monitored in freely moving mice with the use of electrochemical electrodes. Blood concentration of these same metabolites were obtained by tail vein sampling and measured with glucose and lactate meters. Blood and extracellular fluctuations of glucose and lactate were monitored for a 2-h period. We found that the systemic injections of glucose, fructose, lactate, pyruvate, and ß-hydroxybutyrate increased blood lactate levels. Apart for a small transitory rise in brain extracellular lactate levels, the main effect of the systemic injection of glucose, fructose, lactate, pyruvate, and ß-hydroxybutyrate was an increase in brain extracellular glucose levels. Systemic galactose injections produced a small rise in blood glucose and lactate but almost no change in brain extracellular lactate and glucose. Systemic insulin injections led to a decrease in blood glucose and a small rise in blood lactate; however brain extracellular glucose and lactate monotonically decreased at the same rate. Our results support the concept that the brain is able to use alternative fuels and the current experiments suggest some of the mechanisms involved. PMID:28154523

  1. Effects of Systemic Metabolic Fuels on Glucose and Lactate Levels in the Brain Extracellular Compartment of the Mouse.

    PubMed

    Béland-Millar, Alexandria; Larcher, Jeremy; Courtemanche, Justine; Yuan, Tina; Messier, Claude

    2017-01-01

    Classic neuroenergetic research has emphasized the role of glucose, its transport and its metabolism in sustaining normal neural function leading to the textbook statement that it is the necessary and sole metabolic fuel of the mammalian brain. New evidence, including the Astrocyte-to-Neuron Lactate Shuttle hypothesis, suggests that the brain can use other metabolic substrates. To further study that possibility, we examined the effect of intraperitoneally administered metabolic fuels (glucose, fructose, lactate, pyruvate, ß-hydroxybutyrate, and galactose), and insulin, on blood, and extracellular brain levels of glucose and lactate in the adult male CD1 mouse. Primary motor cortex extracellular levels of glucose and lactate were monitored in freely moving mice with the use of electrochemical electrodes. Blood concentration of these same metabolites were obtained by tail vein sampling and measured with glucose and lactate meters. Blood and extracellular fluctuations of glucose and lactate were monitored for a 2-h period. We found that the systemic injections of glucose, fructose, lactate, pyruvate, and ß-hydroxybutyrate increased blood lactate levels. Apart for a small transitory rise in brain extracellular lactate levels, the main effect of the systemic injection of glucose, fructose, lactate, pyruvate, and ß-hydroxybutyrate was an increase in brain extracellular glucose levels. Systemic galactose injections produced a small rise in blood glucose and lactate but almost no change in brain extracellular lactate and glucose. Systemic insulin injections led to a decrease in blood glucose and a small rise in blood lactate; however brain extracellular glucose and lactate monotonically decreased at the same rate. Our results support the concept that the brain is able to use alternative fuels and the current experiments suggest some of the mechanisms involved.

  2. Olanzapine-induced changes in glucose metabolism are independent of the melanin-concentrating hormone system.

    PubMed

    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.

  3. Oncogenic viruses and tumor glucose metabolism: like kids in a candy store.

    PubMed

    Noch, Evan; Khalili, Kamel

    2012-01-01

    Oncogenic viruses represent a significant public health burden in light of the multitude of malignancies that result from chronic or spontaneous viral infection and transformation. Although many of the molecular signaling pathways that underlie virus-mediated cellular transformation are known, the impact of these viruses on metabolic signaling and phenotype within proliferating tumor cells is less well understood. Whether the interaction of oncogenic viruses with metabolic signaling pathways involves enhanced glucose uptake and glycolysis (both hallmark features of transformed cells) or dysregulation of molecular pathways that regulate oxidative stress, viruses are adept at facilitating tumor expansion. Through their effects on cell proliferation pathways, such as the PI3K and MAPK pathways, the cell cycle regulatory proteins p53 and ATM, and the cell stress response proteins HIF-1α and AMPK, viruses exert control over critical metabolic signaling cascades. Additionally, oncogenic viruses modulate the tumor metabolomic profile through direct and indirect interactions with glucose transporters, such as GLUT1, and specific glycolytic enzymes, including pyruvate kinase, glucose 6-phosphate dehydrogenase, and hexokinase. Through these pathways, oncogenic viruses alter the phenotypic characteristics and energy-use methods of transformed cells; therefore, it may be possible to develop novel antiglycolytic therapies to target these dysregulated pathways in virus-derived malignancies.

