Effect to the Glycolit which the glucose absorption marked with a 14 C in rats

International Nuclear Information System (INIS)

Fleitas Estevez, Andres; Simon Carballo, Rafael; Coma Alfonso, Cristina; Derivet Zarzabal, Milagros

2001-01-01

It has been proved that glicolit, a product obtained from natural zeolites, delays the intestinal absorption of glucose and prevents the elevation of its level in blood in the postprandial periods. The authors go deep into the knowledge of the mechanism of action of glicolit as an antihyperglycemic agent by using a radioisotopic technique, since these techniques are very specific and have a certain independence of the environment in which the absorption and incorporation of glucose to blood occurs. l5 rats were studied. They were administered a preparation of glucose marked with a 14 C during fasting. 6 of them received only this preparation (group 1, control) and the other 6 were given this preparation combined with glicolit (group 2). Blood was extracted at different times to measure glucose in plasma by radioactive counts. Differences were observed between both groups of rats in the areas under the curves of absorption of glucose, which shows the usefulness of the this method to measure the antihyperglycemic effect of glicolit. The results obtained by the radioisotopic method with glucose marked with a 14 C confirm what has been reported in previous papers and allow us to advance in the study of this possible drug, on having an efficient method

LX4211 increases serum glucagon-like peptide 1 and peptide YY levels by reducing sodium/glucose cotransporter 1 (SGLT1)-mediated absorption of intestinal glucose.

Science.gov (United States)

Powell, David R; Smith, Melinda; Greer, Jennifer; Harris, Angela; Zhao, Sharon; DaCosta, Christopher; Mseeh, Faika; Shadoan, Melanie K; Sands, Arthur; Zambrowicz, Brian; Ding, Zhi-Ming

2013-05-01

LX4211 [(2S,3R,4R,5S,6R)-2-(4-chloro-3-(4-ethoxybenzyl)phenyl)-6-(methylthio)tetrahydro-2H-pyran-3,4,5-triol], a dual sodium/glucose cotransporter 1 (SGLT1) and SGLT2 inhibitor, is thought to decrease both renal glucose reabsorption by inhibiting SGLT2 and intestinal glucose absorption by inhibiting SGLT1. In clinical trials in patients with type 2 diabetes mellitus (T2DM), LX4211 treatment improved glycemic control while increasing circulating levels of glucagon-like peptide 1 (GLP-1) and peptide YY (PYY). To better understand how LX4211 increases GLP-1 and PYY levels, we challenged SGLT1 knockout (-/-) mice, SGLT2-/- mice, and LX4211-treated mice with oral glucose. LX4211-treated mice and SGLT1-/- mice had increased levels of plasma GLP-1, plasma PYY, and intestinal glucose during the 6 hours after a glucose-containing meal, as reflected by area under the curve (AUC) values, whereas SGLT2-/- mice showed no response. LX4211-treated mice and SGLT1-/- mice also had increased GLP-1 AUC values, decreased glucose-dependent insulinotropic polypeptide (GIP) AUC values, and decreased blood glucose excursions during the 6 hours after a challenge with oral glucose alone. However, GLP-1 and GIP levels were not increased in LX4211-treated mice and were decreased in SGLT1-/- mice, 5 minutes after oral glucose, consistent with studies linking decreased intestinal SGLT1 activity with reduced GLP-1 and GIP levels 5 minutes after oral glucose. These data suggest that LX4211 reduces intestinal glucose absorption by inhibiting SGLT1, resulting in net increases in GLP-1 and PYY release and decreases in GIP release and blood glucose excursions. The ability to inhibit both intestinal SGLT1 and renal SGLT2 provides LX4211 with a novel dual mechanism of action for improving glycemic control in patients with T2DM.

Starfruit Leaves as Glucose Absorption Inhibitor in Mice’s Small Intestinal Epithelial Cells

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Rifqi Y Muhammad

2016-12-01

Full Text Available Background: Starfruit (Averrhoa carambola leaves contain flavone derivatives that exhibit anti-hyperglycemic effects. This study aims to determine the effect of starfruit leaves in reducing glucose absorption in intestinal epithelial cells of mice. Methods: This study was done by performing perfusion on the small intestines of mice. The mice that were used in this study were divided into four groups. The control group was given glucose solution without infused starfruit leaves whereas, the remaining 3 groups were given 3 mmol (540 mg/dL glucose solution with infused starfruit leaves of varying concentrations; 200, 400, and 600 mg/kg. Samples were collected at 0, 15th, 30th, 45th, and 60th minute. The sample was tested for glucose levels using spectrophotometry. Results: Test of significance showed a significant difference between the control group and the test group with p < 0.05. Conclusions: Starfruit leaves have a reduction effect towards glucose absorption in the small intestines in Wistar strains where the group using 600 mg/kg of infused starfruit leaves have the most significant effect as compared to other groups.

Comparison of glucose concentration and glucose absorption from the GI-tract in pigs in whole blood and in plasma

DEFF Research Database (Denmark)

Theil, Peter Kappel; Jørgensen, Henry; Larsen, Torben

2010-01-01

using a biosensitive electrode (Exp. 1) or a standard colourimetric method (Exp. 2). In general, glucose measured in whole blood was 7-11% lower than in plasma at low glucose levels (3.5-5 mM), whereas the methods agreed well at high glucose levels (10-14 mM). Evaluation of the regression lines between......The present investigation was undertaken to compare glucose absorption from the gastro-intestinal tract quantified in either whole blood or plasma using the arterio-venous differences and portal blood flow measurements. Pigs were surgically modified with catheters in the portal vein...... three different diets with similar contents of starch (470-506 g/kg DM). The diets in both studies differed regarding amount and solubility of fibre. Blood samples were collected repeatedly 0-10 h after morning feeding. Glucose was measured in whole blood using a glucometer (Accu-Chek®) and in plasma...

A computer model simulating human glucose absorption and metabolism in health and metabolic disease states [version 1; referees: 2 approved, 1 approved with reservations

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Richard J. Naftalin

2016-04-01

Full Text Available A computer model designed to simulate integrated glucose-dependent changes in splanchnic blood flow with small intestinal glucose absorption, hormonal and incretin circulation and hepatic and systemic metabolism in health and metabolic diseases e.g. non-alcoholic fatty liver disease, (NAFLD, non-alcoholic steatohepatitis, (NASH and type 2 diabetes mellitus, (T2DM demonstrates how when glucagon-like peptide-1, (GLP-1 is synchronously released into the splanchnic blood during intestinal glucose absorption, it stimulates superior mesenteric arterial (SMA blood flow and by increasing passive intestinal glucose absorption, harmonizes absorption with its distribution and metabolism. GLP-1 also synergises insulin-dependent net hepatic glucose uptake (NHGU. When GLP-1 secretion is deficient post-prandial SMA blood flow is not increased and as NHGU is also reduced, hyperglycaemia follows. Portal venous glucose concentration is also raised, thereby retarding the passive component of intestinal glucose absorption.   Increased pre-hepatic sinusoidal resistance combined with portal hypertension leading to opening of intrahepatic portosystemic collateral vessels are NASH-related mechanical defects that alter the balance between splanchnic and systemic distributions of glucose, hormones and incretins.The model reveals the latent contribution of portosystemic shunting in development of metabolic disease. This diverts splanchnic blood content away from the hepatic sinuses to the systemic circulation, particularly during the glucose absorptive phase of digestion, resulting in inappropriate increases in insulin-dependent systemic glucose metabolism.  This hastens onset of hypoglycaemia and thence hyperglucagonaemia. The model reveals that low rates of GLP-1 secretion, frequently associated with T2DM and NASH, may be also be caused by splanchnic hypoglycaemia, rather than to intrinsic loss of incretin secretory capacity. These findings may have therapeutic

Alteration of carbohydrates metabolism and midgut glucose absorption in Gromphadorhina portentosa after subchronic exposure to imidacloprid and fenitrothion.

Science.gov (United States)

Sawczyn, Tomasz; Dolezych, Bogdan; Klosok, Marcin; Augustyniak, Maria; Stygar, Dominika; Buldak, Rafal J; Kukla, Michal; Michalczyk, Katarzyna; Karcz-Socha, Iwona; Zwirska-Korczala, Krystyna

2012-01-01

This study was undertaken to test the hypothesis that following exposure to insecticides, changes take place in the metabolism of carbohydrates and absorption in the midgut of insects. The Madagascar hissing cockroach (Gromphadorhina portentosa) was chosen for the experiment as a model organism, due to it being easy to breed and its relatively large alimentary tract, which was important when preparing the microperfusion midgut bioassay. In each group of cockroaches treated with imidacloprid and fenitrothion, absorption of glucose, expressed as the area under the curve (AUC), was elevated compared to the control group. Glucose in the hemolymph of the examined insects was present in a vestigial amount, often below the threshold of determination, so the determinable carbohydrate indices were: hemolymph trehalose concentration and fat body glycogen content. The level of trehalose found in the hemolymph of insects when exposed to fenitrothion, and irrespective of the level of concentration mixed into food, were significantly lower when comparing to the control samples. Imidacloprid acted analogically with one exception at the concentration of 10 mg·kg(-1) dry food where trehalose concentration did not differ from the control values. Coupling with fat body glycogen concentration was less visible and appeared only at the concentrations of 5 and 10 mg imidacloprid·kg(-1) dry food. As described in this study changes in the sugar distribution and midgut glucose absorption indicate that insects cover the increased energy needs induced by insecticides; also at the gastrointestinal tract level. The result indicates that the midgut glucose absorption parameters could be considered as a non-specific biomarker of insecticide toxicity.

Paracellular absorption: a bat breaks the mammal paradigm.

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Enrique Caviedes-Vidal

Full Text Available Bats tend to have less intestinal tissue than comparably sized nonflying mammals. The corresponding reduction in intestinal volume and hence mass of digesta carried is advantageous because the costs of flight increase with load carried and because take-off and maneuverability are diminished at heavier masses. Water soluble compounds, such as glucose and amino acids, are absorbed in the small intestine mainly via two pathways, the transporter-mediated transcellular and the passive, paracellular pathways. Using the microchiropteran bat Artibeus literatus (mean mass 80.6+/-3.7 g, we tested the predictions that absorption of water-soluble compounds that are not actively transported would be extensive as a compensatory mechanism for relatively less intestinal tissue, and would decline with increasing molecular mass in accord with sieve-like paracellular absorption. Using a standard pharmacokinetic technique, we fed, or injected intraperitoneally the metabolically inert carbohydrates L-rhamnose (molecular mass = 164 Da and cellobiose (molecular mass = 342 Da which are absorbed only by paracellular transport, and 3-O-methyl-D-glucose (3OMD-glucose which is absorbed via both mediated (active and paracellular transport. As predicted, the bioavailability of paracellular probes declined with increasing molecular mass (rhamnose, 90+/-11%; cellobiose, 10+/-3%, n = 8 and was significantly higher in bats than has been reported for laboratory rats and other mammals. In addition, absorption of 3OMD-glucose was high (96+/-11%. We estimated that the bats rely on passive, paracellular absorption for more than 70% of their total glucose absorption, much more than in non-flying mammals. Although possibly compensating for less intestinal tissue, a high intestinal permeability that permits passive absorption might be less selective than a carrier-mediated system for nutrient absorption and might permit toxins to be absorbed from plant and animal material in the

Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway.

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Leem, Kang-Hyun; Kim, Myung-Gyou; Hahm, Young-Tae; Kim, Hye Kyung

2016-12-09

Opuntia ficus-indica var. saboten (OFS) has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na⁺-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK) is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK) has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C ) and p38 MAPK (SB203580) abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4) translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight) in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.

Hypoglycemic Effect of Opuntia ficus-indica var. saboten Is Due to Enhanced Peripheral Glucose Uptake through Activation of AMPK/p38 MAPK Pathway

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Kang-Hyun Leem

2016-12-01

Full Text Available Opuntia ficus-indica var. saboten (OFS has been used in traditional medicine for centuries to treat several illnesses, including diabetes. However, detailed mechanisms underlying hypoglycemic effects remain unclear. In this study, the mechanism underlying the hypoglycemic activity of OFS was evaluated using in vitro and in vivo systems. OFS treatment inhibited α-glucosidase activity and intestinal glucose absorption assessed by Na+-dependent glucose uptake using brush border membrane vesicles. AMP-activated protein kinase (AMPK is widely recognized as an important regulator of glucose transport in skeletal muscle, and p38 mitogen-activated protein kinase (MAPK has been proposed to be a component of AMPK-mediated signaling. In the present study, OFS dose-dependently increased glucose uptake in L6 muscle cells. The AMPK and p38 MAPK phosphorylations were stimulated by OFS, and inhibitors of AMPK (compound C and p38 MAPK (SB203580 abolished the effects of OFS. Furthermore, OFS increased glucose transporter 4 (GLUT4 translocation to the plasma membrane. OFS administration (1 g/kg and 2 g/kg body weight in db/db mice dose-dependently ameliorated hyperglycemia, hyperinsulinemia, and glucose tolerance. Insulin resistance assessed by homeostasis model assessment of insulin resistance and quantitative insulin sensitivity check index were also dose-dependently improved with OFS treatment. OFS administration improved pancreatic function through increased β-cell mass in db/db mice. These findings suggest that OFS acts by inhibiting glucose absorption from the intestine and enhancing glucose uptake from insulin-sensitive muscle cells through the AMPK/p38 MAPK signaling pathway.

Activity-Dependent Regulation of Surface Glucose Transporter-3

OpenAIRE

Ferreira, Jainne M.; Burnett, Arthur L.; Rameau, Gerald A.

2011-01-01

Glucose transporter 3 (GLUT3) is the main facilitative glucose transporter in neurons. Glucose provides neurons with a critical energy source for neuronal activity. However, the mechanism by which neuronal activity controls glucose influx via GLUT3 is unknown. We investigated the influence of synaptic stimulation on GLUT3 surface expression and glucose import in primary cultured cortical and hippocampal neurons. Synaptic activity increased surface expression of GLUT3 leading to an elevation o...

Kinetics of amino acid and glucose absorption following pancreatic diversion in the pig

Science.gov (United States)

Rerat, A.; Calmes, R.; Corring, T.; Vaissade, P.

1996-01-01

An experiment was conducted in the pig to determine the consequences of deprivation of exocrine pancreatic secretion on the composition and quantity of nutrients absorbed after intake of a balanced diet. Five growing pigs (53.8 kg body weight) were fitted with permanent catheters in the portal vein and the carotid artery and with an electromagnetic flow probe around the portal vein to measure the exchanges between the blood and the intestinal lumen. They were also fitted with a permanent catheter in the duct of Wirsung to educe the exocrine pancreatic secretion and another one in the duodenum in order to reintroduce it. In each animal, glucose, amino-N and amino acid absorption as well as insulin and glucagon production were measured over a period of 10 h after the meal (semi-purified diet based on purified starch and containing 180 g fish meal/kg, DM content of the meal 731 g), either in the presence of pancreatic juice (group C: immediate reintroduction), or in the absence of pancreatic juice (group D: deprivation). The deprivation of pancreatic juice provoked a marked depression in the absorption of glucose (D 67.9 (SEM 27.9) g/10 h, C 437.7 (SEM 39.5) g/10 h, P juice. Insulin production was much lower (by 64%, P juice whereas that of glucagon was not affected.

Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

NARCIS (Netherlands)

Smeets, P.A.M.; Vidarsdottir, S.; Graaf, C. de; Stafleu, A.; Osch, M.J.P. van; Viergever, M.A.; Pijl, H.; Grond, J. van der

2007-01-01

We previously showed that hypothalamic neuronal activity, as measured by the blood oxygen level-dependent (BOLD) functional MRI signal, declines in response to oral glucose intake. To further explore the mechanism driving changes in hypothalamic neuronal activity in response to an oral glucose load,

Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion

NARCIS (Netherlands)

Smeets, P.A.M.; Vidarsdottir, S.; Graaf, de C.; Stafleu, A.; Osch, M.J.P.; Viergever, M.A.; Pijl, H.; Grond, van der J.

2007-01-01

Oral glucose intake inhibits hypothalamic neuronal activity more effectively than glucose infusion. Am J Physiol Endocrinol Metab 293: E754-E758, 2007. First published June 12, 2007; doi:10.1152/ajpendo.00231.2007. - We previously showed that hypothalamic neuronal activity, as measured by the blood

Rice (Oryza sativa japonica) Albumin Suppresses the Elevation of Blood Glucose and Plasma Insulin Levels after Oral Glucose Loading.

Science.gov (United States)

Ina, Shigenobu; Ninomiya, Kazumi; Mogi, Takashi; Hase, Ayumu; Ando, Toshiki; Matsukaze, Narumi; Ogihara, Jun; Akao, Makoto; Kumagai, Hitoshi; Kumagai, Hitomi

2016-06-22

The suppressive effect of rice albumin (RA) of 16 kDa on elevation of blood glucose level after oral loading of starch or glucose and its possible mechanism were examined. RA suppressed the increase in blood glucose levels in both the oral starch tolerance test and the oral glucose tolerance test. The blood glucose concentrations 15 min after the oral administration of starch were 144 ± 6 mg/dL for control group and 127 ± 4 mg/dL for RA 200 mg/kg BW group, while those after the oral administration of glucose were 157 ± 7 mg/dL for control group and 137 ± 4 mg/dL for RA 200 mg/kg BW group. However, in the intraperitoneal glucose tolerance test, no significant differences in blood glucose level were observed between RA and the control groups, indicating that RA suppresses the glucose absorption from the small intestine. However, RA did not inhibit the activity of mammalian α-amylase. RA was hydrolyzed to an indigestible high-molecular-weight peptide (HMP) of 14 kDa and low-molecular-weight peptides by pepsin and pancreatin. Furthermore, RA suppressed the glucose diffusion rate through a semipermeable membrane like dietary fibers in vitro. Therefore, the indigestible HMP may adsorb glucose and suppress its absorption from the small intestine.

Exercise, Insulin Absorption Rates, and Artificial Pancreas Control

Science.gov (United States)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Basu, Ananda; Szeri, Andrew J.

2016-11-01

Type 1 Diabetes is characterized by an inability of a person to endogenously produce the hormone insulin. Because of this, insulin must be injected - usually subcutaneously. The size of the injected dose and the rate at which the dose reaches the circulatory system have a profound effect on the ability to control glucose excursions, and therefore control of diabetes. However, insulin absorption rates via subcutaneous injection are variable and depend on a number of factors including tissue perfusion, physical activity (vasodilation, increased capillary throughput), and other tissue geometric and physical properties. Exercise may also have a sizeable effect on the rate of insulin absorption, which can potentially lead to dangerous glucose levels. Insulin-dosing algorithms, as implemented in an artificial pancreas controller, should account accurately for absorption rate variability and exercise effects on insulin absorption. The aforementioned factors affecting insulin absorption will be discussed within the context of both fluid mechanics and data driven modeling approaches.

Effect of petroleum vapors inhalation on intestinal absorption of glucose and some amino acids in the rat

International Nuclear Information System (INIS)

Szablicka, E.; Oledzka, R.

1989-01-01

The proper intestinal absorption of nutrients, particularly sugars and amino acids, is necessary to keep the organism healthy. It is well known that various toxic compounds present in the environment can have an unfavorable influence. On the other hand it is also known that crude oil which pollutes the aqueous environment affects birds' gastrointestinal tract. Little is known about the influence of petroleum vapors on the gastrointestinal tract of animals and humans. The present study was undertaken to determine the effect of petroleum vapors inhalation on intestinal absorption of some nutrients (glucose, leucine, methionine) in rats

Designing a highly active soluble PQQ-glucose dehydrogenase for efficient glucose biosensors and biofuel cells

Energy Technology Data Exchange (ETDEWEB)

Durand, Fabien [Universite de Bordeaux, Centre de Recherche Paul Pascal (CRPP), UPR 8641, Avenue Albert Schweitzer, 33600 Pessac (France); Stines-Chaumeil, Claire [Universite de Bordeaux, CNRS, Institut de Biochimie et de Genetique Cellulaires, 1 rue Camille Saint Saens, 33077 Bordeaux Cedex (France); Flexer, Victoria [Universite de Bordeaux, Centre de Recherche Paul Pascal (CRPP), UPR 8641, Avenue Albert Schweitzer, 33600 Pessac (France); Andre, Isabelle [Universite de Toulouse, INSA, UPS, INP, LISBP, 135 Avenue de Rangueil, F-31077 Toulouse (France); CNRS, UMR5504, F-31400 Toulouse (France); INRA, UMR 792 Ingenierie des Systemes Biologiques et des Procedes, F-31400 Toulouse (France); Mano, Nicolas, E-mail: mano@crpp-bordeaux.cnrs.fr [Universite de Bordeaux, Centre de Recherche Paul Pascal (CRPP), UPR 8641, Avenue Albert Schweitzer, 33600 Pessac (France)

2010-11-26

Research highlights: {yields} A new mutant of PQQ-GDH designed for glucose biosensors application. {yields} First mutant of PQQ-GDH with higher activity for D-glucose than the Wild type. {yields} Position N428 is a key point to increase the enzyme activity. {yields} Molecular modeling shows that the N428 C mutant displays a better interaction for PQQ than the WT. -- Abstract: We report for the first time a soluble PQQ-glucose dehydrogenase that is twice more active than the wild type for glucose oxidation and was obtained by combining site directed mutagenesis, modelling and steady-state kinetics. The observed enhancement is attributed to a better interaction between the cofactor and the enzyme leading to a better electron transfer. Electrochemical experiments also demonstrate the superiority of the new mutant for glucose oxidation and make it a promising enzyme for the development of high-performance glucose biosensors and biofuel cells.

Predicting Insulin Absorption and Glucose Uptake during Exercise in Type 1 Diabetes

Science.gov (United States)

Frank, Spencer; Hinshaw, Ling; Basu, Rita; Szeri, Andrew; Basu, Ananda

2017-11-01

A dose of insulin infused into subcutaneous tissue has been shown to absorb more quickly during exercise, potentially causing hypoglycemia in persons with type 1 diabetes. We develop a model that relates exercise-induced physiological changes to enhanced insulin-absorption (k) and glucose uptake (GU). Drawing on concepts of the microcirculation we derive a relationship that reveals that k and GU are mainly determined by two physiological parameters that characterize the tissue: the tissue perfusion rate (Q) and the capillary permeability surface area (PS). Independently measured values of Q and PS from the literature are used in the model to make predictions of k and GU. We compare these predictions to experimental observations of healthy and diabetic patients that are given a meal followed by rest or exercise. The experiments show that during exercise insulin concentrations significantly increase and that glucose levels fall rapidly. The model predictions are consistent with the experiments and show that increases in Q and PS directly increase k and GU. This mechanistic understanding provides a basis for handling exercise in control algorithms for an artificial pancreas. Now at University of British Columbia.

Ficus Deltoidea Enhance Glucose Uptake Activity in Cultured Muscle Cells

International Nuclear Information System (INIS)

Zainah Adam; Shafii Khamis; Amin Ismail; Muhajir Hamid

2015-01-01

Ficus deltoidea or locally known as Mas cotek is one of the common medicinal plants used in Malaysia. Our previous studies showed that this plant have blood glucose lowering effect. Glucose uptake into muscle and adipocytes cells is one of the known mechanisms of blood glucose lowering effect. This study was performed to evaluate the effect of Ficus deltoidea on glucose uptake activity into muscle cells. The cells were incubated with Ficus deltoidea extracts either alone or combination with insulin. Amount of glucose uptake by L6 myotubes was determined using glucose tracer, 2-deoxy-(1- 3 H 1 )-glucose. The results showed that Ficus deltoidea extracts at particular doses enhanced basal or insulin-mediated glucose uptake into muscle cells significantly. Hot aqueous extract enhanced glucose uptake at the low concentration (10 μg/ ml) whereas methanolic extract enhanced glucose uptake at low and high concentrations. Methanolic extract also mimicked insulin activity during enhancing glucose uptake into L^ muscle cells. Glucose uptake activity of Ficus deltoidea could be attributed by the phenolic compound presence in the plant. This study had shown that Ficus deltoidea has the ability to enhance glucose uptake into muscle cells which is partly contributed the antidiabetic activity of this plant. (author)

Antioxidant activity of the melanoidin fractions formed from D-Glucose and D-Fructose with L-Asparagine in the Maillard reaction

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A.P Echavarría

2013-01-01

Full Text Available Melanoidins formed at the last stage of the Maillard reaction have been shown to possess certain functional properties, such as antioxidant activity. In order to gain more insight into these functional properties, soluble model systems melanoidins from L - Asparagine with D - glucose or D - fructose fractionating by ultrafiltration were analyzed. The fractionating/concentration sequence of the melanoidin fraction (1 - 300 kDa enabled five fractions to be produced. Additionally, the absorption of melanoidins was measured at different wavelengths (280, 325, 405 and browning at 420 nm. The fractionati on effect of melanoidin systems on the color intensity, UV - absorbance scan wavelengths (nm, CIE, L*, a*, b* parameters and antioxidant activity were measured. For this purpose, antioxidant activity was evaluated through the free radical scavenging activit y, including 1,1 - diphenyl - 2 - picryl - hydrazil (DPPH and 2,20 - azinobis (3 - ethylbenothiazoline - 6 - sulfonic acid, diammonium salt (ABTS. The results showed that the absorption of the melanoidins formed from Glucose/L - Asn was higher than for those derived from Fructose/L - Asn. On the other hand, their antioxidant power was lower than that for melanoidins formed from Fructose/L - Asn systems.

Phospholipase D1 mediates AMP-activated protein kinase signaling for glucose uptake.

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Jong Hyun Kim

2010-03-01

Full Text Available Glucose homeostasis is maintained by a balance between hepatic glucose production and peripheral glucose utilization. In skeletal muscle cells, glucose utilization is primarily regulated by glucose uptake. Deprivation of cellular energy induces the activation of regulatory proteins and thus glucose uptake. AMP-activated protein kinase (AMPK is known to play a significant role in the regulation of energy balances. However, the mechanisms related to the AMPK-mediated control of glucose uptake have yet to be elucidated.Here, we found that AMPK-induced phospholipase D1 (PLD1 activation is required for (14C-glucose uptake in muscle cells under glucose deprivation conditions. PLD1 activity rather than PLD2 activity is significantly enhanced by glucose deprivation. AMPK-wild type (WT stimulates PLD activity, while AMPK-dominant negative (DN inhibits it. AMPK regulates PLD1 activity through phosphorylation of the Ser-505 and this phosphorylation is increased by the presence of AMP. Furthermore, PLD1-S505Q, a phosphorylation-deficient mutant, shows no changes in activity in response to glucose deprivation and does not show a significant increase in (14C-glucose uptake when compared to PLD1-WT. Taken together, these results suggest that phosphorylation of PLD1 is important for the regulation of (14C-glucose uptake. In addition, extracellular signal-regulated kinase (ERK is stimulated by AMPK-induced PLD1 activation through the formation of phosphatidic acid (PA, which is a product of PLD. An ERK pharmacological inhibitor, PD98059, and the PLD inhibitor, 1-BtOH, both attenuate (14C-glucose uptake in muscle cells. Finally, the extracellular stresses caused by glucose deprivation or aminoimidazole carboxamide ribonucleotide (AICAR; AMPK activator regulate (14C-glucose uptake and cell surface glucose transport (GLUT 4 through ERK stimulation by AMPK-mediated PLD1 activation.These results suggest that AMPK-mediated PLD1 activation is required for (14C-glucose

Berberine promotes glucose consumption independently of AMP-activated protein kinase activation.

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Miao Xu

Full Text Available Berberine is a plant alkaloid with anti-diabetic action. Activation of AMP-activated protein kinase (AMPK pathway has been proposed as mechanism for berberine's action. This study aimed to examine whether AMPK activation was necessary for berberine's glucose-lowering effect. We found that in HepG2 hepatocytes and C2C12 myotubes, berberine significantly increased glucose consumption and lactate release in a dose-dependent manner. AMPK and acetyl coenzyme A synthetase (ACC phosphorylation were stimulated by 20 µmol/L berberine. Nevertheless, berberine was still effective on stimulating glucose utilization and lactate production, when the AMPK activation was blocked by (1 inhibition of AMPK activity by Compound C, (2 suppression of AMPKα expression by siRNA, and (3 blockade of AMPK pathway by adenoviruses containing dominant-negative forms of AMPKα1/α2. To test the effect of berberine on oxygen consumption, extracellular flux analysis was performed in Seahorse XF24 analyzer. The activity of respiratory chain complex I was almost fully blocked in C2C12 myotubes by berberine. Metformin, as a positive control, showed similar effects as berberine. These results suggest that berberine and metformin promote glucose metabolism by stimulating glycolysis, which probably results from inhibition of mitochondrial respiratory chain complex I, independent of AMPK activation.

Glucose, epithelium, and enteric nervous system: dialogue in the dark.

Science.gov (United States)

Pfannkuche, H; Gäbel, G

2009-06-01

The gastrointestinal epithelium is in close contact with the various components of the chymus, including nutrients, bacteria and toxins. The epithelial barrier has to decide which components are effectively absorbed and which components are extruded. In the small intestine, a nutrient like glucose is mainly absorbed by the sodium linked glucose cotransporter 1 (SGLT1) and the glucose transporter 2 (GLUT2). The expression and activity of both transport proteins is directly linked to the amount of intraluminal glucose. Besides the direct interaction between glucose and the enterocytes, glucose also stimulates different sensory mechanisms within the intestinal wall. The most important types of cells involved in the sensing of intraluminal contents are enteroendocrine cells and neurones of the enteric nervous system. Regarding glucosensing, a distinct type of enteroendocrine cells, the enterochromaffine (EC) cells are involved. Excitation of EC cells by intraluminal glucose results in the release of serotonin (5-HT), which modulates epithelial functions and activates enteric secretomotorneurones. Enteric neurones are not only activated by 5-HT, but also directly by glucose. The activation of different cell types and the subsequent crosstalk between these cells may trigger appropriate absorptive and secretory processes within the intestine.

Intrinsic peroxidase-like catalytic activity of nitrogen-doped graphene quantum dots and their application in the colorimetric detection of H2O2 and glucose

International Nuclear Information System (INIS)

Lin, Liping; Song, Xinhong; Chen, Yiying; Rong, Mingcong; Zhao, Tingting; Wang, Yiru; Jiang, Yaqi; Chen, Xi

2015-01-01

Highlights: • The highly intrinsic peroxidase-like catalytic activity of N-GQDs is revealed. • The activity of N-GQDs depended on pH, temperature and H 2 O 2 concentration. • The activity of N-GQDs has been used to the detection of H 2 O 2 and glucose. • This assay was suitable for the detection of glucose concentrations in real samples. - Abstract: In this paper, the highly intrinsic peroxidase-like catalytic activity of nitrogen-doped graphene quantum dots (N-GQDs) is revealed. This activity was greatly dependent on pH, temperature and H 2 O 2 concentration. The experimental results showed that the stable N-GQDs could be used for the detection of H 2 O 2 and glucose over a wide range of pH and temperature, offering a simple, highly selective and sensitive approach for their colorimetric sensing. The linearity between the analyte concentration and absorption ranged from 20 to 1170 μM for H 2 O 2 and 25 to 375 μM for glucose with a detection limit of 5.3 μM for H 2 O 2 and 16 μM for glucose. This assay was also successfully applied to the detection of glucose concentrations in diluted serum and fruit juice samples

Natural Products as Lead Compounds for Sodium Glucose Cotransporter (SGLT) Inhibitors.

Science.gov (United States)

Blaschek, Wolfgang

2017-08-01

Glucose homeostasis is maintained by antagonistic hormones such as insulin and glucagon as well as by regulation of glucose absorption, gluconeogenesis, biosynthesis and mobilization of glycogen, glucose consumption in all tissues and glomerular filtration, and reabsorption of glucose in the kidneys. Glucose enters or leaves cells mainly with the help of two membrane integrated transporters belonging either to the family of facilitative glucose transporters (GLUTs) or to the family of sodium glucose cotransporters (SGLTs). The intestinal glucose absorption by endothelial cells is managed by SGLT1, the transfer from them to the blood by GLUT2. In the kidney SGLT2 and SGLT1 are responsible for reabsorption of filtered glucose from the primary urine, and GLUT2 and GLUT1 enable the transport of glucose from epithelial cells back into the blood stream.The flavonoid phlorizin was isolated from the bark of apple trees and shown to cause glucosuria. Phlorizin is an inhibitor of SGLT1 and SGLT2. With phlorizin as lead compound, specific inhibitors of SGLT2 were developed in the last decade and some of them have been approved for treatment mainly of type 2 diabetes. Inhibition of SGLT2 eliminates excess glucose via the urine. In recent times, the dual SGLT1/SGLT2 inhibitory activity of phlorizin has served as a model for the development and testing of new drugs exhibiting both activities.Besides phlorizin, also some other flavonoids and especially flavonoid enriched plant extracts have been investigated for their potency to reduce postprandial blood glucose levels which can be helpful in the prevention and supplementary treatment especially of type 2 diabetes. Georg Thieme Verlag KG Stuttgart · New York.

Activation of Skeletal Muscle AMPK Promotes Glucose Disposal and Glucose Lowering in Non-human Primates and Mice.

Science.gov (United States)

Cokorinos, Emily C; Delmore, Jake; Reyes, Allan R; Albuquerque, Bina; Kjøbsted, Rasmus; Jørgensen, Nicolas O; Tran, Jean-Luc; Jatkar, Aditi; Cialdea, Katherine; Esquejo, Ryan M; Meissen, John; Calabrese, Matthew F; Cordes, Jason; Moccia, Robert; Tess, David; Salatto, Christopher T; Coskran, Timothy M; Opsahl, Alan C; Flynn, Declan; Blatnik, Matthew; Li, Wenlin; Kindt, Erick; Foretz, Marc; Viollet, Benoit; Ward, Jessica; Kurumbail, Ravi G; Kalgutkar, Amit S; Wojtaszewski, Jørgen F P; Cameron, Kimberly O; Miller, Russell A

2017-05-02

The AMP-activated protein kinase (AMPK) is a potential therapeutic target for metabolic diseases based on its reported actions in the liver and skeletal muscle. We evaluated two distinct direct activators of AMPK: a non-selective activator of all AMPK complexes, PF-739, and an activator selective for AMPK β1-containing complexes, PF-249. In cells and animals, both compounds were effective at activating AMPK in hepatocytes, but only PF-739 was capable of activating AMPK in skeletal muscle. In diabetic mice, PF-739, but not PF-249, caused a rapid lowering of plasma glucose levels that was diminished in the absence of skeletal muscle, but not liver, AMPK heterotrimers and was the result of an increase in systemic glucose disposal with no impact on hepatic glucose production. Studies of PF-739 in cynomolgus monkeys confirmed translation of the glucose lowering and established activation of AMPK in skeletal muscle as a potential therapeutic approach to treat diabetic patients. Copyright © 2017 Elsevier Inc. All rights reserved.

Concurrent duodenal manometric and impedance recording to evaluate the effects of hyoscine on motility and flow events, glucose absorption, and incretin release

NARCIS (Netherlands)

Chaikomin, Reawika; Wu, Keng Liang; Doran, Selena; Jones, Karen L.; Smout, Andre J. P. M.; Renooij, Willem; Holloway, Richard H.; Meyer, James H.; Horowitz, Michael; Rayner, Christopher K.

2007-01-01

Upper gastrointestinal motor function and incretin hormone secretion are major determinants of postprandial glycemia and insulinemia. However, the impact of small intestinal flow events on glucose absorption and incretin release is poorly defined. Intraluminal impedance monitoring is a novel

Glucose and carbachol activate phospholipase C in digitonin-permeabilized islets

International Nuclear Information System (INIS)

Wolf, B.A.; Florholmen, J.; Turk, J.; McDaniel, M.L.

1987-01-01

Stimulation of intact islets with D-glucose, the major insulin secretagogue, or with carbachol, a muscarinic agonist, results in the accumulation of inositoltrisphosphate (IP 3 ) suggesting that activation of phospholipase C (PLC) has a major role in stimulus-secretion coupling. Carbachol activation of PLC is an example of receptor-mediated activation in islets, whereas, the mechanism of glucose activation of PLC is controversial since a glucose receptor has not been identified. They have measured PLC activity in digitonin-permeabilized islets. Islets were labeled with 3 H-inositol, permeabilized and IP 3 accumulation measured by HPLC. Carbachol, in the presence of ATP, GTP and 1 μM free Ca 2+ released two-fold more Ins 1,3,4-P 3 than control in a time-dependent manner. Glucose, under the same conditions also significantly released more Ins 1,3,4-P 3 than control. This effect was not due to metabolism of glucose nor to an effect on the IP 3 -phosphomonoesterase. Preliminary Ca 2+ -dependency studies indicate that PLC is not activated by Ca 2+ in the submicromolar range. In conclusion, these studies show that Ca 2+ does not activate PLC, and furthermore, that D-glucose may be recognized directly by PLC

Adding glucose to food and solutions to enhance fructose absorption is not effective in preventing fructose-induced functional gastrointestinal symptoms: randomised controlled trials in patients with fructose malabsorption.

Science.gov (United States)

Tuck, C J; Ross, L A; Gibson, P R; Barrett, J S; Muir, J G

2017-02-01

In healthy individuals, the absorption of fructose in excess of glucose in solution is enhanced by the addition of glucose. The present study aimed to assess the effects of glucose addition to fructose or fructans on absorption patterns and genesis of gastrointestinal symptoms in patients with functional bowel disorders. Randomised, blinded, cross-over studies were performed in healthy subjects and functional bowel disorder patients with fructose malabsorption. The area-under-the-curve (AUC) was determined for breath hydrogen and symptom responses to: (i) six sugar solutions (fructose in solution) (glucose; sucrose; fructose; fructose + glucose; fructan; fructan + glucose) and (ii) whole foods (fructose in foods) containing fructose in excess of glucose given with and without additional glucose. Intake of fermentable short chain carbohydrates (FODMAPs; fermentable, oligo-, di-, monosaccharides and polyols) was controlled. For the fructose in solution study, in 26 patients with functional bowel disorders, breath hydrogen was reduced after glucose was added to fructose compared to fructose alone [mean (SD) AUC 92 (107) versus 859 (980) ppm 4 h -1 , respectively; P = 0.034). Glucose had no effect on breath hydrogen response to fructans (P = 1.000). The six healthy controls showed breath hydrogen patterns similar to those with functional bowel disorders. No differences in symptoms were experienced with the addition of glucose, except more nausea when glucose was added to fructose (P = 0.049). In the fructose in foods study, glucose addition to whole foods containing fructose in excess of glucose in nine patients with functional bowel disorders and nine healthy controls had no significant effect on breath hydrogen production or symptom response. The absence of a favourable response on symptoms does not support the concomitant intake of glucose with foods high in either fructose or fructans in patients with functional bowel disorders. © 2016 The British Dietetic

Glucose activates prenyltransferases in pancreatic islet {beta}-cells

Energy Technology Data Exchange (ETDEWEB)

Goalstone, Marc [Department of Medicine, University of Colorado, VA Medical Center, Denver, CO 80220 (United States); Kamath, Vasudeva [Department of Pharmaceutical Sciences, Wayne State University, VA Medical Center, Detroit, MI 48201 (United States); Kowluru, Anjaneyulu, E-mail: akowluru@med.wayne.edu [Department of Pharmaceutical Sciences, Wayne State University, VA Medical Center, Detroit, MI 48201 (United States)

2010-01-01

A growing body of evidence implicates small G-proteins [e.g., Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet {beta}-cell. These signaling proteins undergo post-translational modifications [e.g., prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretory granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological insulin secretogues [e.g., glucose] has not been investigated thus far. Herein, we report immunological localization, sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 {beta}-cells and normal rat islets. Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the {alpha}-subunits of FTase/GGTase-1, but not the {beta}-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets. Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin.

Glucose activates prenyltransferases in pancreatic islet β-cells

International Nuclear Information System (INIS)

Goalstone, Marc; Kamath, Vasudeva; Kowluru, Anjaneyulu

2010-01-01

A growing body of evidence implicates small G-proteins [e.g., Cdc42 and Rac1] in glucose-stimulated insulin secretion [GSIS] in the islet β-cell. These signaling proteins undergo post-translational modifications [e.g., prenylation] at their C-terminal cysteine residue and appear to be essential for the transport and fusion of insulin-containing secretory granules with the plasma membrane and the exocytotic secretion of insulin. However, potential regulation of the prenylating enzymes by physiological insulin secretogues [e.g., glucose] has not been investigated thus far. Herein, we report immunological localization, sub-cellular distribution and regulation of farnesyltransferases [FTases] and geranylgeranyltransferase [GGTase] by glucose in insulin-secreting INS 832/13 β-cells and normal rat islets. Our findings suggest that an insulinotropic concentration of glucose [20 mM] markedly stimulated the expression of the α-subunits of FTase/GGTase-1, but not the β-subunits of FTase or GGTase-1 without significantly affecting the predominantly cytosolic distribution of these holoenzymes in INS 832/13 cells and rodent islets. Under these conditions, glucose significantly stimulated [2.5- to 4.0-fold over basal] the activities of both FTase and GGTase-1 in both cell types. Together, these findings provide the first evidence to suggest that GSIS involves activation of the endogenous islet prenyltransferases by glucose, culminating in the activation of their respective G-protein substrates, which is necessary for cytoskeletal rearrangement, vesicular transport, fusion and secretion of insulin.

Glucose Transporter 3 Potentiates Degranulation and Is Required for Platelet Activation.

Science.gov (United States)

Fidler, Trevor P; Middleton, Elizabeth A; Rowley, Jesse W; Boudreau, Luc H; Campbell, Robert A; Souvenir, Rhonda; Funari, Trevor; Tessandier, Nicolas; Boilard, Eric; Weyrich, Andrew S; Abel, E Dale

2017-09-01

On activation, platelets increase glucose uptake, glycolysis, and glucose oxidation and consume stored glycogen. This correlation between glucose metabolism and platelet function is not well understood and even less is known about the role of glucose metabolism on platelet function in vivo. For glucose to enter a cell, it must be transported through glucose transporters. Here we evaluate the contribution of GLUT3 (glucose transporter 3) to platelet function to better understand glucose metabolism in platelets. Platelet-specific knockout of GLUT3 was generated by crossing mice harboring GLUT3 floxed allele to a PF4 (platelet factor 4)-driven Cre recombinase. In platelets, GLUT3 is localized primarily on α-granule membranes and under basal conditions facilitates glucose uptake into α-granules to be used for glycolysis. After activation, platelets degranulate and GLUT3 translocates to the plasma membrane, which is responsible for activation-mediated increased glucose uptake. In vivo, loss of GLUT3 in platelets increased survival in a collagen/epinephrine model of pulmonary embolism, and in a K/BxN model of autoimmune inflammatory disease, platelet-specific GLUT3 knockout mice display decreased disease progression. Mechanistically, loss of GLUT3 decreased platelet degranulation, spreading, and clot retraction. Decreased α-granule degranulation is due in part to an impaired ability of GLUT3 to potentiate exocytosis. GLUT3-mediated glucose utilization and glycogenolysis in platelets promotes α-granule release, platelet activation, and postactivation functions. © 2017 American Heart Association, Inc.