  4. Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species

    PubMed Central

    Lee, Mi Jin; Lee, Seung Jun; Yun, Su Jin; Jang, Ji-Young; Kang, Hangoo; Kim, Kyongmin; Choi, In-Hong; Park, Sun

    2016-01-01

    The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs’ treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs’ treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS. PMID:26730190

  5. Altered cerebral glucose metabolism in an animal model of diabetes insipidus: a micro-PET study.

    PubMed

    Idbaih, Ahmed; Burlet, Arlette; Adle-Biassette, Homa; Boisgard, Raphaël; Coulon, Christine; Paris, Sophie; Marie, Yannick; Donadieu, Jean; Hoang-Xuan, Khê; Ribeiro, Maria-Joao

    2007-07-16

    The Brattleboro rat is an animal model of genetically induced central diabetes insipidus. These rats show cognitive and behavioral disorders, but no neurodegenerative disease has been observed. We studied brain glucose uptake, a marker of neuronal activity, in 6 Brattleboro rats, in comparison with 6 matched Long-Evans (LE) control rats. A group of 3 Brattleboro rats and 3 Long-Evans rats was studied in vivo and another group of animals was studied ex vivo. In vivo studies were performed using fluorodeoxyglucose labeled with fluorine 18 ((18)F-FDG) and a dedicated small-animal PET device. At 30 min and 60 min p.i., (18)F-FDG uptake was significantly higher in the frontal cortex, striatum, thalamus and cerebellum of Brattleboro rats than in LE rats when measured by PET in vivo (p<0.05), but only a trend towards higher values was found ex vivo. Our results show for the first time that brain glucose metabolism is modified in Brattleboro rats. This altered brain glucose metabolism in Brattleboro rats may be related to the observed cognitive and behavioral disorders. Functional analyses of brain metabolism are promising to investigate cognitive behavioral disturbances observed in Brattleboro rats and their link to diabetes insipidus.

  6. Silver nanoparticles affect glucose metabolism in hepatoma cells through production of reactive oxygen species.

    PubMed

    Lee, Mi Jin; Lee, Seung Jun; Yun, Su Jin; Jang, Ji-Young; Kang, Hangoo; Kim, Kyongmin; Choi, In-Hong; Park, Sun

    2016-01-01

    The silver nanoparticle (AgNP) is a candidate for anticancer therapy because of its effects on cell survival and signaling. Although numerous reports are available regarding their effect on cell death, the effect of AgNPs on metabolism is not well understood. In this study, we investigated the effect of AgNPs on glucose metabolism in hepatoma cell lines. Lactate release from both HepG2 and Huh7 cells was reduced with 5 nm AgNPs as early as 1 hour after treatment, when cell death did not occur. Treatment with 5 nm AgNPs decreased glucose consumption in HepG2 cells but not in Huh7 cells. Treatment with 5 nm AgNPs reduced nuclear factor erythroid 2-like 2 expression in both cell types without affecting its activation at the early time points after AgNPs' treatment. Increased reactive oxygen species (ROS) production was detected 1 hour after 5 nm AgNPs' treatment, and lactate release was restored in the presence of an ROS scavenger. Our results suggest that 5 nm AgNPs affect glucose metabolism by producing ROS.

  7. Metabolic engineering of Escherichia coli for 1-butanol biosynthesis through the inverted aerobic fatty acid β-oxidation pathway.

    PubMed

    Gulevich, Andrey Yu; Skorokhodova, Alexandra Yu; Sukhozhenko, Alexey V; Shakulov, Rustem S; Debabov, Vladimir G

    2012-03-01

    The basic reactions of the clostridial 1-butanol biosynthesis pathway can be regarded to be the inverted reactions of the fatty acid β-oxidation pathway. A pathway for the biosynthesis of fuels and chemicals was recently engineered by combining enzymes from both aerobic and anaerobic fatty acid β-oxidation as well as enzymes from other metabolic pathways. In the current study, we demonstrate the inversion of the entire aerobic fatty acid β-oxidation cycle for 1-butanol biosynthesis. The constructed markerless and plasmidless Escherichia coli strain BOX-3 (MG1655 lacI(Q) attB-P(trc-ideal-4)-SD(φ10)-adhE(Glu568Lys) attB-P(trc-ideal-4)-SD(φ10)-atoB attB-P(trc-ideal-4)-SD(φ10)-fadB attB-P(trc-ideal-4)-SD(φ10)-fadE) synthesises 0.3-1 mg 1-butanol/l in the presence of the specific inducer. No 1-butanol production was detected in the absence of the inducer.

  8. Fully Implantable Arterial Blood Glucose Device for Metabolic Research Applications in Rats for Two Months

    PubMed Central

    Brockway, Robert; Tiesma, Scott; Bogie, Heather; White, Kimberly; Fine, Megan; O’Farrell, Libbey; Michael, Mervyn; Cox, Amy; Coskun, Tamer

    2015-01-01

    Background: Chronic continuous glucose monitoring options for animal research have been very limited due to various technical and biological challenges. We provide an evaluation of a novel telemetry device for continuous monitoring of temperature, activity, and plasma glucose levels in the arterial blood of rats for up to 2 months. Methods: In vivo testing in rats including oral glucose tolerance tests (OGTTs) and intraperitoneal glucose tolerance tests (IPGTTs) and ex vivo waterbath testing were performed to evaluate acute and chronic sensor performance. Animal studies were in accordance with the guidelines for the care and use of laboratory animals and approved by the corresponding animal care and use committees (Data Sciences International, Eli Lilly). Results: Results demonstrated the ability to record continuous measurements for 75 days or longer. Bench testing demonstrated a high degree of linearity over a range of 20-850 mg/dL with R2 = .998 for linear fit and .999 for second order fit (n = 8 sensors). Evaluation of 6 rats over 28 days with 52 daily and OGTT test strip measurements each resulted in mean error of 3.8% and mean absolute relative difference of 16.6%. Conclusions: This device provides significant advantages in the quality and quantity of data that can be obtained relative to existing alternatives such as intermittent blood sampling. These devices provide the opportunity to expand the understanding of both glucose metabolism and homeostasis and to work toward improved therapies and cures for diabetes. PMID:26021562

  9. Galactose metabolic genes in yeast respond to a ratio of galactose and glucose.

    PubMed

    Escalante-Chong, Renan; Savir, Yonatan; Carroll, Sean M; Ingraham, John B; Wang, Jue; Marx, Christopher J; Springer, Michael

    2015-02-03

    Natural environments are filled with multiple, often competing, signals. In contrast, biological systems are often studied in "well-controlled" environments where only a single input is varied, potentially missing important interactions between signals. Catabolite repression of galactose by glucose is one of the best-studied eukaryotic signal integration systems. In this system, it is believed that galactose metabolic (GAL) genes are induced only when glucose levels drop below a threshold. In contrast, we show that GAL gene induction occurs at a constant external galactose:glucose ratio across a wide range of sugar concentrations. We systematically perturbed the components of the canonical galactose/glucose signaling pathways and found that these components do not account for ratio sensing. Instead we provide evidence that ratio sensing occurs upstream of the canonical signaling pathway and results from the competitive binding of the two sugars to hexose transporters. We show that a mutant that behaves as the classical model expects (i.e., cannot use galactose above a glucose threshold) has a fitness disadvantage compared with wild type. A number of common biological signaling motifs can give rise to ratio sensing, typically through negative interactions between opposing signaling molecules. We therefore suspect that this previously unidentified nutrient sensing paradigm may be common and overlooked in biology.

  10. The role of hepatic mitochondria in the regulation of glucose metabolism in BHE rats

    SciTech Connect

    Kim, M.J.C.