Predictive models of glucose control: roles for glucose-sensing neurones

Science.gov (United States)

Kosse, C.; Gonzalez, A.; Burdakov, D.

2018-01-01

The brain can be viewed as a sophisticated control module for stabilizing blood glucose. A review of classical behavioural evidence indicates that central circuits add predictive (feedforward/anticipatory) control to the reactive (feedback/compensatory) control by peripheral organs. The brain/cephalic control is constructed and engaged, via associative learning, by sensory cues predicting energy intake or expenditure (e.g. sight, smell, taste, sound). This allows rapidly measurable sensory information (rather than slowly generated internal feedback signals, e.g. digested nutrients) to control food selection, glucose supply for fight-or-flight responses or preparedness for digestion/absorption. Predictive control is therefore useful for preventing large glucose fluctuations. We review emerging roles in predictive control of two classes of widely projecting hypothalamic neurones, orexin/hypocretin (ORX) and melanin-concentrating hormone (MCH) cells. Evidence is cited that ORX neurones (i) are activated by sensory cues (e.g. taste, sound), (ii) drive hepatic production, and muscle uptake, of glucose, via sympathetic nerves, (iii) stimulate wakefulness and exploration via global brain projections and (iv) are glucose-inhibited. MCH neurones are (i) glucose-excited, (ii) innervate learning and reward centres to promote synaptic plasticity, learning and memory and (iii) are critical for learning associations useful for predictive control (e.g. using taste to predict nutrient value of food). This evidence is unified into a model for predictive glucose control. During associative learning, inputs from some glucose-excited neurones may promote connections between the ‘fast’ senses and reward circuits, constructing neural shortcuts for efficient action selection. In turn, glucose-inhibited neurones may engage locomotion/exploration and coordinate the required fuel supply. Feedback inhibition of the latter neurones by glucose would ensure that glucose fluxes they

Predictive models of glucose control: roles for glucose-sensing neurones.

Science.gov (United States)

Kosse, C; Gonzalez, A; Burdakov, D

2015-01-01

The brain can be viewed as a sophisticated control module for stabilizing blood glucose. A review of classical behavioural evidence indicates that central circuits add predictive (feedforward/anticipatory) control to the reactive (feedback/compensatory) control by peripheral organs. The brain/cephalic control is constructed and engaged, via associative learning, by sensory cues predicting energy intake or expenditure (e.g. sight, smell, taste, sound). This allows rapidly measurable sensory information (rather than slowly generated internal feedback signals, e.g. digested nutrients) to control food selection, glucose supply for fight-or-flight responses or preparedness for digestion/absorption. Predictive control is therefore useful for preventing large glucose fluctuations. We review emerging roles in predictive control of two classes of widely projecting hypothalamic neurones, orexin/hypocretin (ORX) and melanin-concentrating hormone (MCH) cells. Evidence is cited that ORX neurones (i) are activated by sensory cues (e.g. taste, sound), (ii) drive hepatic production, and muscle uptake, of glucose, via sympathetic nerves, (iii) stimulate wakefulness and exploration via global brain projections and (iv) are glucose-inhibited. MCH neurones are (i) glucose-excited, (ii) innervate learning and reward centres to promote synaptic plasticity, learning and memory and (iii) are critical for learning associations useful for predictive control (e.g. using taste to predict nutrient value of food). This evidence is unified into a model for predictive glucose control. During associative learning, inputs from some glucose-excited neurones may promote connections between the 'fast' senses and reward circuits, constructing neural shortcuts for efficient action selection. In turn, glucose-inhibited neurones may engage locomotion/exploration and coordinate the required fuel supply. Feedback inhibition of the latter neurones by glucose would ensure that glucose fluxes they stimulate

Glucose-6-phosphate mediates activation of the carbohydrate responsive binding protein (ChREBP)

International Nuclear Information System (INIS)

Li, Ming V.; Chen, Weiqin; Harmancey, Romain N.; Nuotio-Antar, Alli M.; Imamura, Minako; Saha, Pradip; Taegtmeyer, Heinrich; Chan, Lawrence

2010-01-01

Carbohydrate response element binding protein (ChREBP) is a Mondo family transcription factor that activates a number of glycolytic and lipogenic genes in response to glucose stimulation. We have previously reported that high glucose can activate the transcriptional activity of ChREBP independent of the protein phosphatase 2A (PP2A)-mediated increase in nuclear entry and DNA binding. Here, we found that formation of glucose-6-phosphate (G-6-P) is essential for glucose activation of ChREBP. The glucose response of GAL4-ChREBP is attenuated by D-mannoheptulose, a potent hexokinase inhibitor, as well as over-expression of glucose-6-phosphatase (G6Pase); kinetics of activation of GAL4-ChREBP can be modified by exogenously expressed GCK. Further metabolism of G-6-P through the two major glucose metabolic pathways, glycolysis and pentose-phosphate pathway, is not required for activation of ChREBP; over-expression of glucose-6-phosphate dehydrogenase (G6PD) diminishes, whereas RNAi knockdown of the enzyme enhances, the glucose response of GAL4-ChREBP, respectively. Moreover, the glucose analogue 2-deoxyglucose (2-DG), which is phosphorylated by hexokinase, but not further metabolized, effectively upregulates the transcription activity of ChREBP. In addition, over-expression of phosphofructokinase (PFK) 1 and 2, synergistically diminishes the glucose response of GAL4-ChREBP. These multiple lines of evidence support the conclusion that G-6-P mediates the activation of ChREBP.

Effect of meal composition on calcium absorption: enhancing effect of carbohydrate polymers

International Nuclear Information System (INIS)

Kelly, S.E.; Chawla-Singh, K.; Sellin, J.H.; Yasillo, N.J.; Rosenberg, I.H.

1984-01-01

Meal components including fat, fiber, and carbohydrates can influence the intestinal absorption of calcium; such interactions may be of even greater importance in the presence of intestinal disease. This study compares intestinal absorption of 47CaCl2 administered in four ways: in water, within a standard meal, with a liquid formula (Ensure, Ross Laboratories, Columbus, Ohio), or with a glucose polymer solution (Frodex-15, Ross). Studies were carried out in 9 patients with ileal resection, 3 patients with jejunoileal bypass, and 14 controls. Fractional calcium absorption from water was lower in patients than in controls. Absorption was enhanced 1.5- to 5-fold when 47CaCl2 was administered with a liquid formula diet containing a glucose polymer or with the glucose polymer alone. Patients with the lowest calcium absorption from breakfast showed the greatest effect of calcium ingestion with formula or glucose polymer. These findings further emphasize the importance of meal composition on calcium absorption and provide a possible mechanism for enhancing calcium absorption in some patients with chronically impaired absorption

Glucose oxidase-graphene-chitosan modified electrode for direct electrochemistry and glucose sensing

International Nuclear Information System (INIS)

Kang, Xinhuang; Wang, Jun; Wu, Hong; Aksay, Ilhan A.; Liu, Jun; Lin, Yuehe

2009-01-01

Direct electrochemistry of a glucose oxidase (GOD)/graphene/chitosan nanocomposite was studied. The immobilized enzyme retains its bioactivity, exhibits a surface confined, reversible two-proton and two-electron transfer reaction, and has good stability, activity and a fast heterogeneous electron transfer rate with the rate constant (k s ) of 2.83 s -1 . A much higher enzyme loading (1.12 x 10 -9 mol/cm 2 ) is obtained as compared to the bare glass carbon surface. This GOD/graphene/chitosan nanocomposite film can be used for sensitive detection of glucose. The biosensor exhibits a wider linearity range from 0.08 mM to 12 mM glucose with a detection limit of 0.02 mM and much higher sensitivity (37.93 (micro)A mM -1 cm -2 ) as compared with other nanostructured supports. The excellent performance of the biosensor is attributed to large surface-to-volume ratio and high conductivity of graphene, and good biocompatibility of chitosan, which enhances the enzyme absorption and promotes direct electron transfer between redox enzymes and the surface of electrodes.

Risk factors for glucose intolerance in active acromegaly

Directory of Open Access Journals (Sweden)

Kreze A.

2001-01-01

Full Text Available In the present retrospective study we determined the frequency of glucose intolerance in active untreated acromegaly, and searched for risk factors possibly supporting the emergence of the diabetic condition. Among 43 patients, 8 (19%; 95% CI: 8-33% had diabetes mellitus and 2 (5%; 1-16% impaired glucose tolerance. No impaired fasting glycemia was demonstrable. The frequency of diabetes was on average 4.5 times higher than in the general Slovak population. Ten factors suspected to support progression to glucose intolerance were studied by comparing the frequency of glucose intolerance between patients with present and absent risk factors. A family history of diabetes and arterial hypertension proved to have a significant promoting effect (P<0.05, chi-square test. A significant association with female gender was demonstrated only after pooling our data with literature data. Concomitant prolactin hypersecretion had a nonsignificant promoting effect. In conclusion, the association of active untreated acromegaly with each of the three categories of glucose intolerance (including impaired fasting glycemia, not yet studied in this connection was defined as a confidence interval, thus permitting a sound comparison with the findings of future studies. Besides a family history of diabetes, female gender and arterial hypertension were defined as additional, not yet described risk factors.

Effects of Onion (Allium cepa L. Extract Administration on Intestinal α-Glucosidases Activities and Spikes in Postprandial Blood Glucose Levels in SD Rats Model

Directory of Open Access Journals (Sweden)

Sun-Ho Kim

2011-06-01

Full Text Available Diets high in calories and sweetened foods with disaccharides frequently lead to exaggerated postprandial spikes in blood glucose. This state induces immediate oxidant stress and free radicals which trigger oxidative stress-linked diabetic complications. One of the therapeutic approaches for decreasing postprandial hyperglycemia is to retard absorption of glucose by the inhibition of carbohydrate hydrolyzing enzymes,α-amylase and α-glucosidases, in the digestive organs. Therefore, the inhibitory activity of Korean onion (Allium cepa L. extract against rat intestinal α-glucosidases, such as sucrase, maltase, and porcine pancreatic α-amylase were investigated in vitro and in vivo. The content of quercetin in ethyl alcohol extract of onion skin (EOS was 6.04 g/100 g dried weight of onion skin. The in vitro half-maximal inhibitory concentrations (IC50 of EOS and quercetin, a major phenolic in onion, on rat intestinal sucrase were 0.40 and 0.11 mg/mL, respectively. The postprandial blood glucose lowering effects of EOS and quercetin were compared to a known type 2 diabetes drug (Acarbose, a strong α-glucosidase inhibitor in the Sprague-Dawley (SD rat model. In rats fed on sucrose, EOS significantly reduced the blood glucose spike after sucrose loading. The area under the blood glucose-time curve (AUClast in EOS-treated SD rats (0.5 g-EOS/kg was significantly lower than in untreated SD rats (259.6 ± 5.1 vs. 283.1 ± 19.2 h·mg/dL. The AUClast in quercetin-treated SD rats (0.5 g-quercetin/kg was similar to in EOS-treated group (256.1 ± 3.2 vs. 259.6 ± 5.1 h·mg/dL. Results from this study indicates that although quercetin does have blood glucose lowering potential via α-glucosidase inhibition, there are other bioactive compounds present in onion skin. Furthermore, the effects of two weeks administration of EOS in a high carbohydrate-dietary mixture (Pico 5053 on sucrase and maltase activities in intestine were evaluated in SD rat model

Oral glucose ingestion attenuates exercise-induced activation of 5'-AMP-activated protein kinase in human skeletal muscle

DEFF Research Database (Denmark)

Åkerström, Thorbjörn; Birk, Jesper Bratz; Klein, Ditte Kjærsgaard

2006-01-01

5'-AMP-activated protein kinase (AMPK) has been suggested to be a 'metabolic master switch' regulating various aspects of muscle glucose and fat metabolism. In isolated rat skeletal muscle, glucose suppresses the activity of AMPK and in human muscle glycogen loading decreases exercise-induced AMPK...... activation. We hypothesized that oral glucose ingestion during exercise would attenuate muscle AMPK activation. Nine male subjects performed two bouts of one-legged knee-extensor exercise at 60% of maximal workload. The subjects were randomly assigned to either consume a glucose containing drink or a placebo...... drink during the two trials. Muscle biopsies were taken from the vastus lateralis before and after 2 h of exercise. Plasma glucose was higher (6.0 +/- 0.2 vs. 4.9 +/- 0.1 mmol L-1, P

Optimization of Glucose oxidase towards oxygen independency and high mediator activity for amperometric glucose determination in diabetes analytics

OpenAIRE

Arango Gutierrez, Erik Uwe

2015-01-01

Glucose oxidase is an oxidoreductase exhibiting a high β-D-glucose specificity and high stability which renders glucose oxidase well-suited for applications in diabetes care. Nevertheless, GOx activity is highly oxygen dependent which can lead to inaccuracies in amperometric β-D-glucose determinations. Therefore a directed evolution campaign with two rounds of random mutagenesis (SeSaM followed by epPCR), site saturation mutagenesis studies, and one simultaneous site saturation library (OmniC...

Hydralazine administration activates sympathetic preganglionic neurons whose activity mobilizes glucose and increases cardiovascular function.

Science.gov (United States)

Parker, Lindsay M; Damanhuri, Hanafi A; Fletcher, Sophie P S; Goodchild, Ann K

2015-04-16

Hypotensive drugs have been used to identify central neurons that mediate compensatory baroreceptor reflex responses. Such drugs also increase blood glucose. Our aim was to identify the neurochemical phenotypes of sympathetic preganglionic neurons (SPN) and adrenal chromaffin cells activated following hydralazine (HDZ; 10mg/kg) administration in rats, and utilize this and SPN target organ destination to ascribe their function as cardiovascular or glucose regulating. Blood glucose was measured and adrenal chromaffin cell activation was assessed using c-Fos immunoreactivity (-ir) and phosphorylation of tyrosine hydroxylase, respectively. The activation and neurochemical phenotype of SPN innervating the adrenal glands and celiac ganglia were determined using the retrograde tracer cholera toxin B subunit, in combination with in situ hybridization and immunohistochemistry. Blood glucose was elevated at multiple time points following HDZ administration but little evidence of chromaffin cell activation was seen suggesting non-adrenal mechanisms contribute to the sustained hyperglycemia. 16±0.1% of T4-T11 SPN contained c-Fos and of these: 24.3±1.4% projected to adrenal glands and 29±5.5% projected to celiac ganglia with the rest innervating other targets. 62.8±1.4% of SPN innervating adrenal glands were activated and 29.9±3.3% expressed PPE mRNA whereas 53.2±8.6% of SPN innervating celiac ganglia were activated and 31.2±8.8% expressed PPE mRNA. CART-ir SPN innervating each target were also activated and did not co-express PPE mRNA. Neurochemical coding reveals that HDZ administration activates both PPE+SPN, whose activity increase glucose mobilization causing hyperglycemia, as well as CART+SPN whose activity drive vasomotor responses mediated by baroreceptor unloading to raise vascular tone and heart rate. Copyright © 2015 Elsevier B.V. All rights reserved.

Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption

Science.gov (United States)

Patel, Chirag; Douard, Veronique; Yu, Shiyan; Gao, Nan; Ferraris, Ronaldo P.

2015-01-01

Dietary fructose that is linked to metabolic abnormalities can up-regulate its own absorption, but the underlying regulatory mechanisms are not known. We hypothesized that glucose transporter (GLUT) protein, member 5 (GLUT5) is the primary fructose transporter and that fructose absorption via GLUT5, metabolism via ketohexokinase (KHK), as well as GLUT5 trafficking to the apical membrane via the Ras-related protein-in-brain 11 (Rab11)a-dependent endosomes are each required for regulation. Introducing fructose but not lysine and glucose solutions into the lumen increased by 2- to 10-fold the heterogeneous nuclear RNA, mRNA, protein, and activity levels of GLUT5 in adult wild-type mice consuming chow. Levels of GLUT5 were >100-fold that of candidate apical fructose transporters GLUTs 7, 8, and 12 whose expression, and that of GLUT 2 and the sodium-dependent glucose transporter protein 1 (SGLT1), was not regulated by luminal fructose. GLUT5-knockout (KO) mice exhibited no facilitative fructose transport and no compensatory increases in activity and expression of SGLT1 and other GLUTs. Fructose could not up-regulate GLUT5 in GLUT5-KO, KHK-KO, and intestinal epithelial cell-specific Rab11a-KO mice. The fructose-specific metabolite glyceraldehyde did not increase GLUT5 expression. GLUT5 is the primary transporter responsible for facilitative absorption of fructose, and its regulation specifically requires fructose uptake and metabolism and normal GLUT5 trafficking to the apical membrane.—Patel, C., Douard, V., Yu, S., Gao, N., Ferraris, R. P. Transport, metabolism, and endosomal trafficking-dependent regulation of intestinal fructose absorption. PMID:26071406

Physical activity, fitness, glucose homeostasis, and brain morphology in twins.

Science.gov (United States)

Rottensteiner, Mirva; Leskinen, Tuija; Niskanen, Eini; Aaltonen, Sari; Mutikainen, Sara; Wikgren, Jan; Heikkilä, Kauko; Kovanen, Vuokko; Kainulainen, Heikki; Kaprio, Jaakko; Tarkka, Ina M; Kujala, Urho M

2015-03-01

The main aim of the present study (FITFATTWIN) was to investigate how physical activity level is associated with body composition, glucose homeostasis, and brain morphology in young adult male monozygotic twin pairs discordant for physical activity. From a population-based twin cohort, we systematically selected 10 young adult male monozygotic twin pairs (age range, 32-36 yr) discordant for leisure time physical activity during the past 3 yr. On the basis of interviews, we calculated a mean sum index for leisure time and commuting activity during the past 3 yr (3-yr LTMET index expressed as MET-hours per day). We conducted extensive measurements on body composition (including fat percentage measured by dual-energy x-ray absorptiometry), glucose homeostasis including homeostatic model assessment index and insulin sensitivity index (Matsuda index, calculated from glucose and insulin values from an oral glucose tolerance test), and whole brain magnetic resonance imaging for regional volumetric analyses. According to pairwise analysis, the active twins had lower body fat percentage (P = 0.029) and homeostatic model assessment index (P = 0.031) and higher Matsuda index (P = 0.021) compared with their inactive co-twins. Striatal and prefrontal cortex (subgyral and inferior frontal gyrus) brain gray matter volumes were larger in the nondominant hemisphere in active twins compared with those in inactive co-twins, with a statistical threshold of P physical activity is associated with improved glucose homeostasis and modulation of striatum and prefrontal cortex gray matter volume, independent of genetic background. The findings may contribute to later reduced risk of type 2 diabetes and mobility limitations.

Noninvasive measurement of blood glucose level using mid-infrared quantum cascade lasers

Science.gov (United States)

Yoshioka, Kiriko; Kino, Saiko; Matsuura, Yuji

2017-04-01

For non-invasive measurement of blood glucose level, attenuated total reflection (ATR) absorption spectroscopy system using a QCL as a light source was developed. The results of measurement of glucose solutions showed that the system had a sensitivity that was enough for blood glucose measurement. In-vivo measurement using the proposed system based on QCL showed that there was a correlation between absorptions measured with human lips and blood glucose level.

Enzymatic activity of Glucose Oxidase from Aspergillus niger IPBCC.08.610 On Modified Carbon Paste Electrode as Glucose Biosensor

Science.gov (United States)

Rohmayanti, T.; Ambarsari, L.; Maddu, A.

2017-03-01

Glucose oxidase (GOx) has been developed as glucose sensor for measuring blood glucose level because of its specificity to glucose oxidation. This research aimed to determine kinetic parameters of GOx activity voltametrically and further test its potential as a glucose biosensor. GOx, in this research, was produced by local fungi Aspergillus niger IPBCC.08.610 which was isolated from local vine in Tarakan, East Borneo, Indonesia. GOx was immobilized with glutaraldehyde, which cross-linked onto modified carbon paste electrode (MCPE) nanofiber polyaniline. Intracellular GOx activity was higher than extracellular ones. Immobilized GOx used glutaraldehyde 2.5% and dripped on the surface of MCPE nanofiber polyaniline. MCPE have a high conductance in copper with the diameter of 3 mm. The concentration of glucose in the lowest concentration of 0.2 mM generated a current value of 0.413 mA while 2 mM of glucose induced a current of 3,869 mA value. Km and Imax of GOx in MCPE activities polyaniline nanofiber were 2.88 mM and 3.869 mA,respectively, with turnover (Kcat) of 13 s-1. Sensitivity was 1.09 mA/mM and response time to produce a maximum peak current was 25 seconds. Km value was then converted into units of mg/dL and obtained 56.4 mg/dL. GOximmo-IPB|MCPE electrode is potential to be able to detect blood glucose level in a normal condition and hypoglycemia conditions

Persistent resetting of the cerebral oxygen/glucose uptake ratio by brain activation

DEFF Research Database (Denmark)

Madsen, P L; Hasselbalch, S G; Hagemann, L P

1995-01-01

fraction of the activation-induced excess glucose uptake. These data confirm earlier reports that brain activation can induce resetting of the cerebral oxygen/glucose consumption ratio, and indicate that the resetting persists for a long period after cerebral activation has been terminated and physiologic......Global cerebral blood flow (CBF), global cerebral metabolic rates for oxygen (CMRO2), and for glucose (CMRglc), and lactate efflux were measured during rest and during cerebral activation induced by the Wisconsin card sorting test. Measurements were performed in healthy volunteers using the Kety......-Schmidt technique. Global CMRO2 was unchanged during cerebral activation, whereas global CBF and global CMRglc both increased by 12%, reducing the molar ratio of oxygen to glucose consumption from 6.0 during baseline conditions to 5.4 during activation. Data obtained in the period following cerebral activation...

Helichrysum and grapefruit extracts inhibit carbohydrate digestion and absorption, improving postprandial glucose levels and hyperinsulinemia in rats.

Science.gov (United States)

de la Garza, Ana Laura; Etxeberria, Usune; Lostao, María Pilar; San Román, Belén; Barrenetxe, Jaione; Martínez, J Alfredo; Milagro, Fermín I

2013-12-11

Several plant extracts rich in flavonoids have been reported to improve hyperglycemia by inhibiting digestive enzyme activities and SGLT1-mediated glucose uptake. In this study, helichrysum ( Helichrysum italicum ) and grapefruit ( Citrus × paradisi ) extracts inhibited in vitro enzyme activities. The helichrysum extract showed higher inhibitory activity of α-glucosidase (IC50 = 0.19 mg/mL) than α-amylase (IC50 = 0.83 mg/mL), whereas the grapefruit extract presented similar α-amylase and α-glucosidase inhibitory activities (IC50 = 0.42 mg/mL and IC50 = 0.41 mg/mL, respectively). Both extracts reduced maltose digestion in noneverted intestinal sacs (57% with helichrysum and 46% with grapefruit). Likewise, both extracts inhibited SGLT1-mediated methylglucoside uptake in Caco-2 cells in the presence of Na(+) (56% of inhibition with helichrysum and 54% with grapefruit). In vivo studies demonstrated that helichrysum decreased blood glucose levels after an oral maltose tolerance test (OMTT), and both extracts reduced postprandial glucose levels after the oral starch tolerance test (OSTT). Finally, both extracts improved hyperinsulinemia (31% with helichrysum and 50% with grapefruit) and HOMA index (47% with helichrysum and 54% with grapefruit) in a dietary model of insulin resistance in rats. In summary, helichrysum and grapefruit extracts improve postprandial glycemic control in rats, possibly by inhibiting α-glucosidase and α-amylase enzyme activities and decreasing SGLT1-mediated glucose uptake.

No interactions between previously associated 2-hour glucose gene variants and physical activity or BMI on 2-hour glucose levels

DEFF Research Database (Denmark)

Scott, Robert A; Chu, Audrey Y; Grarup, Niels

2012-01-01

to determine 2-h glucose levels is unknown. We meta-analyzed single nucleotide polymorphism (SNP) × BMI and SNP × physical activity (PA) interaction regression models for five SNPs previously associated with 2-h glucose levels from up to 22 studies comprising 54,884 individuals without diabetes. PA levels were......Gene-lifestyle interactions have been suggested to contribute to the development of type 2 diabetes. Glucose levels 2 h after a standard 75-g glucose challenge are used to diagnose diabetes and are associated with both genetic and lifestyle factors. However, whether these factors interact...... dichotomized, with individuals below the first quintile classified as inactive (20%) and the remainder as active (80%). BMI was considered a continuous trait. Inactive individuals had higher 2-h glucose levels than active individuals (ß = 0.22 mmol/L [95% CI 0.13-0.31], P = 1.63 × 10(-6)). All SNPs were...

Abnormal transient rise in hepatic glucose production after oral glucose in non-insulin-dependent diabetic subjects.

Science.gov (United States)

Thorburn, A; Litchfield, A; Fabris, S; Proietto, J

1995-05-01

A transient rise in hepatic glucose production (HGP) after an oral glucosa load has been reported in some insulin-resistant states such as in obese fa/fa Zucker rats. The aim of this study was to determine whether this rise in HGP also occurs in subjects with established non-insulin-dependent diabetes mellitus (NIDDM). Glucose kinetics were measured basally and during a double-label oral glucose tolerance test (OGTT) in 12 NIDDM subjects and 12 non-diabetic 'control' subjects. Twenty minutes after the glucose load, HGP had increased 73% above basal in the NIDDM subjects (7.29 +/- 0.52 to 12.58 +/- 1.86 mumol/kg/min, P < 0.02). A transient rise in glucagon (12 pg/ml above basal, P < 0.004) occurred at a similar time. In contrast, the control subjects showed no rise in HGP or plasma glucagon. HGP began to suppress 40-50 min after the OGTT in both the NIDDM and control subjects. A 27% increase in the rate of gut-derived glucose absorption was also observed in the NIDDM group, which could be the result of increased gut glucose absorption or decreased first pass extraction of glucose by the liver. Therefore, in agreement with data in animal models of NIDDM, a transient rise in HGP partly contributes to the hyperglycemia observed after an oral glucose load in NIDDM subjects.

Activation-induced resetting of cerebral oxygen and glucose uptake in the rat

DEFF Research Database (Denmark)

Madsen, P L; Linde, R; Hasselbalch, S G

1998-01-01

In the clinical setting it has been shown that activation will increase cerebral glucose uptake in excess of cerebral oxygen uptake. To study this phenomenon further, this study presents an experimental setup that enables precise determination of the ratio between cerebral uptake of glucose...... and oxygen in the awake rat. Global CBF was measured by the Kety-Schmidt technique, and the ratio between cerebral uptake rates for oxygen, glucose, and lactate was calculated from cerebral arterial-venous differences. During baseline conditions, rats were kept in a closed box designed to minimize...... interference. During baseline conditions CBF was 1.08 +/- 0.25 mL x g(-1) x minute(-1), and the cerebral oxygen to glucose uptake ratio was 5.5. Activation was induced by opening the sheltering box for 6 minutes. Activation increased CBF to 1.81 mL x g(-1) x minute(-1). During activation cerebral glucose...

Study on the mechanism of human blood glucose concentration measuring using mid-infrared spectral analysis technology

Science.gov (United States)

Li, Xiang

2016-10-01

All forms of diabetes increase the risk of long-term complications. Blood glucose monitoring is of great importance for controlling diabetes procedure, preventing the complications and improving the patient's life quality. At present, the clinical blood glucose concentration measurement is invasive and could be replaced by noninvasive spectroscopy analytical techniques. The mid-infrared spectral region contains strong characteristic and well-defined absorption bands. Therefore, mid-infrared provides an opportunity for monitoring blood glucose invasively with only a few discrete bonds. Although the blood glucose concentration measurement using mid-infrared spectroscopy has a lot of advantages, the disadvantage is also obvious. The absorption in this infrared region is fundamental molecular group vibration. Absorption intensity is very strong, especially for biological molecules. In this paper, it figures out that the osmosis rate of glucose has a certain relationship with the blood glucose concentration. Therefore, blood glucose concentration could be measured indirectly by measuring the glucose exudate in epidermis layer. Human oral glucose tolerance tests were carried out to verify the correlation of glucose exudation in shallow layer of epidermis layer and blood glucose concentration. As it has been explained above, the mid-infrared spectral region contains well-defined absorption bands, the intensity of absorption peak around 1123 cm-1 was selected to measure the glucose and that around 1170 cm-1 was selected as reference. Ratio of absorption peak intensity was recorded for each set of measurement. The effect and importance of the cleaning the finger to be measured before spectrum measuring are discussed and also verified by experiment.

Binding of navy bean (Phaseolus vulgaris) lectin to the intestinal cells of the rat and its effect on the absorption of glucose

International Nuclear Information System (INIS)

Donatucci, D.A.; Liener, I.E.; Gross, C.J.

1987-01-01

The main objectives of this investigation were to study the binding of a lectin from navy beans with the epithelial cells of the rat intestine and to assess the effect of such binding on the ability of the intestine to absorb glucose. A Scatchard plot, based on the binding of 125 I-labeled lectin to isolated intestinal epithelial cells, was used to calculate an association constant (Ka) of 15 x 10(6)M-1 and the number of binding sites per cell, 12 x 10(6). Metabolic studies were conducted over a period of 5 d on groups of rats fed raw or autoclaved navy bean flour and casein with or without the purified lectin. Growth, protein digestibility, biological value and net protein utilization were significantly lower in animals that had been fed raw navy bean flour or casein plus lectin than in control groups fed diets containing autoclaved navy bean flour or casein alone. Vascular perfusion was used to measure the rate of uptake of glucose by the intestines of rats that had received the various dietary treatments. The rate of absorption of [ 14 C]glucose by intestines from rats fed raw navy bean flour or casein plus lectin was approximately one-half that of their counterparts fed the autoclaved flour or casein alone. These results provide evidence that the lectin, by virtue of its interference with intestinal absorption, is responsible, at least in part, for the nutritional inferiority of raw navy beans

Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity.

Science.gov (United States)

Shi, Xuemei; Chacko, Shaji; Li, Feng; Li, Depei; Burrin, Douglas; Chan, Lawrence; Guan, Xinfu

2017-11-01

Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected excitatory hM3Dq-mCherry AAV into their brainstem NTS. We characterized the metabolic impact of PPG neuron activation on glucose homeostasis and insulin sensitivity using stable isotopic tracers coupled with hyperinsulinemic euglycemic clamp. We showed that after ip injection of clozapine N-oxide, Gcg-Cre lean mice transduced with hM3Dq in the brainstem NTS downregulated basal endogenous glucose production and enhanced glucose tolerance following ip glucose tolerance test. Moreover, acute activation of PPG neurons NTS enhanced whole-body insulin sensitivity as indicated by increased glucose infusion rate as well as augmented insulin-suppression of endogenous glucose production and gluconeogenesis. In contrast, insulin-stimulation of glucose disposal was not altered significantly. We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity. Copyright © 2017 The Authors. Published by Elsevier GmbH.. All rights reserved.

Xanthene derivatives increase glucose utilization through activation of LKB1-dependent AMP-activated protein kinase.

Directory of Open Access Journals (Sweden)

Yonghoon Kwon

Full Text Available 5' AMP-activated protein kinase (AMPK is a highly conserved serine-threonine kinase that regulates energy expenditure by activating catabolic metabolism and suppressing anabolic pathways to increase cellular energy levels. Therefore AMPK activators are considered to be drug targets for treatment of metabolic diseases such as diabetes mellitus. To identify novel AMPK activators, we screened xanthene derivatives. We determined that the AMPK activators 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-nitro-phenyl-thioureido]-ethyl}-amide (Xn and 9H-xanthene-9-carboxylic acid {2,2,2-trichloro-1-[3-(3-cyano-phenyl-thioureido]-ethyl}-amide (Xc elevated glucose uptake in L6 myotubes by stimulating translocation of glucose transporter type 4 (GLUT4. Treatment with the chemical AMPK inhibitor compound C and infection with dominant-negative AMPKa2-virus inhibited AMPK phosphorylation and glucose uptake in myotubes induced by either Xn or Xc. Of the two major upstream kinases of AMPK, we found that Xn and Xc showed LKB1 dependency by knockdown of STK11, an ortholog of human LKB1. Single intravenous administration of Xn and Xc to high-fat diet-induced diabetic mice stimulated AMPK phosphorylation of skeletal muscle and improved glucose tolerance. Taken together, these results suggest that Xn and Xc regulate glucose homeostasis through LKB1-dependent AMPK activation and that the compounds are potential candidate drugs for the treatment of type 2 diabetes mellitus.

Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

Energy Technology Data Exchange (ETDEWEB)

Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji; Yoon, Kun-Ho; Ko, Seung-Hyun; Ahn, Yu-Bae; Song, Ki-Ho, E-mail: kihos@catholic.ac.kr

2013-09-20

Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation.

Oxidative stress plays a role in high glucose-induced activation of pancreatic stellate cells

International Nuclear Information System (INIS)

Ryu, Gyeong Ryul; Lee, Esder; Chun, Hyun-Ji; Yoon, Kun-Ho; Ko, Seung-Hyun; Ahn, Yu-Bae; Song, Ki-Ho

2013-01-01

Highlights: •High glucose increased production of reactive oxygen species in cultured pancreatic stellate cells. •High glucose facilitated the activation of these cells. •Antioxidant treatment attenuated high glucose-induced activation of these cells. -- Abstract: The activation of pancreatic stellate cells (PSCs) is thought to be a potential mechanism underlying islet fibrosis, which may contribute to progressive β-cell failure in type 2 diabetes. Recently, we demonstrated that antioxidants reduced islet fibrosis in an animal model of type 2 diabetes. However, there is no in vitro study demonstrating that high glucose itself can induce oxidative stress in PSCs. Thus, PSCs were isolated and cultured from Sprague Dawley rats, and treated with high glucose for 72 h. High glucose increased the production of reactive oxygen species. When treated with high glucose, freshly isolated PSCs exhibited myofibroblastic transformation. During early culture (passage 1), PSCs treated with high glucose contained an increased number of α-smooth muscle actin-positive cells. During late culture (passages 2–5), PSCs treated with high glucose exhibited increases in cell proliferation, the expression of fibronectin and connective tissue growth factor, release of interleukin-6, transforming growth factor-β and collagen, and cell migration. Finally, the treatment of PSCs with high glucose and antioxidants attenuated these changes. In conclusion, we demonstrated that high glucose increased oxidative stress in primary rat PSCs, thereby facilitating the activation of these cells, while antioxidant treatment attenuated high glucose-induced PSC activation

The rate of intestinal glucose absorption is correlated with plasma glucose-dependent insulinotropic polypeptide concentrations in healthy men

DEFF Research Database (Denmark)

Wachters-Hagedoorn, Renate E; Priebe, Marion G; Heimweg, Janneke A J

2006-01-01

and slowly available glucose. In a crossover study, glucose, insulin, GLP-1, and GIP concentrations were monitored for 6 h after consumption of glucose, uncooked cornstarch (UCCS) or corn pasta in 7 healthy men. All test meals were naturally labeled with 13C. Using a primed, continuous D-[6,6-2H2]glucose...... in the early postprandial phase (15-90 min) occurred after consumption of glucose. There was a strong positive within-subject correlation between RaEx and GIP concentrations (r = 0.73, P meals. Rapidly and slowly digestible carbohydrates differ considerably in their ability to stimulate...

Orexins control intestinal glucose transport by distinct neuronal, endocrine and direct epithelial pathways. : Orexins regulate intestinal glucose absorption

OpenAIRE

Ducroc, Robert; Voisin, Thierry; El Firar, Aadil; Laburthe, Marc

2007-01-01

International audience; Objective : Orexins are neuropeptides involved in energy homeostasis. We investigated the effect of orexin A (OxA) and OxB on intestinal glucose transport in the rat. Research Design and Methods : Injection of orexins led to a decrease in the blood glucose level in OGTT. Effects of orexins on glucose entry were analysed in Ussing chamber using the Na+-dependent increase in short-circuit current to quantify jejunal glucose transport. Results & Conclusions : The rapid an...

Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington’s disease mice

International Nuclear Information System (INIS)

Li, Xueyi; Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B.; DiFiglia, Marian

2012-01-01

Highlights: ► Primary Huntington’s disease neurons are impaired in taking up glucose. ► Rab11 modulates glucose uptake in neurons. ► Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. ► We provide a novel mechanism for glucose hypometabolism in Huntington’s disease. -- Abstract: Huntington’s disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD 140Q/140Q ). Primary HD 140Q/140Q cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD 140Q/140Q neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD 140Q/140Q neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

Glucose-induced serum- and glucocorticoid-regulated kinase activation in oncofetal fibronectin expression

International Nuclear Information System (INIS)

Khan, Zia A.; Barbin, Yousef P.; Farhangkhoee, Hana; Beier, Norbert; Scholz, Wolfgang; Chakrabarti, Subrata

2005-01-01

Preferential expression of oncofetal extra domain-B fibronectin (EDB + FN), a proposed angiogenic marker, has been shown in proliferative diabetic retinopathy. High levels of glucose also increase EDB + FN expression in endothelial cells (ECs) via transforming growth factor-β1 (TGF-β1) and endothelin-1 (ET-1). The present study was aimed at elucidating the role of serum- and glucocorticoid-regulated kinase (SGK-1) in glucose-induced EDB + FN expression. Using human macro- and microvascular ECs, we show that high levels of glucose, TGF-β1, and ET-1 increase the EDB + FN expression via SGK-1 alteration at the mRNA, protein, and activity levels. Inhibition of TGF-β1 and ET-1 prevented glucose-induced SGK-1 activation and the EDB + FN expression. Furthermore, using siRNA-mediated SGK-1 gene silencing, we show that glucose-induced EDB + FN expression can be completely prevented. These findings provide first evidence of glucose-induced SGK-1 activation in altered EDB + FN expression and provide novel avenues for therapeutic modalities

Glycosylation site-targeted PEGylation of glucose oxidase retains native enzymatic activity.

Science.gov (United States)

Ritter, Dustin W; Roberts, Jason R; McShane, Michael J

2013-04-10

Targeted PEGylation of glucose oxidase at its glycosylation sites was investigated to determine the effect on enzymatic activity, as well as the bioconjugate's potential in an optical biosensing assay. Methoxy-poly(ethylene glycol)-hydrazide (4.5kDa) was covalently coupled to periodate-oxidized glycosylation sites of glucose oxidase from Aspergillus niger. The bioconjugate was characterized using gel electrophoresis, liquid chromatography, mass spectrometry, and dynamic light scattering. Gel electrophoresis data showed that the PEGylation protocol resulted in a drastic increase (ca. 100kDa) in the apparent molecular mass of the protein subunit, with complete conversion to the bioconjugate; liquid chromatography data corroborated this large increase in molecular size. Mass spectrometry data proved that the extent of PEGylation was six poly(ethylene glycol) chains per glucose oxidase dimer. Dynamic light scattering data indicated the absence of higher-order oligomers in the PEGylated GOx sample. To assess stability, enzymatic activity assays were performed in triplicate at multiple time points over the course of 29 days in the absence of glucose, as well as before and after exposure to 5% w/v glucose for 24h. At a confidence level of 95%, the bioconjugate's performance was statistically equivalent to native glucose oxidase in terms of activity retention over the 29 day time period, as well as following the 24h glucose exposure. Finally, the bioconjugate was entrapped within a poly(2-hydroxyethyl methacrylate) hydrogel containing an oxygen-sensitive phosphor, and the construct was shown to respond approximately linearly with a 220±73% signal change (n=4, 95% confidence interval) over the physiologically-relevant glucose range (i.e., 0-400mg/dL); to our knowledge, this represents the first demonstration of PEGylated glucose oxidase incorporated into an optical biosensing assay. Copyright © 2013 Elsevier Inc. All rights reserved.

Inhibition by nucleosides of glucose-transport activity in human erythrocytes.

OpenAIRE

Jarvis, S M

1988-01-01

The interaction of nucleosides with the glucose carrier of human erythrocytes was examined by studying the effect of nucleosides on reversible cytochalasin B-binding activity and glucose transport. Adenosine, inosine and thymidine were more potent inhibitors of cytochalasin B binding to human erythrocyte membranes than was D-glucose [IC50 (concentration causing 50% inhibition) values of 10, 24, 28 and 38 mM respectively]. Moreover, low concentrations of thymidine and adenosine inhibited D-glu...

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

Science.gov (United States)

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. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

Basal cerebral glucose distribution in long-term post-traumatic stress disorder.

Science.gov (United States)

Molina, Mario Enrique; Isoardi, Roberto; Prado, Marcela Nathalie; Bentolila, Silvia

2010-03-01

The purpose of this investigation was to study basal cerebral glucose absorption patterns associated to long-term post-traumatic stress disorder. Fluorodeoxyglucose positron emission tomography (FDG-PET) and statistic parametric mapping (SPM) were used to compare regional cerebral glucose absorption between 15 war veterans (Hispanic men, aged 39-41 (M = 39.5, SD = 0.84)) diagnosed with post-traumatic stress disorder (PTSD) based on DSM-IV criteria, and a matching control group of six asymptomatic veterans. This study was conducted 20 years after the traumatic events. PTSD patients presented relatively diminished activity (P<0.005) in: cingulate gyri, precuneus, insula, hippocampus; frontal, pre-frontal and post-central regions; lingual, calcarine, occipital medial and superior gyri, and verbal and paraverbal areas. Relativeley augmented activity (P<0.005) was observed in PTSD patients in: fusiform, temporal superior, medial, and inferior gyri; occipital medial, inferior and lingual gyri; precuneus, and cerebellum. The amygdala and the thalamus showed normal metabolic activity. Various brain regions that showed diminished activity (limbic, frontal and prefrontal cortex, multimodal parieto-occipital areas and verbal and paraverbal areas) have evolved lately, and sub-serve highly complex cognitive and behavioural functions. Metabolic activity patterns are comparable to those observed in personality disorders of the borderline type.

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

Science.gov (United States)

Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John D R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

2015-04-23

Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus of glucose uptake as visualized by functional brain imaging.

Direct neuronal glucose uptake heralds activity-dependent increases in cerebral metabolism

Science.gov (United States)

Lundgaard, Iben; Li, Baoman; Xie, Lulu; Kang, Hongyi; Sanggaard, Simon; Haswell, John Douglas R; Sun, Wei; Goldman, Siri; Blekot, Solomiya; Nielsen, Michael; Takano, Takahiro; Deane, Rashid; Nedergaard, Maiken

2015-01-01

Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using 2-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover, hexokinase, which catalyze the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identifies the neuron as the principal locus of glucose uptake as visualized by functional brain imaging. PMID:25904018

Optical absorption of irradiated carbohydrates

International Nuclear Information System (INIS)

Supe, A.A.; Tiliks, Yu.E.

1994-01-01

The optical absorption spectra of γ-irradiated carbohydrates (glucose, lactose, sucrose, maltose, and starch) and their aqueous solutions were studied. The comparison of the data obtained with the determination of the concentrations of molecular and radical products of radiolysis allows the absorption bands with maxima at 250 and 310 nm to be assigned to the radicals trapped in the irradiated carbohydrates

Effect of absorbable and nonabsorbable sugars on intestinal calcium absorption in humans

International Nuclear Information System (INIS)

Griessen, M.; Speich, P.V.; Infante, F.; Bartholdi, P.; Cochet, B.; Donath, A.; Courvoisier, B.; Bonjour, J.P.

1989-01-01

The effects of glucose, galactose, and lactitol on intestinal calcium absorption and gastric emptying were studied in 9, 8, and 20 healthy subjects, respectively. Calcium absorption was measured by using a double-isotope technique and the kinetic parameters were obtained by a deconvolution method. The gastric emptying rate was determined with /sup 99m/Tc-diethylenetriaminepentaacetic acid and was expressed as the half-time of the emptying curve. Each subject was studied under two conditions: (a) with calcium alone and (b) with calcium plus sugar. Glucose and galactose increased the calcium mean transit time and improved the total fractional calcium absorption by 30% (p less than 0.02). Lactitol decreased the mean rate of absorption (p less than 0.001) and reduced the total fractional calcium absorption by 15% (p less than 0.001). The gastric emptying rate did not appear to influence directly the kinetic parameters of calcium absorption. These results show that both glucose and galactose exert the same stimulatory effect as lactose on calcium absorption in subjects with normal lactase whereas lactitol mimics the effects of lactose in lactase-deficient patients. Thus the absorbability of sugars determines their effect on calcium absorption

Antiangiogenic activity of 2-deoxy-D-glucose.

Directory of Open Access Journals (Sweden)

Jaime R Merchan

2010-10-01

Full Text Available During tumor angiogenesis, endothelial cells (ECs are engaged in a number of energy consuming biological processes, such as proliferation, migration, and capillary formation. Since glucose uptake and metabolism are increased to meet this energy need, the effects of the glycolytic inhibitor 2-deoxy-D-glucose (2-DG on in vitro and in vivo angiogenesis were investigated.In cell culture, 2-DG inhibited EC growth, induced cytotoxicity, blocked migration, and inhibited actively forming but not established endothelial capillaries. Surprisingly, 2-DG was a better inhibitor of these EC properties than two more efficacious glycolytic inhibitors, 2-fluorodeoxy-D-glucose and oxamate. As an alternative to a glycolytic inhibitory mechanism, we considered 2-DG's ability to interfere with endothelial N-linked glycosylation. 2-DG's effects were reversed by mannose, an N-linked glycosylation precursor, and at relevant concentrations 2-DG also inhibited synthesis of the lipid linked oligosaccharide (LLO N-glycosylation donor in a mannose-reversible manner. Inhibition of LLO synthesis activated the unfolded protein response (UPR, which resulted in induction of GADD153/CHOP and EC apoptosis (TUNEL assay. Thus, 2-DG's effects on ECs appeared primarily due to inhibition of LLOs synthesis, not glycolysis. 2-DG was then evaluated in two mouse models, inhibiting angiogenesis in both the matrigel plug assay and the LH(BETAT(AG transgenic retinoblastoma model.In conclusion, 2-DG inhibits endothelial cell angiogenesis in vitro and in vivo, at concentrations below those affecting tumor cells directly, most likely by interfering with N-linked glycosylation rather than glycolysis. Our data underscore the importance of glucose metabolism on neovascularization, and demonstrate a novel approach for anti-angiogenic strategies.

Thyroid states regulate subcellular glucose phosphorylation activity in male mice

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Flavia Letícia Martins Peçanha

2017-07-01

Full Text Available The thyroid hormones (THs, triiodothyronine (T3 and thyroxine (T4, are very important in organism metabolism and regulate glucose utilization. Hexokinase (HK is responsible for the first step of glycolysis, catalyzing the conversion of glucose to glucose 6-phosphate. HK has been found in different cellular compartments, and new functions have been attributed to this enzyme. The effects of hyperthyroidism on subcellular glucose phosphorylation in mouse tissues were examined. Tissues were removed, subcellular fractions were isolated from eu- and hyperthyroid (T3, 0.25 μg/g, i.p. during 21 days mice and HK activity was assayed. Glucose phosphorylation was increased in the particulate fraction in soleus (312.4% ± 67.1, n = 10, gastrocnemius (369.2% ± 112.4, n = 10 and heart (142.2% ± 13.6, n = 10 muscle in the hyperthyroid group compared to the control group. Hexokinase activity was not affected in brain or liver. No relevant changes were observed in HK activity in the soluble fraction for all tissues investigated. Acute T3 administration (single dose of T3, 1.25 μg/g, i.p. did not modulate HK activity. Interestingly, HK mRNA levels remained unchanged and HK bound to mitochondria was increased by T3 treatment, suggesting a posttranscriptional mechanism. Analysis of the AKT pathway showed a 2.5-fold increase in AKT and GSK3B phosphorylation in the gastrocnemius muscle in the hyperthyroid group compared to the euthyroid group. Taken together, we show for the first time that THs modulate HK activity specifically in particulate fractions and that this action seems to be under the control of the AKT and GSK3B pathways.

Linking neuronal brain activity to the glucose metabolism.

Science.gov (United States)

Göbel, Britta; Oltmanns, Kerstin M; Chung, Matthias

2013-08-29

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. 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. 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. The hypothesis of the central role of the brain in whole body energy homeostasis as active controller is supported.

Protein Kinase A Activation Promotes Cancer Cell Resistance to Glucose Starvation and Anoikis.

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Roberta Palorini

2016-03-01

Full Text Available Cancer cells often rely on glycolysis to obtain energy and support anabolic growth. Several studies showed that glycolytic cells are susceptible to cell death when subjected to low glucose availability or to lack of glucose. However, some cancer cells, including glycolytic ones, can efficiently acquire higher tolerance to glucose depletion, leading to their survival and aggressiveness. Although increased resistance to glucose starvation has been shown to be a consequence of signaling pathways and compensatory metabolic routes activation, the full repertoire of the underlying molecular alterations remain elusive. Using omics and computational analyses, we found that cyclic adenosine monophosphate-Protein Kinase A (cAMP-PKA axis activation is fundamental for cancer cell resistance to glucose starvation and anoikis. Notably, here we show that such a PKA-dependent survival is mediated by parallel activation of autophagy and glutamine utilization that in concert concur to attenuate the endoplasmic reticulum (ER stress and to sustain cell anabolism. Indeed, the inhibition of PKA-mediated autophagy or glutamine metabolism increased the level of cell death, suggesting that the induction of autophagy and metabolic rewiring by PKA is important for cancer cellular survival under glucose starvation. Importantly, both processes actively participate to cancer cell survival mediated by suspension-activated PKA as well. In addition we identify also a PKA/Src mechanism capable to protect cancer cells from anoikis. Our results reveal for the first time the role of the versatile PKA in cancer cells survival under chronic glucose starvation and anoikis and may be a novel potential target for cancer treatment.

Deficient Rab11 activity underlies glucose hypometabolism in primary neurons of Huntington's disease mice

Energy Technology Data Exchange (ETDEWEB)

Li, Xueyi, E-mail: xli12@partners.org [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); Valencia, Antonio; McClory, Hollis; Sapp, Ellen; Kegel, Kimberly B. [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States); DiFiglia, Marian, E-mail: difiglia@helix.mgh.harvard.edu [Department of Neurology, Massachusetts General Hospital and Harvard Medical School, Charlestown, MA 02129 (United States)

2012-05-18

Highlights: Black-Right-Pointing-Pointer Primary Huntington's disease neurons are impaired in taking up glucose. Black-Right-Pointing-Pointer Rab11 modulates glucose uptake in neurons. Black-Right-Pointing-Pointer Increasing Rab11 activity attenuates the glucose uptake defect in disease neurons. Black-Right-Pointing-Pointer We provide a novel mechanism for glucose hypometabolism in Huntington's disease. -- Abstract: Huntington's disease (HD) is a progressive neurodegenerative disorder caused by a CAG repeat expansion in the huntingtin gene. Positron emission tomography studies have revealed a decline in glucose metabolism in the brain of patients with HD by a mechanism that has not been established. We examined glucose utilization in embryonic primary cortical neurons of wild-type (WT) and HD knock-in mice, which have 140 CAG repeats inserted in the endogenous mouse huntingtin gene (HD{sup 140Q/140Q}). Primary HD{sup 140Q/140Q} cortical neurons took up significantly less glucose than did WT neurons. Expression of permanently inactive and permanently active forms of Rab11 correspondingly altered glucose uptake in WT neurons, suggesting that normal activity of Rab11 is needed for neuronal uptake of glucose. It is known that Rab11 activity is diminished in HD{sup 140Q/140Q} neurons. Expression of dominant active Rab11 to enhance the activity of Rab11 normalized glucose uptake in HD{sup 140Q/140Q} neurons. These results suggest that deficient activity of Rab11 is a novel mechanism for glucose hypometabolism in HD.

Intestinal absorption of copper: influence of carbohydrates.

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Wapnir, R A; Balkman, C

1992-02-01

Macronutrients can modulate the intestinal absorption of trace elements by binding the metal or altering mucosal function. We investigated whether certain simple and complex carbohydrates modify copper (Cu) absorption, using an in vivo perfusion technique in the rat. Corn syrup solids, which contain a mixture of glucose polymers of diverse length, added at either 20 or 50 mosm/kg enhanced Cu absorption from a 31.5 microM (2 mg/liter) Cu solution (128 +/- 11 and 130 +/- 11 pmol/min x cm, respectively, vs 101 +/- 4 pmol/min x cm, P less than 0.05, in the absence of carbohydrate). This was concomitant with a stimulation of net water absorption (1.05 +/- 0.08 and 0.84 +/- 0.08 microliter/min x cm, respectively, vs 0.63 +/- 0.02 microliter/min x cm with no carbohydrate, P less than 0.05). Glucose, fructose, lactose, or sucrose had no influence on Cu absorption, although they altered water exchanges, an effect attributable to a reduction of the outflow component of fluid recirculation. Low concentrations of lactose resulted in a greater accumulation of Cu in the intestinal mucosa (8.75 +/- 0.71 micrograms/g vs 5.77 +/- 0.68 micrograms/g for controls, P less than 0.05). Hence, solutes that moderately stimulate mucosa-to-serosa fluid influx in a progressive manner, such as glucose polymers, may contribute to functionally increase Cu absorption. Conversely, conditions which tend to reduce water inflow or increase water outflow across the small intestinal mucosa, as may occur with high lactose diets or in cases of chronic diarrhea, may have negative effects.

CREBH Regulates Systemic Glucose and Lipid Metabolism

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Yoshimi Nakagawa

2018-05-01

Full Text Available The cyclic adenosine monophosphate (cAMP-responsive element-binding protein H (CREBH, encoded by CREB3L3 is a membrane-bound transcriptional factor that primarily localizes in the liver and small intestine. CREBH governs triglyceride metabolism in the liver, which mediates the changes in gene expression governing fatty acid oxidation, ketogenesis, and apolipoproteins related to lipoprotein lipase (LPL activation. CREBH in the small intestine reduces cholesterol transporter gene Npc1l1 and suppresses cholesterol absorption from diet. A deficiency of CREBH in mice leads to severe hypertriglyceridemia, fatty liver, and atherosclerosis. CREBH, in synergy with peroxisome proliferator-activated receptor α (PPARα, has a crucial role in upregulating Fgf21 expression, which is implicated in metabolic homeostasis including glucose and lipid metabolism. CREBH binds to and functions as a co-activator for both PPARα and liver X receptor alpha (LXRα in regulating gene expression of lipid metabolism. Therefore, CREBH has a crucial role in glucose and lipid metabolism in the liver and small intestine.

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

DEFF Research Database (Denmark)

Lundgaard, Iben; Li, Baoman; Xie, Lulu

2015-01-01

Metabolically, the brain is a highly active organ that relies almost exclusively on glucose as its energy source. According to the astrocyte-to-neuron lactate shuttle hypothesis, glucose is taken up by astrocytes and converted to lactate, which is then oxidized by neurons. Here we show, using two......-photon imaging of a near-infrared 2-deoxyglucose analogue (2DG-IR), that glucose is taken up preferentially by neurons in awake behaving mice. Anaesthesia suppressed neuronal 2DG-IR uptake and sensory stimulation was associated with a sharp increase in neuronal, but not astrocytic, 2DG-IR uptake. Moreover......, hexokinase, which catalyses the first enzymatic steps in glycolysis, was highly enriched in neurons compared with astrocytes, in mouse as well as in human cortex. These observations suggest that brain activity and neuronal glucose metabolism are directly linked, and identify the neuron as the principal locus...

Synthesis of high specific activity [1-3H]-D-glucose

International Nuclear Information System (INIS)

Saljoughian, M.; Morimoto, Hiromi; Williams, P.G.; Lee, Hakno

1991-01-01

Specifically labeled [1- 3 H]-D-glucose has been used for metabolic and mechanistic studies in erythrocytes. In vitro metabolism of the a and b anomers of the tritiated glucose was readily traced by 3 H NMR spectroscopy. Initial studies used labeled glucose obtained by catalytic exchange labeling (at 4.5-9 Ci/mmole, or 15-30% tritiated at the C-1 position), and this necessitated sample glucose concentrations of 2-4 times physiological. The availability of glucose at maximum specific activity (28.7 Ci/mmole, 100% at the C-1 position) would allow the authors to observe metabolic behavior using 1 mM levels of glucose. Accordingly, they have devised a new route for the synthesis of C-1 tritiated glucose, involving the synthesis of 4,6-O-benzylidene-D-gluconolactone followed by reduction with supertritide. Preliminary work with commercial superdeuteride is complete, and chromatographic and NMR analyses are promising. The analogous tritium reactions are currently underway, and experimental results are presented for all stages of investigation. This strategy should be generally applicable to the labeling of many reducing sugars, with the substrates 2-deoxyglucose and maltotriose being of particular interest to their research

Glucose decouples intracellular Ca2+ activity from glucagon secretion in mouse pancreatic islet alpha-cells.

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Sylvain J Le Marchand

Full Text Available The mechanisms of glucagon secretion and its suppression by glucose are presently unknown. This study investigates the relationship between intracellular calcium levels ([Ca(2+](i and hormone secretion under low and high glucose conditions. We examined the effects of modulating ion channel activities on [Ca(2+](i and hormone secretion from ex vivo mouse pancreatic islets. Glucagon-secreting α-cells were unambiguously identified by cell specific expression of fluorescent proteins. We found that activation of L-type voltage-gated calcium channels is critical for α-cell calcium oscillations and glucagon secretion at low glucose levels. Calcium channel activation depends on K(ATP channel activity but not on tetrodotoxin-sensitive Na(+ channels. The use of glucagon secretagogues reveals a positive correlation between α-cell [Ca(2+](i and secretion at low glucose levels. Glucose elevation suppresses glucagon secretion even after treatment with secretagogues. Importantly, this inhibition is not mediated by K(ATP channel activity or reduction in α-cell [Ca(2+](i. Our results demonstrate that glucose uncouples the positive relationship between [Ca(2+](i and secretory activity. We conclude that glucose suppression of glucagon secretion is not mediated by inactivation of calcium channels, but instead, it requires a calcium-independent inhibitory pathway.

Blood glucose measurement with multiple quantum cascade lasers using hollow-optical fiber-based ATR spectroscopy

Science.gov (United States)

Yoshioka, K.; Kino, S.; Matsuura, Y.

2018-02-01

For non-invasive blood glucose measurement, a measurement system based on mid-infrared ATR spectroscopy equipped with a combination of a QCL as a light source and a hollow-optical fiber as a beam delivery medium is developed. Firstly the measurement sensitivity of the system is evaluated by using glucose solutions and the result shows a significant correlation between optical absorbance and solution concentration. It is also confirmed that the system has a sensitivity that is enough for blood glucose measurement. Then optical absorption of human lips in the mid-infrared wavelength region is measured using a QCL with a wavenumber of 1080 cm-1 where human tissue exhibits strong absorption of glucose and its metabolites. As a result, the measured absorption follows the change of blood glucose well with a time delay of around 10 minutes and correlation factor between the absorbance and the blood glucose level is 0.42.

Activation of Wnt Signaling in Cortical Neurons Enhances Glucose Utilization through Glycolysis.

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Cisternas, Pedro; Salazar, Paulina; Silva-Álvarez, Carmen; Barros, L Felipe; Inestrosa, Nibaldo C

2016-12-09

The Wnt signaling pathway is critical for a number of functions in the central nervous system, including regulation of the synaptic cleft structure and neuroprotection against injury. Deregulation of Wnt signaling has been associated with several brain pathologies, including Alzheimer's disease. In recent years, it has been suggested that the Wnt pathway might act as a central integrator of metabolic signals from peripheral organs to the brain, which would represent a new role for Wnt signaling in cell metabolism. Energy metabolism is critical for normal neuronal function, which mainly depends on glucose utilization. Brain energy metabolism is important in almost all neurological disorders, to which a decrease in the capacity of the brain to utilize glucose has been linked. However, little is known about the relationship between Wnt signaling and neuronal glucose metabolism in the cellular context. In the present study, we found that acute treatment with the Wnt3a ligand induced a large increase in glucose uptake, without changes in the expression or localization of glucose transporter type 3. In addition, we observed that Wnt3a treatment increased the activation of the metabolic sensor Akt. Moreover, we observed an increase in the activity of hexokinase and in the glycolytic rate, and both processes were dependent on activation of the Akt pathway. Furthermore, we did not observe changes in the activity of glucose-6-phosphate dehydrogenase or in the pentose phosphate pathway. The effect of Wnt3a was independent of both the transcription of Wnt target genes and synaptic effects of Wnt3a. Together, our results suggest that Wnt signaling stimulates glucose utilization in cortical neurons through glycolysis to satisfy the high energy demand of these cells. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

Fructose and related food carbohydrates. Sources, intake, absorption, and clinical implications

DEFF Research Database (Denmark)

Rumessen, J J

1992-01-01

It is possible to point out subjects consuming considerable quantities of fructose and sorbitol, and the intake seems to be increasing both from added and natural sources. Studies of the absorption of fructose in animals are inconsistent, and the mechanisms of fructose uptake seem to vary...... in accordance with the species. In most species fructose absorption takes place by a specific carrier (facilitated transport), but it may be active in the rat. In vitro studies of human intestine are very scarce; there is no evidence of active intestinal fructose transport in the human intestine. By means...... interest. Fructans are not absorbed in the small intestine but are strongly fermented in the large bowel. Fructans may be of potential benefit for large-bowel function and blood glucose regulation....

Inhibitory Effects of Ecklonia cava Extract on High Glucose-Induced Hepatic Stellate Cell Activation

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Akiko Kojima-Yuasa

2011-12-01

Full Text Available Nonalcoholic steatohepatitis (NASH is a disease closely associated with obesity and diabetes. A prevalence of type 2 diabetes and a high body mass index in cryptogenic cirrhosis may imply that obesity leads to cirrhosis. Here, we examined the effects of an extract of Ecklonia cava, a brown algae, on the activation of high glucose-induced hepatic stellate cells (HSCs, key players in hepatic fibrosis. Isolated HSCs were incubated with or without a high glucose concentration. Ecklonia cava extract (ECE was added to the culture simultaneously with the high glucose. Treatment with high glucose stimulated expression of type I collagen and α-smooth muscle actin, which are markers of activation in HSCs, in a dose-dependent manner. The activation of high glucose-treated HSCs was suppressed by the ECE. An increase in the formation of intracellular reactive oxygen species (ROS and a decrease in intracellular glutathione levels were observed soon after treatment with high glucose, and these changes were suppressed by the simultaneous addition of ECE. High glucose levels stimulated the secretion of bioactive transforming growth factor-β (TGF-β from the cells, and the stimulation was also suppressed by treating the HSCs with ECE. These results suggest that the suppression of high glucose-induced HSC activation by ECE is mediated through the inhibition of ROS and/or GSH and the downregulation of TGF-β secretion. ECE is useful for preventing the development of diabetic liver fibrosis.

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

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John A Findlay

2015-10-01

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

PCAF Improves Glucose Homeostasis by Suppressing the Gluconeogenic Activity of PGC-1α

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Cheng Sun

2014-12-01

Full Text Available PGC-1α plays a central role in hepatic gluconeogenesis and has been implicated in the onset of type 2 diabetes. Acetylation is an important posttranslational modification for regulating the transcriptional activity of PGC-1α. Here, we show that PCAF is a pivotal acetyltransferase for acetylating PGC-1α in both fasted and diabetic states. PCAF acetylates two lysine residues K328 and K450 in PGC-1α, which subsequently triggers its proteasomal degradation and suppresses its transcriptional activity. Adenoviral-mediated expression of PCAF in the obese mouse liver greatly represses gluconeogenic enzyme activation and glucose production and improves glucose homeostasis and insulin sensitivity. Moreover, liver-specific knockdown of PCAF stimulates PGC-1α activity, resulting in an increase in blood glucose and hepatic glucose output. Our results suggest that PCAF might be a potential pharmacological target for developing agents against metabolic disorders associated with hyperglycemia, such as obesity and diabetes.

Influence of temperature on water and aqueous glucose absorption spectra in the near- and mid-infrared regions at physiologically relevant temperatures

DEFF Research Database (Denmark)

Jensen, P.S.; Bak, J.; Andersson-Engels, S.

2003-01-01

transmission cell controlled within 0.02 degreesC. Pathlengths of 50 mum and 0.4 mm were used in the mid- and near-infrared spectral region, respectively. Difference spectra were used to determine the effect of temperature on the water spectra quantitatively. These spectra were obtained by subtracting the 37...... degreesC water spectrum from the spectra measured at other temperatures. The difference spectra reveal that the effect of temperature is highest in the vicinity of the strong absorption bands, with a number of isosbestic points with no temperature dependence and relatively flat plateaus in between......Near- and mid-infrared absorption spectra of pure water and aqueous 1.0 g/dL glucose solutions in the wavenumber range 8000-950 cm(-1) were measured in the temperature range 30-42 C in steps of 2 degreesC. Measurements were carried out with an FT-IR spectrometer and a variable pathlength...

Sweet taste receptor serves to activate glucose- and leptin-responsive neurons in the hypothalamic arcuate nucleus and participates in glucose responsiveness.

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Daisuke Kohno

2016-11-01

Full Text Available The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC: glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanism underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2 and taste type 1 receptor 3 (T1R3 and senses sweet tastes. T1R2 and T1R3 receptors are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca2+ concentration ([Ca2+]i in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10-5 M-10-2 M dose dependently increased [Ca2+]i in 12-16% of ARC neurons. The sucralose-induced [Ca2+]i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca2+]i increase was inhibited under an extracellular Ca2+-free condition and in the presence of an L-type Ca2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentage of proopiomelanocortin (POMC neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular

Sweet Taste Receptor Serves to Activate Glucose- and Leptin-Responsive Neurons in the Hypothalamic Arcuate Nucleus and Participates in Glucose Responsiveness.

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Kohno, Daisuke; Koike, Miho; Ninomiya, Yuzo; Kojima, Itaru; Kitamura, Tadahiro; Yada, Toshihiko

2016-01-01

The hypothalamic feeding center plays an important role in energy homeostasis. In the feeding center, whole-body energy signals including hormones and nutrients are sensed, processed, and integrated. As a result, food intake and energy expenditure are regulated. Two types of glucose-sensing neurons exist in the hypothalamic arcuate nucleus (ARC): glucose-excited neurons and glucose-inhibited neurons. While some molecules are known to be related to glucose sensing in the hypothalamus, the mechanisms underlying glucose sensing in the hypothalamus are not fully understood. The sweet taste receptor is a heterodimer of taste type 1 receptor 2 (T1R2) and taste type 1 receptor 3 (T1R3) and senses sweet tastes. T1R2 and T1R3 are distributed in multiple organs including the tongue, pancreas, adipose tissue, and hypothalamus. However, the role of sweet taste receptors in the ARC remains to be clarified. To examine the role of sweet taste receptors in the ARC, cytosolic Ca 2+ concentration ([Ca 2+ ] i ) in isolated single ARC neurons were measured using Fura-2 fluorescent imaging. An artificial sweetener, sucralose at 10 -5 -10 -2 M dose dependently increased [Ca 2+ ] i in 12-16% of ARC neurons. The sucralose-induced [Ca 2+ ] i increase was suppressed by a sweet taste receptor inhibitor, gurmarin. The sucralose-induced [Ca 2+ ] i increase was inhibited under an extracellular Ca 2+ -free condition and in the presence of an L-type Ca 2+ channel blocker, nitrendipine. Sucralose-responding neurons were activated by high-concentration of glucose. This response to glucose was markedly suppressed by gurmarin. More than half of sucralose-responding neurons were activated by leptin but not ghrelin. Percentages of proopiomelanocortin (POMC) neurons among sucralose-responding neurons and sweet taste receptor expressing neurons were low, suggesting that majority of sucralose-responding neurons are non-POMC neurons. These data suggest that sweet taste receptor-mediated cellular activation

Correction for sample self-absorption in activity determination by gamma spectrometry

International Nuclear Information System (INIS)

Galloway, R.B.

1991-01-01

Gamma ray spectrometry is a convenient method of determining the activity of the radioactive components in environmental samples. Commonly samples vary in gamma absorption or differ in absorption from the calibration standards available, so that accurate correction for self-absorption in the sample is essential. A versatile correction procedure is described. (orig.)

Effect of vigorous physical activity on blood lipid and glucose.

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Kwon, Hyoung-Jeong; Lee, Han-Joon

2017-12-01

The aim of the study is to investigate how the participation of vigorous physical activities in the health examination contributes to blood lipid and blood glucose. A total of 56,810 workers from the Ulsan University Hospital in Ulsan, Subjects were tested for health checkups from February to November in 2016. The subject is those who does not have medical history, current ailments, and medication histories, and selected those who conducted the study of subjects tested to research. And this study did not consider their drinking and smoking. The final selected population was 11,557 and categorized as a vigorous physical activity of the health survey items. In this study, the group participated by the vigorous physical activity activities, group 1 (n= 70) had more than 6 days of vigorous physical activity, group 2 (n= 2,960) is 3 to 5 days of vigorous physical activity, the group 3 (n= 7,389) is 1 to 2 days of vigorous physical activity. The group 4 (n= 1,138) were classified as those who did not perform vigorous physical activity. To achieve the purpose of the study, the questionnaire examined blood lipid and blood glucose, using questions related to physical activity related to health examination in the Ulsan University Hospital. We obtained the mean and standard deviation for each group and conducted the one-way analysis of variance as an independent variable. Post hoc is least significant difference test and significant level is 0.05. Vigorous physical activity more than 3 days of participation had a positive affect high-density lipoprotein cholesterol and triglyceride. But participation in vigorous physical activity did not affect blood glucose.

Errors in instumental neutron activation analysis caused by matrix absorption

International Nuclear Information System (INIS)

Croudace, I.W.

1979-01-01

Instrumental neutron activation analysis of the geochemically important rare earth elements, together with Ta, Hf and U involves energies below 150 keV where absorption of radiation by the sample becomes inceasingly important. Determinations of the total mass absorption coefficients have been made. (C.F.)

Association of radiowave absorption with E(sporadic)-activity

International Nuclear Information System (INIS)

Ganguly, S.

1975-01-01

Noontime radiowave absorption data for frequencies which are reflected below the height of sporadic-E layers show a strong positive correlation with the sporadic-E layer activity. The possibilities of atmospheric waves affecting both the sporadic-E activity as well as mesospheric ionization are suggested to explain this association

Pre-gravid physical activity and reduced risk of glucose intolerance in pregnancy: the role of insulin sensitivity.

Science.gov (United States)

Retnakaran, Ravi; Qi, Ying; Sermer, Mathew; Connelly, Philip W; Zinman, Bernard; Hanley, Anthony J G

2009-04-01

Pre-gravid physical activity has been associated with a reduced risk of gestational diabetes mellitus (GDM), although neither the types of exercise nor the physiologic mechanisms underlying this protective effect have been well-studied. Thus, we sought to study the relationships between types of pre-gravid physical activity and metabolic parameters in pregnancy, including glucose tolerance, insulin sensitivity and beta-cell function. A total of 851 women underwent a glucose challenge test (GCT) and a 3-h oral glucose tolerance test (OGTT) in late pregnancy, yielding four glucose tolerance groups: (i) GDM; (ii) gestational impaired glucose tolerance (GIGT); (iii) abnormal GCT with normal glucose tolerance on OGTT (abnormal GCT NGT); and (iv) normal GCT with NGT on OGTT (normal GCT NGT). Pre-gravid physical activity was assessed using the Baecke questionnaire, which measures (i) total physical activity and (ii) its three component domains: work, nonsport leisure-time, and vigorous/sports activity. Glucose tolerance status improved across increasing quartiles of pre-gravid total physical activity (P = 0.0244). Whereas neither work nor nonsport leisure-time activity differed between glucose tolerance groups, pre-gravid vigorous/sports activity was significantly higher in women with normal GCT NGT compared to women with (i) abnormal GCT NGT (P = 0.0018) (ii) GIGT (P = 0.0025), and (iii) GDM (P = 0.0044). In particular, vigorous/sports activity correlated with insulin sensitivity (measured by IS(OGTT)) (r = 0.21, P sports activity emerged as a significant independent predictor of IS(OGTT) in pregnancy (t = 4.97, P sports activity is associated with a reduced risk of glucose intolerance in pregnancy, an effect likely mediated by enhanced insulin sensitivity.

Roles of the Gut in Glucose Homeostasis

DEFF Research Database (Denmark)

Holst, Jens Juul; Gribble, Fiona; Horowitz, Michael

2016-01-01

The gastrointestinal tract plays a major role in the regulation of postprandial glucose profiles. Gastric emptying is a highly regulated process, which normally ensures a limited and fairly constant delivery of nutrients and glucose to the proximal gut. The subsequent digestion and absorption...... of nutrients are associated with the release of a set of hormones that feeds back to regulate subsequent gastric emptying and regulates the release of insulin, resulting in downregulation of hepatic glucose production and deposition of glucose in insulin-sensitive tissues. These remarkable mechanisms normally...... keep postprandial glucose excursions low, regardless of the load of glucose ingested. When the regulation of emptying is perturbed (e.g., pyloroplasty, gastric sleeve or gastric bypass operation), postprandial glycemia may reach high levels, sometimes followed by profound hypoglycemia. This article...

Glucose de-repression by yeast AMP-activated protein kinase SNF1 is controlled via at least two independent steps.

Science.gov (United States)

García-Salcedo, Raúl; Lubitz, Timo; Beltran, Gemma; Elbing, Karin; Tian, Ye; Frey, Simone; Wolkenhauer, Olaf; Krantz, Marcus; Klipp, Edda; Hohmann, Stefan

2014-04-01

The AMP-activated protein kinase, AMPK, controls energy homeostasis in eukaryotic cells but little is known about the mechanisms governing the dynamics of its activation/deactivation. The yeast AMPK, SNF1, is activated in response to glucose depletion and mediates glucose de-repression by inactivating the transcriptional repressor Mig1. Here we show that overexpression of the Snf1-activating kinase Sak1 results, in the presence of glucose, in constitutive Snf1 activation without alleviating glucose repression. Co-overexpression of the regulatory subunit Reg1 of the Glc-Reg1 phosphatase complex partly restores glucose regulation of Snf1. We generated a set of 24 kinetic mathematical models based on dynamic data of Snf1 pathway activation and deactivation. The models that reproduced our experimental observations best featured (a) glucose regulation of both Snf1 phosphorylation and dephosphorylation, (b) determination of the Mig1 phosphorylation status in the absence of glucose by Snf1 activity only and (c) a regulatory step directing active Snf1 to Mig1 under glucose limitation. Hence it appears that glucose de-repression via Snf1-Mig1 is regulated by glucose via at least two independent steps: the control of activation of the Snf1 kinase and directing active Snf1 to inactivating its target Mig1. © 2014 FEBS.

Vasopressin activates Akt/mTOR pathway in smooth muscle cells cultured in high glucose concentration

Energy Technology Data Exchange (ETDEWEB)

Montes, Daniela K.; Brenet, Marianne; Muñoz, Vanessa C.; Burgos, Patricia V.; Villanueva, Carolina I. [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Figueroa, Carlos D. [Department of Anatomy, Histology and Pathology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); González, Carlos B., E-mail: cbgonzal@uach.cl [Department of Physiology, Universidad Austral de Chile, Valdivia 509-9200 (Chile); Department of Neuroscience and Cell Biology, University of Texas Medical Branch, Galveston, TX 77555 (United States)

2013-11-29

Highlights: •AVP induces mTOR phosphorylation in A-10 cells cultured in high glucose concentration. •The mTOR phosphorylation is mediated by the PI3K/Akt pathway activation. •The AVP-induced mTOR phosphorylation inhibited autophagy and stimulated cell proliferation. -- Abstract: Mammalian target of rapamycin (mTOR) complex is a key regulator of autophagy, cell growth and proliferation. Here, we studied the effects of arginine vasopressin (AVP) on mTOR activation in vascular smooth muscle cells cultured in high glucose concentration. AVP induced the mTOR phosphorylation in A-10 cells grown in high glucose, in contrast to cells cultured in normal glucose; wherein, only basal phosphorylation was observed. The AVP-induced mTOR phosphorylation was inhibited by a PI3K inhibitor. Moreover, the AVP-induced mTOR activation inhibited autophagy and increased thymidine incorporation in cells grown in high glucose. This increase was abolished by rapamycin which inhibits the mTORC1 complex formation. Our results suggest that AVP stimulates mTOR phosphorylation by activating the PI3K/Akt signaling pathway and, subsequently, inhibits autophagy and raises cell proliferation in A-10 cells maintained in high glucose concentration.

Quantify Glucose Level in Freshly Diabetic's Blood by Terahertz Time-Domain Spectroscopy

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Chen, Hua; Chen, Xiaofeng; Ma, Shihua; Wu, Xiumei; Yang, Wenxing; Zhang, Weifeng; Li, Xiao

2018-04-01

We demonstrate the capability of terahertz (THz) time-domain spectroscopy (TDS) to quantify glucose level in ex vivo freshly diabetic's blood. By investigating the THz spectra of different human blood, we find out THz absorption coefficients reflect a high sensitivity to the glucose level in blood. With a quantitative analysis of 70 patients, we demonstrate that the THz absorption coefficients and the blood glucose levels perform a linear relationship. A comparative experiment between THz measurement and glucometers is also conducted with another 20 blood samples, and the results confirm that the relative error is as less as 15%. Our ex vivo human blood study indicates that THz technique has great potential application to diagnose blood glucose level in clinical practice.

Non-invasive optical detection of glucose in cell culture nutrient medium

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Cote, Gerald L.

1993-01-01

The objective of the proposed research was to begin the development of a non-invasive optical sensor for measuring glucose concentration in the output medium of cell cultures grown in a unique NASA bioreactor referred to as an integrated rotating-wall vessel (IRWV). The input, a bovine serum based nutrient media, has a known glucose concentration. The cells within the bioreactor digest a portion of the glucose. Thus, the non-invasive optical sensor is needed to monitor the decrease in glucose due to cellular consumption since the critical parameters for sustained cellular productivity are glucose and pH. Previous glucose sensing techniques have used chemical reactions to quantify the glucose concentration. Chemical reactions, however, cannot provide for continuous, real time, non-invasive measurement as is required in this application. Our effort while in the fellowship program was focused on the design, optical setup, and testing of one bench top prototype non-invasive optical sensor using a mid-infrared absorption spectroscopy technique. Glucose has a fundamental vibrational absorption peak in the mid-infrared wavelength range at 9.6 micron. Preliminary absorption data using a CO2 laser were collected at this wavelength for water based glucose solutions at different concentrations and one bovine serum based nutrient medium (GTSF) with added glucose. The results showed near linear absorption responses for the glucose-in-water data with resolutions as high at 108 mg/dl and as low as 10 mg/dl. The nutrient medium had a resolution of 291 mg/dl. The variability of the results was due mainly to thermal and polarization drifts of the laser while the decrease in sensitivity to glucose in the nutrient medium was expected due to the increase in the number of confounders present in the nutrient medium. A multispectral approach needs to be used to compensate for these confounders. The CO2 laser used for these studies was wavelength tunable (9.2 to 10.8 micrometers), however

Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons.

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Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula; Waagepetersen, Helle S

2006-10-01

Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity including vesicular release. The incorporation of 13C label into intracellular lactate, alanine, succinate, glutamate, and aspartate was determined by mass spectrometry. The metabolism of [U-13C]lactate under non-depolarizing conditions was high compared with that of [U-13C]glucose; however, it decreased significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx and efflux of glutamate was examined using preloaded D-[3H]aspartate as a glutamate tracer and DL-threo-beta-benzyloxyaspartate to inhibit glutamate transporters. The results suggest that glucose is essential to prevent depolarization-induced reversal of the transporter (efflux), whereas vesicular release was unaffected by the choice of substrate. In conclusion, the present study shows that glucose is a necessary substrate to maintain neurotransmitter homeostasis during synaptic activity and that synaptic activity does not induce an upregulation of lactate metabolism in glutamatergic neurons.

P21-activated kinase 2 (PAK2) regulates glucose uptake and insulin sensitivity in neuronal cells.

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Varshney, Pallavi; Dey, Chinmoy Sankar

2016-07-05

P21-activated kinases (PAKs) are recently reported as important players of insulin signaling and glucose homeostasis in tissues like muscle, pancreas and liver. However, their role in neuronal insulin signaling is still unknown. Present study reports the involvement of PAK2 in neuronal insulin signaling, glucose uptake and insulin resistance. Irrespective of insulin sensitivity, insulin stimulation decreased PAK2 activity. PAK2 downregulation displayed marked enhancement of GLUT4 translocation with increase in glucose uptake whereas PAK2 over-expression showed its reduction. Treatment with Akti-1/2 and wortmannin suggested that Akt and PI3K are mediators of insulin effect on PAK2 and glucose uptake. Rac1 inhibition demonstrated decreased PAK2 activity while inhibition of PP2A resulted in increased PAK2 activity, with corresponding changes in glucose uptake. Taken together, present study demonstrates an inhibitory role of insulin signaling (via PI3K-Akt) and PP2A on PAK2 activity and establishes PAK2 as a Rac1-dependent negative regulator of neuronal glucose uptake and insulin sensitivity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

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

DEFF Research Database (Denmark)

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

2015-01-01

Aim/hypothesis: Little is known about the relative roles of physical activity energy expenditure (PAEE) and cardiorespiratory fitness (CRF) as determinants of glucose regulation. The aim of this study was to examine the associations of PAEE and CRF with markers of glucose metabolism, and to test...... the hypothesis that CRF modifies the association between PAEE and glucose metabolism. Methods: We analysed cross-sectional data from 755 adults from the Danish ADDITION-PRO study. On the basis of OGTT results, participants without known diabetes were classified as having normal glucose tolerance, isolated...... impaired fasting glycaemia (i-IFG), isolated impaired glucose tolerance (i-IGT), combined IFG + IGT or screen-detected diabetes mellitus. Markers of insulin sensitivity and beta cell function were determined. PAEE was measured using a combined heart rate and movement sensor. CRF (maximal oxygen uptake...

Inhibition of glucose intestinal absorption by kaempferol 3-O-α-rhamnoside purified from Bauhinia megalandra leaves.

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Rodríguez, Patricia; González-Mujica, Freddy; Bermúdez, Jairo; Hasegawa, Masahisa

2010-12-01

Glucose intestinal absorption (GIA) is one of the factors that increase glycemia. Its reduction could be an important factor in decreasing hyperglycemia in diabetic patients. It has been shown that the aqueous extract of Bauhinia megalandra leaves inhibits GIA. In the present study we identified a compound present in the extract of B. megalandra responsible for the biological effect. The methanol extract of B. megalandra leaves was fractionated using different solvents, and high-speed counter-current chromatography yielding two pure compounds identified by (1)H NMR and (13)C NMR as kaempferol 3-O-α-rhamnoside and quercetin 3-O-α-rhamnoside. The first one increased the K(M) without changes in the V(MAX) of GIA. In addition it exerted an additive inhibitory effect, on GIA, when combined with phlorizin. We suggest that kaempferol 3-O-α-rhamnoside is a competitive inhibitor of intestinal SGLT1 cotransporter. Copyright © 2010 Elsevier B.V. All rights reserved.

A study of glucose handling by Buddhist monks.

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Aung, T; Myint, H; Thein, M

1988-04-01

Fourteen Buddhist monks and comparable male subjects were studied in relation to their handling of glucose after a meal (consisting of 1190 kcal, 29 g protein, 21 g fat and 221 g carbohydrate) and afterwards subjected to an oral glucose tolerance test (oGTT). The time course of blood glucose levels after the meal indicated that the monks had enhanced absorption and utilization of glucose. The monks were also found to have increased tolerance to glucose on oGTT. In addition the mean total serum cholesterol level in the monks (157.2 +/- 5.53 mg/dl) was found to be significantly higher than that of the control subjects (117.4 +/- 2.85 mg/dl).