    1988-01-01

    The interacting effects of dietary fat source and thyroxine treatment on the hepatic mitochondrial function and glucose metabolism were studied. In the first study, three different sources of dietary fatty acids and thyroxine treatment were used to investigate the hepatic mitochondrial thermotropic behavior in two strains of rat. The NIDDM BHE and Sprague-Dawley rats were used. Feeding coconut oil increased serum T{sub 4} levels and T{sub 4} treatment increased serum T{sub 3} levels in the BHE rats. In the mitochondria from BHE rats fed coconut oil and treated with T{sub 4}, the transition temperature disappeared due to a decoupling of succinate supported respiration. This was not observed in the Sprague-Dawley rats. In the second study, two different sources of dietary fat and T{sub 4} treatment were used to investigate hepatic mitochondrial function. Coconut oil feeding increased Ca{sup ++}Mg{sup ++}ATPase and Mg{sup ++}ATPase. T{sub 4} treatment had potentiated this effect. T{sub 4} increased the malate-aspartate shuttle and {alpha}-glycerophosphate shuttle activities. In the third study, the glucose turnover rate from D-({sup 14}C-U)/(6-{sup 3}H)-glucose and gluconeogeneis from L-({sup 14}C-U)-alanine was examined. Dietary fat or T{sub 4} did not affect the glucose mass. T{sub 4} increased the irreversible fractional glucose turnover rate.

  11. Alterations in aerobic-anaerobic proportions of metabolism during work in heat.

    PubMed

    Dimri, G P; Malhotra, M S; Sen Gupta, J; Kumar, T S; Arora, B S

    1980-01-01

    With a view to investigating the aerobic and anaerobic proportions of oxygen supply during different grades of muscular activity in varying thermal stress, studies have been conducted on six young healthy Indians naturally acclimatized to heat. The subjects were given submaximal exercises of 400, 500, and 600 kgm/min (equivalent to 65.40, 81.75, and 98.10 W) for 6 min on a bicycle ergometer in three different simulated conditions, i.e., comfortable, hot humid, and very hot humid. Their O2 consumption (VO2), pulmonary ventilation (VE) and heart rate (HR) were measured during rest and throughout the exercise period (6 min) and for 30 min post exercise. Blood lactate level (LA) was measured during rest and recovery. From these, the total O2 cost with aerobic and anaerobic proportions were calculated. Results indicated a significant increase in the total O2 cost for each exercise with increasing thermal stress, along with a significant increase in the anaerobic fraction and a decrease in the aerobic fraction. The increase in anaerobic contribution to the energy supply processes was further confirmed by a significant increase in relative O2 debt (l/kg) and in blood lactate level at each work load. Thus, a highly significant correlation (P < 0.001) was found between O2 debt contracted and increase in thermal stress. A significant fall in VO2 max was also observed in hot humid and very hot humid conditions as against comfortable temperature, with no change in HR max and VE max.

  12. Basal and insulin-regulated free fatty acid and glucose metabolism in humans.

    PubMed

    Shadid, Samyah; Kanaley, Jill A; Sheehan, Michael T; Jensen, Michael D

    2007-06-01

    These studies were done to examine the effects of body composition, resting energy expenditure (REE), sex, and fitness on basal and insulin-regulated FFA and glucose metabolism. We performed 137 experiments in 101 nondiabetic, premenopausal women and men, ranging from low normal weight to class III obese (BMI 18.0-40.5 kg/m2). Glucose flux was measured using [6-(2)H2]glucose and FFA kinetics with [9,10-(3)H]oleate under either basal (74 experiments) or euglycemic hyperinsulinemic (1.0 mU.kg FFM(-1).min(-1)) clamp conditions (63 experiments). Consistent with our previous findings, REE and sex independently predicted basal FFA flux, whereas fat-free mass was the best predictor of basal glucose flux; in addition, percent body fat was independently and positively associated with basal glucose flux (total r2 = 0.52, P < 0.0001). Insulin-suppressed lipolysis remained significantly associated with REE (r = 0.25, P < 0.05), but percent body fat also contributed (total adjusted r2 = 0.36, P < 0.0001), whereas sex was not significantly related to insulin-suppressed FFA flux. Glucose disposal during hyperinsulinemia was independently associated with peak VO2, percent body fat, and FFA concentrations (total r2 = 0.63, P < 0.0001) but not with sex. We conclude that basal glucose production is independently related to both FFM and body fatness. In addition, hyperinsulinemia obscures the sex differences in FFA release relative to REE, but brings out the effects of fatness on lipolysis.

  13. Comparative effects of quinine and quinidine on glucose metabolism in healthy volunteers.

    PubMed Central

    Davis, T M; Karbwang, J; Looareesuwan, S; Turner, R C; White, N J

    1990-01-01

    1. To investigate the relative effects of quinine and quinidine on glucose metabolism, 11 healthy males aged 17-32 years were given three separate 1 h intravenous infusions; normal saline alone, quinine dihydrochloride 10 mg base kg-1 body weight (BW) in normal saline, and quinidine dihydrochloride 10 mg base kg-1 BW in normal saline. A constant infusion of 5 mg glucose kg-1 ideal BW min-1 was given for 1 h before and during each study. 2. Assessment of pancreatic beta cell function and tissue insulin sensitivity from plasma glucose and insulin concentrations at the end of the first hour using the Continuous Infusion of Glucose with Model Assessment (CIGMA) technique confirmed normal glucose tolerance for each subject on each test day. 3. Plasma glucose concentrations at 1 h were similar to those at 2 h. There was no significant difference between the plasma glucose profiles during the three infusion regimes (P greater than 0.05). Plasma insulin rose significantly during the second hour (P less than 0.0001); increments after quinine (geometric mean [-1 s.d- +1 s.d.]; 47.0 [27.8-79.4] mu l-1) were significantly greater than those after quinidine (19.8 [6.1-65.2] mu l-1) and saline (7.5 [0-21.5] mu l-1; P less than 0.05). Plasma quinine concentrations at the end of the infusion (6.5 +/- 4.4 mg l-1) correlated with insulin increments during the second hour (r = 0.662, P = 0.028) and were significantly greater than those of quinidine (3.0 +/- 0.8 mg l-1; P less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS) PMID:2223418

  14. Association between DNA Methylation in Whole Blood and Measures of Glucose Metabolism: KORA F4 Study

    PubMed Central

    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-related traits

  15. Insulin-dependent glucose metabolism in dairy cows with variable fat mobilization around calving.

    PubMed

    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% total fat/dry matter (DM); n=9] and high (HLFC; 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

  16. Critical Role of Glucose Metabolism in Rheumatoid Arthritis Fibroblast-like Synoviocytes

    PubMed Central

    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

  17. Aerobic Capacity, Physical Activity and Metabolic Risk Factors in Firefighters Compared with Police Officers and Sedentary Clerks

    PubMed Central

    Leischik, Roman; Foshag, Peter; Strauß, Markus; Littwitz, Henning; Garg, Pankaj; Dworrak, Birgit; Horlitz, Marc

    2015-01-01

    Background This study examined the association between the physical work environment and physiological performance measures, physical activity levels and metabolic parameters among German civil servants. A main focus in this study was to examine the group differences rather than measuring the absolute values in an occupational group. Methods We prospectively examined 198 male German civil servants (97 firefighters [FFs], 55 police officers [POs] and 46 sedentary clerks [SCs]). For each parameter, the groups were compared using a linear regression adjusted for age. Results The 97 FFs showed a similar maximal aerobic power (VO2max l/min) of 3.17±0.44 l/min compared with the POs, who had a maximal aerobic power of 3.13±0.62 l/min (estimated difference, POs vs. FFs: 0.05, CI: -0.12-0.23, p=0.553). The maximal aerobic power of the FFs was slightly higher than that of the SCs, who had a maximal aerobic power of 2.85±0.52 l/min (-0.21, CI: -0.39-0.04, p=0.018 vs. FFs). The average physical activity (in metabolic equivalents [METS]/week) of the FFs was 3818.8±2843.5, whereas those of the POs and SCs were 2838.2±2871.9 (-808.2, CI: 1757.6-141.2, p=0.095) and 2212.2±2292.8 (vs. FFs: -1417.1, CI: -2302-531.88, p=0.002; vs. POs: -2974.4, CI: -1611.2-393.5, p=0.232), respectively. For the FFs, the average body fat percentage was 17.7%±6.2, whereas it was 21.4%±5.6 for the POs (vs. FFs: 2.75, CI: 0.92-4.59, p=0.004) and 20.8%±6.5 for the SCs (vs. FFs: 1.98, CI: -0.28-4.25, p=0.086; vs. POs: -0.77, CI: 3.15-1.61, p=0.523). The average waist circumference was 89.8 cm±10.0 for the FFs, 97.8 cm±12.4 (5.63, CI: 2.10-9.15, p=0.002) for the POs, and 97.3±11.7 (vs. FFs: -4.89, CI: 1.24-8.55, p=0.009; vs. POs: -0.73, CI: -5.21-3.74, p=0.747) for the SCs. Conclusions The FFs showed significantly higher physical activity levels compared with the SCs. The PO group had the highest cardiovascular risk of all of the groups because it included more participants with metabolic

  18. Effect of dispersed crude oil exposure upon the aerobic metabolic scope in juvenile golden grey mullet (Liza aurata).