Glucose stimulates intestinal epithelial crypt proliferation by modulating cellular energy metabolism.

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Zhou, Weinan; Ramachandran, Deepti; Mansouri, Abdelhak; Dailey, Megan J

2018-04-01

The intestinal epithelium plays an essential role in nutrient absorption, hormone release, and barrier function. Maintenance of the epithelium is driven by continuous cell renewal by stem cells located in the intestinal crypts. The amount and type of diet influence this process and result in changes in the size and cellular make-up of the tissue. The mechanism underlying the nutrient-driven changes in proliferation is not known, but may involve a shift in intracellular metabolism that allows for more nutrients to be used to manufacture new cells. We hypothesized that nutrient availability drives changes in cellular energy metabolism of small intestinal epithelial crypts that could contribute to increases in crypt proliferation. We utilized primary small intestinal epithelial crypts from C57BL/6J mice to study (1) the effect of glucose on crypt proliferation and (2) the effect of glucose on crypt metabolism using an extracellular flux analyzer for real-time metabolic measurements. We found that glucose increased both crypt proliferation and glycolysis, and the glycolytic pathway inhibitor 2-deoxy-d-glucose (2-DG) attenuated glucose-induced crypt proliferation. Glucose did not enhance glucose oxidation, but did increase the maximum mitochondrial respiratory capacity, which may contribute to glucose-induced increases in proliferation. Glucose activated Akt/HIF-1α signaling pathway, which might be at least in part responsible for glucose-induced glycolysis and cell proliferation. These results suggest that high glucose availability induces an increase in crypt proliferation by inducing an increase in glycolysis with no change in glucose oxidation. © 2017 Wiley Periodicals, Inc.

Active coping with stress suppresses glucose metabolism in the rat hypothalamus.

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Ono, Yumie; Lin, Hsiao-Chun; Tzen, Kai-Yuan; Chen, Hui-Hsing; Yang, Pai-Feng; Lai, Wen-Sung; Chen, Jyh-Horng; Onozuka, Minoru; Yen, Chen-Tung

2012-03-01

We used 18F-fluorodeoxyglucose small-animal positron-emission tomography to determine whether different styles of coping with stress are associated with different patterns of neuronal activity in the hypothalamus. Adult rats were subjected to immobilization (IMO)-stress or to a non-immobilized condition for 30 min, in random order on separate days, each of which was followed by brain-scanning. Some rats in the immobilized condition were allowed to actively cope with the stress by chewing a wooden stick during IMO, while the other immobilized rats were given nothing to chew on. Voxel-based statistical analysis of the brain imaging data shows that chewing counteracted the stress-induced increased glucose uptake in the hypothalamus to the level of the non-immobilized condition. Region-of-interest analysis of the glucose uptake values further showed that chewing significantly suppressed stress-induced increased glucose uptake in the paraventricular hypothalamic nucleus and the anterior hypothalamic area but not in the lateral hypothalamus. Together with the finding that the mean plasma corticosterone concentration at the termination of the IMO was also significantly suppressed when rats had an opportunity to chew a wooden stick, our results showed that active coping by chewing inhibited the activation of the hypothalamic-pituitary-adrenal axis to reduce the endocrine stress response.

Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

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Xuemei Shi

2017-11-01

Conclusions: We conclude that acute activation of PPG neurons in the brainstem reduces basal glucose production, enhances intraperitoneal glucose tolerance, and augments hepatic insulin sensitivity, suggesting an important physiological role of PPG neurons-mediated circuitry in promoting glycemic control and insulin sensitivity.

Parsing glucose entry into the brain: novel findings obtained with enzyme-based glucose biosensors.

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Kiyatkin, Eugene A; Wakabayashi, Ken T

2015-01-21

Extracellular levels of glucose in brain tissue reflect dynamic balance between its gradient-dependent entry from arterial blood and its use for cellular metabolism. In this work, we present several sets of previously published and unpublished data obtained by using enzyme-based glucose biosensors coupled with constant-potential high-speed amperometry in freely moving rats. First, we consider basic methodological issues related to the reliability of electrochemical measurements of extracellular glucose levels in rats under physiologically relevant conditions. Second, we present data on glucose responses induced in the nucleus accumbens (NAc) by salient environmental stimuli and discuss the relationships between local neuronal activation and rapid glucose entry into brain tissue. Third, by presenting data on changes in NAc glucose induced by intravenous and intragastric glucose delivery, we discuss other mechanisms of glucose entry into the extracellular domain following changes in glucose blood concentrations. Lastly, by showing the pattern of NAc glucose fluctuations during glucose-drinking behavior, we discuss the relationships between "active" and "passive" glucose entry to the brain, its connection to behavior-related metabolic activation, and the possible functional significance of these changes in behavioral regulation. These data provide solid experimental support for the "neuronal" hypothesis of neurovascular coupling, which postulates the critical role of neuronal activity in rapid regulation of vascular tone, local blood flow, and entry of glucose and oxygen to brain tissue to maintain active cellular metabolism.

Investigation of repressive and enhancive effects of fruit extracts on the activity of glucose-6-phophatase.

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Zahoor, Muhammad; Jan, Muhammad Rasul; Naz, Sumaira

2016-11-01

Glucose-6-phosphatase is a key enzyme of glucose metabolic pathways. Deficiency of this enzyme leads to glycogen storage disease. This enzyme also plays a negative role in diabetes mellitus disorder in which the catalytic activity of this enzyme increases. Thus there is need for activators to enhance the activity of glucose-6-phosphatase in glycogen storage disease of type 1b while in diabetes mellitus repressors are needed to reduce its activity. Crude extracts of apricot, fig, mulberry and apple fruits were investigated for their repressive/enhancive effects on glucose-6-phosphatase in vivo. Albino mice were used as experimental animal. All the selected extracts showed depressive effects on glucose-6-phosphatase, which shows that all these extracts can be used as antidiabetic supplement of food. The inhibitory pattern was competitive one, which was evident from the effect of increasing dose from 1g/Kg body weight to 3g/Kg body weight for all the selected fruit extracts. However fig and apple fruit extracts showed high repressive effects for high doses as compared to apricot and mulberry fruit extracts. None of these selected fruit extracts showed enhancive effect on glucose-6-phosphatase activity. All these fruits or their extracts can be used as antidiabetic dietary supplement for diabetes mellitus.

Astrocyte glycogen as an emergency fuel under conditions of glucose deprivation or intense neural activity.

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Brown, Angus M; Ransom, Bruce R

2015-02-01

Energy metabolism in the brain is a complex process that is incompletely understood. Although glucose is agreed as the main energy support of the brain, the role of glucose is not clear, which has led to controversies that can be summarized as follows: the fate of glucose, once it enters the brain is unclear. It is not known the form in which glucose enters the cells (neurons and glia) within the brain, nor the degree of metabolic shuttling of glucose derived metabolites between cells, with a key limitation in our knowledge being the extent of oxidative metabolism, and how increased tissue activity alters this. Glycogen is present within the brain and is derived from glucose. Glycogen is stored in astrocytes and acts to provide short-term delivery of substrates to neural elements, although it may also contribute an important component to astrocyte metabolism. The roles played by glycogen awaits further study, but to date its most important role is in supporting neural elements during increased firing activity, where signaling molecules, proposed to be elevated interstitial K(+), indicative of elevated neural firing rates, activate glycogen phosphorylase leading to increased production of glycogen derived substrate.

In vitro glucose uptake activity of Aegles marmelos and Syzygium cumini by activation of Glut-4, PI3 kinase and PPARgamma in L6 myotubes.

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Anandharajan, R; Jaiganesh, S; Shankernarayanan, N P; Viswakarma, R A; Balakrishnan, A

2006-06-01

The purpose of the present study is to investigate the effect of methanolic extracts of Aegles marmelos and Syzygium cumini on a battery of targets glucose transporter (Glut-4), peroxisome proliferator activator receptor gamma (PPARgamma) and phosphatidylinositol 3' kinase (PI3 kinase) involved in glucose transport. A. marmelos and S. cumini are anti-diabetic medicinal plants being used in Indian traditional medicine. Different solvent extracts extracted sequentially were analysed for glucose uptake activity at each step and methanol extracts were found to be significantly active at 100ng/ml dose comparable with insulin and rosiglitazone. Elevation of Glut-4, PPARgamma and PI3 kinase by A. marmelos and S. cumini in association with glucose transport supported the up-regulation of glucose uptake. The inhibitory effect of cycloheximide on A. marmelos- and S. cumini-mediated glucose uptake suggested that new protein synthesis is required for the elevated glucose transport. Current observation concludes that methanolic extracts of A. marmelos and S. cumini activate glucose transport in a PI3 kinase-dependent fashion.

Buddleja officinalis inhibits high glucose-induced matrix metalloproteinase activity in human umbilical vein endothelial cells.

Science.gov (United States)

Lee, Yun Jung; Kang, Dae Gill; Kim, Jin Sook; Lee, Ho Sub

2008-12-01

The aim of the present investigation was to investigate whether an aqueous extract of Buddleja officinalis (ABO), a traditional Korean herbal medicine, suppresses the endothelial extracellular matrix degradation under high glucose condition. The incubation with high concentration of glucose (25 mM) increased significantly matrix metalloproteinase (MMP)-2/-9 expressions and activities in primary cultured human umbilical vein endothelial cells (HUVEC). Pretreatment with ABO decreased high glucose-induced increase of MMP-2/-9 activities in a dose-dependent manner. Real time qRT-PCR revealed that high glucose-induced MMP-2/-9 mRNA expression levels were attenuated by pretreatment with ABO. High glucose-induced MCP-1 and IL-8 mRNA expression levels also decreased by ABO. ABO decreased high glucose-induced hydrogen peroxide production, oxidative stress marker. These results provide new insights into the pathophysiological mechanisms for anti-inflammatory properties of ABO in vascular diseases associated with diabetes mellitus. (c) 2008 John Wiley & Sons, Ltd.

The influence of adsorption capacity on enhanced gas absorption in activated carbon slurries

NARCIS (Netherlands)

Holstvoogd, R.D.; van Swaaij, Willibrordus Petrus Maria

1990-01-01

The enhanced absorption of gases in aqueous activated carbbon slurries of fine particles is studied with a non-steady-state absorption model, taking into account the finite adsorption capacity of the carbon particles. It has been found that, for the different gas/activated carbon slurry systems

Blood plasma separation in ZnO nanoflowers-supported paper based microfluidic for glucose sensing

Science.gov (United States)

Muhimmah, Luthviyah Choirotul; Roekmono, Hadi, Harsono; Yuwono, Rio Akbar; Wahyuono, Ruri Agung

2018-04-01

Blood plasma separation is essential to analyze and quantify the bio-substances in the human blood and hence, allows for diagnosing various diseases. This paper presents the two layer paper-based microfluidic analytical devices coated with ZnO nanoflowers (ZnO NF-µPAD) for a rapid blood plasma separation and glucose sensing. Plasma separation in ZnO NF-µPAD was evaluated experimentally and numerically using computational fluid dynamics package for a flow over porous networks. Glucose detection was carried out using Fourier-transform infrared (FTIR) measurements. The glucose concentrations in the red blood samples investigated here vary in the range of 150 - 310 mg.dl-1. The plasma separation process on ZnO NF-μPAD requires 240 ± 93 s. The spectroscopic data reveals that the IR absorptions and Raman signals at the typical vibrational frequencies of glucose are increasing at higher glucose concentration. After subtraction from absorption background arising from ZnO NF and the paper, linearly increasing IR absorption (913 and 1349 cm-1) and Raman signals (1346 and 1461 cm-1) are observable with a relatively good sensitivity.

Pancreatic α-Amylase Controls Glucose Assimilation by Duodenal Retrieval through N-Glycan-specific Binding, Endocytosis, and Degradation*

Science.gov (United States)

Date, Kimie; Satoh, Ayano; Iida, Kaoruko; Ogawa, Haruko

2015-01-01

α-Amylase, a major pancreatic protein and starch hydrolase, is essential for energy acquisition. Mammalian pancreatic α-amylase binds specifically to glycoprotein N-glycans in the brush-border membrane to activate starch digestion, whereas it significantly inhibits glucose uptake by Na+/glucose cotransporter 1 (SGLT1) at high concentrations (Asanuma-Date, K., Hirano, Y., Le, N., Sano, K., Kawasaki, N., Hashii, N., Hiruta, Y., Nakayama, K., Umemura, M., Ishikawa, K., Sakagami, H., and Ogawa, H. (2012) Functional regulation of sugar assimilation by N-glycan-specific interaction of pancreatic α-amylase with glycoproteins of duodenal brush border membrane. J. Biol. Chem. 287, 23104–23118). However, how the inhibition is stopped was unknown. Here, we show a new mechanism for the regulation of intestinal glucose absorption. Immunohistochemistry revealed that α-amylase in the duodena of non-fasted, but not fasted, pigs was internalized from the pancreatic fluid and immunostained. We demonstrated that after N-glycan binding, pancreatic α-amylase underwent internalization into lysosomes in a process that was inhibited by α-mannoside. The internalized α-amylase was degraded, showing low enzymatic activity and molecular weight at the basolateral membrane. In a human intestinal Caco-2 cell line, Alexa Fluor 488-labeled pancreatic α-amylase bound to the cytomembrane was transported to lysosomes through the endocytic pathway and then disappeared, suggesting degradation. Our findings indicate that N-glycan recognition by α-amylase protects enterocytes against a sudden increase in glucose concentration and restores glucose uptake by gradual internalization, which homeostatically controls the postprandial blood glucose level. The internalization of α-amylase may also enhance the supply of amino acids required for the high turnover of small intestine epithelial cells. This study provides novel and significant insights into the control of blood sugar during the absorption

Effects of glucose on the formation of PhIP in a model system.

Science.gov (United States)

Skog, K; Jägerstad, M

1991-12-01

The effect of glucose on the formation of the food mutagen PhIP (2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine) was studied in a model system. When a mixture of creatine (0.9 mmol), phenylalanine (0.9 mmol) and glucose (0.45 mmol) was heated in diethylene glycol and water (3 ml, 5:1) for 10 min at 180 or 225 degrees C several mutagens were produced. Identification by HPLC, UV absorption spectroscopy and mass spectrometry revealed the presence of PhIP as well as 2-amino-3,8-dimethylimidazo[4,5-f]quinoxaline and minor amounts of 2-amino-3,4,8-trimethylimidazo[4,5-f]quinoxaline. Heating the system without glucose produced PhIP as a single mutagen, but in considerably lower amount. An inhibiting effect of glucose in high concentrations was demonstrated. When glucose was added in more than or equimolar amounts of the other two reactants, the formation of mutagens was markedly reduced. Tyrosine heated under the same conditions, with creatine and glucose, showed mutagenic activity. However, no PhIP nor any other known food mutagen was identified from the tyrosine mixture.

Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

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Hsiao-Ya Tsai

2016-01-01

Full Text Available Coenzyme Q10 (CoQ10, an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM or high glucose (25 mM enviroment for 3 days, followed by treatment with CoQ10 (10 μM for 24 hr. Cell proliferation, nitric oxide (NO production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK, eNOS/Akt, and heme oxygenase-1 (HO-1 were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients.

Coenzyme Q10 Attenuates High Glucose-Induced Endothelial Progenitor Cell Dysfunction through AMP-Activated Protein Kinase Pathways

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Tsai, Hsiao-Ya; Lin, Chih-Pei; Huang, Po-Hsun; Li, Szu-Yuan; Chen, Jia-Shiong; Lin, Feng-Yen; Chen, Jaw-Wen; Lin, Shing-Jong

2016-01-01

Coenzyme Q10 (CoQ10), an antiapoptosis enzyme, is stored in the mitochondria of cells. We investigated whether CoQ10 can attenuate high glucose-induced endothelial progenitor cell (EPC) apoptosis and clarified its mechanism. EPCs were incubated with normal glucose (5 mM) or high glucose (25 mM) enviroment for 3 days, followed by treatment with CoQ10 (10 μM) for 24 hr. Cell proliferation, nitric oxide (NO) production, and JC-1 assay were examined. The specific signal pathways of AMP-activated protein kinase (AMPK), eNOS/Akt, and heme oxygenase-1 (HO-1) were also assessed. High glucose reduced EPC functional activities, including proliferation and migration. Additionally, Akt/eNOS activity and NO production were downregulated in high glucose-stimulated EPCs. Administration of CoQ10 ameliorated high glucose-induced EPC apoptosis, including downregulation of caspase 3, upregulation of Bcl-2, and increase in mitochondrial membrane potential. Furthermore, treatment with CoQ10 reduced reactive oxygen species, enhanced eNOS/Akt activity, and increased HO-1 expression in high glucose-treated EPCs. These effects were negated by administration of AMPK inhibitor. Transplantation of CoQ10-treated EPCs under high glucose conditions into ischemic hindlimbs improved blood flow recovery. CoQ10 reduced high glucose-induced EPC apoptosis and dysfunction through upregulation of eNOS, HO-1 through the AMPK pathway. Our findings provide a potential treatment strategy targeting dysfunctional EPC in diabetic patients. PMID:26682233

Mathematical Modeling of Interacting Glucose-Sensing Mechanisms and Electrical Activity Underlying Glucagon-Like Peptide 1 Secretion.

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Michela Riz

2015-12-01

Full Text Available Intestinal L-cells sense glucose and other nutrients, and in response release glucagon-like peptide 1 (GLP-1, peptide YY and other hormones with anti-diabetic and weight-reducing effects. The stimulus-secretion pathway in L-cells is still poorly understood, although it is known that GLP-1 secreting cells use sodium-glucose co-transporters (SGLT and ATP-sensitive K+-channels (K(ATP-channels to sense intestinal glucose levels. Electrical activity then transduces glucose sensing to Ca2+-stimulated exocytosis. This particular glucose-sensing arrangement with glucose triggering both a depolarizing SGLT current as well as leading to closure of the hyperpolarizing K(ATP current is of more general interest for our understanding of glucose-sensing cells. To dissect the interactions of these two glucose-sensing mechanisms, we build a mathematical model of electrical activity underlying GLP-1 secretion. Two sets of model parameters are presented: one set represents primary mouse colonic L-cells; the other set is based on data from the GLP-1 secreting GLUTag cell line. The model is then used to obtain insight into the differences in glucose-sensing between primary L-cells and GLUTag cells. Our results illuminate how the two glucose-sensing mechanisms interact, and suggest that the depolarizing effect of SGLT currents is modulated by K(ATP-channel activity. Based on our simulations, we propose that primary L-cells encode the glucose signal as changes in action potential amplitude, whereas GLUTag cells rely mainly on frequency modulation. The model should be useful for further basic, pharmacological and theoretical investigations of the cellular signals underlying endogenous GLP-1 and peptide YY release.

[Activities and properties of glucose-6-phosphatase of turbellaria Phagocata sibirica and cestodes Bothriocephalus scorpii].

Science.gov (United States)

Burenina, E A

2009-01-01

There were studied activities and properties of mitochondrial and microsomal glucose-6-phosphatases (G6Pases) in free living turbellaria Phagocata sibirica and cestodes Bothriocephalus scorpii. Action of various effectors (sodium fluoride, glucose, HCO3-, citrate, Cu2+, DTT, EDTA, ATP, AFP) on the enzyme activity was studied. The obtained results and literature data demonstrate that G6Pase is present in various muscles of representatives of the animal kingdom. The conclusion can be made that invertebrate G6Pase releases glucose from glycogen and gluconeogenic precursors.

Incorporation of 14C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication

International Nuclear Information System (INIS)

Sikorska, M.; Gorzkowski, B.; Szumanska, G.; Smialek, M.

1975-01-01

Incorporation of 14 C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication was studied. In brains of rats tested on the 20, 30 and 60th minute of exposure to CO and immediately after removal from the chamber the enzyme activity showed no essential deviation from the control level. In the group of rats tested 1 hour after taking them out from the chamber increase of the enzyme activity was noticed, amounting to about 33% of the control value. The brains tested 24 hours after exposure showed the largest increase of the enzyme activity by about 94%. In the next time periods, 48 and 72 hours after intoxication, the enzyme activity was decreasing. The glycogen content in brains of control animals increased 3 hours after CO intoxication by about 69%. The increase of glycogen synthesis was expressed by increase of the total radioactivity, which amounted to 160% of the control value. (Z.M.)

Variation in 125I-Insulin absorption and blood glucose concentration

International Nuclear Information System (INIS)

Lauritzen, T.; Faber, O.K.; Binder, C.

1979-01-01

The absorption of monocomponent porcine 125 I-insulin Monotard and Isophane was studied in six insulin dependent diabetic patients over a period of 12 days. The absorption of insulin was measured as the disappearance of radioactivity from sites of injection. The daily 125 I-insulin doses ranged from 20 to 48 IU between patients. The insulin absorbed varied considerably within and between patients. The range of individual daily absorbed insulin varied from 19 to 104 per cent of the 125 I-insulin dose. A significant correlation (p [de

Tin-containing zeolites are highly active catalysts for the isomerization of glucose in water.

Science.gov (United States)

Moliner, Manuel; Román-Leshkov, Yuriy; Davis, Mark E

2010-04-06

The isomerization of glucose into fructose is a large-scale reaction for the production of high-fructose corn syrup (HFCS; reaction performed by enzyme catalysts) and recently is being considered as an intermediate step in the possible route of biomass to fuels and chemicals. Here, it is shown that a large-pore zeolite that contains tin (Sn-Beta) is able to isomerize glucose to fructose in aqueous media with high activity and selectivity. Specifically, a 10% (wt/wt) glucose solution containing a catalytic amount of Sn-Beta (150 Sn:glucose molar ratio) gives product yields of approximately 46% (wt/wt) glucose, 31% (wt/wt) fructose, and 9% (wt/wt) mannose after 30 min and 12 min of reaction at 383 K and 413 K, respectively. This reactivity is achieved also when a 45 wt% glucose solution is used. The properties of the large-pore zeolite greatly influence the reaction behavior because the reaction does not proceed with a medium-pore zeolite, and the isomerization activity is considerably lower when the metal centers are incorporated in ordered mesoporous silica (MCM-41). The Sn-Beta catalyst can be used for multiple cycles, and the reaction stops when the solid is removed, clearly indicating that the catalysis is occurring heterogeneously. Most importantly, the Sn-Beta catalyst is able to perform the isomerization reaction in highly acidic, aqueous environments with equivalent activity and product distribution as in media without added acid. This enables Sn-Beta to couple isomerizations with other acid-catalyzed reactions, including hydrolysis/isomerization or isomerization/dehydration reaction sequences [starch to fructose and glucose to 5-hydroxymethylfurfural (HMF) demonstrated here].

High glucose increases Cdk5 activity in podocytes via transforming growth factor-β1 signaling pathway

International Nuclear Information System (INIS)

Zhang, Yue; Li, Hongbo; Hao, Jun; Zhou, Yi; Liu, Wei

2014-01-01

Podocytes are highly specialized and terminally differentiated glomerular cells that play a vital role in the development and progression of diabetic nephropathy (DN). Cyclin-dependent kinase 5 (Cdk5), who is an atypical but essential member of the Cdk family of proline-directed serine/threonine kinases, has been shown as a key regulator of podocyte differentiation, proliferation and morphology. Our previous studies demonstrated that the expression of Cdk5 was significantly increased in podocytes of diabetic rats, and was closely related with podocyte injury of DN. However, the mechanisms of how expression and activity of Cdk5 are regulated under the high glucose environment have not yet been fully elucidated. In this study, we showed that high glucose up-regulated the expression of Cdk5 and its co-activator p35 with a concomitant increase in Cdk5 kinase activity in conditionally immortalized mouse podocytes in vitro. When exposed to 30 mM glucose, transforming growth factor-β1 (TGF-β1) was activated. Most importantly, we found that SB431542, the Tgfbr1 inhibitor, significantly decreased the expression of Cdk5 and p35 and Cdk5 kinase activity in high glucose-treated podocytes. Moreover, high glucose increased the expression of early growth response-1 (Egr-1) via TGF-β1-ERK1/2 pathway in podocytes and inhibition of Egr-1 by siRNA decreased p35 expression and Cdk5 kinase activity. Furthermore, inhibition of Cdk5 kinase activity effectively alleviated podocyte apoptosis induced by high glucose or TGF-β1. Thus, the TGF-β1-ERK1/2-Egr-1 signaling pathway may regulate the p35 expression and Cdk5 kinase activity in high glucose-treated podocytes, which contributes to podocyte injury of DN. - Highlights: • HG up-regulated the expression of Cdk5 and p35, and Cdk5 activity in podocytes. • HG activated TGF-β1 pathway and SB431542 inhibited Cdk5 expression and activity. • HG increased the expression of Egr-1 via TGF-β1-ERK1/2 pathway. • Inhibition of Egr-1

In uncontrolled diabetes, thyroid hormone and sympathetic activators induce thermogenesis without increasing glucose uptake in brown adipose tissue.

Science.gov (United States)

Matsen, Miles E; Thaler, Joshua P; Wisse, Brent E; Guyenet, Stephan J; Meek, Thomas H; Ogimoto, Kayoko; Cubelo, Alex; Fischer, Jonathan D; Kaiyala, Karl J; Schwartz, Michael W; Morton, Gregory J

2013-04-01

Recent advances in human brown adipose tissue (BAT) imaging technology have renewed interest in the identification of BAT activators for the treatment of obesity and diabetes. In uncontrolled diabetes (uDM), activation of BAT is implicated in glucose lowering mediated by intracerebroventricular (icv) administration of leptin, which normalizes blood glucose levels in streptozotocin (STZ)-induced diabetic rats. The potent effect of icv leptin to increase BAT glucose uptake in STZ-diabetes is accompanied by the return of reduced plasma thyroxine (T4) levels and BAT uncoupling protein-1 (Ucp1) mRNA levels to nondiabetic controls. We therefore sought to determine whether activation of thyroid hormone receptors is sufficient in and of itself to lower blood glucose levels in STZ-diabetes and whether this effect involves activation of BAT. We found that, although systemic administration of the thyroid hormone (TR)β-selective agonist GC-1 increases energy expenditure and induces further weight loss in STZ-diabetic rats, it neither increased BAT glucose uptake nor attenuated diabetic hyperglycemia. Even when GC-1 was administered in combination with a β(3)-adrenergic receptor agonist to mimic sympathetic nervous system activation, glucose uptake was not increased in STZ-diabetic rats, nor was blood glucose lowered, yet this intervention potently activated BAT. Similar results were observed in animals treated with active thyroid hormone (T3) instead of GC-1. Taken together, our data suggest that neither returning normal plasma thyroid hormone levels nor BAT activation has any impact on diabetic hyperglycemia, and that in BAT, increases of Ucp1 gene expression and glucose uptake are readily dissociated from one another in this setting.

Dexamethasone increases glucose cycling, but not glucose production, in healthy subjects

International Nuclear Information System (INIS)

Wajngot, A.; Khan, A.; Giacca, A.; Vranic, M.; Efendic, S.

1990-01-01

We established that measurement of glucose fluxes through glucose-6-phosphatase (G-6-Pase; hepatic total glucose output, HTGO), glucose cycling (GC), and glucose production (HGP), reveals early diabetogenic changes in liver metabolism. To elucidate the mechanism of the diabetogenic effect of glucocorticoids, we treated eight healthy subjects with oral dexamethasone (DEX; 15 mg over 48 h) and measured HTGO with [2-3H]glucose and HGP with [6-3H]glucose postabsorptively and during a 2-h glucose infusion (11.1 mumol.kg-1.min-1). [2-3H]- minus [6-3H]glucose equals GC. DEX significantly increased plasma glucose, insulin, C peptide, and HTGO, while HGP was unchanged. In controls and DEX, glucose infusion suppressed HTGO (82 vs. 78%) and HGP (87 vs. 91%). DEX increased GC postabsorptively (three-fold) P less than 0.005 and during glucose infusion (P less than 0.05) but decreased metabolic clearance and glucose uptake (Rd), which eventually normalized, however. Because DEX increased HTGO (G-6-Pase) and not HGP (glycogenolysis + gluconeogenesis), we assume that DEX increases HTGO and GC in humans by activating G-6-Pase directly, rather than by expanding the glucose 6-phosphate pool. Hyperglycemia caused by peripheral effects of DEX can also contribute to an increase in GC by activating glucokinase. Therefore, measurement of glucose fluxes through G-6-Pase and GC revealed significant early effects of DEX on hepatic glucose metabolism, which are not yet reflected in HGP

Specific Sirt1 Activator-mediated Improvement in Glucose Homeostasis Requires Sirt1-Independent Activation of AMPK

Directory of Open Access Journals (Sweden)

Sung-Jun Park

2017-04-01

Full Text Available The specific Sirt1 activator SRT1720 increases mitochondrial function in skeletal muscle, presumably by activating Sirt1. However, Sirt1 gain of function does not increase mitochondrial function, which raises a question about the central role of Sirt1 in SRT1720 action. Moreover, it is believed that the metabolic effects of SRT1720 occur independently of AMP-activated protein kinase (AMPK, an important metabolic regulator that increases mitochondrial function. Here, we show that SRT1720 activates AMPK in a Sirt1-independent manner and SRT1720 activates AMPK by inhibiting a cAMP degrading phosphodiesterase (PDE in a competitive manner. Inhibiting the cAMP effector protein Epac prevents SRT1720 from activating AMPK or Sirt1 in myotubes. Moreover, SRT1720 does not increase mitochondrial function or improve glucose tolerance in AMPKα2 knockout mice. Interestingly, weight loss induced by SRT1720 is not sufficient to improve glucose tolerance. Therefore, contrary to current belief, the metabolic effects produced by SRT1720 require AMPK, which can be activated independently of Sirt1.

Colorimetric Glucose Assay Based on Magnetic Particles Having Pseudo-peroxidase Activity and Immobilized Glucose Oxidase.

Science.gov (United States)

Martinkova, Pavla; Opatrilova, Radka; Kruzliak, Peter; Styriak, Igor; Pohanka, Miroslav

2016-05-01

Magnetic particles (MPs) are currently used as a suitable alternative for peroxidase in the construction of novel biosensors, analytic and diagnostic methods. Their better chemical and thermal stabilities predestine them as appropriate pseudo-enzymatic catalysts. In this point of view, our research was focused on preparation of simply and fast method for immobilization of glucose oxidase onto surface of MPs with peroxidase-like activity. Spectrophotometric method (wavelength 450 nm) optimized for glucose determination using modified MPs has been successfully developed. Concentration curve for optimization of method was assayed, and Michaelis-Menten constant (K m) calculated, maximum reaction rate (V max), limit of detection, and correlation coefficient were determined to be 0.13 mmol/l (2.34 mg/dl), 1.79 pkat, 3.74 µmol/l (0.067 mg/dl), and 0.996, respectively. Interferences of other sugars such as sucrose, sorbitol, deoxyribose, maltose, and fructose were determined as well as effect of substances presenting in plasma (ascorbic acid, reduced glutathione, trolox, and urea). Results in comparison with positive and negative controls showed no interferences of the other sugars and no influence of plasma substances to measuring of glucose. The constructed method showed corresponding results with linear dependence and a correlation coefficient of 0.997. Possibility of repeated use of modified MPs was successfully proved.

U-Shaped and Surface Functionalized Polymer Optical Fiber Probe for Glucose Detection.

Science.gov (United States)

Azkune, Mikel; Ruiz-Rubio, Leire; Aldabaldetreku, Gotzon; Arrospide, Eneko; Pérez-Álvarez, Leyre; Bikandi, Iñaki; Zubia, Joseba; Vilas-Vilela, Jose Luis

2017-12-25

In this work we show an optical fiber evanescent wave absorption probe for glucose detection in different physiological media. High selectivity is achieved by functionalizing the surface of an only-core poly(methyl methacrylate) (PMMA) polymer optical fiber with phenilboronic groups, and enhanced sensitivity by using a U-shaped geometry. Employing a supercontinuum light source and a high-resolution spectrometer, absorption measurements are performed in the broadband visible light spectrum. Experimental results suggest the feasibility of such a fiber probe as a low-cost and selective glucose detector.

A new methodology for the determination of enzyme activity based on carbon nanotubes and glucose oxidase.

Science.gov (United States)

Yeşiller, Gülden; Sezgintürk, Mustafa Kemal

2015-11-10

In this research, a novel enzyme activity analysis methodology is introduced as a new perspective for this area. The activity of elastase enzyme, which is a digestive enzyme mostly of found in the digestive system of vertebrates, was determined by an electrochemical device composed of carbon nanotubes and a second enzyme, glucose oxidase, which was used as a signal generator enzyme. In this novel methodology, a complex bioactive layer was constructed by using carbon nanotubes, glucose oxidase and a supporting protein, gelatin on a solid, conductive substrate. The activity of elastase was determined by monitoring the hydrolysis rate of elastase enzyme in the bioactive layer. As a result of this hydrolysis of elastase, glucose oxidase was dissociated from the bioactive layer, and following this the electrochemical signal due to glucose oxidase was decreased. The progressive elastase-catalyzed digestion of the bioactive layer containing glucose oxidase decreased the layer's enzymatic efficiency, resulting in a decrease of the glucose oxidation current as a function of the enzyme activity. The ratio of the decrease was correlated to elastase activity level. In this study, optimization experiments of bioactive components and characterization of the resulting new electrochemical device were carried out. A linear calibration range from 0.0303U/mL to 0.0729U/mL of elastase was reported. Real sample analyses were also carried out by the new electrochemical device. Copyright © 2015 Elsevier B.V. All rights reserved.

Activation of glycolysis and inhibition of glucose transport into leaves by fluoride

Energy Technology Data Exchange (ETDEWEB)

Lustinec, J; Pokorna, V; Ruzicka, J

1962-01-01

During stimulation of wheat leaf respiration by fluoride at 100 to 200 ppM fluorine in dry tissue the ratio of radioactivities of /sup 14/CO/sub 2/ released from glucose-6-/sup 14/C and that released from glucose-1-/sup 14/C (C/sub 6//C/sub 1/) increases due especially to an increased output of 6-/sup 14/CO/sub 2/ which suggests an activation of glycolysis. The absolute values of radioactivity of /sup 14/CO/sub 2/, however, are decreased by the action of fluoride due to its inhibition of the transport of glucose into leaves. 15 references, 2 figures, 2 tables.

Changes in glucose-induced plasma active glucagon-like peptide-1 levels by co-administration of sodium–glucose cotransporter inhibitors with dipeptidyl peptidase-4 inhibitors in rodents

Directory of Open Access Journals (Sweden)

Takahiro Oguma

2016-12-01

Full Text Available We investigated whether structurally different sodium–glucose cotransporter (SGLT 2 inhibitors, when co-administered with dipeptidyl peptidase-4 (DPP4 inhibitors, could enhance glucagon-like peptide-1 (GLP-1 secretion during oral glucose tolerance tests (OGTTs in rodents. Three different SGLT inhibitors—1-(β-d-Glucopyranosyl-4-chloro-3-[5-(6-fluoro-2-pyridyl-2-thienylmethyl]benzene (GTB, TA-1887, and canagliflozin—were examined to assess the effect of chemical structure. Oral treatment with GTB plus a DPP4 inhibitor enhanced glucose-induced plasma active GLP-1 (aGLP-1 elevation and suppressed glucose excursions in both normal and diabetic rodents. In DPP4-deficient rats, GTB enhanced glucose-induced aGLP-1 elevation without affecting the basal level, whereas metformin, previously reported to enhance GLP-1 secretion, increased both the basal level and glucose-induced elevation. Oral treatment with canagliflozin and TA-1887 also enhanced glucose-induced aGLP-1 elevation when co-administered with either teneligliptin or sitagliptin. These data suggest that structurally different SGLT2 inhibitors enhance plasma aGLP-1 elevation and suppress glucose excursions during OGTT when co-administered with DPP4 inhibitors, regardless of the difference in chemical structure. Combination treatment with DPP4 inhibitors and SGLT2 inhibitors having moderate SGLT1 inhibitory activity may be a promising therapeutic option for improving glycemic control in patients with type 2 diabetes mellitus.

Effects of Fat and Protein Preloads on Pouch Emptying, Intestinal Transit, Glycaemia, Gut Hormones, Glucose Absorption, Blood Pressure and Gastrointestinal Symptoms After Roux-en-Y Gastric Bypass.

Science.gov (United States)

Nguyen, Nam Q; Debreceni, Tamara L; Burgstad, Carly M; Neo, Melissa; Bellon, Max; Wishart, Judith M; Standfield, Scott; Bartholomeusz, Dylan; Rayner, Chris K; Wittert, Gary; Horowitz, Michael

2016-01-01

The aim was to determine the effects of fat and protein preloads on pouch emptying (PE), caecal arrival time (CAT), glucose absorption, blood glucose (BSL), gut hormones, haemodynamics and gastrointestinal (GI) symptoms in subjects who had undergone Roux-en-Y gastric bypass (RYGB) >12 months previously. Ten RYGB subjects were studied on three occasions, in randomised order, receiving 200-ml preloads of either water, fat (30 ml olive oil) or whey protein (55 g), 30 min before a mixed meal. PE, CAT, BSL, plasma 3-O-methyl-D-glucopyranose (3-OMG), insulin, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide 1 (GLP-1) and glucagon, blood pressure (BP), heart rate (HR) and GI symptoms were assessed over 270 min. Although fat and protein preloads did not alter PE of either solids or liquids, the CAT of solids, but not liquids, was longer than that after the water preload (fat 68 ± 5 min and protein 71 ± 6 min vs. water 46 ± 5 min; P = 0.02). BSL elevated promptly after the meal on all days (P area under the curve (AUC(0-75 min)), 18.7 ± 18.2 vs. 107.2 ± 30.4 and 76.1 ± 19.3 mmol/L/min; P < 0.05). Compared to water preload, the protein and fat preloads were associated with greater increases in plasma insulin, GLP-1 and glucagon concentrations, a reduction in BP, and greater increases in HR, fullness, bloating and nausea. Plasma 3-OMG levels were lower after the protein than after the water and fat preloads (P < 0.001). Given its effects to attenuate post-prandial glycaemia, reduce intestinal glucose absorption and potentiate the "incretin response", without inducing more adverse post-prandial GI symptom, protein preload may prove clinically useful in RYGB patients and warrant further evaluation, particularly in those with type 2 diabetes (T2DM) and/or dumping syndrome.

The effect of ISM absorption on stellar activity measurements and its relevance for exoplanet studies

Science.gov (United States)

Fossati, L.; Marcelja, S. E.; Staab, D.; Cubillos, P. E.; France, K.; Haswell, C. A.; Ingrassia, S.; Jenkins, J. S.; Koskinen, T.; Lanza, A. F.; Redfield, S.; Youngblood, A.; Pelzmann, G.

2017-05-01

Past ultraviolet and optical observations of stars hosting close-in Jupiter-mass planets have shown that some of these stars present an anomalously low chromospheric activity, significantly below the basal level. For the hot Jupiter planet host WASP-13, observations have shown that the apparent lack of activity is possibly caused by absorption from the intervening interstellar medium (ISM). Inspired by this result, we study the effect of ISM absorption on activity measurements (S and log R 'HK indices) for main-sequence late-type stars. To this end, we employ synthetic stellar photospheric spectra combined with varying amounts of chromospheric emission and ISM absorption. We present the effect of ISM absorption on activity measurements by varying several instrumental (spectral resolution), stellar (projected rotational velocity, effective temperature, and chromospheric emission flux), and ISM parameters (relative velocity between stellar and ISM Ca II lines, broadening b-parameter, and Ca II column density). We find that for relative velocities between the stellar and ISM lines smaller than 30-40 km s-1 and for ISM Ca II column densities log NCaII ⪆ 12, the ISM absorption has a significant influence on activity measurements. Direct measurements and three dimensional maps of the Galactic ISM absorption indicate that an ISM Ca II column density of log NCaII = 12 is typically reached by a distance of about 100 pc along most sight lines. In particular, for a Sun-like star lying at a distance greater than 100 pc, we expect a depression (bias) in the log R'HK value larger than 0.05-0.1 dex, about the same size as the typical measurement and calibration uncertainties on this parameter. This work shows that the bias introduced by ISM absorption must always be considered when measuring activity for stars lying beyond 100 pc. We also consider the effect of multiple ISM absorption components. We discuss the relevance of this result for exoplanet studies and revise the

Glucose administration enhances fMRI brain activation and connectivity related to episodic memory encoding for neutral and emotional stimuli.

Science.gov (United States)

Parent, Marise B; Krebs-Kraft, Desiree L; Ryan, John P; Wilson, Jennifer S; Harenski, Carla; Hamann, Stephan

2011-04-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with episodic memory encoding and whether these effects would differ depending on the emotional valence of the material. We used a double-blind, within-participants, crossover design in which either glucose (50g) or a saccharin placebo were administered before scanning, on days approximately 1 week apart. We scanned healthy young male participants with fMRI as they viewed emotionally arousing negative pictures and emotionally neutral pictures, intermixed with baseline fixation. Free recall was tested at 5 min after scanning and again after 1 day. Glucose administration increased activation in brain regions associated with successful episodic memory encoding. Glucose also enhanced activation in regions whose activity was correlated with subsequent successful recall, including the hippocampus, prefrontal cortex, and other regions, and these effects differed for negative vs. neutral stimuli. Finally, glucose substantially increased functional connectivity between the hippocampus and amygdala and a network of regions previously implicated in successful episodic memory encoding. These findings fit with evidence from nonhuman animals indicating glucose modulates memory by selectively enhancing neural activity in brain regions engaged during memory tasks. Our results highlight the modulatory effects of glucose and the importance of examining both regional changes in activity and functional connectivity to fully characterize the effects of glucose on brain function and memory. Copyright © 2011 Elsevier Ltd. All rights reserved.