    PubMed

    Milinkovitch, Thomas; Lucas, Julie; Le Floch, Stéphane; Thomas-Guyon, Hélène; Lefrançois, Christel

    2012-04-01

    This study evaluated the toxicity of dispersant application which is, in nearshore area, a controversial response technique to oil spill. Through an experimental approach with juveniles of Liza aurata, the toxicity of five exposure conditions was evaluated: (i) a chemically dispersed oil simulating dispersant application; (ii) a single dispersant as an internal control of chemically dispersed oil; (iii) a mechanically dispersed oil simulating natural dispersion of oil; (iv) a water soluble fraction of oil simulating an undispersed and untreated oil slick and (v) uncontaminated seawater as a control exposure condition. The relative concentration of PAHs (polycyclic aromatic hydrocarbons) biliary metabolites showed that the incorporation of these toxic compounds was increased if the oil was dispersed, whether mechanically or chemically. However, toxicity was not observed at the organism level since the aerobic metabolic scope and the critical swimming speed of exposed fish were not impaired.

  19. Validity of COSMED's quark CPET mixing chamber system in evaluating energy metabolism during aerobic exercise in healthy male adults.

    PubMed

    Nieman, David C; Austin, Melanie D; Dew, Dustin; Utter, Alan C

    2013-01-01

    This study validated the accuracy of COSMED's Quark cardiopulmonary exercise testing (CPET) metabolic mixing chamber system in measuring metabolic factors during maximal, graded exercise testing. Subjects included 32 physically active men between the ages of 18 and 34 years. During the first test session, subjects were measured for maximal oxygen consumption twice (15 min separation) with the CPET and Douglas bag systems (random order). During the second test session, subjects exercised through four stages of the Bruce treadmill protocol with measurement by the CPET and Douglas bag systems (random order) during steady state at the end of each 3-minute stage. Statistical analysis using a 2 (systems) x 5 (time) repeated measures ANOVA showed that the pattern of change in VO2, VCO2, VE, FeO2, FeCO2, and RER did not differ significantly between CPET and Douglas bag systems. This validation study indicates that the CPET mixing chamber system provides valid metabolic measurements that compare closely with the Douglas bag system during aerobic exercise.

  20. Metabolic regulation of lateral hypothalamic glucose-inhibited orexin neurons may influence midbrain reward neurocircuitry.

    PubMed

    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, P<0.001) and 41±24% (n=8, P<0.05), respectively. GABA or neurotensin receptor blockade prevented leptin's effect on glucose sensitivity. Fasting 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

  1. Analysis of tumor metabolism reveals mitochondrial glucose oxidation in genetically diverse, human glioblastomas in the mouse brain in vivo

    PubMed Central

    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

  2. Metatranscriptomic analysis of a high-sulfide aquatic spring reveals insights into sulfur cycling and unexpected aerobic metabolism.

    PubMed

    Spain, Anne M; Elshahed, Mostafa S; Najar, Fares Z; Krumholz, Lee R

    2015-01-01

    Zodletone spring is a sulfide-rich spring in southwestern Oklahoma characterized by shallow, microoxic, light-exposed spring water overlaying anoxic sediments. Previously, culture-independent 16S rRNA gene based diversity surveys have revealed that Zodletone spring source sediments harbor a highly diverse microbial community, with multiple lineages putatively involved in various sulfur-cycling processes. Here, we conducted a metatranscriptomic survey of microbial populations in Zodletone spring source sediments to characterize the relative prevalence and importance of putative phototrophic, chemolithotrophic, and heterotrophic microorganisms in the sulfur cycle, the identity of lineages actively involved in various sulfur cycling processes, and the interaction between sulfur cycling and other geochemical processes at the spring source. Sediment samples at the spring's source were taken at three different times within a 24-h period for geochemical analyses and RNA sequencing. In depth mining of datasets for sulfur cycling transcripts revealed major sulfur cycling pathways and taxa involved, including an unexpected potential role of Actinobacteria in sulfide oxidation and thiosulfate transformation. Surprisingly, transcripts coding for the cyanobacterial Photosystem II D1 protein, methane monooxygenase, and terminal cytochrome oxidases were encountered, indicating that genes for oxygen production and aerobic modes of metabolism are actively being transcribed, despite below-detectable levels (<1 µM) of oxygen in source sediment. Results highlight transcripts involved in sulfur, methane, and oxygen cycles, propose that oxygenic photosynthesis could support aerobic methane and sulfide oxidation in anoxic sediments exposed to sunlight, and provide a viewpoint of microbial metabolic lifestyles under conditions similar to those seen during late Archaean and Proterozoic eons.