Clinical Observations of Abnormal Glucose Tolerance in Hyperthyroidism

Energy Technology Data Exchange (ETDEWEB)

Lee, Kyung Ja; Lee, Hong Kyu [Seoul National University College of Medicine, Seoul (Korea, Republic of)

1969-09-15

Plasma glucose levels before and after oral glucose administration have been compared in g group of 76 thyrotoxic subjects and a group of 8 normal control subjects in order to study the effect of glucose loading in thyrotoxicosis. Following were the results: 1) The mean fasting plasma glucose level was elevated in thyrotoxic group (95.5 mg%) compared to normal control group (88 mg%). 2) The peak of glucose tolerance curve is at 30 minutes after glucose administration in both groups, but its mean value was 44 mg% higher in thyrotoxic group than in control group. 3) The plasma glucose levels returned towards the fasting level in the later stage of the test more rapidly in thyrotoxic group than in control group. 4) 69.6% of oral glucose tolerance tests were impaired in the thyrotoxic group, and the occurrence of abnormal glucose tolerance could be related to the degree of thyrotoxicity, sex and age. 5) The mechanisms of the impaired glucose tolerance in thyrotoxicosis are thought to be related to an increased rate of glucose absorption from gastrointestinal tract, abnormal liver function with decreased hepatic glycogenesis, increased glucose oxidation, decreased pancreatic release of insulin, and genetic relationship between diabetes and thyrotoxicosis.

Determination of NIR informative wavebands for transmission non-invasive blood glucose measurement using a Fourier transform spectrometer

Science.gov (United States)

Yang, Wenming; Liao, Ningfang; Cheng, Haobo; Li, Yasheng; Bai, Xueqiong; Deng, Chengyang

2018-03-01

Non-invasive blood glucose measurement using near infrared (NIR) spectroscopy relies on wavebands that provide reliable information about spectral absorption. In this study, we investigated wavebands which are informative for blood glucose in the NIR shortwave band (900˜1450 nm) and the first overtone band (1450˜1700 nm) through a specially designed NIR Fourier transform spectrometer (FTS), which featured a test fixture (where a sample or subject's finger could be placed) and all-reflective optics, except for a Michelson structure. Different concentrations of glucose solution and seven volunteers who had undergone oral glucose tolerance tests (OGTT) were studied to acquire transmission spectra in the shortwave band and the first overtone band. Characteristic peaks of glucose absorption were identified from the spectra of glucose aqueous solution by second-order derivative processing. The wavebands linked to blood glucose were successfully estimated through spectra of the middle fingertip of OGTT participants by a simple linear regression and correlation coefficient. The light intensity difference showed that glucose absorption in the first overtone band was much more prominent than it was in the shortwave band. The results of the SLR model established from seven OGTTs in total on seven participants enabled a positive estimation of the glucose-linked wavelength. It is suggested that wavebands with prominent characteristic peaks, a high correlation coefficient between blood glucose and light intensity difference and a relatively low standard deviation of predicted values will be the most informative wavebands for transmission non-invasive blood glucose measurement methods. This work provides a guidance for waveband selection for the development of non-invasive NIR blood glucose measurement.

Incorporation of /sup 14/C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication

Energy Technology Data Exchange (ETDEWEB)

Sikorska, M; Gorzkowski, B; Szumanska, G; Smialek, M [Polska Akademia Nauk, Warsaw. Centrum Medycyny Doswiadczalnej i Klinicznej; Panstwowy Zaklad Higieny, Warsaw (Poland))

1975-01-01

Incorporation of /sup 14/C glucose into glycogen and glucose-6-phosphate dehydrogenase activity in rat brain following carbon monoxide intoxication was studied. In brains of rats tested on the 20, 30 and 60th minute of exposure to CO and immediately after removal from the chamber the enzyme activity showed no essential deviation from the control level. In the group of rats tested 1 hour after taking them out from the chamber increase of the enzyme activity was noticed, amounting to about 33% of the control value. The brains tested 24 hours after exposure showed the largest increase of the enzyme activity by about 94%. In the next time periods, 48 and 72 hours after intoxication, the enzyme activity was decreasing. The glycogen content in brains of control animals increased 3 hours after CO intoxication by about 69%. The increase of glycogen synthesis was expressed by increase of the total radioactivity, which amounted to 160% of the control value.

Study on CO{sub 2} absorption enhancement by adding active carbon particles into MEA solution

Energy Technology Data Exchange (ETDEWEB)

Qian, Juan; Sun, Rui; Ma, Lian; Sun, Shaozeng [Harbin Institute of Technology, Harbin (China). School of Energy Science and Engineering

2013-07-01

The chemical absorption of CO{sub 2} is generally recognized as the most efficient post-combustion technology of CO{sub 2} separation at present. A study on CO{sub 2} absorption enhancement by adding small particles of active carbon into MEA solution is investigated within a self-designed glass stirring tank. Experiments of different particle loadings and different particle sizes have been conducted. When active carbon particle concentration is fewer, compared to the absorption rate of CO{sub 2} gas absorbed by MEA aqueous solution, the role of active carbon adsorption CO{sub 2} gas is negligible. The enhancement efficiency of CO{sub 2} absorption could be improved by 10% to the upmost in this liquid-particle system.

Effect of vanadate on glucose transporter (GLUT4) intrinsic activity in skeletal muscle plasma membrane giant vesicles

DEFF Research Database (Denmark)

Kristiansen, S; Youn, J; Richter, Erik

1996-01-01

of vanadate (NaVO3) on glucose transporter (GLUT4) intrinsic activity (V(max) = intrinsic activity x [GLUT4 protein]) was studied in muscle plasma membrane giant vesicles. Giant vesicles (average diameter 7.6 microns) were produced by collagenase treatment of rat skeletal muscle. The vesicles were incubated......) 55% and 60%, respectively, compared with control. The plasma membrane GLUT4 protein content was not changed in response to vanadate. It is concluded that vanadate decreased glucose transport per GLUT4 (intrinsic activity). This finding suggests that regulation of glucose transport in skeletal muscle...

[Enhancing effect of Ulex europaeus agglutinin I modified liposomes on oral insulin absorption in mice].

Science.gov (United States)

Zhang, Na; Ping, Qi-neng; Xu, Wen-fang

2004-12-01

To investigate the enhancing effect on insulin absorption through GI. tract in mice by using the Ulex europaeus agglutinin I (UEA1) modified liposomes as the carrier. UEA1 modified phosphatidylethanolamine (PE) was prepared by conjugating method of 1-ethyl-3-(3'-dimethylaminopropyl) carbodiimide (EDC), then the modified compound (PE-UEA1) was incorporated into the conventional liposomes of insulin to obtain UEA1 modified liposomes. The agglutination test was performed to examine the UEA1 biological activities after synthesis and modification. When liposomes were applied to healthy mice or diabetic mice at insulin dose of 350 u x kg(-1) orally, the hypoglycemic effect was investigated according to the blood glucose level determination. The blood glucose levels of the healthy mice reduced by UEA1 modified liposomes were (84 +/- 15)% at 4 h, (78 +/- 11)% at 8 h and (90 +/- 12)% at 12 h after oral administration. The conventional liposomes and saline showed no effect. The blood glucose levels of the diabetic mice reduced by UEA1 modified liposomes were (73 +/- 7)% at 4 h, (74 +/- 9)% at 8 h, (86 +/- 9)% at 12 h after oral administration. The UEA1 modified liposomes promote the oral absorption of insulin due to the specific-site combination on M cell membrane.

Green tea extract with polyethylene glycol-3350 reduces body weight and improves glucose tolerance in db/db and high-fat diet mice.

Science.gov (United States)

Park, Jae-Hyung; Choi, Yoon Jung; Kim, Yong Woon; Kim, Sang Pyo; Cho, Ho-Chan; Ahn, Shinbyoung; Bae, Ki-Cheor; Im, Seung-Soon; Bae, Jae-Hoon; Song, Dae-Kyu

2013-08-01

Green tea extract (GTE) is regarded to be effective against obesity and type 2 diabetes, but definitive evidences have not been proven. Based on the assumption that the gallated catechins (GCs) in GTE attenuate intestinal glucose and lipid absorption, while enhancing insulin resistance when GCs are present in the circulation through inhibiting cellular glucose uptake in various tissues, this study attempted to block the intestinal absorption of GCs and prolong their residence time in the lumen. We then observed whether GTE containing the nonabsorbable GCs could ameliorate body weight (BW) gain and glucose intolerance in db/db and high-fat diet mice. Inhibition of the intestinal absorption of GCs was accomplished by co-administering the nontoxic polymer polyethylene glycol-3350 (PEG). C57BLKS/J db/db and high-fat diet C57BL/6 mice were treated for 4 weeks with drugs as follows: GTE, PEG, GTE+PEG, voglibose, or pioglitazone. GTE mixed with meals did not have any ameliorating effects on BW gain and glucose intolerance. However, the administration of GTE plus PEG significantly reduced BW gain, insulin resistance, and glucose intolerance, without affecting food intake and appetite. The effect was comparable to the effects of an α-glucosidase inhibitor and a peroxisome proliferator-activated receptor-γ/α agonist. These results indicate that prolonging the action of GCs of GTE in the intestinal lumen and blocking their entry into the circulation may allow GTE to be used as a prevention and treatment for both obesity and obesity-induced type 2 diabetes.

Subcellular localization, mobility, and kinetic activity of glucokinase in glucose-responsive insulin-secreting cells.

Science.gov (United States)

Stubbs, M; Aiston, S; Agius, L

2000-12-01

We investigated the subcellular localization, mobility, and activity of glucokinase in MIN6 cells, a glucose-responsive insulin-secreting beta-cell line. Glucokinase is present in the cytoplasm and a vesicular/granule compartment that is partially colocalized with insulin granules. The granular staining of glucokinase is preserved after permeabilization of the cells with digitonin. There was no evidence for changes in distribution of glucokinase between the cytoplasm and the granule compartment during incubation of the cells with glucose. The rate of release of glucokinase and of phosphoglucoisomerase from digitonin-permeabilized cells was slower when cells were incubated at an elevated glucose concentration (S0.5 approximately 15 mmol/l). This effect of glucose was counteracted by competitive inhibitors of glucokinase (5-thioglucose and mannoheptulose) but was unaffected by fructose analogs and may be due to changes in cell shape or conformation of the cytoskeleton that are secondary to glucose metabolism. Based on the similar release of glucokinase and phosphoglucoisomerase, we found no evidence for specific binding of cytoplasmic digitonin-extractable glucokinase. The affinity of beta-cells for glucose is slightly lower than that in cell extracts and, unlike that in hepatocytes, is unaffected by fructose, tagatose, or a high-K+ medium, which is consistent with the lack of change in glucokinase distribution or release. We conclude that glucokinase is present in two locations, cytoplasm and the granular compartment, and that it does not translocate between them. This conclusion is consistent with the lack of adaptive changes in the glucose phosphorylation affinity. The glucokinase activity associated with the insulin granules may have a role in either direct or indirect coupling between glucose phosphorylation and insulin secretion.

Indian culinary plants enhance glucose-induced insulin secretion and glucose consumption in INS-1 β-cells and 3T3-L1 adipocytes.

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Kaur, Lovedeep; Han, Kyoung-Sik; Bains, Kiran; Singh, Harjinder

2011-12-01

Six Indian plants, commonly used as culinary plants, herbs or spices (kikar; jamun; neem; harad; fenugreek; bitter gourd), were screened and compared for their antidiabetic potential in vitro. Aqueous plant extracts were prepared and assessed for their effect on the insulin secretion activity of rat pancreatic INS-1 β-cells and glucose consumption in mouse 3T3-L1 adipocytes in order to study their specific mechanisms of action. The effect of the plant extract concentration (25-1000μg/ml) on insulin release and glucose consumption was also studied. All the extracts had a significant stimulatory effect on the insulin secretion of INS-1 cells. In the presence of kikar extract (100μg/ml), an increase of 228% in insulin release was recorded compared to the control (5.6mM glucose) whereas that was 270% and 367% in the presence of kikar and jamun extracts (500μg/ml), respectively. 3T3-L1 cells treated with jamun extract (100μg/ml) exhibited the highest increase in glucose consumption by the cells (94%, compared with the control) followed by harad (53%) and fenugreek (50%) extracts. A significant inhibitory effect of the fenugreek, kikar and jamun extracts on glucose diffusion across a dialysis membrane suggested that these extracts could partly act by decreasing glucose absorption in the small intestine. The results showed that a combination of these plants in diet could help in the management of both type 1 and type 2 diabetes. Copyright © 2011 Elsevier Ltd. All rights reserved.

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

DEFF Research Database (Denmark)

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

2012-01-01

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

Differential photoacoustic spectroscopy with continuous wave lasers for non-invasive blood glucose monitoring

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Tanaka, Y.; Tajima, T.; Seyama, M.

2018-02-01

We propose a differential photoacoustic spectroscopy (PAS), wherein two wavelengths of light with the same absorbance are selected, and differential signal is linearized by one of the two signals for a non-invasive blood glucose monitoring. PAS has the possibility to overcome the strong optical scattering in tissue, but there are still remaining issues: the water background and instability due to the variation in acoustic resonance conditions. A change in sample solution temperature is one of the causes of the variation in acoustic resonance conditions. Therefore, in this study, we investigated the sensitivity against glucose concentration under the condition where the temperature of the sample water solution ranges 30 to 40 °C. The glucose concentration change is simulated by shifting the wavelength of irradiated laser light, which can effectively change optical absorption. The temperature also affects optical absorption and the acoustic resonance condition (acoustic velocity). A distributed-feedback (DFB) laser, tunable wavelength laser (TWL) and an acoustic sensor were used to obtain the differential PAS signal. The wavelength of the DFB laser was 1.382 μm, and that of TWL was switched from 1.600 to 1.610 μm to simulate the glucose concentration change. Optical absorption by glucose occurs at around 1.600 μm. The sensitivities against temperature are almost the same: 1.9 and 1.8 %/°C for 1.600 and 1.610 μm. That is, the glucose dependence across the whole temperature range remains constant. This implies that temperature correction is available.

Absorption and activation techniques in measurements of fast-neutron capture cross sections

International Nuclear Information System (INIS)

Bergqvist, I.

1982-01-01

The absorption and activation methods have been applied for a long time to systematic studies of fast neutron capture cross sections. Both methods are simple in principle but difficult in practice. The simplicity should ensure a wider use of the methods in particular for problems which may be complicated to approach with other methods. The difficulties encountered in absorption measurements are related to multiple scattering and resonance shielding effects. In activation experiments the influence of secondary low-energy neutrons causes the main problems

Experiment of Industrial Waste Absorption using Activated Carbon from Coal of Tanjung Tabalong, South Kalimantan

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M. Ulum Gani

2014-06-01

Full Text Available DOI: 10.17014/ijog.v6i4.130Activated carbon made from Tanjung Tabalong coal was investigated its absorption capability to organic and inorganic elements in industrial waste. Coal was carbonized at low temperature of 600C to produce semicoke, and then was activated at temperature of 700C with activation time of 120 minutes with water steam flow. The absorption capability of activated carbon to chemical oxygen demand (COD was performed using 2.5 and 9.0 g activated carbon for 250 ml and 300 ml COD waste respectively. The agitation time of each experiment were 30, 60, and 90 minutes. Atomic absorption spectrophotometer (AAS was used to analyze the COD waste. The result shows that 2.5 g activated carbon could absorb COD waste ranging from 6.9-67.5 %, while the utilization of 9 g could absorb COD waste ranging from 88.9 - 100 %. The more activated carbon and the longer time of agitation used in this experiment, the more the absorption of COD waste.

Tin-containing zeolites are highly active catalysts for the isomerization of glucose in water

OpenAIRE

Moliner, Manuel; Román-Leshkov, Yuriy; Davis, Mark E.

2010-01-01

The isomerization of glucose into fructose is a large-scale reaction for the production of high-fructose corn syrup (HFCS; reaction performed by enzyme catalysts) and recently is being considered as an intermediate step in the possible route of biomass to fuels and chemicals. Here, it is shown that a large-pore zeolite that contains tin (Sn-Beta) is able to isomerize glucose to fructose in aqueous media with high activity and selectivity. Specifically, a 10% (wt/wt) glucose solution containin...

Lowering blood glucose during hip surgery does not influence coagulation activation

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Marjolein K. Sechterberger

2015-06-01

Conclusion: Although the human GLP-1 analogue liraglutide moderately reduced post-operative blood glucose levels in non-diabetic and prediabetic obese patients undergoing elective hip surgery, no changes were observed with respect to coagulation activation.

The effect of carbohydrates in milk on the absorption of calcium by postmenopausal women

International Nuclear Information System (INIS)

Schuette, S.A.; Yasillo, N.J.; Thompson, C.M.

1991-01-01

The purpose of this investigation was to determine if the presence of carbohydrate in milk, either lactose or its hydrolysis products, enhance the bioavailability of calcium (Ca) in milk. Two studies were performed. In study A, fractional Ca absorption was measured in 11 lactose-tolerant postmenopausal women after an oral dose of 47 Ca-equilibrated milk formula containing no carbohydrate (NOCHO), lactose (LACTOSE), or an equivalent amount of glucose plus galactose (SUGAR); all participated in three absorption studies in random order. The NOCHO formula contained 10.0 g protein and 217 mg Ca from a combination of milk mineral and protein isolates; the LACTOSE and SUGAR formulae contained in addition 12 g lactose or 6 g glucose plus 6 g galactose, respectively. In study B, fractional Ca absorption was measured in five postmenopausal women after an oral dose of 47 Ca-equilibrated skim milk (217 mg Ca) and lactase-treated milk, each with sufficient carbohydrate added to equal 12 g. For both studies, the increase in forearm radioactivity 4 and 8 hours after oral 47 Ca administration relative to the increase observed after IV administration was used to estimate fractional Ca absorption. The addition of lactose but not glucose plus galactose to the NOCHO formula enhanced Ca absorption (p less than 0.05). Fractional absorption at 4 hours was 0.386 from the LACTOSE formula compared with 0.310 for both the NOCHO and SUGAR formulae. Those individuals with the lowest absorption in the absence of carbohydrate had the greatest increase with lactose. In contrast, Ca absorption was the same from skim milk as from lactase-treated skim milk (study B)

Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons

DEFF Research Database (Denmark)

Bak, Lasse K; Schousboe, Arne; Sonnewald, Ursula

2006-01-01

Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis was inves......Glucose is the primary energy substrate for the adult mammalian brain. However, lactate produced within the brain might be able to serve this purpose in neurons. In the present study, the relative significance of glucose and lactate as substrates to maintain neurotransmitter homeostasis...... was investigated. Cultured cerebellar (primarily glutamatergic) neurons were superfused in medium containing [U-13C]glucose (2.5 mmol/L) and lactate (1 or 5 mmol/L) or glucose (2.5 mmol/L) and [U-13C]lactate (1 mmol/L), and exposed to pulses of N-methyl-D-aspartate (300 micromol/L), leading to synaptic activity...... significantly during induced depolarization. In contrast, at both concentrations of extracellular lactate, the metabolism of [U-13C]glucose was increased during neuronal depolarization. The role of glucose and lactate as energy substrates during vesicular release as well as transporter-mediated influx...

Mangiferin Upregulates Glyoxalase 1 Through Activation of Nrf2/ARE Signaling in Central Neurons Cultured with High Glucose.

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Liu, Yao-Wu; Cheng, Ya-Qin; Liu, Xiao-Li; Hao, Yun-Chao; Li, Yu; Zhu, Xia; Zhang, Fan; Yin, Xiao-Xing

2017-08-01

Mangiferin, a natural C-glucoside xanthone, has anti-inflammatory, anti-oxidative, neuroprotective actions. Our previous study showed that mangiferin could attenuate diabetes-associated cognitive impairment of rats by enhancing the function of glyoxalase 1 (Glo-1) in brain. The aim of this study was to investigate whether Glo-1 upregulation by mangiferin in central neurons exposed to chronic high glucose may be related to activation of Nrf2/ARE pathway. Compared with normal glucose (25 mmol/L) culture, Glo-1 protein, mRNA, and activity levels were markedly decreased in primary hippocampal and cerebral cortical neurons cultured with high glucose (50 mmol/L) for 72 h, accompanied by the declined Nrf2 nuclear translocation and protein expression of Nrf2 in cell nucleus, as well as protein expression and mRNA level of γ-glutamylcysteine synthetase (γ-GCS) and superoxide dismutase activity, target genes of Nrf2/ARE signaling. Nonetheless, high glucose cotreating with mangiferin or sulforaphane, a typical inducer of Nrf2 activation, attenuated the above changes in both central neurons. In addition, mangiferin and sulforaphane significantly prevented the formation of advanced glycation end-products (AGEs) reflecting Glo-1 activity, while elevated the level of glutathione, a cofactor of Glo-1 activity and production of γ-GCS, in high glucose cultured central neurons. These findings demonstrated that Glo-1 was greatly downregulated in central neurons exposed to chronic high glucose, which is expected to lead the formation of AGEs and oxidative stress damages. We also proved that mangiferin enhanced the function of Glo-1 under high glucose condition by inducing activation of Nrf2/ARE signaling pathway.

Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-to-neuron lactate shuttle.

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Patel, Anant B; Lai, James C K; Chowdhury, Golam M I; Hyder, Fahmeed; Rothman, Douglas L; Shulman, Robert G; Behar, Kevin L

2014-04-08

Previous (13)C magnetic resonance spectroscopy experiments have shown that over a wide range of neuronal activity, approximately one molecule of glucose is oxidized for every molecule of glutamate released by neurons and recycled through astrocytic glutamine. The measured kinetics were shown to agree with the stoichiometry of a hypothetical astrocyte-to-neuron lactate shuttle model, which predicted negligible functional neuronal uptake of glucose. To test this model, we measured the uptake and phosphorylation of glucose in nerve terminals isolated from rats infused with the glucose analog, 2-fluoro-2-deoxy-D-glucose (FDG) in vivo. The concentrations of phosphorylated FDG (FDG6P), normalized with respect to known neuronal metabolites, were compared in nerve terminals, homogenate, and cortex of anesthetized rats with and without bicuculline-induced seizures. The increase in FDG6P in nerve terminals agreed well with the increase in cortical neuronal glucose oxidation measured previously under the same conditions in vivo, indicating that direct uptake and oxidation of glucose in nerve terminals is substantial under resting and activated conditions. These results suggest that neuronal glucose-derived pyruvate is the major oxidative fuel for activated neurons, not lactate-derived from astrocytes, contradicting predictions of the original astrocyte-to-neuron lactate shuttle model under the range of study conditions.

The Effects of Fenarimol and Methyl Parathion on Glucose 6-Phosphate Dehydrogenase Enzyme Activity in Rats

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Ferda ARI

2017-10-01

Full Text Available Fenarimol and methyl parathion are pesticides that have been used in agriculture for several years. These pesticides have significant effects on environmental and human health. Therefore, we investigated the effects of methyl parathion and fenarimol on glucose 6-phosphate dehydrogenase (EC 1.1.1.49 enzyme activity in rats. The glucose 6- phosphate dehydrogenase is the first enzyme of the pentose phosphate pathway and it is important in detoxifying reactions by NADPH generated. In this study, wistar albino rats administrated with methyl parathion (7 mg kg–1 and fenarimol (200 mg kg−1 by intraperitoneally for different periods (2, 4, 8, 16, 32, 64, and 72 h. The glucose 6-phosphate dehydrogenase enzyme activity was assayed in liver, kidney, brain, and small intestine in male and female rats. The exposure of fenarimol and methyl parathion caused increase of glucose 6-phosphate dehydrogenase enzyme activity in rat tissues, especially at last periods. We suggest that this increment of enzyme activity may be the reason of toxic effects of fenarimol and methyl parathion.

Low blood glucose precipitates spike-and-wave activity in genetically predisposed animals.

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Reid, Christopher A; Kim, Tae Hwan; Berkovic, Samuel F; Petrou, Steven

2011-01-01

Absence epilepsies are common, with a major genetic contribution to etiology. Certain environmental factors can influence absence occurrence but a complete understanding of absence precipitation is lacking. Herein we investigate if lowering blood glucose increases spike-wave activity in mouse models with varying seizure susceptibility. Three mouse models were used: an absence seizure model based on the knockin of a human GABA(A) γ2(R43Q) mutation (DBA(R43Q)), the spike-wave discharge (SWD)-prone DBA/2J strain, and the seizure resistant C57Bl/6 strain. Electrocorticography (ECoG) studies were recorded to determine SWDs during hypoglycemia induced by insulin or overnight fasting. An insulin-mediated reduction in blood glucose levels to 4 mm (c.a. 40% reduction) was sufficient to double SWD occurrence in the DBA(R43Q) model and in the SWD-prone DBA/2J mouse strain. Larger reductions in blood glucose further increased SWDs in both these models. However, even with large reductions in blood glucose, no discharges were observed in the seizure-resistant C57Bl/6 mouse strain. Injection of glucose reversed the impact of insulin on SWDs in the DBA(R43Q) model, supporting a reduction in blood glucose as the modulating influence. Overnight fasting reduced blood glucose levels to 4.5 mm (c.a. 35% reduction) and, like insulin, caused a doubling in occurrence of SWDs. Low blood glucose can precipitate SWDs in genetically predisposed animal models and should be considered as a potential environmental risk factor in patients with absence epilepsy. Wiley Periodicals, Inc. © 2010 International League Against Epilepsy.

Characterization of an inducible UDP-glucose:salicylic acid O-glucosyltransferase from oat roots

International Nuclear Information System (INIS)

Yalpani, N.; Schulz, M.; Balke, N.E.

1990-01-01

Phytotoxicity of salicylic acid (SA), a phenolic acid that inhibits ion absorption in plant roots, is reduced in oat roots by the action of a UDP-glucose:SA glucosyltransferase (GTase). GTase activity, extracted from oat roots and assayed with [ 14 C]SA, was present at low constitutive levels but increased within 1.5 h of incubation of roots in 0.5 mM SA at pH 6.5. This induction was the result of de novo RNA and protein synthesis. Induction was highly specific towards SA as the inducer. The partially purified, soluble enzyme has a M t of about 50,000 and high specificity towards UDP-glucose as the sugar donor (K m = 0.28 mM) and SA as the glucose acceptor (K m = 0.11 mM). 2-D PAGE of [ 35 S]methionine-labeled proteins extracted from induced and uninduced roots revealed a candidate peptide representing the GTase. This peptide was also present on gels of partially purified GTase

Renal glucose metabolism in normal physiological conditions and in diabetes.

Science.gov (United States)

Alsahli, Mazen; Gerich, John E

2017-11-01

The kidney plays an important role in glucose homeostasis via gluconeogenesis, glucose utilization, and glucose reabsorption from the renal glomerular filtrate. After an overnight fast, 20-25% of glucose released into the circulation originates from the kidneys through gluconeogenesis. In this post-absorptive state, the kidneys utilize about 10% of all glucose utilized by the body. After glucose ingestion, renal gluconeogenesis increases and accounts for approximately 60% of endogenous glucose release in the postprandial period. Each day, the kidneys filter approximately 180g of glucose and virtually all of this is reabsorbed into the circulation. Hormones (most importantly insulin and catecholamines), substrates, enzymes, and glucose transporters are some of the various factors influencing the kidney's role. Patients with type 2 diabetes have an increased renal glucose uptake and release in the fasting and the post-prandial states. Additionally, glucosuria in these patients does not occur at plasma glucose levels that would normally produce glucosuria in healthy individuals. The major abnormality of renal glucose metabolism in type 1 diabetes appears to be impaired renal glucose release during hypoglycemia. Copyright © 2017 Elsevier B.V. All rights reserved.

Carbohydrate absorption from one serving of fruit juice in young children: age and carbohydrate composition effects.

Science.gov (United States)

Nobigrot, T; Chasalow, F I; Lifshitz, F

1997-04-01

To test the hypotheses that: the efficiency of carbohydrate absorption in childhood increases with age, and decreased carbohydrate absorption occurs more frequently with juices containing more fructose than glucose and/or sorbitol than with juices which contain equal amounts of fructose and glucose and are sorbitol-free. One hundred and four healthy children were recruited from the Ambulatory Center at Maimonides Children's Center. They were assigned to one of three age groups: approximately 1, 3 and 5 years of age. Each child received one age-specific dose (by randomization) of one of four juices: a) pear juice which contains fructose in excess to glucose and a large amount of sorbitol; b) apple juice which is similar to pear juice in its fructose to glucose ratio but contains four times less sorbitol than pear juice; c) white grape juice or d) purple grape juice both of which contain equal amounts of fructose and glucose and are sorbitol-free. Breath hydrogen excretion (BH2) was utilized as the index of carbohydrate absorption. It was measured in fasting children and at 30-minute intervals for 3 hours after drinking the single serving of juice. Multiple breath hydrogen related parameters were quantified and results were expressed as: BH2 peak, area under the curve, and degree of carbohydrate malabsorption. After the test, parents completed a questionnaire and recorded signs and symptoms of intestinal malabsorption for 24 hours. Pear juice related BH2 levels were significantly higher among children 1 and 3 years of age as compared to the levels achieved after the other juices. Apple juice related BH2 levels were significantly higher only among the youngest age group of children. There was no significant difference in carbohydrate absorption among the 5 year old children regardless of the juice consumed. Incomplete carbohydrate absorption (BH2 peak above 20 ppm) occurred more frequently after pear juice consumption (84%) than after apple juice (41%) or grape juice

Changes in plasma glucose in Otsuka Long-Evans Tokushima Fatty rats after oral administration of maple syrup.

Science.gov (United States)

Nagai, Noriaki; Yamamoto, Tetsushi; Tanabe, Wataru; Ito, Yoshimasa; Kurabuchi, Satoshi; Mitamura, Kuniko; Taga, Atsushi

2015-01-01

We investigate whether maple syrup is a suitable sweetener in the management of type 2 diabetes using the Otsuka Long-Evans Tokushima Fatty (OLETF) rat. The enhancement in plasma glucose (PG) and glucose absorption in the small intestine were lower after the oral administration of maple syrup than after sucrose administration in OLETF rats, and no significant differences were observed in insulin levels. These data suggested that maple syrup might inhibit the absorption of glucose from the small intestine and preventing the enhancement of PG in OLETF rats. Therefore, maple syrup might help in the prevention of type 2 diabetes.

THE CHALLENGE OF PD PATIENTS: GLUCOSE AND GLUCOSE DEGRADATION PRODUCTS IN PD SOLUTION

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Yong-Lim Kim

2012-06-01

Full Text Available The main osmotic agent found in the peritoneal dialysis (PD solution is glucose. It has been of a wide use for great crystalloid osmotic power at a low concentration, simple metabolism, and excellent safety. On the other hand, anywhere between 60 to 80% of the glucose in the PD solution is absorbed - a 100 to 300 mg of daily glucose absorption. Once into the systemic circulation, glucose can be a cause for metabolic complications including obesity. Indeed, the diabetiform change observed in the peritoneal membrane in the long-term PD patients is believed attributable to the high-concentration glucose in the PD solution. The glucose absorbed from peritoneal cavity raises the risk of ‘glucose toxicity’, leading to insulin resistance and beta cell failure. Clinical similarity can be found in postprandial hyperglycemia, which is known to be associated with oxidative stress, endothelial dysfunction, NF-κb, and inflammation, affecting myocardial blood flow. Moreover, it is a proven independent risk factor of coronary artery disease in patients with type 2 diabetes, particularly of female gender. Though speculative yet, glucose toxicity might explain a higher mortality of PD patients after the first year compared with those on hemodialysis (more so in female, advanced-age patients with diabetes. Also included in the picture are glucose degradation products (GDPs generated along the course of heat sterilization or storage of the PD solution. They have been shown to induce apoptosis of peritoneal mesothelial cells, renal tubular epithelial cells, and endothelial cells, while spurring production of TGF-β and VEGF and facilitating epithelial mesenchymal transition. GDPs provide a stronger reactivity than glucose in the formation of AGEs, a known cause for microvascular complications and arteriosclerosis. Unfortunately, clinical studies using a low-GDP PD solution have provided mixed results on the residual renal function, peritonitis, peritoneal

The Role of Leptin in Maintaining Plasma Glucose During Starvation.

Science.gov (United States)

Perry, Rachel J; Shulman, Gerald I

2018-03-01

For 20 years it has been known that concentrations of leptin, a hormone produced by the white adipose tissue (WAT) largely in proportion to body fat, drops precipitously with starvation, particularly in lean humans and animals. The role of leptin to suppress the thyroid and reproductive axes during a prolonged fast has been well defined; however, the impact of leptin on metabolic regulation has been incompletely understood. However emerging evidence suggests that, in starvation, hypoleptinemia increases activity of the hypothalamic-pituitary-adrenal axis, promoting WAT lipolysis, increasing hepatic acetyl-CoA concentrations, and maintaining euglycemia. In addition, leptin may be largely responsible for mediating a shift from a reliance upon glucose metabolism (absorption and glycogenolysis) to fat metabolism (lipolysis increasing gluconeogenesis) which preserves substrates for the brain, heart, and other critical organs. In this way a leptin-mediated glucose-fatty acid cycle appears to maintain glycemia and permit survival in starvation.

Flurbiprofen ameliorates glucose deprivation-induced leptin resistance

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Toru Hosoi

2016-09-01

Full Text Available Leptin resistance is one of the mechanisms involved in the pathophysiology of obesity. The present study showed that glucose deprivation inhibited leptin-induced phosphorylation of signal transducer and activator of transcription 3 (STAT3 and signal transducer and activator of transcription 5 (STAT5 in neuronal cells. Flurbiprofen reversed glucose deprivation-mediated attenuation of STAT3, but not STAT5 activation, in leptin-treated cells. Glucose deprivation increased C/EBP-homologous protein (CHOP and glucose regulated protein 78 (GRP78 induction, indicating the activation of unfolded protein responses (UPR. Flurbiprofen did not affect the glucose deprivation-induced activation of UPR, but did attenuate the glucose deprivation-mediated induction of AMP-activated protein kinase (AMPK phosphorylation. Flurbiprofen may ameliorate glucose deprivation-induced leptin resistance in neuronal cells.

Evaluation of Antimicrobial Activity of Glucose Oxidase from Aspergillus niger EBL-A and Penicillium notatum

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Muhammad Anjum Zia

2013-12-01

Full Text Available This work aimed to study the production and purification of glucose oxidase by Aspergillus niger and Penicillium notatum using corn steep liquor as the substrate and evaluate its antimicrobial activity for use in pharmaceutical and food industries. The enzyme was purified by ammonium sulfate precipitation (60-85%, DEAE-cellulose ion exchange and Sephadex G-200 size exclusion chromatography. The crude enzyme extracts of A. niger and P. notatum showed 2.32 and 5.53 U mg-1 specific activities, respectively, which after desalting was 15.52 and 12.05 U mg-1, and after ion exchange and gel filtration chromatography was 29.09 - 62 and 25.72 - 59.37 U mg-1 for A. niger and P. notatum, respectively. The antimicrobial activity was determined by disc diffusion method against selected microbial strains where glucose oxidase from A. niger showed anti-bacterial activity, while no fungicidal effects were shown by both A. niger and P. notatum glucose oxidases.

Semi-analytical Model for Estimating Absorption Coefficients of Optically Active Constituents in Coastal Waters

Science.gov (United States)

Wang, D.; Cui, Y.

2015-12-01

The objectives of this paper are to validate the applicability of a multi-band quasi-analytical algorithm (QAA) in retrieval absorption coefficients of optically active constituents in turbid coastal waters, and to further improve the model using a proposed semi-analytical model (SAA). The ap(531) and ag(531) semi-analytically derived using SAA model are quite different from the retrievals procedures of QAA model that ap(531) and ag(531) are semi-analytically derived from the empirical retrievals results of a(531) and a(551). The two models are calibrated and evaluated against datasets taken from 19 independent cruises in West Florida Shelf in 1999-2003, provided by SeaBASS. The results indicate that the SAA model produces a superior performance to QAA model in absorption retrieval. Using of the SAA model in retrieving absorption coefficients of optically active constituents from West Florida Shelf decreases the random uncertainty of estimation by >23.05% from the QAA model. This study demonstrates the potential of the SAA model in absorption coefficients of optically active constituents estimating even in turbid coastal waters. Keywords: Remote sensing; Coastal Water; Absorption Coefficient; Semi-analytical Model

Glucose oxidase-functionalized fluorescent gold nanoclusters as probes for glucose

International Nuclear Information System (INIS)

Xia, Xiaodong; Long, Yunfei; Wang, Jianxiu

2013-01-01

Highlights: ► A glucose oxidase/gold nanocluster conjugates formed by etching chemistry. ► Integration of the bioactivities and fluorescence properties within a single unit. ► These conjugates serve as novel fluorescent probe for glucose. -- Abstract: Creation and application of noble metal nanoclusters have received continuous attention. By integrating enzyme activity and fluorescence for potential applications, enzyme-capped metal clusters are more desirable. This work demonstrated a glucose oxidase (an enzyme for glucose)-functionalized gold cluster as probe for glucose. Under physiological conditions, such bioconjugate was successfully prepared by an etching reaction, where tetrakis (hydroxylmethyl) phosphonium-protected gold nanoparticle and thioctic acid-modified glucose oxidase were used as precursor and etchant, respectively. These bioconjugates showed unique fluorescence spectra (λ em max = 650 nm, λ ex max = 507 nm) with an acceptable quantum yield (ca. 7%). Moreover, the conjugated glucose oxidase remained active and catalyzed reaction of glucose and dissolved O 2 to produce H 2 O 2 , which quenched quantitatively the fluorescence of gold clusters and laid a foundation of glucose detection. A linear range of 2.0 × 10 −6 –140 × 10 −6 M and a detection limit of 0.7 × 10 −6 M (S/N = 3) were obtained. Also, another horseradish peroxidase/gold cluster bioconjugate was produced by such general synthesis method. Such enzyme/metal cluster bioconjugates represented a promising class of biosensors for biologically important targets in organelles or cells

Construction of mutant glucose oxidases with increased dye-mediated dehydrogenase activity.

Science.gov (United States)

Horaguchi, Yohei; Saito, Shoko; Kojima, Katsuhiro; Tsugawa, Wakako; Ferri, Stefano; Sode, Koji

2012-11-02

Mutagenesis studies on glucose oxidases (GOxs) were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe) and Aspergillus niger GOx (PDB ID; 1cf3). We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC) oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor.

Construction of Mutant Glucose Oxidases with Increased Dye-Mediated Dehydrogenase Activity

Science.gov (United States)

Horaguchi, Yohei; Saito, Shoko; Kojima, Katsuhiro; Tsugawa, Wakako; Ferri, Stefano; Sode, Koji

2012-01-01

Mutagenesis studies on glucose oxidases (GOxs) were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe) and Aspergillus niger GOx (PDB ID; 1cf3). We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC) oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor. PMID:23203056

The Effect of D-Tagatose on Fructose Absorption in a Rat Model.

Science.gov (United States)

Williams, Jarrod; Spitnale, Michael; Lodder, Robert

D-tagatose is in development as a medication for the treatment of type 2 diabetes. The effect of oral D-tagatose on the absorption of D-fructose was assessed when co-administered in this study. In the pilot study, male Sprague-Dawley rats were fed C14 labeled fructose and glucose concomitantly to establish dose levels for the treatment group of rats fed C14 labeled fructose together with D-tagatose. Rats were administered 0, 600, 2000, 6000, or 12000 mg/kg of D-tagatose along with 2000 mg/kg of fructose. Blood samples were taken over 60 minutes and were assessed using scintillation counting. 600, 2000, and 6000 mg/kg of D-tagatose decreased fructose absorption by 1%, 26%, and 30% respectively (12000 mg/kg group was stopped short of completion due to intolerance) as measured by AUC of scintillation counts. The 600 and 2000 mg/kg of D-tagatose groups showed no difference in plasma glucose concentrations compared to placebo while a rise in glucose was seen in the 6000 mg/kg of D-tagatose groups. The results indicate that D-tagatose may be useful in reducing fructose absorption, which could lead to a beneficial outcome.

Effect to the Glycolit which the absorption to the solution of sacarose marked with a 14C

International Nuclear Information System (INIS)

Fleitas Estevez, Andres; Simon Carballo, Rafael; Perez Perez, Luisa; Derivet Zarzabal, Milagros

2001-01-01

Previous studies conducted in vitro and in experimental animals have served as the basis for a working hypothesis about the antihyperglycemic effect of a product derived from a natural zeolite (Fz), called glicolit. The objective of this paper was to demonstrate by the use of a radioisotopic method the effect of the joint administration of this product and a source of glucose (sacarose) on the blood levels of this monosaccharide. The study group was composed of 10 rats; 5 were administered glicolit and the other 5 were used as controls. Measurements of glucose in plasma were made at different times by a radioisotopic method after the oral administration of a solution of sacarose marked with a 14 C. The results showed a decrease of the levels of blood glucose in those rats that received glicolit. A graphic of absorption kinetics was made (specific activities against time) and it was obtained an area under the curve that was 16,2% lower in the group of animals that received glicolit. The radioisotopic method proved to be useful for studying the absorption kinetics of glucose when it is administered in the form of sacarose together with glicolit, which showed that it is effective in the reduction of the postprandial glycemic peaks in the studied rats. It seems that glicolit catches the glucose released by the intestinal alpha glucosidases enzymes. The radioisotopic method was also used to verify the hypothesis on the usefulness of glicolit to reduce the levels of glycemic after the ingestion of carbohydrates

Glucose and triglyceride lowering activity of Pterocarpus ...

African Journals Online (AJOL)

The leaf extracts of P. santalinoides possess triglyceride and glucose lowering properties in dexamethasone induced hyperlipidemia and insulin resistance and could be of therapeutic value in the management of metabolic syndrome. Key words: Pterocarpus santalinoides, leaf extracts, glucose tolerance, hyperlipidemia, ...

Synthesis of Silver-Chitosan Nanocomposites Colloidal by Glucose as Reducing Agent

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Endang Susilowati

2015-03-01

Full Text Available Silver-chitosan nanocomposites colloidal was successfully performed by chemical reduction method at room temperature using glucose as reducing agent, sodium hydroxide (NaOH as accelerator reagent, silver nitrate (AgNO3 as metal precursor and chitosan as stabilizing agent. Compared to other synthetic methods, this work is green and simple. The effect of the amount of NaOH, molar ratio of AgNO3 to glucose and AgNO3 concentration towards Localized Surface Plasmon Resonance (LSPR absorption band of silver nanoparticles was investigated using UV-Vis spectrophotometer. The stability of the colloid was also studied for the first 16 weeks of storage at ambient temperature. The formation of silver nanoparticles was confirmed by the appearance of LSPR absorption peak at 402.4–414.5 nm. It is also shown that the absorption peak of LSPR were affected by NaOH amount, ratio molar AgNO3/glucose and concentration of AgNO3. The produced silver nanoparticles were spherical with dominant size range of 6 to 18 nm as shown by TEM images. All colloidals were stable without any aggregation for 16 weeks after preparation. The newly prepared silver-chitosan nanocomposites colloidal may have potential for antibacterial applications.

AMP-activated protein kinase plays an important evolutionary conserved role in the regulation of glucose metabolism in fish skeletal muscle cells.

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Leonardo J Magnoni

Full Text Available AMPK, a master metabolic switch, mediates the observed increase of glucose uptake in locomotory muscle of mammals during exercise. AMPK is activated by changes in the intracellular AMP:ATP ratio when ATP consumption is stimulated by contractile activity but also by AICAR and metformin, compounds that increase glucose transport in mammalian muscle cells. However, the possible role of AMPK in the regulation of glucose metabolism in skeletal muscle has not been investigated in other vertebrates, including fish. In this study, we investigated the effects of AMPK activators on glucose uptake, AMPK activity, cell surface levels of trout GLUT4 and expression of GLUT1 and GLUT4 as well as the expression of enzymes regulating glucose disposal and PGC1α in trout myotubes derived from a primary muscle cell culture. We show that AICAR and metformin significantly stimulated glucose uptake (1.6 and 1.3 fold, respectively and that Compound C completely abrogated the stimulatory effects of the AMPK activators on glucose uptake. The combination of insulin and AMPK activators did not result in additive nor synergistic effects on glucose uptake. Moreover, exposure of trout myotubes to AICAR and metformin resulted in an increase in AMPK activity (3.8 and 3 fold, respectively. We also provide evidence suggesting that stimulation of glucose uptake by AMPK activators in trout myotubes may take place, at least in part, by increasing the cell surface and mRNA levels of trout GLUT4. Finally, AICAR increased the mRNA levels of genes involved in glucose disposal (hexokinase, 6-phosphofructokinase, pyruvate kinase and citrate synthase and mitochondrial biogenesis (PGC-1α and did not affect glycogen content or glycogen synthase mRNA levels in trout myotubes. Therefore, we provide evidence, for the first time in non-mammalian vertebrates, suggesting a potentially important role of AMPK in stimulating glucose uptake and utilization in the skeletal muscle of fish.

Effect of radioactive isotope 32P upon alpha amylase activity and glucose concentration in chickens

International Nuclear Information System (INIS)

Kraljevic, P.; Emanovic, D.; Simpraga, M.; Nejedli, S.; Stojevic, Z.

1996-01-01

An attempt has been made to investigate whether alpha amylase activity and glucose concentration in blood plasma can serve as the help in establishing on early diagnosis of organic or functional damage caused by ionizing radiation in chickens. Fifty day old hybrid chickens of heavy 'Jata' breeds of both sexes, were treated by 32 P administered intramusculary as sodium orthophosphate in a single dose of 333 MBq per kilogram of body weight. Blood samples was taken from the wing vein on day 1, 3, 5, 7 and 10 after administration of 32 P. Alpha amylase activity and glucose concentration were determined spectrophotometrically using kits produced by 'Radonja', Sisak. Alpha amylase activity was decreased and glucose concentration was increased during investigated period. Yet, the further investigations are needed to find out whether these two parameters can be used for early diagnosis of injury in chicken organism by ionizing radiation. (author)

Improved water and sodium absorption from oral rehydration solutions based on rice syrup in a rat model of osmotic diarrhea.

Science.gov (United States)

Wapnir, R A; Litov, R E; Zdanowicz, M M; Lifshitz, F

1991-04-01

Rice syrup solids, rice protein, and casein hydrolysate were added to experimental oral rehydration solutions in various combinations and tested in a rat intestinal perfusion system. Chronic osmotic diarrhea was induced in juvenile rats by supplying the cathartic agents, magnesium citrate and phenolphthalein, in their drinking water for 1 week. The experimental oral rehydration solutions were compared with standard oral rehydration solutions containing 20 gm/L or 30 gm/L of glucose and with each other to determine if there were significant differences in net water, sodium, or potassium absorption. An oral rehydration solution containing 30 gm/L of rice syrup solids had a net water absorption rate significantly higher than that of the standard 20 gm/L glucose-based oral rehydration solution (2.1 +/- 0.62 versus 1.5 +/- 0.48 microliters/[min x cm], p less than 0.05). Casein hydrolysate did not significantly affect net water absorption. However, combinations of 30 gm/L rice syrup solids and 5 gm/L casein hydrolysate significantly increased (p less than 0.05) net sodium and potassium absorption compared with the 20 gm/L glucose-based oral rehydration solution but not versus rice syrup solids alone. Oral rehydration solutions containing 30 gm/L rice syrup solids plus 5 gm/L rice protein, and 30 gm/L rice syrup solids plus 5 gm/L casein hydrolysate, had net water absorption rates significantly higher than the rate of a 30 gm/L glucose-based oral rehydration solution (2.5 +/- 0.36 and 2.4 +/- 0.38, respectively, versus 0.87 +/- 0.40 microliters/[min x cm], p less than 0.05). Rice protein and casein hydrolysate, however, did not significantly affect net water, sodium, or potassium absorption when added to rice protein glucose-based oral rehydration solutions. An inverse correlation between osmolality and net water absorption was observed (r = -0.653, p less than 0.02). The data suggest that substitution of rice syrup solids for glucose in oral rehydration solutions will

Glucose oxidase variants with improved properities

OpenAIRE

Fischer, Rainer; Ostafe, Raluca; Prodanovic, Radivoje

2014-01-01

Source: WO14173822A3 [EN] The technology provided herein relates to novel variants of microbial glucose oxidase with improved properties, more specifically to polypeptides having glucose oxidase activity as their major enzymatic activity; to nucleic acid molecules encoding said glucose oxidases; vectors and host cells containing the nucleic acids and methods for producing the glucose oxidase; compositions comprising said glucose oxidase; methods for the preparation and production of such enzy...

Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

Energy Technology Data Exchange (ETDEWEB)

Bolado-Carrancio, A. [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain); Riancho, J.A. [Department of Internal Medicine, Hospital U.M. Valdecilla-IDIVAL, University of Cantabria, RETICEF, Santander (Spain); Sainz, J. [Institute of Biomedicine and Biotechnology of Cantabria (IBBTEC), CSIC-University of Cantabria, Santander (Spain); Rodríguez-Rey, J.C., E-mail: rodriguj@unican.es [Department of Molecular Biology, University of Cantabria, IDIVAL, Santander (Spain)

2014-04-04

Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity.

Activation of nuclear receptor NR5A2 increases Glut4 expression and glucose metabolism in muscle cells

International Nuclear Information System (INIS)

Bolado-Carrancio, A.; Riancho, J.A.; Sainz, J.; Rodríguez-Rey, J.C.

2014-01-01

Highlights: • NR5A2 expression in C2C12 is associated with myotube differentiation. • DLPC induces an increase in GLUT4 levels and glucose uptake in C2C12 myotubes. • In high glucose conditions the activation of NR5A2 inhibits fatty acids oxidation. - Abstract: NR5A2 is a nuclear receptor which regulates the expression of genes involved in cholesterol metabolism, pluripotency maintenance and cell differentiation. It has been recently shown that DLPC, a NR5A2 ligand, prevents liver steatosis and improves insulin sensitivity in mouse models of insulin resistance, an effect that has been associated with changes in glucose and fatty acids metabolism in liver. Because skeletal muscle is a major tissue in clearing glucose from blood, we studied the effect of the activation of NR5A2 on muscle metabolism by using cultures of C2C12, a mouse-derived cell line widely used as a model of skeletal muscle. Treatment of C2C12 with DLPC resulted in increased levels of expression of GLUT4 and also of several genes related to glycolysis and glycogen metabolism. These changes were accompanied by an increased glucose uptake. In addition, the activation of NR5A2 produced a reduction in the oxidation of fatty acids, an effect which disappeared in low-glucose conditions. Our results suggest that NR5A2, mostly by enhancing glucose uptake, switches muscle cells into a state of glucose preference. The increased use of glucose by muscle might constitute another mechanism by which NR5A2 improves blood glucose levels and restores insulin sensitivity

Effective Peroxidase-Like Activity of Co-Aminoclay [CoAC] and Its Application for Glucose Detection

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Han Pill Song

2018-02-01

Full Text Available In this study, we describe a novel peroxidase-like activity of Co-aminoclay [CoAC] present at pH ~5.0 and its application to fluorescent biosensor for the determination of H2O2 and glucose. It is synthesized with aminoclays (ACs entrapping cationic metals such as Fe, Cu, Al, Co., Ce, Ni, Mn, and Zn to find enzyme mimicking ACs by sol–gel ambient conditions. Through the screening of catalytic activities by the typical colorimetric reaction employing 2,2′-azino-bis(3-ethylbenzo-thiazoline-6-sulfonic aciddiammonium salt (ABTS as a substrate with or without H2O2, Fe, Cu, and CoACs are found to exhibit peroxidase-like activity, as well as oxidase-like activity was observed from Ce and MnACs. Among them, CoAC shows exceptionally high peroxidase-like activity, presumably due to its ability to induce electron transfer between substrates and H2O2. CoAC is then used to catalyze the oxidation of Amplex® UltraRed (AUR into a fluorescent end product, which enables a sensitive fluorescent detection of H2O2. Moreover, a highly sensitive and selective glucose biosensing strategy is developed, based on enzyme cascade reaction between glucose oxidase (GOx and CoAC. Using this strategy, a highly linear fluorescence enhancement is verified when the concentration of glucose is increased in a wide range from 10 μM to 1 mM with a lower detection limit of 5 μM. The practical diagnostic capability of the assay system is also verified by its use to detect glucose in human blood serum. Based on these results, it is anticipated that CoAC can serve as potent peroxidase mimetics for the detection of clinically important target molecules.

Duodenal activation of cAMP-dependent protein kinase induces vagal afferent firing and lowers glucose production in rats.

Science.gov (United States)

Rasmussen, Brittany A; Breen, Danna M; Luo, Ping; Cheung, Grace W C; Yang, Clair S; Sun, Biying; Kokorovic, Andrea; Rong, Weifang; Lam, Tony K T

2012-04-01

The duodenum senses nutrients to maintain energy and glucose homeostasis, but little is known about the signaling and neuronal mechanisms involved. We tested whether duodenal activation of adenosine 3',5'-cyclic monophosphate (cAMP)-dependent protein kinase A (PKA) is sufficient and necessary for cholecystokinin (CCK) signaling to trigger vagal afferent firing and regulate glucose production. In rats, we selectively activated duodenal PKA and evaluated changes in glucose kinetics during the pancreatic (basal insulin) pancreatic clamps and vagal afferent firing. The requirement of duodenal PKA signaling in glucose regulation was evaluated by inhibiting duodenal activation of PKA in the presence of infusion of the intraduodenal PKA agonist (Sp-cAMPS) or CCK1 receptor agonist (CCK-8). We also assessed the involvement of a neuronal network and the metabolic impact of duodenal PKA activation in rats placed on high-fat diets. Intraduodenal infusion of Sp-cAMPS activated duodenal PKA and lowered glucose production, in association with increased vagal afferent firing in control rats. The metabolic and neuronal effects of duodenal Sp-cAMPS were negated by coinfusion with either the PKA inhibitor H89 or Rp-CAMPS. The metabolic effect was also negated by coinfusion with tetracaine, molecular and pharmacologic inhibition of NR1-containing N-methyl-d-aspartate (NMDA) receptors within the dorsal vagal complex, or hepatic vagotomy in rats. Inhibition of duodenal PKA blocked the ability of duodenal CCK-8 to reduce glucose production in control rats, whereas duodenal Sp-cAMPS bypassed duodenal CCK resistance and activated duodenal PKA and lowered glucose production in rats on high-fat diets. We identified a neural glucoregulatory function of duodenal PKA signaling. Copyright © 2012 AGA Institute. Published by Elsevier Inc. All rights reserved.

Glucose oxidase-functionalized fluorescent gold nanoclusters as probes for glucose

Energy Technology Data Exchange (ETDEWEB)

Xia, Xiaodong [College of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China); School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Long, Yunfei, E-mail: l_yunfei927@163.com [School of Chemistry and Chemical Engineering, Hunan University of Science and Technology, Xiangtan 411201 (China); Wang, Jianxiu, E-mail: jxiuwang@csu.edu.cn [College of Chemistry and Chemical Engineering, Central South University, Changsha 410083 (China)

2013-04-15

Highlights: ► A glucose oxidase/gold nanocluster conjugates formed by etching chemistry. ► Integration of the bioactivities and fluorescence properties within a single unit. ► These conjugates serve as novel fluorescent probe for glucose. -- Abstract: Creation and application of noble metal nanoclusters have received continuous attention. By integrating enzyme activity and fluorescence for potential applications, enzyme-capped metal clusters are more desirable. This work demonstrated a glucose oxidase (an enzyme for glucose)-functionalized gold cluster as probe for glucose. Under physiological conditions, such bioconjugate was successfully prepared by an etching reaction, where tetrakis (hydroxylmethyl) phosphonium-protected gold nanoparticle and thioctic acid-modified glucose oxidase were used as precursor and etchant, respectively. These bioconjugates showed unique fluorescence spectra (λ{sub em} {sub max} = 650 nm, λ{sub ex} {sub max} = 507 nm) with an acceptable quantum yield (ca. 7%). Moreover, the conjugated glucose oxidase remained active and catalyzed reaction of glucose and dissolved O{sub 2} to produce H{sub 2}O{sub 2}, which quenched quantitatively the fluorescence of gold clusters and laid a foundation of glucose detection. A linear range of 2.0 × 10{sup −6}–140 × 10{sup −6} M and a detection limit of 0.7 × 10{sup −6} M (S/N = 3) were obtained. Also, another horseradish peroxidase/gold cluster bioconjugate was produced by such general synthesis method. Such enzyme/metal cluster bioconjugates represented a promising class of biosensors for biologically important targets in organelles or cells.

Insulin Induces an Increase in Cytosolic Glucose Levels in 3T3-L1 Cells with Inhibited Glycogen Synthase Activation

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Helena H. Chowdhury

2014-10-01

Full Text Available Glucose is an important source of energy for mammalian cells and enters the cytosol via glucose transporters. It has been thought for a long time that glucose entering the cytosol is swiftly phosphorylated in most cell types; hence the levels of free glucose are very low, beyond the detection level. However, the introduction of new fluorescence resonance energy transfer-based glucose nanosensors has made it possible to measure intracellular glucose more accurately. Here, we used the fluorescent indicator protein (FLIPglu-600µ to monitor cytosolic glucose dynamics in mouse 3T3-L1 cells in which glucose utilization for glycogen synthesis was inhibited. The results show that cells exhibit a low resting cytosolic glucose concentration. However, in cells with inhibited glycogen synthase activation, insulin induced a robust increase in cytosolic free glucose. The insulin-induced increase in cytosolic glucose in these cells is due to an imbalance between the glucose transported into the cytosol and the use of glucose in the cytosol. In untreated cells with sensitive glycogen synthase activation, insulin stimulation did not result in a change in the cytosolic glucose level. This is the first report of dynamic measurements of cytosolic glucose levels in cells devoid of the glycogen synthesis pathway.

Determination of dehydrogenase activities involved in D-glucose oxidation in Gluconobacter and Acetobacter strains

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Florencia Sainz

2016-08-01

Full Text Available Acetic acid bacteria (AAB are known for rapid and incomplete oxidation of an extensively variety of alcohols and carbohydrates, resulting in the accumulation of organic acids as the final products. These oxidative fermentations in AAB are catalyzed by PQQ- or FAD- dependent membrane bound dehydrogenases. In the present study, the enzyme activity of the membrane bound dehydrogenases (membrane-bound PQQ-glucose dehydrogenase (mGDH, D-gluconate dehydrogenase (GADH and membrane-bound glycerol dehydrogenase (GLDH involved in the oxidation of D-glucose and D-gluconic acid (GA was determined in six strains of three different species of AAB (three natural and three type strains. Moreover, the effect of these activities on the production of related metabolites (GA, 2-keto-D-gluconic acid (2KGA and 5-keto-D-gluconic acid (5KGA was analyzed. The natural strains belonging to Gluconobacter showed a high mGDH activity and low activity in GADH and GLDH, whereas the A. malorum strain presented low activity in the three enzymes. Nevertheless, no correlation was observed between the activity of these enzymes and the concentration of the corresponding metabolites. In fact, all the tested strains were able to oxidize D-glucose to GA, being maximal at the late exponential phase of the AAB growth (24 h, which coincided with glucose exhaustion and the maximum mGDH activity. Instead, only some of the tested strains were capable of producing 2KGA and/or 5KGA. In the case of G. oxydans strains, no 2KGA production was detected which is related to the absence of GADH activity after 24 h, while in the remaining strains, detection of GADH activity after 24h resulted in a high accumulation of 2KGA. Therefore, it is possible to choose the best strain depending on the desired product composition.Moreover, the sequences of these genes were used to construct phylogenetic trees. According to the sequence of gcd, gene coding for mGDH, Acetobacter and Komagataeibacter were

Modified starch enhances absorption and accelerates recovery in experimental diarrhea in rats.

Science.gov (United States)

Wingertzahn, M A; Teichberg, S; Wapnir, R A

1999-03-01

Rice gruels have been used as home remedies to treat dehydration associated with diarrheal illness in developing countries. These preparations have produced conflicting results, most likely due to the heterogeneity of starch used. We investigated whether the modified tapioca starch, Textra (TX), at 5.0 or 10.0 g/L added to a 90 mmol/L Na+-111 mmol glucose oral rehydration solution (ORS) enhanced water and electrolyte absorption in two models of diarrhea. To induce a secretory state (model A), the jejunum of juvenile rats was perfused with 10 mmol/L theophylline (THEO) under anesthesia and then perfused with the solutions indicated above. To produce chronic osmotic-secretory diarrhea (model B), rats had a magnesium citrate-phenolphthalein solution as the sole fluid source for 1 wk, and then were perfused as the THEO-treated rats. Water, electrolyte, and glucose absorption were measured during both perfusions. As an extension of the perfusion studies, we compared how fast rats recovered from chronic osmotic diarrhea by offering them either water, ORS, or ORS containing 5.0 g/L TX along with solid food. Recovery rate markers were measured after 24 h and included weight gain, food and fluid intake, and stool output. In model A, addition of 5.0 g/L TX to ORS reversed Na+ secretion and improved net water as well as K+ and glucose absorption, compared with THEO-treated rats perfused with ORS without TX. In model B, addition of TX to ORS increased water, Na+, K+, and glucose absorption, compared with rats perfused without TX. Increasing TX from 5.0 to 10.0 g/L had no additional benefit. In recovery experiments, animals with free access to ORS with TX had significantly greater weight gain and decreased stool output compared with animals recovering with water or ORS without TX. Our experiments suggest that TX may be a useful additive to standard ORS to promote fluid and electrolyte absorption and may provide additional energy without increasing ORS osmotic load.

Duodenal Ca2+ absorption is not stimulated by calcitriol during early postnatal development of pigs.

Science.gov (United States)

Schroeder, B; Dahl, M R; Breves, G

1998-08-01

The role of calcitriol in stimulating intestinal active Ca2+ absorption during postnatal life was studied in newborn, suckling, and weaned control (Con) piglets and piglets suffering from inherited calcitriol deficiency (Def piglets). In addition, a group of Def piglets was treated with vitamin D3 (Def-D3 piglets), which normalized plasma calcitriol levels. Regardless of age, duodenal calbindin-D9k concentrations ranged between 1,839 and 2,846 microg/g mucosa in Con piglets, between 821 and 1,219 microg/g mucosa in Def piglets, and between 2,960 and 3,692 microg/g mucosa in Def-D3 animals. In weaned animals, active Ca2+ absorption as calculated from in vitro 45Ca2+ flux rate measurements in Ussing chambers could be related to calbindin-D9k levels. Thus active Ca2+ absorption was completely absent in Def animals but was reconstituted in Def-D3 animals. In contrast, in newborn Def piglets active Ca2+ absorption functioned normally despite the low plasma calcitriol and mucosal calbindin-D9k levels and could not be affected by treatment with vitamin D3. Similar results were obtained from suckling Def piglets. The microtubule-disrupting agent colchicine caused significant inhibition of transepithelial net Ca2+ absorption in duodenal epithelia from newborn piglets without exerting an effect in suckling and weaned animals. Colchicine had no effect on Ca2+ uptake across the brush border membrane of mucosal enterocytes or on glucose-dependent electrogenic net ion flux rates in duodenal preparations from newborn Con piglets. In conclusion, our findings reveal intestinal active Ca2+ absorption during early postnatal life of pigs that involves calcitriol-independent mechanisms and that may include intact microtubule actions.

Maintenance of Gastrointestinal Glucose Homeostasis by the Gut-Brain Axis.

Science.gov (United States)

Chen, Xiyue; Eslamfam, Shabnam; Fang, Luoyun; Qiao, Shiyan; Ma, Xi

2017-01-01

Gastrointestinal homeostasis is a dynamic balance under the interaction between the host, GI tract, nutrition and energy metabolism. Glucose is the main energy source in living cells. Thus, glucose metabolic disorders can impair normal cellular function and endanger organisms' health. Diseases that are associated with glucose metabolic disorders such as obesity, diabetes, hypertension, and other metabolic syndromes are in fact life threatening. Digestive system is responsible for food digestion and nutrient absorption. It is also involved in neuronal, immune, and endocrine pathways. In addition, the gut microbiota plays an essential role in initiating signal transduction, and communication between the enteric and central nervous system. Gut-brain axis is composed of enteric neural system, central neural system, and all the efferent and afferent neurons that are involved in signal transduction between the brain and gut-brain. Gut-brain axis is influenced by the gut-microbiota as well as numerous neurotransmitters. Properly regulated gut-brain axis ensures normal digestion, absorption, energy production, and subsequently maintenance of glucose homeostasis. Understanding the underlying regulatory mechanisms of gut-brain axis involved in gluose homeostasis would enable us develop more efficient means of prevention and management of metabolic disease such as diabetic, obesity, and hypertension. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

The Proton-Activated Receptor GPR4 Modulates Glucose Homeostasis by Increasing Insulin Sensitivity

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Luca Giudici

2013-11-01

Full Text Available Background: The proton-activated G protein-coupled receptor GPR4 is expressed in many tissues including white adipose tissue. GPR4 is activated by extracellular protons in the physiological pH range (i.e. pH 7.7 - 6.8 and is coupled to the production of cAMP. Methods: We examined mice lacking GPR4 and examined glucose tolerance and insulin sensitivity in young and aged mice as well as in mice fed with a high fat diet. Expression profiles of pro- and anti-inflammatory cytokines in white adipose tissue, liver and skeletal muscle was assessed. Results: Here we show that mice lacking GPR4 have an improved intraperitoneal glucose tolerance test and increased insulin sensitivity. Insulin levels were comparable but leptin levels were increased in GPR4 KO mice. Gpr4-/- showed altered expression of PPARα, IL-6, IL-10, TNFα, and TGF-1β in skeletal muscle, white adipose tissue, and liver. High fat diet abolished the differences in glucose tolerance and insulin sensitivity between Gpr4+/+ and Gpr4-/- mice. In contrast, in aged mice (12 months old, the positive effect of GPR4 deficiency on glucose tolerance and insulin sensitivity was maintained. Liver and adipose tissue showed no major differences in the mRNA expression of pro- and anti-inflammatory factors between aged mice of both genotypes. Conclusion: Thus, GPR4 deficiency improves glucose tolerance and insulin sensitivity. The effect may involve an altered balance between pro- and anti-inflammatory factors in insulin target tissues.

Plain to point network reduced graphene oxide - activated carbon composites decorated with platinum nanoparticles for urine glucose detection

Science.gov (United States)

Hossain, Mohammad Faruk; Park, Jae Y.

2016-02-01

In this study, a hydrothermal technique was applied to synthesize glucose-treated reduced graphene oxide-activated carbon (GRGO/AC) composites. Platinum nanoparticles (PtNP) were electrochemically deposited on the modified GRGO/AC surface, and chitosan-glucose oxidase (Chit-GOx) composites and nafion were integrated onto the modified surface of the working electrode to prepare a highly sensitive glucose sensor. The fabricated biosensor exhibited a good amperometric response to glucose in the detection range from 0.002 mM to 10 mM, with a sensitivity of 61.06 μA/mMcm2, a short response time (4 s) and a low detection limit of 2 μM (signal to noise ratio is 3). The glucose sensor exhibited a negligible response to interference and good stability. In addition, the glucose levels in human urine were tested in order to conduct a practical assessment of the proposed sensor, and the results indicate that the sensor had superior urine glucose recognition. These results thus demonstrate that the noble nano-structured electrode with a high surface area and electrocatalytic activity offers great promise for use in urine glucose sensing applications.

Glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

Science.gov (United States)

Suyama, Shigetomo; Maekawa, Fumihiko; Maejima, Yuko; Kubota, Naoto; Kadowaki, Takashi; Yada, Toshihiko

2016-08-09

Adiponectin regulates glucose and lipid metabolism, acting against metabolic syndrome and atherosclerosis. Accumulating evidence suggest that adiponectin acts on the brain including hypothalamic arcuate nucleus (ARC), where proopiomelanocortin (POMC) neurons play key roles in feeding regulation. Several studies have examined intracerebroventricular (ICV) injection of adiponectin and reported opposite effects, increase or decrease of food intake. These reports used different nutritional states. The present study aimed to clarify whether adiponectin exerts distinct effects on food intake and ARC POMC neurons depending on the glucose concentration. Adiponectin was ICV injected with or without glucose for feeding experiments and administered to ARC slices with high or low glucose for patch clamp experiments. We found that adiponectin at high glucose inhibited POMC neurons and increased food intake while at low glucose it exerted opposite effects. The results demonstrate that glucose level determines excitatory or inhibitory effects of adiponectin on arcuate POMC neuron activity and feeding.

Glucose repression in Saccharomyces cerevisiae.

Science.gov (United States)

Kayikci, Ömur; Nielsen, Jens

2015-09-01

Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration and gluconeogenesis. This dominant effect of glucose on yeast carbon metabolism is coordinated by several signaling and metabolic interactions that mainly regulate transcriptional activity but are also effective at post-transcriptional and post-translational levels. This review describes effects of glucose repression on yeast carbon metabolism with a focus on roles of the Snf3/Rgt2 glucose-sensing pathway and Snf1 signal transduction in establishment and relief of glucose repression. © FEMS 2015.

Construction of Mutant Glucose Oxidases with Increased Dye-Mediated Dehydrogenase Activity

Directory of Open Access Journals (Sweden)

Koji Sode

2012-11-01

Full Text Available Mutagenesis studies on glucose oxidases (GOxs were conducted to construct GOxs with reduced oxidase activity and increased dehydrogenase activity. We focused on two representative GOxs, of which crystal structures have already been reported—Penicillium amagasakiense GOx (PDB ID; 1gpe and Aspergillus niger GOx (PDB ID; 1cf3. We constructed oxygen-interacting structural models for GOxs, and predicted the residues responsible for oxidative half reaction with oxygen on the basis of the crystal structure of cholesterol oxidase as well as on the fact that both enzymes are members of the glucose/methanol/choline (GMC oxidoreductase family. Rational amino acid substitution resulted in the construction of an engineered GOx with drastically decreased oxidase activity and increased dehydrogenase activity, which was higher than that of the wild-type enzyme. As a result, the dehydrogenase/oxidase ratio of the engineered enzyme was more than 11-fold greater than that of the wild-type enzyme. These results indicate that alteration of the dehydrogenase/oxidase activity ratio of GOxs is possible by introducing a mutation into the putative functional residues responsible for oxidative half reaction with oxygen of these enzymes, resulting in a further increased dehydrogenase activity. This is the first study reporting the alteration of GOx electron acceptor preference from oxygen to an artificial electron acceptor.

Acute activation of GLP-1-expressing neurons promotes glucose homeostasis and insulin sensitivity

OpenAIRE

Xuemei Shi; Shaji Chacko; Feng Li; Depei Li; Douglas Burrin; Lawrence Chan; Xinfu Guan

2017-01-01

Objective: Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. Methods: We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected...

Effect of various absorption enhancers based on tight junctions on the intestinal absorption of forsythoside A in Shuang-Huang-Lian, application to its antivirus activity.

Science.gov (United States)

Zhou, Wei; Zhu, Xuan Xuan; Yin, Ai Ling; Cai, Bao Chang; Wang, Hai Dan; Di, Liuqing; Shan, Jin Jun

2014-01-01

Forsythoside A (FTA), one of the main active ingredients in Shuang-Huang-Lian (SHL), possesses strong antibacterial, antioxidant and antiviral effects, and its pharmacological effects was higher than that of other ingredients, but the absolute bioavailability orally was approximately 0.72%, which was significantly low, influencing clinical efficacies of its oral preparations seriously. In vitro Caco-2 cell and in vivo pharmacokinetics study were simultaneously performed to investigate the effects of absorption enhancers based on tight junctions: sodium caprate and water-soluble chitosan on the intestinal absorption of FTA, and the eventual mucosal epithelial damage resulted from absorption enhancers was evaluated by MTT test and morphology observation, respectively. The pharmacological effects such as antivirus activity improvement by absorption enhancers were verified by MDCK damage inhibition rate after influenza virus propagation. The observations from in vitro Caco-2 cell showed that the absorption of FTA in SHL could be improved by absorption enhancers. Meanwhile, the absorption enhancing effect of water-soluble chitosan may be almost saturable up to 0.0032% (w/v), and sodium caprate at concentrations up to 0.64 mg/mL was safe, but water-soluble chitosan at different concentrations was all safe for these cells. In pharmacokinetics study, water-soluble chitosan at dosage of 50 mg/kg improved the bioavailability of FTA in SHL to the greatest extent, and was safe for gastrointestine from morphological observation. Besides, treatment with SHL with water-soluble chitosan at dosage of 50 mg/kg prevented MDCK damage after influenza virus propagation better significantly than that of control. Water-soluble chitosan at dosage of 50 mg/kg might be safe and effective absorption enhancer for improving the bioavailability of FTA and the antivirus activity in vitro in SHL.

Elevated glucose concentrations promote receptor-independent activation of adherent human neutrophils: an experimental and computational approach

DEFF Research Database (Denmark)

Kummer, Ursula; Zobeley, Jürgen; Brasen, Jens Christian

2007-01-01

of NO and superoxide formation were observed. However, these changes were not observed for sorbitol, a nonmetabolizable carbohydrate. Glucose transport appears to be important in this process as phloretin interferes with the glucose-specific receptor-independent activation of neutrophils. However, LY83583...

Regulation of intracellular glucose and polyol pathway by thiamine and benfotiamine in vascular cells cultured in high glucose.

Science.gov (United States)

Berrone, Elena; Beltramo, Elena; Solimine, Carmela; Ape, Alessandro Ubertalli; Porta, Massimo

2006-04-07

Hyperglycemia is a causal factor in the development of the vascular complications of diabetes. One of the biochemical mechanisms activated by excess glucose is the polyol pathway, the key enzyme of which, aldose reductase, transforms d-glucose into d-sorbitol, leading to imbalances of intracellular homeostasis. We aimed at verifying the effects of thiamine and benfotiamine on the polyol pathway, transketolase activity, and intracellular glucose in endothelial cells and pericytes under high ambient glucose. Human umbilical vein endothelial cells and bovine retinal pericytes were cultured in normal (5.6 mmol/liter) or high (28 mmol/liter) glucose, with or without thiamine or benfotiamine 50 or 100 mumol/liter. Transketolase and aldose reductase mRNA expression was determined by reverse transcription-PCR, and their activity was measured spectrophotometrically; sorbitol concentrations were quantified by gas chromatography-mass spectrometry and intracellular glucose concentrations by fluorescent enzyme-linked immunosorbent assay method. Thiamine and benfotiamine reduce aldose reductase mRNA expression, activity, sorbitol concentrations, and intracellular glucose while increasing the expression and activity of transketolase, for which it is a coenzyme, in human endothelial cells and bovine retinal pericytes cultured in high glucose. Thiamine and benfotiamine correct polyol pathway activation induced by high glucose in vascular cells. Activation of transketolase may shift excess glycolytic metabolites into the pentose phosphate cycle, accelerate the glycolytic flux, and reduce intracellular free glucose, thereby preventing its conversion to sorbitol. This effect on the polyol pathway, together with other beneficial effects reported for thiamine in high glucose, could justify testing thiamine as a potential approach to the prevention and/or treatment of diabetic complications.

UDP-[14C]glucose-labelable polypeptides from pea: Possible components of glucan synthase I activity

International Nuclear Information System (INIS)

Ray, P.M.; Dhugga, K.S.; Gallaghar, S.R.

1989-01-01

A membrane-bound polypeptide doublet of about 40 kD can be rapidly labeled with UDP-[ 14 C]glucose under the assay conditions for glucan synthase I (GS-I). Label seems covalently bound, and chases when unlabeled UDPG is added; it might represent a covalent intermediate in polysaccharide synthesis. Labeling and GS-I activity show several common features: they co-sediment with Golgi membranes in sucrose gradients; they depend similarly on Mg 2+ or Mn 2+ (not Ca 2+ ); they decrease dramatically from stem apex to base, and are higher in epidermis than internal tissue; they show similar sensitivities to several inhibitors. But the doublet still labels after polysaccharide-synthesizing activity has been destroyed by Triton X-100. The doublet polypeptides might be glucosyl tranferases whose ability to transfer glucose units to a glucan chain is detergent-sensitive, but to accept glucose from UDPG is not; or they might be detergent-insensitive primary glucose acceptors, from which a distinct, detergent-sensitive transferase(s) move(s) these units to glucan chains

The Effect of D-Tagatose on Fructose Absorption in a Rat Model

Science.gov (United States)

Williams, Jarrod; Spitnale, Michael; Lodder, Robert

2014-01-01

D-tagatose is in development as a medication for the treatment of type 2 diabetes. The effect of oral D-tagatose on the absorption of D-fructose was assessed when co-administered in this study. In the pilot study, male Sprague-Dawley rats were fed C14 labeled fructose and glucose concomitantly to establish dose levels for the treatment group of rats fed C14 labeled fructose together with D-tagatose. Rats were administered 0, 600, 2000, 6000, or 12000 mg/kg of D-tagatose along with 2000 mg/kg of fructose. Blood samples were taken over 60 minutes and were assessed using scintillation counting. 600, 2000, and 6000 mg/kg of D-tagatose decreased fructose absorption by 1%, 26%, and 30% respectively (12000 mg/kg group was stopped short of completion due to intolerance) as measured by AUC of scintillation counts. The 600 and 2000 mg/kg of D-tagatose groups showed no difference in plasma glucose concentrations compared to placebo while a rise in glucose was seen in the 6000 mg/kg of D-tagatose groups. The results indicate that D-tagatose may be useful in reducing fructose absorption, which could lead to a beneficial outcome. PMID:25621289

Rapid fluctuations in extracellular brain glucose levels induced by natural arousing stimuli and intravenous cocaine: fueling the brain during neural activation

Science.gov (United States)

Lenoir, Magalie

2012-01-01

Glucose, a primary energetic substrate for neural activity, is continuously influenced by two opposing forces that tend to either decrease its extracellular levels due to enhanced utilization in neural cells or increase its levels due to entry from peripheral circulation via enhanced cerebral blood flow. How this balance is maintained under physiological conditions and changed during neural activation remains unclear. To clarify this issue, enzyme-based glucose sensors coupled with high-speed amperometry were used in freely moving rats to evaluate fluctuations in extracellular glucose levels induced by brief audio stimulus, tail pinch (TP), social interaction with another rat (SI), and intravenous cocaine (1 mg/kg). Measurements were performed in nucleus accumbens (NAcc) and substantia nigra pars reticulata (SNr), which drastically differ in neuronal activity. In NAcc, where most cells are powerfully excited after salient stimulation, glucose levels rapidly (latency 2–6 s) increased (30–70 μM or 6–14% over baseline) by all stimuli; the increase differed in magnitude and duration for each stimulus. In SNr, where most cells are transiently inhibited by salient stimuli, TP, SI, and cocaine induced a biphasic glucose response, with the initial decrease (−20–40 μM or 5–10% below baseline) followed by a reboundlike increase. The critical role of neuronal activity in mediating the initial glucose response was confirmed by monitoring glucose currents after local microinjections of glutamate (GLU) or procaine (PRO). While intra-NAcc injection of GLU transiently increased glucose levels in this structure, intra-SNr PRO injection resulted in rapid, transient decreases in SNr glucose. Therefore, extracellular glucose levels in the brain change very rapidly after physiological and pharmacological stimulation, the response is structure specific, and the pattern of neuronal activity appears to be a critical factor determining direction and magnitude of physiological

Glucose and fructose 6-phosphate cycle in humans

International Nuclear Information System (INIS)

Karlander, S.; Roovete, A.; Vranic, M.; Efendic, S.

1986-01-01

We have determined the rate of glucose cycling by comparing turnovers of [2- 3 H]- and [6- 3 H]glucose under basal conditions and during a glucose infusion. Moreover, the activity of the fructose 6-phosphate cycle was assessed by comparing [3- 3 H]- and [6- 3 H]glucose. The study included eight lean subjects with normal glucose tolerance. They participated in two randomly performed investigations. In one experiment [2- 3 H]- and [6- 3 H]glucose were given simultaneously, while in the other only [3- 3 H]glucose was given. The basal rate of glucose cycling was 0.32 +/- 0.08 mg X kg-1 X min-1 or 17% of basal glucose production (P less than 0.005). During glucose infusion the activity of endogenous glucose cycling did not change but since glucose production was suppressed it amounted to 130% of glucose production. The basal fructose 6-phosphate cycle could be detected only in three subjects and was suppressed during glucose infusion. In conclusion, the glucose cycle is active in healthy humans both in basal conditions and during moderate hyperglycemia. In some subjects, the fructose 6-phosphate cycle also appears to be active. Thus it is preferable to use [6- 3 H]glucose rather than [3- 3 H]glucose when measuring glucose production and particularly when assessing glucose cycle

Glucose-6-phosphate dehydrogenase activity decreases during storage of leukoreduced red blood cells

NARCIS (Netherlands)

Peters, Anna L.; van Bruggen, Robin; de Korte, Dirk; van Noorden, Cornelis J. F.; Vlaar, Alexander P. J.

2016-01-01

During storage, the activity of the red blood cell (RBC) antioxidant system decreases. Glucose-6-phosphate dehydrogenase (G6PD) is essential for protection against oxidative stress by producing NADPH. G6PD function of RBC transfusion products is reported to remain stable during storage, but activity

AMP-activated protein kinase-mediated glucose transport as a novel target of tributyltin in human embryonic carcinoma cells.

Science.gov (United States)

Yamada, Shigeru; Kotake, Yaichiro; Sekino, Yuko; Kanda, Yasunari

2013-05-01

Organotin compounds such as tributyltin (TBT) are known to cause various forms of cytotoxicity, including developmental toxicity and neurotoxicity. However, the molecular target of the toxicity induced by nanomolar levels of TBT has not been identified. In the present study, we found that exposure to 100 nM TBT induced growth arrest in human pluripotent embryonic carcinoma cell line NT2/D1. Since glucose provides metabolic energy, we focused on the glycolytic system. We found that exposure to TBT reduced the levels of both glucose-6-phosphate and fructose-6-phosphate. To investigate the effect of TBT exposure on glycolysis, we examined glucose transporter (GLUT) activity. TBT exposure inhibited glucose uptake via a decrease in the level of cell surface-bound GLUT1. Furthermore, we examined the effect of AMP-activated protein kinase (AMPK), which is known to regulate glucose transport by facilitating GLUT translocation. Treatment with the potent AMPK activator, AICAR, restored the TBT-induced reduction in cell surface-bound GLUT1 and glucose uptake. In conclusion, these results suggest that exposure to nanomolar levels of TBT causes growth arrest by targeting glycolytic systems in human embryonic carcinoma cells. Thus, understanding the energy metabolism may provide new insights into the mechanisms of metal-induced cytotoxicity.

Vibrational imaging of glucose uptake activity in live cells and tissues by stimulated Raman scattering microscopy (Conference Presentation)

Science.gov (United States)

Hu, Fanghao; Chen, Zhixing; Zhang, Luyuan; Shen, Yihui; Wei, Lu; Min, Wei

2016-03-01

Glucose is consumed as an energy source by virtually all living organisms, from bacteria to humans. Its uptake activity closely reflects the cellular metabolic status in various pathophysiological transformations, such as diabetes and cancer. Extensive efforts such as positron emission tomography, magnetic resonance imaging and fluorescence microscopy have been made to specifically image glucose uptake activity but all with technical limitations. Here, we report a new platform to visualize glucose uptake activity in live cells and tissues with subcellular resolution and minimal perturbation. A novel glucose analogue with a small alkyne tag (carbon-carbon triple bond) is developed to mimic natural glucose for cellular uptake, which can be imaged with high sensitivity and specificity by targeting the strong and characteristic alkyne vibration on stimulated Raman scattering (SRS) microscope to generate a quantitative three dimensional concentration map. Cancer cells with differing metabolic characteristics can be distinguished. Heterogeneous uptake patterns are observed in tumor xenograft tissues, neuronal culture and mouse brain tissues with clear cell-cell variations. Therefore, by offering the distinct advantage of optical resolution but without the undesirable influence of bulky fluorophores, our method of coupling SRS with alkyne labeled glucose will be an attractive tool to study energy demands of living systems at the single cell level.

Posttranslational regulation of glucose-6-phosphate dehydrogenase activity in tongue epithelium

NARCIS (Netherlands)

Biagiotti, E.; Bosch, K. S.; Ninfali, P.; Frederiks, W. M.; van Noorden, C. J.