  3. Genome Sequence of Azotobacter vinelandii, an Obligate Aerobe Specialized To Support Diverse Anaerobic Metabolic Processes▿ †

    PubMed Central

    Setubal, João C.; dos Santos, Patricia; Goldman, Barry S.; Ertesvåg, Helga; Espin, Guadelupe; Rubio, Luis M.; Valla, Svein; Almeida, Nalvo F.; Balasubramanian, Divya; Cromes, Lindsey; Curatti, Leonardo; Du, Zijin; Godsy, Eric; Goodner, Brad; Hellner-Burris, Kaitlyn; Hernandez, José A.; Houmiel, Katherine; Imperial, Juan; Kennedy, Christina; Larson, Timothy J.; Latreille, Phil; Ligon, Lauren S.; Lu, Jing; Mærk, Mali; Miller, Nancy M.; Norton, Stacie; O'Carroll, Ina P.; Paulsen, Ian; Raulfs, Estella C.; Roemer, Rebecca; Rosser, James; Segura, Daniel; Slater, Steve; Stricklin, Shawn L.; Studholme, David J.; Sun, Jian; Viana, Carlos J.; Wallin, Erik; Wang, Baomin; Wheeler, Cathy; Zhu, Huijun; Dean, Dennis R.; Dixon, Ray; Wood, Derek

    2009-01-01

    Azotobacter vinelandii is a soil bacterium related to the Pseudomonas genus that fixes nitrogen under aerobic conditions while simultaneously protecting nitrogenase from oxygen damage. In response to carbon availability, this organism undergoes a simple differentiation process to form cysts that are resistant to drought and other physical and chemical agents. Here we report the complete genome sequence of A. vinelandii DJ, which has a single circular genome of 5,365,318 bp. In order to reconcile an obligate aerobic lifestyle with exquisitely oxygen-sensitive processes, A. vinelandii is specialized in terms of its complement of respiratory proteins. It is able to produce alginate, a polymer that further protects the organism from excess exogenous oxygen, and it has multiple duplications of alginate modification genes, which may alter alginate composition in response to oxygen availability. The genome analysis identified the chromosomal locations of the genes coding for the three known oxygen-sensitive nitrogenases, as well as genes coding for other oxygen-sensitive enzymes, such as carbon monoxide dehydrogenase and formate dehydrogenase. These findings offer new prospects for the wider application of A. vinelandii as a host for the production and characterization of oxygen-sensitive proteins. PMID:19429624

  4. Cattle temperament influences metabolism: 1. Metabolic response to a glucose tolerance test in beef steers

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Temperamental cattle are behaviorally, physiologically, and immunologically different in comparison to calm cattle. Recently, the metabolic differences between temperamental and calm cattle have begun to be explored; temperamental cattle maintain greater circulating concentrations of non-esterified ...

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

    PubMed

    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.

  6. Fetal deficiency of Lin28 programs life-long aberrations in growth and glucose metabolism

    PubMed Central

    Shinoda, Gen; Shyh-Chang, Ng; de Soysa, T. Yvanka; 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.