2000-01-01

Expression of glucose-6-phosphate dehydrogenase (G6PD) activity is high in tongue epithelium, but its exact function is still unknown, it may be related;either to the high proliferation rate of this tissue or to protection against oxidative stress. To elucidate its exact role, we localized

Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Science.gov (United States)

Wu, Jing; Tao, Wei-Wei; Chong, Dan-Yang; Lai, Shan-Shan; Wang, Chuang; Liu, Qi; Zhang, Tong-Yu; Xue, Bin; Li, Chao-Jun

2018-03-15

Postprandial insulin desensitization plays a critical role in maintaining whole-body glucose homeostasis by avoiding the excessive absorption of blood glucose; however, the detailed mechanisms that underlie how the major player, skeletal muscle, desensitizes insulin action remain to be elucidated. Herein, we report that early growth response gene-1 ( Egr-1) is activated by insulin in skeletal muscle and provides feedback inhibition that regulates insulin sensitivity after a meal. The inhibition of the transcriptional activity of Egr-1 enhanced the phosphorylation of the insulin receptor (InsR) and Akt, thus increasing glucose uptake in L6 myotubes after insulin stimulation, whereas overexpression of Egr-1 decreased insulin sensitivity. Furthermore, deletion of Egr-1 in the skeletal muscle improved systemic insulin sensitivity and glucose tolerance, which resulted in lower blood glucose levels after refeeding. Mechanistic analysis demonstrated that EGR-1 inhibited InsR phosphorylation and glucose uptake in skeletal muscle by binding to the proximal promoter region of protein tyrosine phosphatase-1B (PTP1B) and directly activating transcription. PTP1B knockdown largely restored insulin sensitivity and enhanced glucose uptake, even under conditions of EGR-1 overexpression. Our results indicate that EGR-1/PTP1B signaling negatively regulates postprandial insulin sensitivity and suggest a potential therapeutic target for the prevention and treatment of excessive glucose absorption.-Wu, J., Tao, W.-W., Chong, D.-Y., Lai, S.-S., Wang, C., Liu, Q., Zhang, T.-Y., Xue, B., Li, C.-J. Early growth response-1 negative feedback regulates skeletal muscle postprandial insulin sensitivity via activating Ptp1b transcription.

Active feedback regulation of a Michelson interferometer to achieve zero-background absorption measurements.

Science.gov (United States)

Lundin, Patrik; Guan, Zuguang; Svanberg, Sune

2011-01-20

An active phase-controlling scheme based on a proportional-integral-derivative-controlled piezoelectric transducer is presented with the purpose of stabilizing a quasi-zero-background absorption spectrometer. A fiber-based balanced Michelson interferometer is used, and absorption due to a gas sample in one of its arms results in an increased light signal to a detector, which otherwise, thanks to destructive interference, experiences a very low light level. With the presented approach, the sensitivity of already potent absorption measurement techniques, e.g., based on modulation, could be improved even further.

7,8-Dihydroxyflavone ameliorates high-glucose induced diabetic apoptosis in human retinal pigment epithelial cells by activating TrkB.

Science.gov (United States)

Yu, Xiaoyi; Liu, Qiuhong; Wang, Xiaochuan; Liu, Hong; Wang, Yan

2018-01-01

In diabetic retinopathy, prolonged high-level blood glucose induced significant impairments among various retinal tissues, including retinal pigment epithelial (RPE) cells. In an in vitro model of human RPE cells, we evaluated whether 7,8-Dihydroxyflavone (DHF) may effectively prevent high glucose-induced diabetic apoptosis among human RPE cells. ARPE-19 cells, a Human RPE cell line, were treated with d-glucose (50 mM) to induce apoptosis in vitro. Prior to glucose, ARPE-19 cells were pre-incubated with various concentrations of DHF. The effect of DHF on d-glucose-induced apoptosis was examined by TUNEL assay, in a concentration-dependent manner. The biological effects of DHF on Caspase-9 (Casp-9) and TrkB signaling pathways in d-glucose-injured ARPE-19 cells were evaluated by qRT-PCR and western blot (WB) assays. A TrkB antagonist, K252a, was also applied in DHF and d-glucose treated ARPE-19 cells. Possible effect of K252a blocking TrkB signaling pathway, thus reversing DHF-modulated apoptosis prevention was also examined by TUNEL and WB assays. DHF ameliorated d-glucose-induced diabetic apoptosis in ARPE-19 cells. Apoptotic factor Casp-9, at both mRNA and protein levels, were drastically inhibited by DHF in d-glucose-injured ARPE-19 cells. Also, DHF activated TrkB signaling pathway through phosphorylation. K252a dramatically reversed the preventive effect of DHF on d-glucose-induced apoptosis in ARPE-19 cells. Further investigation showed that K252a functioned through de-activating or de-phosphorylating TrkB signaling pathway. This work demonstrates that DHF, through activation of TrkB signaling pathway, has a preventive function in d-glucose-induced apoptosis in PRE cells in diabetic retinopathy. Copyright © 2017. Published by Elsevier Inc.

Sweet Taste Receptor Activation in the Gut Is of Limited Importance for Glucose-Stimulated GLP-1 and GIP Secretion

DEFF Research Database (Denmark)

Saltiel, Monika Yosifova; Kuhre, Rune Ehrenreich; Christiansen, Charlotte Bayer

2017-01-01

Glucose stimulates the secretion of the incretin hormones: glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP). It is debated whether the sweet taste receptor (STR) triggers this secretion. We investigated the role of STR activation for glucose-stimulated incretin...

Condensation reactions of glucose and aromatic ring; Glucose to hokokan tono shukugo hanno

Energy Technology Data Exchange (ETDEWEB)

Komano, T.; Mashimo, K.; Wainai, T.; Tanaka, C.; Yoshioka, T. [Nihon University, Tokyo (Japan). College of Science and Technology; Sugimoto, Y.; Miki, Y. [National Institute of Materials and Chemical Research, Tsukuba (Japan)

1996-10-28

For artificial coalification, condensation reactions of aromatic ring and activated compounds produced by dehydrating reaction of glucose were studied experimentally. In heat treatment experiment in water, three reaction specimens such as glucose, glucose and phenol, and glucose and benzaldehyde were fed into an autoclave together with distilled water, and subjected to reaction at 180{degree}C under spontaneous pressure for 50 hours. In hydrogenation experiment, the specimens were fed into an autoclave together with tetradecane and sulfurization catalyst, and subjected to reaction at 350{degree}C under initial pressure of 9.8MPa for 2 hours for gas chromatography (GC) analysis of products. As the experimental result, the reaction between glucose and aromatic ring in heat treatment in water occurred between aromatic ring and active fragment with a mean carbon number of 4-5 produced by decomposition of glucose. The reactivity was higher in benzaldehyde addition than phenol addition. 3 refs., 4 figs., 1 tab.

A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators.

Science.gov (United States)

Lai, Yu-Chiang; Kviklyte, Samanta; Vertommen, Didier; Lantier, Louise; Foretz, Marc; Viollet, Benoît; Hallén, Stefan; Rider, Mark H

2014-06-15

AMPK (AMP-activated protein kinase) is an attractive therapeutic drug target for treating metabolic disorders. We studied the effects of an AMPK activator developed by Merck (ex229 from patent application WO2010036613), comparing chemical activation with contraction in intact incubated skeletal muscles. We also compared effects of ex229 with those of the Abbott A769662 compound and AICAR (5-amino-4-imidazolecarboxamide riboside). In rat epitrochlearis muscle, ex229 dose-dependently increased AMPK activity of α1-, α2-, β1- and β2-containing complexes with significant increases in AMPK activity seen at a concentration of 50 μM. At a concentration of 100 μM, AMPK activation was similar to that observed after contraction and importantly led to an ~2-fold increase in glucose uptake. In AMPK α1-/α2-catalytic subunit double-knockout myotubes incubated with ex229, the increases in glucose uptake and ACC (acetyl-CoA carboxylase) phosphorylation seen in control cells were completely abolished, suggesting that the effects of the compound were AMPK-dependent. When muscle glycogen levels were reduced by ~50% after starvation, ex229-induced AMPK activation and glucose uptake were amplified in a wortmannin-independent manner. In L6 myotubes incubated with ex229, fatty acid oxidation was increased. Furthermore, in mouse EDL (extensor digitorum longus) and soleus muscles, ex229 increased both AMPK activity and glucose uptake at least 2-fold. In summary, ex229 efficiently activated skeletal muscle AMPK and elicited metabolic effects in muscle appropriate for treating Type 2 diabetes by stimulating glucose uptake and increasing fatty acid oxidation.

Glucose repression in Saccharomyces cerevisiae

DEFF Research Database (Denmark)

Kayikci, Omur; Nielsen, Jens

2015-01-01

Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration and gluc......Glucose is the primary source of energy for the budding yeast Saccharomyces cerevisiae. Although yeast cells can utilize a wide range of carbon sources, presence of glucose suppresses molecular activities involved in the use of alternate carbon sources as well as it represses respiration...

Non-invasive method to detect the changes of glucose concentration in whole blood using photometric technique.

Science.gov (United States)

Rajan, Shiny Amala Priya; Towe, Bruce C

2014-01-01

A non-invasive method is developed to monitor rapid changes in blood glucose levels in diabetic patients. The system depends on an optical cell built with a LED that emits light of wavelength 535nm, which is a peak absorbance of hemoglobin. As the glucose concentration in blood decreases, its osmolarity also decreases and the Red Blood Cells (RBCs) swell and decrease the path length absorption coefficient. Decreasing absorption coefficient increases the transmission of light through the whole blood. The system was tested with a constructed optical cell that held whole blood in a capillary tube. As expected the light transmitted to the photodiode increases with decreasing glucose concentration. The average response time of the system was between 30-40 seconds.

Atypical Mechanism of Glucose Modulation by Colesevelam in Patients with Type 2 Diabetes

Directory of Open Access Journals (Sweden)

Oliseyenum M. Nwose

2013-01-01

Full Text Available Colesevelam's glucose-lowering mechanism of action is not completely understood. Clinical trials of colesevelam suggest that its mechanism, and often adverse effects, differ from those of other oral antidiabetes drugs. Colesevelam does not affect insulin sensitivity (unlike thiazolidinediones, insulin secretion (unlike sulfonylureas and meglitinides, or early insulin response or glucagon (unlike dipeptidyl peptidase-4 inhibitors. Colesevelam may have some effect on glucose absorption, but likely via a different mechanism than α-glucosidase inhibitors. Colesevelam and metformin have similarities regarding hepatic glucose production, but divergent effects on gluconeogenesis versus glycogenolysis, suggesting differing mechanisms of drug action for improving glycemic control. Colesevelam is thought to be a portal glucagon-like peptide-1 (GLP-1 secretagogue with primarily hepatic effects. Bile acid binding by colesevelam leads to TGR5 activation, increased secretion of GLP-1 or other incretins, and inhibition of hepatic glycogenolysis. Colesevelam's mechanism of action appears to be atypical of other antidiabetes medications, making it a potentially suitable component of many combination regimens in the treatment of type 2 diabetes.

Bayesian model discrimination for glucose-insulin homeostasis

DEFF Research Database (Denmark)

Andersen, Kim Emil; Brooks, Stephen P.; Højbjerre, Malene

In this paper we analyse a set of experimental data on a number of healthy and diabetic patients and discuss a variety of models for describing the physiological processes involved in glucose absorption and insulin secretion within the human body. We adopt a Bayesian approach which facilitates...... as parameter uncertainty. Markov chain Monte Carlo methods are used, combining Metropolis Hastings, reversible jump and simulated tempering updates to provide rapidly mixing chains so as to provide robust inference. We demonstrate the methodology for both healthy and type II diabetic populations concluding...... that whilst both populations are well modelled by a common insulin model, their glucose dynamics differ considerably....

High glucose induces activation of NF-κB inflammatory signaling through IκBα sumoylation in rat mesangial cells

International Nuclear Information System (INIS)

Huang, Wei; Xu, Ling; Zhou, Xueqin; Gao, Chenlin; Yang, Maojun; Chen, Guo; Zhu, Jianhua; Jiang, Lan; Gan, Huakui; Gou, Fang; Feng, Hong; Peng, Juan; Xu, Yong

2013-01-01

Highlights: •The expression of SUMO1, SUMO2/3 under high glucose was obviously enhanced. •High glucose induced degradation of IκBα and activation of NF-κB pathway. •Sumoylation of IκBα in high glucose were significantly decreased. •The proteasome inhibitor MG132 could partially revert the degradation of IκBα. -- Abstract: The posttranslational modification of proteins by small ubiquitin-like modifiers (SUMOs) has emerged as an important regulatory mechanism for the alteration of protein activity, stability, and cellular localization. The latest research demonstrates that sumoylation is extensively involved in the regulation of the nuclear factor κB (NF-κB) pathway, which plays a critical role in the regulation of inflammation and contributes to fibrosis in diabetic nephropathy (DN). However, the role of sumoylation in the regulation of NF-κB signaling in DN is still unclear. In the present study, we cultured rat glomerular mesangial cells (GMCs) stimulated by high glucose and divided GMCs into six groups: normal glucose group (5.6 mmol/L), high glucose groups (10, 20, and 30 mmol/L), mannitol group (i.e., osmotic control group), and MG132 intervention group (30 mmol/L glucose with MG132, a proteasome inhibitor). The expression of SUMO1, SUMO2/3, IκBα, NF-κBp65, and monocyte chemotactic protein 1 (MCP-1) was measured by Western blot, reverse-transcription polymerase chain reaction, and indirect immunofluorescence laser scanning confocal microscopy. The interaction between SUMO1, SUMO2/3, and IκBα was observed by co-immunoprecipitation. The results showed that the expression of SUMO1 and SUMO2/3 was dose- and time-dependently enhanced by high glucose (p < 0.05). However, the expression of IκBα sumoylation in high glucose was significantly decreased compared with the normal glucose group (p < 0.05). The expression of IκBα was dose- and time-dependently decreased, and NF-κBp65 and MCP-1 were increased under high glucose conditions, which

Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

Energy Technology Data Exchange (ETDEWEB)

Tsukahara, Tamotsu, E-mail: ttamotsu@shinshu-u.ac.jp [Department of Integrative Physiology and Bio-System Control, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Haniu, Hisao [Department of Orthopedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, Nagano 390-8621 (Japan); Matsuda, Yoshikazu [Clinical Pharmacology Educational Center, Nihon Pharmaceutical University, Ina-machi, Saitama 362-0806 (Japan)

2013-04-12

Highlights: •Alkyl-LPA specifically interacts with PPARγ. •Alkyl-LPA treatments induces lipid accumulation in C2C12 cells. •Alkyl-LPA enhanced glucose uptake in C2C12 cells. •Alkyl-LPA-treated C2C12 cells express increased amounts of GLUT4 mRNA. •Alkyl-LPA is a novel therapeutic agent that can be used for the treatment of obesity and diabetes. -- Abstract: Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA–PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance.

Effect of alkyl glycerophosphate on the activation of peroxisome proliferator-activated receptor gamma and glucose uptake in C2C12 cells

International Nuclear Information System (INIS)

Tsukahara, Tamotsu; Haniu, Hisao; Matsuda, Yoshikazu

2013-01-01

Highlights: •Alkyl-LPA specifically interacts with PPARγ. •Alkyl-LPA treatments induces lipid accumulation in C2C12 cells. •Alkyl-LPA enhanced glucose uptake in C2C12 cells. •Alkyl-LPA-treated C2C12 cells express increased amounts of GLUT4 mRNA. •Alkyl-LPA is a novel therapeutic agent that can be used for the treatment of obesity and diabetes. -- Abstract: Studies on the effects of lipids on skeletal muscle cells rarely examine the effects of lysophospholipids. Through our recent studies, we identified select forms of phospholipids, such as alkyl-LPA, as ligands for the intracellular receptor peroxisome proliferator-activated receptor gamma (PPARγ). PPARγ is a nuclear hormone receptor implicated in many human diseases, including diabetes and obesity. We previously showed that alkyl-LPA is a specific agonist of PPARγ. However, the mechanism by which the alkyl-LPA–PPARγ axis affects skeletal muscle cells is poorly defined. Our objective in the present study was to determine whether alkyl-LPA and PPARγ activation promotes glucose uptake in skeletal muscle cells. Our findings indicate that PPARγ1 mRNA is more abundant than PPARγ2 mRNA in C2C12 cells. We showed that alkyl-LPA (3 μM) significantly activated PPARγ and increased intracellular glucose levels in skeletal muscle cells. We also showed that incubation of C2C12 cells with alkyl-LPA led to lipid accumulation in the cells. These findings suggest that alkyl-LPA activates PPARγ and stimulates glucose uptake in the absence of insulin in C2C12 cells. This may contribute to the plasma glucose-lowering effect in the treatment of insulin resistance

Leaf absorption of 32P in the pumpkin

International Nuclear Information System (INIS)

Chamel, Andre; Roux-Aubert, M.T.

1964-04-01

The author presents a method to study the influence of various factors of the absorption of 32 P applied under the form of phosphates by a plant cultivated in conditions ensuring a normal development. Experiments provided indications on leaf absorption and 32 P transport by pumpkin leaves: phosphor 32 is absorbed and then quickly transported into the different organs of the plant (24 hours after treatment, it is present in aerial and underground parts), the quantity of absorbed phosphor increases with phosphor concentration in the applied solution, atmosphere humidity is an important factor for phosphor penetration into the leaves, plants absorb phosphor in darkness as well as in light, and the absorption of phosphor is not modified when applied with low glucose concentrations [fr

Blood Glucose Levels and Problem Behavior

Science.gov (United States)

Valdovinos, Maria G.; Weyand, David

2006-01-01

The relationship between varying blood glucose levels and problem behavior during daily scheduled activities was examined. The effects that varying blood glucose levels had on problem behavior during daily scheduled activities were examined. Prior research has shown that differing blood glucose levels can affect behavior and mood. Results of this…

Changes in enzyme activity and functional diversity in soil induced by Cd and glucose addition

Science.gov (United States)

Gilmullina, A. R.; Galitskaya, P. Yu; Selivanovskaya, S. Yu

2018-01-01

Toxic heavy metal (HM) contamination is a major global issue as it may have an indirect effect on the health of soil, plants, animals and, consequently, on human health. Agricultural soils’ fertilization is one of the reported sources of HM pollution in the world. In this case simultaneous input of stimulating and inhibiting agents into soil takes place, and effects of the combined influence of these agents is hardly predictable. In this study, a simultaneous inhibiting and stimulating effect of Cd and glucose on soil microbes was studied in a model experiment. Enzyme activities (phosphatase, β-glucosidase and cellobiohydrolase) and functional diversity (BIOLOG®EcoPlates ™) were assessed as a test functions. Cd (300 μg Cd g-1 ) amendment had a negative effect only on phosphatase activity. Glucose (3 mg C g-1) addition inhibited β-glucosidase activity and stimulated functional diversity. In joint addition of Cd and Glucose the leading effect belonged to that agent which had the greatest effect in case when it was added separately.

Reengineered glucose oxidase for amperometric glucose determination in diabetes analytics.

Science.gov (United States)

Arango Gutierrez, Erik; Mundhada, Hemanshu; Meier, Thomas; Duefel, Hartmut; Bocola, Marco; Schwaneberg, Ulrich

2013-12-15

Glucose oxidase is an oxidoreductase exhibiting a high β-D-glucose specificity and high stability which renders glucose oxidase well-suited for applications in diabetes care. Nevertheless, GOx activity is highly oxygen dependent which can lead to inaccuracies in amperometric β-D-glucose determinations. Therefore a directed evolution campaign with two rounds of random mutagenesis (SeSaM followed by epPCR), site saturation mutagenesis studies on individual positions, and one simultaneous site saturation library (OmniChange; 4 positions) was performed. A diabetes care well suited mediator (quinone diimine) was selected and the GOx variant (T30V I94V) served as starting point. For directed GOx evolution a microtiter plate detection system based on the quinone diimine mediator was developed and the well-known ABTS-assay was applied in microtiter plate format to validate oxygen independency of improved GOx variants. Two iterative rounds of random diversity generation and screening yielded to two subsets of amino acid positions which mainly improved activity (A173, A332) and oxygen independency (F414, V560). Simultaneous site saturation of all four positions with a reduced subset of amino acids using the OmniChange method yielded finally variant V7 with a 37-fold decreased oxygen dependency (mediator activity: 7.4 U/mg WT, 47.5 U/mg V7; oxygen activity: 172.3 U/mg WT, 30.1 U/mg V7). V7 is still highly β-D-glucose specific, highly active with the quinone diimine mediator and thermal resistance is retained (prerequisite for GOx coating of diabetes test stripes). The latter properties and V7's oxygen insensitivity make V7 a very promising candidate to replace standard GOx in diabetes care applications. Copyright © 2013 Elsevier B.V. All rights reserved.

Highly sensitive glucose sensor based on monodisperse palladium nickel/activated carbon nanocomposites.

Science.gov (United States)

Koskun, Yağmur; Şavk, Aysun; Şen, Betül; Şen, Fatih

2018-06-20

Glucose enzyme biosensors have been used for a variety of applications such as medical diagnosis, bioprocess engineering, beverage industry and environmental scanning etc. and there is still a growing interest in glucose sensors. For this purpose, addressed herein, as a novel glucose sensor, highly sensitive activated carbon (AC) decorated monodisperse nickel and palladium alloy nanocomposites modified glassy carbon electrode (Ni-Pd@AC/GCE NCs) have been synthesized by in-situ reduction technique. Raman Spectroscopy (RS), X-ray Photoelectron Spectroscopy (XPS), X-ray Diffraction (XRD), Transmission Electron Microscopy (TEM), cyclic voltammetry (CV) and chronoamperometry (CA) were used for the characterization of the prepared non-enzymatic glucose sensor. The characteristic sensor properties of the Ni-Pd@AC/GCE electrode were compared with Ni-Pd NCs/GCE, Ni@AC/GCE and Pd@AC/GCE and the results demonstrate that the AC is very effective in the enhancement of the electrocatalytic properties of sensor. In addition, the Ni-Pd@AC/GCE nanocomposites showed a very low detection limit of 0.014 μM, a wide linear range of 0.01 mM-1 mM and a very high sensitivity of 90 mA mM -1  cm -2 . Furthermore, the recommended sensor offer the various advantageous such as facile preparation, fast response time, high selectivity and sensitivity. Lastly, monodisperse Ni-Pd@AC/GCE was utilized to detect glucose in real sample species. Copyright © 2018 Elsevier B.V. All rights reserved.

Performance of Active Wave Absorption Systems

DEFF Research Database (Denmark)

Hald, Tue; Frigaard, Peter

on a horisontal and vertical velocity are treated. All three systems are based on digital FIR-filters. For numerical comparison a performance function combining the frequency response of the set of filters for each system is derived enabling discussion on optimal filter design and system setup. Irregular wave......A comparison of wave gauge based on velocity meter based active absorption systems is presented discussing advantages and disadvantages of the systems. In detail one system based on two surface elevations, one system based on a surface elevation and a horisontal velocity and one system based...... tests with a highly reflective structure with the purely wave gauge based system and the wave gauge velocity meter based system are performed. The wave test depict the differences between the systems....

Glucose Administration Enhances fMRI Brain Activation and Connectivity Related to Episodic Memory Encoding for Neutral and Emotional Stimuli

Science.gov (United States)

Parent, Marise B.; Krebs-Kraft, Desiree L.; Ryan, John P.; Wilson, Jennifer S.; Harenski, Carla; Hamann, Stephan

2011-01-01

Glucose enhances memory in a variety of species. In humans, glucose administration enhances episodic memory encoding, although little is known regarding the neural mechanisms underlying these effects. Here we examined whether elevating blood glucose would enhance functional MRI (fMRI) activation and connectivity in brain regions associated with…

Autophagy activation, not peroxisome proliferator-activated receptor γ coactivator 1α, may mediate exercise-induced improvements in glucose handling during diet-induced obesity.

Science.gov (United States)

Rosa-Caldwell, Megan E; Brown, Jacob L; Lee, David E; Blackwell, Thomas A; Turner, Kyle W; Brown, Lemuel A; Perry, Richard A; Haynie, Wesley S; Washington, Tyrone A; Greene, Nicholas P

2017-09-01

What is the central question of this study? What are the individual and combined effects of muscle-specific peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) overexpression and physical activity during high-fat feeding on glucose and exercise tolerance? What is the main finding and its importance? Our main finding is that muscle-specific PGC-1α overexpression provides no protection against lipid-overload pathologies nor does it enhance exercise adaptations. Instead, physical activity, regardless of PGC-1α content, protects against high-fat diet-induced detriments. Activation of muscle autophagy was correlated with exercise protection, suggesting that autophagy might be a mediating factor for exercise-induced protection from lipid overload. The prevalence of glucose intolerance is alarmingly high. Efforts to promote mitochondrial biogenesis through peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) to mitigate glucose intolerance have been controversial. However, physical activity remains a primary means to alleviate the condition. The aim of this study was to determine the combined effects of muscle-specific overexpression of PGC-1α and physical activity on glucose handling during diet-induced obesity. Wild-type (WT, ∼20) and PGC-1α muscle transgenic (MCK-PGC-1α, ∼20) mice were given a Western diet (WD) at 8 weeks age and allowed to consume food ab libitum throughout the study. At 12 weeks of age, all animals were divided into sedentary (SED) or voluntary wheel running (VWR) interventions. At 7, 11 and 15 weeks of age, animals underwent glucose tolerance tests (GTT) and graded exercise tests (GXT). At 16 weeks of age, tissues were collected. At 11 weeks, the MCK-PGC-1α animals had 50% greater glucose tolerance integrated area under the curve compared with WT. However, at 15 weeks, SED animals also had greater GTT integrated area under the curve compared with VWR, regardless of genotype; furthermore, SED

Glucagon-like peptide-1 decreases intracerebral glucose content by activating hexokinase and changing glucose clearance during hyperglycemia

DEFF Research Database (Denmark)

Gejl, Michael; Egefjord, Lærke; Lerche, Susanne

2012-01-01

Type 2 diabetes and hyperglycemia with the resulting increase of glucose concentrations in the brain impair the outcome of ischemic stroke, and may increase the risk of developing Alzheimer's disease (AD). Reports indicate that glucagon-like peptide-1 (GLP-1) may be neuroprotective in models of AD...... in the actions of GLUT1 and glucose metabolism: GLP-1 ensures less fluctuation of brain glucose levels in response to alterations in plasma glucose, which may prove to be neuroprotective during hyperglycemia....

Enhanced Photocatalytic Activity of La3+-Doped TiO2 Nanotubes with Full Wave-Band Absorption

Science.gov (United States)

Xia, Minghao; Huang, Lingling; Zhang, Yubo; Wang, Yongqian

2018-06-01

TiO2 nanotubes doped with La3+ were synthesized by anodic oxidation method and the photocatalytic activity was detected by photodegrading methylene blue. As-prepared samples improved the absorption of both ultraviolet light and visible light and have a great enhancement on the photocatalytic activity while contrasting with the pristine TiO2 nanotubes. A tentative mechanism for the enhancement of photocatalytic activity with full wave-band absorption is proposed.

The acute glucose lowering effect of specific GPR120 activation in mice is mainly driven by glucagon-like peptide 1.

Directory of Open Access Journals (Sweden)

Linda Sundström

Full Text Available The mechanism behind the glucose lowering effect occurring after specific activation of GPR120 is not completely understood. In this study, a potent and selective GPR120 agonist was developed and its pharmacological properties were compared with the previously described GPR120 agonist Metabolex-36. Effects of both compounds on signaling pathways and GLP-1 secretion were investigated in vitro. The acute glucose lowering effect was studied in lean wild-type and GPR120 null mice following oral or intravenous glucose tolerance tests. In vitro, in GPR120 overexpressing cells, both agonists signaled through Gαq, Gαs and the β-arrestin pathway. However, in mouse islets the signaling pathway was different since the agonists reduced cAMP production. The GPR120 agonists stimulated GLP-1 secretion both in vitro in STC-1 cells and in vivo following oral administration. In vivo GPR120 activation induced significant glucose lowering and increased insulin secretion after intravenous glucose administration in lean mice, while the agonists had no effect in GPR120 null mice. Exendin 9-39, a GLP-1 receptor antagonist, abolished the GPR120 induced effects on glucose and insulin following an intravenous glucose challenge. In conclusion, GLP-1 secretion is an important mechanism behind the acute glucose lowering effect following specific GPR120 activation.

Inhibition by natural dietary substances of gastrointestinal absorption of starch and sucrose in rats and pigs: 1. Acute studies.

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Preuss, Harry G; Echard, Bobby; Bagchi, Debasis; Stohs, Sidney

2007-08-06

Rapid gastrointestinal absorption of refined carbohydrates (CHO) is linked to perturbed glucose-insulin metabolism that is, in turn, associated with many chronic health disorders. We assessed the ability of various natural substances, commonly referred to as "CHO blockers," to influence starch and sucrose absorption in vivo in ninety-six rats and two pigs. These natural enzyme inhibitors of amylase/sucrase reportedly lessen breakdown of starches and sucrose in the gastrointestinal tract, limiting their absorption. To estimate absorption, groups of nine SD rats were gavaged with water or water plus rice starch and/or sucrose; and circulating glucose was measured at timed intervals thereafter. For each variation in the protocol a total of at least nine different rats were studied with an equal number of internal controls on three different occasions. The pigs rapidly drank CHO and inhibitors in their drinking water. In rats, glucose elevations above baseline over four hours following rice starch challenge as estimated by area-under-curve (AUC) were 40%, 27%, and 85% of their internal control after ingesting bean extract, hibiscus extract, and l-arabinose respectively in addition to the rice starch. The former two were significantly different from control. L-Arabinose virtually eliminated the rising circulating glucose levels after sucrose challenge, whereas hibiscus and bean extracts were associated with lesser decreases than l-arabinose that were still significantly lower than control. The glucose elevations above baseline over four hours in rats receiving sucrose (AUC) were 51%, 43% and 2% of control for bean extract, hibiscus extract, and L-arabinose, respectively. Evidence for dose-response of bean and hibiscus extracts is reported. Giving the natural substances minus CHO challenge caused no significant changes in circulating glucose concentrations, indicating no major effects on overall metabolism. A formula combining these natural products significantly

Capacity for absorption of water-soluble secondary metabolites greater in birds than in rodents.

Science.gov (United States)

Karasov, William H; Caviedes-Vidal, Enrique; Bakken, Bradley Hartman; Izhaki, Ido; Samuni-Blank, Michal; Arad, Zeev

2012-01-01

Plant secondary metabolites (SMs) are pervasive in animal foods and potentially influence feeding behavior, interspecies interactions, and the distribution and abundance of animals. Some of the major classes of naturally occurring SMs in plants include many water-soluble compounds in the molecular size range that could cross the intestinal epithelium via the paracellular space by diffusion or solvent drag. There are differences among species in paracellular permeability. Using Middle Eastern rodent and avian consumers of fruits containing SMs, we tested the hypothesis that avian species would have significantly higher paracellular permeability than rodent species. Permeability in intact animals was assessed using standard pharmacological methodology to measure absorption of two radiolabeled, inert, neutral water-soluble probes that do not interact with intestinal nutrient transporters, L-arabinose (M(r) = 150.1 Da) and lactulose (M(r) = 342.3 Da). We also measured absorption of labeled 3-O-methyl-D-glucose (3OMD-glucose; M(r) = 194.2 Da), which is a nonmetabolized analogue of D-glucose that is passively absorbed through the paracellular space but also transported across the enterocyte membranes. Most glucose was absorbed by all species, but arabinose fractional absorption (f) was nearly three times higher in birds (1.03±0.17, n = 15 in two species) compared to rodents (0.37±0.06, n = 10 in two species) (Pbirds of arabinose exceeded those of 3OMD-glucose. Our findings are in agreement with previous work showing that the paracellular pathway is more prominent in birds relative to nonflying mammals, and suggests that birds may be challenged by greater absorption of water-soluble, dietary SMs. The increased expression of the paracellular pathway in birds hints at a tradeoff: the free energy birds gain by absorbing water-soluble nutrients passively may be offset by the metabolic demands placed on them to eliminate concomitantly absorbed SMs.

Glucose dependence of glycogen synthase activity regulation by GSK3 and MEK/ERK inhibitors and angiotensin-(1-7) action on these pathways in cultured human myotubes.

Science.gov (United States)

Montori-Grau, Marta; Tarrats, Núria; Osorio-Conles, Oscar; Orozco, Anna; Serrano-Marco, Lucía; Vázquez-Carrera, Manuel; Gómez-Foix, Anna M

2013-05-01

Glycogen synthase (GS) is activated by glucose/glycogen depletion in skeletal muscle cells, but the contributing signaling pathways, including the chief GS regulator GSK3, have not been fully defined. The MEK/ERK pathway is known to regulate GSK3 and respond to glucose. The aim of this study was to elucidate the GSK3 and MEK/ERK pathway contribution to GS activation by glucose deprivation in cultured human myotubes. Moreover, we tested the glucose-dependence of GSK3 and MEK/ERK effects on GS and angiotensin (1-7) actions on these pathways. We show that glucose deprivation activated GS, but did not change phospho-GS (Ser640/1), GSK3β activity or activity-activating phosphorylation of ERK1/2. We then treated glucose-replete and -depleted cells with SB415286, U0126, LY294 and rapamycin to inhibit GSK3, MEK1/2, PI3K and mTOR, respectively. SB415286 activated GS and decreased the relative phospho-GS (Ser640/1) level, more in glucose-depleted than -replete cells. U0126 activated GS and reduced the phospho-GS (Ser640/1) content significantly in glucose-depleted cells, while GSK3β activity tended to increase. LY294 inactivated GS in glucose-depleted cells only, without affecting relative phospho-GS (Ser640/1) level. Rapamycin had no effect on GS activation. Angiotensin-(1-7) raised phospho-ERK1/2 but not phospho-GSK3β (Ser9) content, while it inactivated GS and increased GS phosphorylation on Ser640/1, in glucose-replete cells. In glucose-depleted cells, angiotensin-(1-7) effects on ERK1/2 and GS were reverted, while relative phospho-GSK3β (Ser9) content decreased. In conclusion, activation of GS by glucose deprivation is not due to GS Ser640/1 dephosphorylation, GSK3β or ERK1/2 regulation in cultured myotubes. However, glucose depletion enhances GS activation/Ser640/1 dephosphorylation due to both GSK3 and MEK/ERK inhibition. Angiotensin-(1-7) inactivates GS in glucose-replete cells in association with ERK1/2 activation, not with GSK3 regulation, and glucose

Targeted Delivery and Sustained Antitumor Activity of Triptolide through Glucose Conjugation.

Science.gov (United States)

He, Qing-Li; Minn, Il; Wang, Qiaoling; Xu, Peng; Head, Sarah A; Datan, Emmanuel; Yu, Biao; Pomper, Martin G; Liu, Jun O

2016-09-19

Triptolide, a key ingredient from the traditional Chinese medicinal plant thunder god vine, which has been used to treat inflammation and autoimmune diseases for centuries, has been shown to be an irreversible inhibitor of the XPB subunit of the transcription factor TFIIH and initiation of RNA polymerase II mediated transcription. The clinical development of triptolide over the past two decades has been limited by its toxicity and low water solubility. Herein, we report the development of a glucose conjugate of triptolide, named glutriptolide, which was intended to target tumor cells overexpressing glucose transporters selectively. Glutriptolide did not inhibit XPB activity in vitro but demonstrated significantly higher cytotoxicity against tumor cells over normal cells with greater water solubility than triptolide. Furthermore, it exhibited remarkable tumor control in vivo, which is likely due to sustained stepwise release of active triptolide within cancer cells. These findings indicate that glutriptolide may serve as a promising lead for developing a new mechanistic class of anticancer drugs. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

A new active absorption system and its performance to linear and non-linear waves

DEFF Research Database (Denmark)

Andersen, Thomas Lykke; Clavero, M.; Frigaard, Peter Bak

2016-01-01

Highlights •An active absorption system for wavemakers has been developed. •The theory for flush mounted gauges has been extended to cover also small gaps. •The new system has been validated in a wave flume with wavemakers in both ends. •A generation and absorption procedure for highly non-linear...

The flavonoid-rich fraction of Coreopsis tinctoria promotes glucose tolerance regain through pancreatic function recovery in streptozotocin-induced glucose-intolerant rats.

Science.gov (United States)

Dias, Teresa; Bronze, Maria Rosário; Houghton, Peter J; Mota-Filipe, Hélder; Paulo, Alexandra

2010-11-11

Infusions of Coreopsis tinctoria Nutt. flowering tops have been used traditionally in Portugal to control hyperglycaemia and a previous study revealed that daily administration of the infusion during a 3-week period promoted the recovery of glucose tolerance by a mechanism different from inhibition of glucose absorption and direct promotion of insulin secretion. We know report the study of the ethyl acetate fraction of Coreopsis tinctoria flowers infusion aiming to confirm flavonoids as bioactive metabolites. To give one step forward into the antihyperglycaemic mechanism of action of this traditionally used plant we also studied the activity of Coreopsis tinctoria flavonoids on the pancreatic function of glucose-intolerant rats. A standard antioxidant, Trolox, was also studied for comparative purposes as the antioxidant mechanism has been frequently purposed as one of the mechanisms mediating antihyperglycaemic effects of flavonoid-rich extracts. Thirteen compounds, mainly of flavanone and chalcone flavonoidal type, have been identified in this fraction by HPLC-DAD-ESI-MS/MS, and the major one (marein) quantified by HPLC-UV. The fraction (125 mg containing 20 mg of marein/kg b.w.) and Trolox (50 mg/kg b.w.) were administered daily by oral gavage to normal and STZ (40 mg/kg b.w.)-induced glucose-intolerant Wistar rats for 3 weeks. Blood glucose levels were measured weekly by Oral Glucose Tolerance Test. Pancreatic function was evaluated by plasma lipase of treated and non-treated glucose-tolerant and- intolerant rats after the 3-week treatment period. After 2 weeks oral treatment with Coreopsis tinctoria AcOEt fraction the animals were no longer glucose-intolerant, an effect maintained over the remaining experimental period. Additionally, plasma lipase values of glucose-intolerant animals treated with the AcOEt fraction (13.5 ± 0.84 U/L) showed a clear reduction when compared with the glucose-intolerant group (34.60 ± 1.76 U/L; P<0.001) and normoglycaemic control

Differential relationship between physical activity and progression to diabetes by glucose tolerance status: the Inter99 Study

DEFF Research Database (Denmark)

Engberg, S; Glümer, C; Witte, D R

2010-01-01

The aim of the study was to analyse how strongly commuting and leisure-time physical activity affect progression to diabetes and to study whether this relationship is different in individuals with isolated impaired fasting glucose (i-IFG) and isolated impaired glucose tolerance (i-IGT)....

Comparing the effects of sucrose and glucose on functional properties of pregelatinized maize starch.

Science.gov (United States)

Hedayati, Sara; Shahidi, Fakhri; Koocheki, Arash; Farahnaky, Asgar; Majzoobi, Mahsa

2016-07-01

Pregelatinized (PG) starches are extensively used in food products which are processed at low temperature, to increase viscosity and offer a desirable texture. The functional properties of PG starch can be influenced by other constituents used in food matrices. Therefore the main purpose of this study was to investigate the effects of different levels of sucrose and glucose (0, 10, 20, 30 and 40% of dry starch weight basis) as two common sweeteners on drum dried pregelatinized maize starch. Samples were characterized by light microscopy, water absorption, syneresis, cold paste viscosity, texture and turbidity measurements. The results indicated that the amount of leached glucose chains to the aqueous phase, water absorption, viscosity and mechanical properties increased when increasing the sugar concentration while, syneresis and turbidity decreased. However, these effects were more obvious in samples containing sucrose than those with glucose. Copyright © 2016. Published by Elsevier B.V.

Acute but not chronic activation of brain glucagon-like peptide-1 receptors enhances glucose-stimulated insulin secretion in mice.

Science.gov (United States)

Tudurí, E; Beiroa, D; Porteiro, B; López, M; Diéguez, C; Nogueiras, R

2015-08-01

To investigate the role of brain glucagon-like peptide-1 (GLP-1) in pancreatic β-cell function. To determine the role of brain GLP-1 receptor (GLP-1R) on β-cell function, we administered intracerebroventricular (i.c.v.) infusions of GLP-1 or the specific GLP-1 antagonist exendin-9 (Ex-9), in both an acute and a chronic setting. We observed that acute i.c.v. GLP-1 infusion potentiates glucose-stimulated insulin secretion (GSIS) and improves glucose tolerance, whereas central GLP-1R blockade with Ex-9 impaired glucose excursion after a glucose load. Sustained activation of central nervous system GLP-1R, however, did not produce any effect on either GSIS or glucose tolerance. Similarly, ex vivo GSIS performed in islets from mice chronically infused with i.c.v. GLP-1 resulted in no differences compared with controls. In addition, in mice fed a high-fat diet we observed that acute i.c.v. GLP-1 infusion improved glucose tolerance without changes in GSIS, while chronic GLP-1R activation had no effect on glucose homeostasis. Our results indicate that, under non-clamped conditions, brain GLP-1 plays a functional neuroendocrine role in the acute regulation of glucose homeostasis in both lean and obese rodents. © 2015 John Wiley & Sons Ltd.

The importance of regulation of blood glucose levels through activation of peripheral 5'-AMP-activated protein kinase on ischemic neuronal damage.

Science.gov (United States)

Harada, Shinichi; Fujita-Hamabe, Wakako; Tokuyama, Shogo

2010-09-10

5'-AMP-activated protein kinase (AMPK) is a serine/threonine kinase that plays a key role in energy homeostasis. Recently, it was reported that centrally activated AMPK is involved in the development of ischemic neuronal damage, while the effect of peripherally activated AMPK on ischemic neuronal damage is not known. In addition, we have previously reported that the development of post-ischemic glucose intolerance could be one of the triggers for the aggravation of neuronal damage. In this study, we focused on effect of activation of peripheral or central AMPK on the development of ischemic neuronal damage. Male ddY mice were subjected to 2 h of middle cerebral artery occlusion (MCAO). Neuronal damage was estimated by histological and behavioral analysis after MCAO. In the liver and skeletal muscle, AMPK activity was not affected by MCAO. But, application of intraperitoneal metformin (250 mg/kg), an AMPK activator, significantly suppressed the development of post-ischemic glucose intolerance and ischemic neuronal damage without alteration of central AMPK activity. On the other hand, application of intracerebroventricular metformin (25, 100 microg/mouse) significantly exacerbated the development of neuronal damage observed on day 1 after MCAO, in a dose-dependent manner. These effects were significantly blocked by compound C, a specific AMPK inhibitor. These results suggest that central AMPK was activated by ischemic stress per se, however, peripheral AMPK was not altered. Furthermore, the regulation of post-ischemic glucose intolerance by activation of peripheral AMPK is of assistance for the suppression of cerebral ischemic neuronal damage. 2010 Elsevier B.V. All rights reserved.

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

Science.gov (United States)

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 change in lactate concentration. The ratio of phosphorylated to total AMPK was increased (P managing IR requires investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Effects of Undaria pinnatifida, Himanthalia elongata and Porphyra umbilicalis extracts on in vitro α-glucosidase activity and glucose diffusion.