    2013-01-01

    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 can 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. PMID:23666760

  7. Lipopolysaccharide markedly changes glucose metabolism and mitochondrial function in the longissimus muscle of pigs.

    PubMed

    Sun, H; Huang, Y; Yin, C; Guo, J; Zhao, R; Yang, X

    2016-07-01

    Most previous studies on the effects of lipopolysaccharide (LPS) in pigs focused on the body's immune response, and few reports paid attention to body metabolism changes. To better understand the glucose metabolism changes in skeletal muscle following LPS challenge and to clarify the possible mechanism, 12 growing pigs were employed. Animals were treated with either 2 ml of saline or 15 µg/kg BW LPS, and samples were collected 6 h later. The glycolysis status and mitochondrial function in the longissimus dorsi (LD) muscle of pigs were analyzed. The results showed that serum lactate content and NADH content in LD muscle significantly increased compared with the control group. Most glycolysis-related genes expression, as well as hexokinase, pyruvate kinase and lactic dehydrogenase activity, in LD muscle was significantly higher compared with the control group. Mitochondrial complexes I and IV significantly increased, while mitochondrial ATP concentration markedly decreased. Significantly increased calcium content in the mitochondria was observed, and endoplasm reticulum (ER) stress has been demonstrated in the present study. The results showed that LPS treatment markedly changes glucose metabolism and mitochondrial function in the LD muscle of pigs, and increased calcium content induced by ER stress was possibly involved. The results provide new clues for clarifying metabolic diseases in muscle induced by LPS.

  8. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    DOE PAGES

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; ...

    2015-02-18

    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 (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) 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 tomore » 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 to 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 heavy drinkers, which might make them vulnerable to energy deficits during withdrawal.« less

  9. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases

    SciTech Connect

    Volkow, Nora D.; Fowler, Joanna S.; Wang, Gene-Jack; Kojori, Eshan Shokri; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    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 (0.75g/kg alcohol versus placebo) on brain glucose metabolism during video-stimulation (VS) versus when given with no-stimulation (NS), in 25 heavy drinkers (HD) 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 to 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 to 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 heavy drinkers, which might make them vulnerable to energy deficits during withdrawal.

  10. Alcohol decreases baseline brain glucose metabolism more in heavy drinkers than controls but has no effect on stimulation-induced metabolic increases.

    PubMed

    Volkow, Nora D; Wang, Gene-Jack; Shokri Kojori, Ehsan; Fowler, Joanna S; Benveniste, Helene; Tomasi, Dardo

    2015-02-18

    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-(18)FDG 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.

  11. Alcohol Decreases Baseline Brain Glucose Metabolism More in Heavy Drinkers Than Controls But Has No Effect on Stimulation-Induced Metabolic Increases

    PubMed Central

    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

  12. Fatty acid metabolism during maturation affects glucose uptake and is essential to oocyte competence.

    PubMed

    Paczkowski, M; Schoolcraft, W B; Krisher, R L

    2014-10-01

    Fatty acid β-oxidation (FAO) is essential for oocyte maturation in mice. The objective of this study was to determine the effect of etomoxir (a FAO inhibitor; 100 μM), carnitine (1 mM), and palmitic acid (1 or 100 μM) during maturation on metabolism and gene expression of the oocyte and cumulus cells, and subsequent embryo development in the mouse. Carnitine significantly increased embryo development, while there was a decrease in development following maturation with 100 μM palmitic acid or etomoxir (P<0.05) treatment. Glucose consumption per cumulus-oocyte complex (COC) was decreased after treatment with carnitine and increased following etomoxir treatment (P<0.05). Intracellular oocyte lipid content was decreased after carnitine or etomoxir exposure (P<0.05). Abundance of Slc2a1 (Glut1) was increased after etomoxir treatment in the oocyte and cumulus cells (P<0.05), suggesting stimulation of glucose transport and potentially the glycolytic pathway for energy production when FAO is inhibited. Abundance of carnitine palmitoyltransferase 2 (Cpt2) tended to increase in oocytes (P=0.1) after treatment with 100 μM palmitic acid and in cumulus cells after exposure to 1 μM palmitic acid (P=0.07). Combined with carnitine, 1 μM palmitic acid increased the abundance of Acsl3 (P<0.05) and Cpt2 tended to increase (P=0.07) in cumulus cells, suggesting FAO was increased during maturation in response to stimulators and fatty acids. In conclusion, fatty acid and glucose metabolism are related to the mouse COC, as inhibition of FAO increases glucose consumption. Stimulation of FAO decreases glucose consumption and lipid stores, positively affecting subsequent embryo development, while an overabundance of fatty acid or reduced FAO negatively affects oocyte quality.

  13. Effects of sleep disruption and high fat intake on glucose metabolism in mice.

    PubMed

    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