Science.gov (United States)

Schultz Moreira, Adriana R; Garcimartín, Alba; Bastida, Sara; Jiménez-Escrig, Antonio; Rupérez, Pilar; Green, Brian D; Rafferty, Eamon; Sánchez-Muniz, Francisco J; Benedí, Juana

2014-06-01

Seaweeds are good sources of dietary fibre, which can influence glucose uptake and glycemic control. To investigate and compare the in vitro inhibitory activity of different extracts from Undaria pinnatifida (Wakame), Himanthalia elongata (Sea spaghetti) and Porphyra umbilicalis (Nori) on α-glucosidase activity and glucose diffusion. The in vitro effects Chloroform-, ethanol- and water-soluble extracts of the three algae were assayed on α- glucosidase activity and glucose diffusion through membrane. Principal Components Analysis (PCA) was applied to identify patterns in the data and to discriminate which extract will show the most proper effect. Only water extracts of Sea spaghetti possessed significant in vitro inhibitory effects on α-glucosidase activity (26.2% less mmol/L glucose production than control, p < 0.05) at 75 min. PCA distinguished Sea spaghetti effects, supporting that soluble fibre and polyphenols were involved. After 6 h, Ethanol-Sea spaghetti and water-Wakame extracts exerted the highest inhibitory effects on glucose diffusion (65.0% and 60.2% vs control, respectively). This extracts displayed the lowest slopes for glucose diffusion-time lineal adjustments (68.2% and 62.8% vs control, respectively). The seaweed hypoglycemic effects appear multi-faceted and not necessarily concatenated. According to present results, ethanol and water extracts of Sea spaghetti, and water extracts of Wakame could be useful for the development of functional foods with specific hypoglycemic properties. Copyright AULA MEDICA EDICIONES 2014. Published by AULA MEDICA. All rights reserved.

Physical Activity Dimensions Associated with Impaired Glucose Metabolism

DEFF Research Database (Denmark)

Amadid, Hanan; Johansen, Nanna B.; Bjerregaard, Anne-Louise

2017-01-01

Purpose Physical activity (PA) is important in the prevention of Type 2 diabetes, yet little is known about the role of specific dimensions of PA, including sedentary time in subgroups at risk for impaired glucose metabolism (IGM). We applied a data-driven decision tool to identify dimensions of PA...... identified subgroups in which different activity dimensions were associated with IGM. Methodology and results from this study may suggest a preliminary step toward the goal of tailoring and targeting PA interventions aimed at Type 2 diabetes prevention....... associated with IGM across age, sex, and body mass index (BMI) groups. Methods This cross-sectional study included 1501 individuals (mean (SD) age, 65.6 (6.8) yr) at high risk for Type 2 diabetes from the ADDITION-PRO study. PA was measured by an individually calibrated combined accelerometer and heart rate...

Simulation of the effect of hydrogen bonds on water activity of glucose and dextran using the Veytsman model.

Science.gov (United States)

De Vito, Francesca; Veytsman, Boris; Painter, Paul; Kokini, Jozef L

2015-03-06

Carbohydrates exhibit either van der Waals and ionic interactions or strong hydrogen bonding interactions. The prominence and large number of hydrogen bonds results in major contributions to phase behavior. A thermodynamic framework that accounts for hydrogen bonding interactions is therefore necessary. We have developed an extension of the thermodynamic model based on the Veytsman association theory to predict the contribution of hydrogen bonds to the behavior of glucose-water and dextran-water systems and we have calculated the free energy of mixing and its derivative leading to chemical potential and water activity. We compared our calculations with experimental data of water activity for glucose and dextran and found excellent agreement far superior to the Flory-Huggins theory. The validation of our calculations using experimental data demonstrated the validity of the Veytsman model in properly accounting for the hydrogen bonding interactions and successfully predicting water activity of glucose and dextran. Our calculations of the concentration of hydrogen bonds using the Veytsman model were instrumental in our ability to explain the difference between glucose and dextran and the role that hydrogen bonds play in contributing to these differences. The miscibility predictions showed that the Veytsman model is also able to correctly describe the phase behavior of glucose and dextran. Copyright © 2014 Elsevier Ltd. All rights reserved.

Towards a continuous glucose monitoring system using tunable quantum cascade lasers

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Haase, Katharina; Müller, Niklas; Petrich, Wolfgang

2018-02-01

We present a reagent-free approach for long-term continuous glucose monitoring (cgm) of liquid samples using midinfrared absorption spectroscopy. This method could constitute an alternative to enzymatic glucose sensors in order to manage the widespread disease of Diabetes. In order to acquire spectra of the liquid specimen, we use a spectrally tunable external-cavity (EC-) quantum cascade laser (QCL) as radiation source in combination with a fiber-based in vitro sensor setup. Hereby we achieve a glucose sensitivity in pure glucose solutions of 3 mg/dL (RMSEP). Furthermore, the spectral tunability of the EC-QCL enables us to discriminate glucose from other molecules. We exemplify this by detecting glucose among other saccharides with an accuracy of 8 mg/dL (within other monosaccharides, RMSEVC) and 14 mg/dL (within other mono- and disaccharides, RMSECV). Moreover, we demonstrate a characterization of the significance of each wavenumber for an accurate prediction of glucose among other saccharides using an evolutionary algorithm. We show, that by picking 10 distinct wavenumbers we can achieve comparable accuracies to the use of a complete spectrum.

Physical activity and change in fasting glucose and HbA1c: a quantitative meta-analysis of randomized trials.

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Boniol, Mathieu; Dragomir, Miruna; Autier, Philippe; Boyle, Peter

2017-11-01

A systematic review was conducted of randomized trials which evaluated the impact of physical activity on the change in fasting glucose and HbA1c. A literature search was conducted in PubMed until December 2015. Studies reporting glucose or HbA1c at baseline and at the end of study were included, and the change and its variance were estimated from studies with complete data. Mixed-effect random models were used to estimate the change of fasting glucose (mg/dl) and HbA1c (%) per additional minutes of physical activity per week. A total of 125 studies were included in the meta-analysis. Based on 105 studies, an increase of 100 min in physical activity per week was associated with an average change of -2.75 mg/dl of fasting glucose (95% CI -3.96; -1.55), although there was a high degree of heterogeneity (83.5%). When restricting the analysis on type 2 diabetes and prediabetes subjects (56 studies), the average change in fasting glucose was -4.71 mg/dl (95% CI -7.42; -2.01). For HbA1c, among 76 studies included, an increase of 100 min in physical activity per week was associated with an average change of -0.14% of HbA1c (95% CI -0.18; -0.09) with heterogeneity (73%). A large degree of publication bias was identified (Egger test p HbA1c was -0.16% (95% CI -0.21; -0.11). This analysis demonstrates that moderate increases in physical activity are associated with significant reductions in both fasting glucose and HbA1c.

Possible involvement of 12-lipoxygenase activation in glucose-deprivation/reload-treated neurons.

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Nagasawa, Kazuki; Kakuda, Taichi; Higashi, Youichirou; Fujimoto, Sadaki

2007-12-18

The aim of this study was to clarify whether 12-lipoxygenase (12-LOX) activation was involved in reactive oxygen species (ROS) generation, extensive poly(ADP-ribose) polymerase (PARP) activation and neuronal death induced by glucose-deprivation, followed by glucose-reload (GD/R). The decrease of neuronal viability and accumulation of poly(ADP-ribose) induced by GD/R were prevented 3-aminobenzamide, a representative PARP inhibitor, demonstrating this treatment protocol caused the same oxidative stress with the previously reported one. The PARP activation, ROS generation and decrease of neuron viability induced by GD/R treatment were almost completely abolished by an extracellular zinc chelator, CaEDTA. p47(phox), a cytosolic component of NADPH oxidase was translocated the membrane fraction by GD/R, indicating its activation, but it did not generate detectable ROS. Surprisingly, pharmacological inhibition of NADPH oxidase with apocynin and AEBSF further decreased the decreased neuron viability induced by GD/R. On the other hand, AA861, a 12-LOX inhibitor, prevented ROS generation and decrease of neuron viability caused by GD/R. Interestingly, an antioxidant, N-acetyl-l-cysteine rescued the neurons from GD/R-induced oxidative stress, implying effectiveness of antioxidant administration. These findings suggested that activation of 12-LOX, but not NADPH oxidase, following to zinc release might play an important role in ROS generation and decrease of viability in GD/R-treated neurons.

Hyperglycemia (High Blood Glucose)

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Full Text Available ... Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day ... DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ...

cAMP response element binding protein (CREB activates transcription via two distinct genetic elements of the human glucose-6-phosphatase gene

Directory of Open Access Journals (Sweden)

Stefano Luisa

2005-01-01

Full Text Available Abstract Background The enzyme glucose-6-phosphatase catalyzes the dephosphorylation of glucose-6-phosphatase to glucose, the final step in the gluconeogenic and glycogenolytic pathways. Expression of the glucose-6-phosphatase gene is induced by glucocorticoids and elevated levels of intracellular cAMP. The effect of cAMP in regulating glucose-6-phosphatase gene transcription was corroborated by the identification of two genetic motifs CRE1 and CRE2 in the human and murine glucose-6-phosphatase gene promoter that resemble cAMP response elements (CRE. Results The cAMP response element is a point of convergence for many extracellular and intracellular signals, including cAMP, calcium, and neurotrophins. The major CRE binding protein CREB, a member of the basic region leucine zipper (bZIP family of transcription factors, requires phosphorylation to become a biologically active transcriptional activator. Since unphosphorylated CREB is transcriptionally silent simple overexpression studies cannot be performed to test the biological role of CRE-like sequences of the glucose-6-phosphatase gene. The use of a constitutively active CREB2/CREB fusion protein allowed us to uncouple the investigation of target genes of CREB from the variety of signaling pathways that lead to an activation of CREB. Here, we show that this constitutively active CREB2/CREB fusion protein strikingly enhanced reporter gene transcription mediated by either CRE1 or CRE2 derived from the glucose-6-phosphatase gene. Likewise, reporter gene transcription was enhanced following expression of the catalytic subunit of cAMP-dependent protein kinase (PKA in the nucleus of transfected cells. In contrast, activating transcription factor 2 (ATF2, known to compete with CREB for binding to the canonical CRE sequence 5'-TGACGTCA-3', did not transactivate reporter genes containing CRE1, CRE2, or both CREs derived from the glucose-6-phosphatase gene. Conclusions Using a constitutively active CREB2

Effects of ozone on adult and aged lung oxygen consumption, glucose metabolism and G6PDH activity

International Nuclear Information System (INIS)

Raska-Emery, P.; Balis, J.U.; Montgomery, M.R.

1991-01-01

Fischer-344 male adult (4-6 mo) and aged (24-26 mo) rats were exposed to 0-3.0 ppm O 3 for 8h, sacrificed immediately, and O 2 consumption, 1 C 14 -glucose metabolism and G6PDH activity were determined. For O 2 consumption, the exp to 0.5 ppm O 3 produced a stimulation in both age groups. Decrements in O 2 consumption were only evident in aged rats after 1.5 and 3.0 ppm. Glucose metabolism showed a marked difference rats were 40% adult rats. Control values in aged rats were 40% of adults. Exp to 0.5 ppm was stimulatory in adults and aged, while 1.5 and 3.0 pp, decreased glucose metabolism in both groups. No age-related difference in G6PDH activity between control and exposed was seen. However, in both age groups, 0.5 ppm O 3 resulted in a significant increase in activity (33-41%)l 1.5 and 3.0 ppm were without effect. The combined results show a biphasic response of adult and aged lung to severe, acute O 3 exp. One-half ppm O 3 for 8h is stimulatory for all three parameters examined in both age groups. Three ppm O 3 inhibits O 2 consumption and glucose metabolism in both age groups but is ineffective on G6PDH activity

Magnetic Fe3S4 nanoparticles with peroxidase-like activity, and their use in a photometric enzymatic glucose assay

International Nuclear Information System (INIS)

Ding, Caiping; Yan, Yinghan; Zhang, Cuiling; Xian, Yuezhong; Xiang, Dongshan

2016-01-01

Greigite magnetic nanoparticles (Fe 3 S 4 -MNPs) were prepared and reveal a peroxidase-like activity. Kinetic studies revealed a pseudo-enzymatic activity that is much higher than that of other magnetic nanomaterial-based enzyme mimetics. This finding was exploited to design a photometric enzymatic glucose assay based on the formation of H 2 O 2 during enzymatic oxidation of glucose by glucose oxidase, and the formation of a blue product from an enzyme substrate that is catalytically oxidized by H 2 O 2 in the presence of Fe 3 S 4 -MNPs. Glucose can be detected in the 2 to 100 μM concentration range, and the low detection limit is 0.16 μM. The method was applied to quantify glucose in human serum. In our perception, this enzyme mimetic has a large potential in that it may be used in other oxidase based assays, but also in ELISAs. (author)

In vitro degradation of pure Mg in response to glucose

Science.gov (United States)

Zeng, Rong-Chang; Li, Xiao-Ting; Li, Shuo-Qi; Zhang, Fen; Han, En-Hou

2015-08-01

Magnesium and its alloys are promising biodegradable biomaterials but are still challenging to be used in person with high levels of blood glucose or diabetes. To date, the influence of glucose on magnesium degradation has not yet been elucidated, this issue requires more attention. Herein, we present pure Mg exhibiting different corrosion responses to saline and Hank’s solutions with different glucose contents, and the degradation mechanism of pure Mg in the saline solution with glucose in comparison with mannitol as a control. On one hand, the corrosion rate of pure Mg increases with the glucose concentration in saline solutions. Glucose rapidly transforms into gluconic acid, which attacks the oxides of the metal and decreases the pH of the solution; it also promotes the absorption of chloride ions on the Mg surface and consequently accelerates corrosion. On the other hand, better corrosion resistance is obtained with increasing glucose content in Hank’s solution due to the fact that glucose coordinates Ca2+ ions in Hank’s solution and thus improves the formation of Ca-P compounds on the pure Mg surface. This finding will open up new avenues for research on the biodegradation of bio-Mg materials in general, which could yield many new and interesting results.

PFOS induces adipogenesis and glucose uptake in association with activation of Nrf2 signaling pathway

Energy Technology Data Exchange (ETDEWEB)

Xu, Jialin [Institute of Biochemistry and Molecular Biology, College of Life and Health Sciences, Northeastern University, Shenyang 110819 (China); Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881 (United States); Shimpi, Prajakta; Armstrong, Laura; Salter, Deanna [Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881 (United States); Slitt, Angela L., E-mail: aslitt@uri.edu [Department of Biomedical and Pharmaceutical Sciences, University of Rhode Island, Kingston, RI 02881 (United States)

2016-01-01

PFOS is a chemical of nearly ubiquitous exposure in humans. Recent studies have associated PFOS exposure to adipose tissue-related effects. The present study was to determine whether PFOS alters the process of adipogenesis and regulates insulin-stimulated glucose uptake in mouse and human preadipocytes. In murine-derived 3T3-L1 preadipocytes, PFOS enhanced hormone-induced differentiation to adipocytes and adipogenic gene expression, increased insulin-stimulated glucose uptake at concentrations ranging from 10 to 100 μM, and enhanced Glucose transporter type 4 and Insulin receptor substrate-1 expression. Nuclear factor (erythroid-derived 2)-like 2 (Nrf2), NAD(P)H dehydrogenase, quinone 1 and Glutamate-cysteine ligase, catalytic subunit were significantly induced in 3T3-L1 cells treated with PFOS, along with a robust induction of Antioxidant Response Element (ARE) reporter in mouse embryonic fibroblasts isolated from ARE-hPAP transgenic mice by PFOS treatment. Chromatin immunoprecipitation assays further illustrated that PFOS increased Nrf2 binding to ARE sites in mouse Nqo1 promoter, suggesting that PFOS activated Nrf2 signaling in murine-derived preadipocytes. Additionally, PFOS administration in mice (100 μg/kg/day) induced adipogenic gene expression and activated Nrf2 signaling in epididymal white adipose tissue. Moreover, the treatment on human visceral preadipocytes illustrated that PFOS (5 and 50 μM) promoted adipogenesis and increased cellular lipid accumulation. It was observed that PFOS increased Nrf2 binding to ARE sites in association with Nrf2 signaling activation, induction of Peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α expression, and increased adipogenesis. This study points to a potential role of PFOS in dysregulation of adipose tissue expandability, and warrants further investigations on the adverse effects of persistent pollutants on human health. - Highlights: • PFOS induces adipogenesis in association

AJS1669, a novel small-molecule muscle glycogen synthase activator, improves glucose metabolism and reduces body fat mass in mice

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Nakano, Kazuhiro; Takeshita, Sen; Kawasaki, Noriko; Miyanaga, Wataru; Okamatsu, Yoriko; Dohi, Mizuki; Nakagawa, Tadakiyo

2017-01-01

Impaired glycogen synthesis and turnover are common in insulin resistance and type 2 diabetes. As glycogen synthase (GS) is a key enzyme involved in the synthetic process, it presents a promising therapeutic target for the treatment of type 2 diabetes. In the present study, we identified a novel, potent and orally available GS activator AJS1669 {sodium 2-[[5-[[4-(4,5-difluoro-2-methylsulfanyl-phenyl) phenoxy] methyl]furan-2-carbonyl]-(2-furylmethyl)amino] acetate}. In vitro, we performed a glycogen synthase 1 (GYS1) activation assay for screening GS activators and identified that the activity of AJS1669 was further potentiated in the presence of glucose-6-phosphate (G6P). In vivo, we used ob/ob mice to evaluate the novel anti-diabetic effects of AJS1669 by measuring basal blood glucose levels, glucose tolerance and body fat mass index. Repeated administration of AJS1669 over 4 weeks reduced blood glucose and hemoglobin A1c (HbA1c) levels in ob/ob mice. AJS1669 also improved glucose tolerance in a dose-dependent manner, and decreased body fat mass. The mRNA levels of genes involved in mitochondrial fatty acid oxidation and mitochondrial biogenesis were elevated in skeletal muscle tissue following AJS1669 treatment. Hepatic tissue of treated mice also exhibited elevated expression of genes associated with fatty acid oxidation. In contrast to ob/ob mice, in C57Bl/6 mice AJS1669 administration did not alter body weight or reduce glucose levels. These results demonstrate that pharmacological agents that activate GYS1, the main GS subtype found in skeletal muscle, have potential for use as novel treatments for diabetes that improve glucose metabolism in skeletal muscle. PMID:28290602

Comparable attenuation of sympathetic nervous system activity in obese subjects with normal glucose tolerance, impaired glucose tolerance and treatment naïve type 2 diabetes following equivalent weight loss

Directory of Open Access Journals (Sweden)

Nora E. Straznicky

2016-11-01

Full Text Available Background and Purpose: Elevated sympathetic nervous system (SNS activity is a characteristic of obesity and type 2 diabetes (T2D that contributes to target organ damage and cardiovascular risk. In this study we examined whether baseline metabolic status influences the degree of sympathoinhibition attained following equivalent dietary weight loss. Methods: Un-medicated obese individuals categorized as normal glucose tolerant (NGT, n=15, impaired glucose tolerant (IGT, n=24 and newly-diagnosed T2D (n=15 consumed a hypocaloric diet (29% fat, 23% protein, 45% carbohydrate for 4-months. The three groups were matched for baseline age (56 + 1 years, body mass index (BMI, 32.9 + 0.7 kg/m2 and gender. Clinical measurements included whole-body norepinephrine kinetics, muscle sympathetic nerve activity (MSNA, by microneurography, spontaneous cardiac baroreflex sensitivity (BRS and oral glucose tolerance test. Results: Weight loss averaged -7.5 + 0.8, -8.1 + 0.5 and -8.0 + 0.9 % of body weight in NGT, IGT and T2D groups, respectively. T2D subjects had significantly greater reductions in fasting glucose, 2-h glucose and glucose area under the curve (AUC0-120 compared to NGT and IGT (group effect, P<0.001. Insulinogenic index decreased in IGT and NGT groups and increased in T2D (group x time, P=0.04. The magnitude of reduction in MSNA (-7 + 3, -8 + 4, -15 + 4 burst/100hb, respectively and whole-body norepinephrine spillover rate (-28 + 8, -18 + 6 and -25 + 7 %, respectively, time effect both P<0.001, did not differ between groups. After adjustment for age and change in body weight, ∆ insulin AUC0-120 was independently associated with reduction in arterial norepinephrine concentration, whilst ∆ LDL-cholesterol and improvement in BRS were independently associated with decrease in MSNA. Conclusions: Equivalent weight loss through hypocaloric diet is accompanied by similar sympathoinhibition in matched obese subjects with different baseline glucose tolerance

Autophagy Inhibition Contributes to ROS-Producing NLRP3-Dependent Inflammasome Activation and Cytokine Secretion in High Glucose-Induced Macrophages.

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Dai, Jiezhi; Zhang, Xiaotian; Li, Li; Chen, Hua; Chai, Yimin

2017-01-01

Type 2 diabetes is a persistent inflammatory response that impairs the healing process. We hypothesized that stimulation with high glucose following a pro-inflammatory signal would lead to autophagy inhibition, reactive oxygen species (ROS) production and eventually to the activation of the Nod-like receptor protein (NLRP) -3. Macrophages were isolated from human diabetic wound. We measured the expression of NLRP3, caspase1 and interleukin-1 beta (IL-1β) by western blot and real-time PCR, and the surface markers on cells by flow cytometry. THP-1-derived macrophages exposed to high glucose were applied to study the link between autophagy, ROS and NLRP3 activation. LC3-II, P62, NLRP3 inflammation and IL-1β expression were measured by western blot and real-time PCR. ROS production was measured with a Cellular Reactive Oxygen Species Detection Assay Kit. Macrophages isolated from diabetic wounds exhibited a pro-inflammatory phenotype, including sustained NLRP3 inflammasome activity associated with IL-1β secretion. Our data showed that high glucose inhibited autophagy, induced ROS production, and activated NLRP3 inflammasome and cytokine secretion in THP-1-derived macrophages. To study high glucose-induced NLRP3 inflammasome signalling, we performed studies using an autophagy inducer, a ROS inhibitor and a NLRP3 inhibitor and found that all reduced the NLRP3 inflammasome activation and cytokine secretion. Sustained NLRP3 inflammasome activity in wound-derived macrophages contributes to the hyper-inflammation in human diabetic wounds. Autophagy inhibition and ROS generation play an essential role in high glucose-induced NLRP3 inflammasome activation and cytokine secretion in macrophages. © 2017 The Author(s). Published by S. Karger AG, Basel.

Alligators and Crocodiles Have High Paracellular Absorption of Nutrients, But Differ in Digestive Morphology and Physiology.

Science.gov (United States)

Tracy, Christopher R; McWhorter, Todd J; Gienger, C M; Starck, J Matthias; Medley, Peter; Manolis, S Charlie; Webb, Grahame J W; Christian, Keith A

2015-12-01

Much of what is known about crocodilian nutrition and growth has come from animals propagated in captivity, but captive animals from the families Crocodilidae and Alligatoridae respond differently to similar diets. Since there are few comparative studies of crocodilian digestive physiology to help explain these differences, we investigated young Alligator mississippiensis and Crocodylus porosus in terms of (1) gross and microscopic morphology of the intestine, (2) activity of the membrane-bound digestive enzymes aminopeptidase-N, maltase, and sucrase, and (3) nutrient absorption by carrier-mediated and paracellular pathways. We also measured gut morphology of animals over a larger range of body sizes. The two species showed different allometry of length and mass of the gut, with A. mississippiensis having a steeper increase in intestinal mass with body size, and C. porosus having a steeper increase in intestinal length with body size. Both species showed similar patterns of magnification of the intestinal surface area, with decreasing magnification from the proximal to distal ends of the intestine. Although A. mississippiensis had significantly greater surface-area magnification overall, a compensating significant difference in gut length between species meant that total surface area of the intestine was not significantly different from that of C. porosus. The species differed in enzyme activities, with A. mississippiensis having significantly greater ability to digest carbohydrates relative to protein than did C. porosus. These differences in enzyme activity may help explain the differences in performance between the crocodilian families when on artificial diets. Both A. mississippiensis and C. porosus showed high absorption of 3-O methyl d-glucose (absorbed via both carrier-mediated and paracellular transport), as expected. Both species also showed surprisingly high levels of l-glucose-uptake (absorbed paracellularly), with fractional absorptions as high as those

Hepatic glycogen in humans. I. Direct formation after oral and intravenous glucose or after a 24-h fast

International Nuclear Information System (INIS)

Radziuk, J.

1989-01-01

The formation of hepatic glycogen by the direct pathway is assessed in humans after a 12-h fast and oral loading (100 g) or intravenous infusion (90 g) and after a 24-h fast and the same oral glucose load. The methodology used is based on the double tracer method. [3- 3 H]glucose is infused at a constant rate for the determination of the metabolic clearance of glucose. [1- 14 C]glucose is administered with the glucose load. One hour after absorption or the intravenous glucose infusion is terminated, a glucagon infusion is initiated to mobilize the glycogen labeled with [1- 14 C]glucose and formed during the absorptive period. At this time a third tracer, [6- 3 H]glucose, is administered to measure glucose clearance. It was found that after the 12-h fast and oral glucose loading 7.2 +/- 1.1 g of hepatic glycogen appears to be formed directly from glucose compared with 8.4 +/- 1.0 g after the same load and a 24-h fast and 8.5 +/- 0.4 g after a 12-h fast and an equivalent intravenous glucose infusion. When the amount of label ([ 14 C]glucose) mobilized that was not corrected for metabolic recycling was calculated, the data suggested that the amount of glycogen formed by gluconeogenic pathways was probably at least equal to that formed by direct uptake. It was also approximately 60% greater after a 24-h fast. It can be concluded that the amount of hepatic glycogen formed directly from glucose during glucose loading is not significantly altered by the route of entry or the extension of the fasting period to 24 h. The data suggest, however, that gluconeogenetic formation of glycogen increases with fasting

Investigation of the Blood Glucose Lowering Potential of the Jamaican Momordica charantia (Cerasee) Fruit in Sprague-Dawley Rats

Science.gov (United States)

Burnett, A; McKoy, M-L; Singh, P

2015-01-01

ABSTRACT The Momordica charantia (MC) fruit has been documented to possess antidiabetic properties. However, these studies were not without controversy surrounding the blood glucose-lowering ability and the mechanism of action in diabetes therapy. In an effort to evaluate such claims in the Jamaican MC species known as cerasee, aqueous extracts of the unripe fruit were studied in normal and diabetic rats. Normal male Sprague-Dawley rats were divided into groups (n = 6) orally administered distilled water, 10% dimethyl sulfoxide (DMSO) solution, the aqueous extract (400 mg/kg body weight) and glibenclamide (15 mg/kg body weight), respectively prior to assessment of fasting blood glucose (FBG) concentration. The oral glucose tolerance test (OGTT) was conducted in normoglycaemic rats orally administered distilled water, 10% DMSO solution, glibenclamide (15 mg/kg body weight) or aqueous extracts of the fruit (200 and 400 mg/kg body weight). Blood glucose concentration was also monitored in streptozotocin-induced diabetic rats administered the aqueous extract (250 mg/kg body weight) or water vehicle after an overnight fast. The aqueous extracts showed no hypoglycaemic or antidiabetic activity. However, the administration of the aqueous extracts (200 and 400 mg/kg body weight) resulted in significant improvement in glucose tolerance of glucose-primed normoglycaemic rats during the OGTT. These data suggest that the glucose-lowering mechanism of the Jamaican MC fruit species likely involves altered glucose absorption across the gastrointestinal tract. PMID:26624580

Mechanistic understanding of time-dependent oral absorption based on gastric motor activity in humans.

Science.gov (United States)

Higaki, Kazutaka; Choe, Sally Y; Löbenberg, Raimar; Welage, Lynda S; Amidon, Gordon L

2008-09-01

The relationship of gastric motor activity and gastric emptying of 0.7 mm caffeine pellets with their absorption was investigated in the fed state in healthy human subjects by simultaneous monitoring of antral motility and plasma concentrations. A kinetic model for gastric emptying-dependent absorption yielded multiple phases of gastric emptying and rate constants (k(g)) with large inter-individual differences and large variability in onset of gastric emptying (50-175 min). The model suggests that 50% of the dose is emptied in 1-2h and over 90% emptied by 3.5h following dosing, in all subjects. The maximum values of k(g) (k(g)(max)) were much greater than those reported for emptying of liquids in the fasted state and were comparable to k(g) values in the late Phase II/III of the migrating motor complex (MMC). The model described the observed irregular absorption rate-time and plasma concentration-time profiles adequately but not in detail. The model was more successful at simulating double-peak phenomena in absorption rate profiles and onset of caffeine absorption. The results suggest that gastric emptying regulates drug absorption of small particles in the fed state. Further, estimates of k(a) derived using the time-dependent absorption model were closer to the intrinsic absorption rate constant for caffeine.

The UPR reduces glucose metabolism via IRE1 signaling.

Science.gov (United States)

van der Harg, Judith M; van Heest, Jessica C; Bangel, Fabian N; Patiwael, Sanne; van Weering, Jan R T; Scheper, Wiep

2017-04-01

Neurons are highly dependent on glucose. A disturbance in glucose homeostasis therefore poses a severe risk that is counteracted by activation of stress responses to limit damage and restore the energy balance. A major stress response that is activated under conditions of glucose deprivation is the unfolded protein response (UPR) that is aimed to restore proteostasis in the endoplasmic reticulum. The key signaling of the UPR involves the transient activation of a transcriptional program and an overall reduction of protein synthesis. Since the UPR is strategically positioned to sense and integrate metabolic stress signals, it is likely that - apart from its adaptive response to restore proteostasis - it also directly affects metabolic pathways. Here we investigate the direct role of the UPR in glucose homeostasis. O-GlcNAc is a post-translational modification that is highly responsive to glucose fluctuations. We find that UPR activation results in decreased O-GlcNAc modification, in line with reduced glucose metabolism. Our data indicate that UPR activation has no direct impact on the upstream processes in glucose metabolism; glucose transporter expression, glucose uptake and hexokinase activity. In contrast, prolonged UPR activation decreases glycolysis and mitochondrial metabolism. Decreased mitochondrial respiration is not accompanied by apoptosis or a structural change in mitochondria indicating that the reduction in metabolic rate upon UPR activation is a physiological non-apoptotic response. Metabolic decrease is prevented if the IRE1 pathway of the UPR is inhibited. This indicates that activation of IRE1 signaling induces a reduction in glucose metabolism, as part of an adaptive response. Copyright © 2017 Elsevier B.V. All rights reserved.

Studies of gene expression and activity of hexokinase, phosphofructokinase and glycogen synthase in human skeletal muscle in states of altered insulin-stimulated glucose metabolism

DEFF Research Database (Denmark)

Vestergaard, H

1999-01-01

been reported to increase the basal concentration of muscle GS mRNA in NIDDM patients to a level similar to that seen in control subjects although insulin-stimulated glucose disposal rates remain reduced in NIDDM patients. In the insulin resistant states examined so far, basal and insulin-stimulated......When whole body insulin-stimulated glucose disposal rate is measured in man applying the euglycaemic, hyperinsulinaemic clamp technique it has been shown that approximately 75% of glucose is taken up by skeletal muscle. After the initial transport step, glucose is rapidly phosphorylated to glucose...... critical roles in glucose oxidation/glycolysis and glucose storage, respectively. Glucose transporters and glycogen synthase activities are directly and acutely stimulated by insulin whereas the activities of hexokinases and phosphofructokinase may primarily be allosterically regulated. The aim...

Glucose regulates hypothalamic long-chain fatty acid metabolism via AMP-activated kinase (AMPK) in neurons and astrocytes.

Science.gov (United States)

Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

2013-12-27

Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance.

Lycium barbarum L. Polysaccharide (LBP Reduces Glucose Uptake via Down-Regulation of SGLT-1 in Caco2 Cell

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Huizhen Cai

2017-02-01

Full Text Available Lycium barbarum L. polysaccharide (LBP is prepared from Lycium barbarum L. (L. barbarum, which is a traditional Chinese medicine. LPB has been shown to have hypoglycemic effects. In order to gain some mechanistic insights on the hypoglycemic effects of LBP, we investigated the uptake of LBP and its effect on glucose absorption in the human intestinal epithelial cell line Caco2 cell. The uptake of LBP through Caco2 cell monolayer was time-dependent and was inhibited by phloridzin, a competitive inhibitor of SGLT-1. LPB decreased the absorption of glucose in Caco2 cell, and down-regulated the expression of SGLT-1. These results suggest that LBP might be transported across the human intestinal epithelium through SGLT-1 and it inhibits glucose uptake via down-regulating SGLT-1.

Dynamic changes in cytosolic ATP levels in cultured glutamatergic neurons during NMDA-induced synaptic activity supported by glucose or lactate

DEFF Research Database (Denmark)

Lange, Sofie Cecilie; Winkler, Ulrike; Andresen, Lars

2015-01-01

is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis...... biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined...... in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis...

Protective Effects of Ferulic Acid on High Glucose-Induced Protein Glycation, Lipid Peroxidation, and Membrane Ion Pump Activity in Human Erythrocytes.

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Weerachat Sompong

Full Text Available Ferulic acid (FA is the ubiquitous phytochemical phenolic derivative of cinnamic acid. Experimental studies in diabetic models demonstrate that FA possesses multiple mechanisms of action associated with anti-hyperglycemic activity. The mechanism by which FA prevents diabetes-associated vascular damages remains unknown. The aim of study was to investigate the protective effects of FA on protein glycation, lipid peroxidation, membrane ion pump activity, and phosphatidylserine exposure in high glucose-exposed human erythrocytes. Our results demonstrated that FA (10-100 μM significantly reduced the levels of glycated hemoglobin (HbA1c whereas 0.1-100 μM concentrations inhibited lipid peroxidation in erythrocytes exposed to 45 mM glucose. This was associated with increased glucose consumption. High glucose treatment also caused a significant reduction in Na+/K+-ATPase activity in the erythrocyte plasma membrane which could be reversed by FA. Furthermore, we found that FA (0.1-100 μM prevented high glucose-induced phosphatidylserine exposure. These findings provide insights into a novel mechanism of FA for the prevention of vascular dysfunction associated with diabetes.

Optical determination of glucose and hydrogen peroxide using a nanocomposite prepared from glucose oxidase and magnetite nanoparticles immobilized on graphene oxide

International Nuclear Information System (INIS)

Chang, Qing; Tang, Heqing

2014-01-01

Fe 3 O 4 nanoparticles were deposited on sheets of graphene oxide (GO) by a precipitation method, and glucose oxidase (GOx) was then immobilized on this material to produce a GOx/Fe 3 O 4 /GO magnetic nanocomposite containing crosslinked enzyme clusters. The 3-component composite functions as a binary enzyme that was employed in a photometric method for the determination of glucose and hydrogen peroxide where the GOx/Fe 3 O 4 /GO nanoparticles cause the generation of H 2 O 2 which, in turn, oxidize the substrate N,N-diethyl-p-phenylenediamine to form a purple product with an absorption maximum at 550 nm. The absorbance at 550 nm can be correlated to the concentration of glucose and/or hydrogen peroxide. Under optimized conditions, the calibration plot is linear in the 0.5 to 600 μM glucose concentration range, and the detection limit is 0.2 μM. The respective plot for H 2 O 2 ranges from 0.1 to 10 μM, and the detection limit is 0.04 μM. The method was successfully applied to the determination of glucose in human serum samples. The GOx/Fe 3 O 4 /GO nanoparticles are reusable. (author)

Improved model of activation energy absorption for different electrical breakdowns in semi-crystalline insulating polymers

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Sima, Wenxia; Jiang, Xiongwei; Peng, Qingjun; Sun, Potao

2018-05-01

Electrical breakdown is an important physical phenomenon in electrical equipment and electronic devices. Many related models and theories of electrical breakdown have been proposed. However, a widely recognized understanding on the following phenomenon is still lacking: impulse breakdown strength which varies with waveform parameters, decrease in the breakdown strength of AC voltage with increasing frequency, and higher impulse breakdown strength than that of AC. In this work, an improved model of activation energy absorption for different electrical breakdowns in semi-crystalline insulating polymers is proposed based on the Harmonic oscillator model. Simulation and experimental results show that, the energy of trapped charges obtained from AC stress is higher than that of impulse voltage, and the absorbed activation energy increases with the increase in the electric field frequency. Meanwhile, the frequency-dependent relative dielectric constant ε r and dielectric loss tanδ also affect the absorption of activation energy. The absorbed activation energy and modified trap level synergistically determine the breakdown strength. The mechanism analysis of breakdown strength under various voltage waveforms is consistent with the experimental results. Therefore, the proposed model of activation energy absorption in the present work may provide a new possible method for analyzing and explaining the breakdown phenomenon in semi-crystalline insulating polymers.

Are barriers to physical activity similar for adults with and without abnormal glucose metabolism?

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Hume, Clare; Dunstan, David; Salmon, Jo; Healy, Genevieve; Andrianopoulos, Nick; Owen, Neville

2010-01-01

The purpose of this study was to examine perceived barriers to physical activity among adults with and without abnormal glucose metabolism (AGM), and whether barriers varied according to physical activity status. The 1999 to 2000 Australian Diabetes, Obesity, and Lifestyle Study (AusDiab) was a population-based cross-sectional study among adults aged > or =25 years. AGM was identified through an oral glucose tolerance test. The previous week's physical activity and individual, social, and environmental barriers to physical activity were self-reported. Logistic regression analyses examined differences in barriers to physical activity between those with and without AGM, and for those with and without AGM who did and did not meet the minimum recommendation of 150 minutes/week of moderate-to-vigorous intensity physical activity. Of the 7088 participants (47.5 +/- 12.7 years; 46% male), 18.5% had AGM. Approximately 47.5% of those with AGM met the physical activity recommendation, compared to 54.7% of those without AGM (P barriers to physical activity included lack of time, other priorities, and being tired. Following adjustment for sociodemographic and behavioral factors, there were few differences in barriers to physical activity between those with and without AGM, even after stratifying according to physical activity. Adults with AGM report similar barriers to physical activity, as do those without AGM. Programs for those with AGM can therefore focus on the known generic adult-reported barriers to physical activity.

The Relationship between Physical Activity and Plasma Glucose Level amongst Ellisras Rural Young Adult Males and Females: Ellisras Longitudinal Study

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Moloko Matshipi

2017-02-01

Full Text Available Unhealthy lifestyle characteristics such as low physical activity (PA and high plasma glucose levels (PGLs may lead to the development of type 2 diabetes mellitus in adulthood. The aim of this study was to investigate (i the level of physical activity; (ii the prevalence of pre-diabetes and (iii the relationship between PA and plasma glucose level in a rural Ellisras adult population aged 18 to 28 years. A total of 713 young adults (349 males and 364 females who took part in the Ellisras Longitudinal Study participated in the study. Fasting plasma glucose levels were analysed using Accutrend glucose meters. Physical activity data was collected using a validated questionnaire. Linear regression was used to assess the relationship between PA and pre-diabetes. The prevalence of pre-diabetes was between 45.7% and 50.2% and that of physical inactivity was 67.3% and 71.0% for males and females, respectively. There was no significant (p > 0.05 relationship between PA and pre-diabetes (beta = 1.016; 95% Confidence Interval from 0.352 to 2.777. The health benefits of PA increased with the increasing frequency, duration and intensity of exercise. The prevalence of pre-diabetes was found to be very high in this population. Our results suggest that greater physical activity is associated with low plasma glucose levels.

The effects of consuming carbohydrate-electrolyte beverages on gastric emptying and fluid absorption during and following exercise.

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Murray, R

1987-01-01

A variety of beverages formulated to provide fluid, carbohydrates, and electrolytes during and following exercise are commercially available. Such 'sport drinks' commonly contain 4 to 8% carbohydrate (as glucose, fructose, sucrose or maltodextrins) and small amounts of electrolytes (most often sodium, potassium, and chloride). The efficacy of consuming such beverages has been questioned primarily because of concern that beverage carbohydrate content may inhibit gastric emptying rate and fluid absorption during exercise, thereby jeopardizing physiological homeostasis and impairing exercise performance. Gastric motor activity, and consequently gastric emptying rate, is governed by neural and humoral feedback provided by receptors found in the gastric musculature and proximal small intestine. Gastric emptying rate may be influenced by a variety of factors including, but not limited to, the caloric content, volume, osmolality, temperature, and pH of the ingested fluid, diurnal and interindividual variation, metabolic state (rest/exercise), and the ambient temperature. The caloric content of the ingested fluid appears to be the most important variable governing gastric emptying rate, providing a mean caloric efflux from the stomach of 2.0 to 2.5 kcal/min for ingested fluid volumes less than 400 ml. At rest, gastric emptying is inhibited by solutions containing calories in a manner independent of the nutrient source (i.e. carbohydrate, fat or protein). Consequently, plain water is known to empty from the stomachs of resting subjects at rates faster than solutions containing calories. Gastric emptying is increasingly inhibited as the caloric content of the ingested fluid increases. During moderate exercise (less than 75% VO2max), gastric emptying occurs at a rate similar to that during rest; more intense exercise appears to inhibit gastric emptying. When fluids are consumed at regular intervals throughout prolonged exercise (greater than 2 hours), postexercise aspiration

Glucose pathways adaptation supports acquisition of activated microglia phenotype.

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Gimeno-Bayón, J; López-López, A; Rodríguez, M J; Mahy, N

2014-06-01

With its capacity to survey the environment and phagocyte debris, microglia assume a diversity of phenotypes to respond specifically through neurotrophic and toxic effects. Although these roles are well accepted, the underlying energetic mechanisms associated with microglial activation remain largely unclear. This study investigates microglia metabolic adaptation to ATP, NADPH, H(+) , and reactive oxygen species production. To this end, in vitro studies were performed with BV-2 cells before and after activation with lipopolysaccharide + interferon-γ. Nitric oxide (NO) was measured as a marker of cell activation. Our results show that microglial activation triggers a metabolic reprogramming based on an increased glucose uptake and a strengthening of anaerobic glycolysis, as well as of the pentose pathway oxidative branch, while retaining the mitochondrial activity. Based on this energy commitment, microglial defense capacity increases rapidly as well as ribose-5-phosphate and nucleic acid formation for gene transcription, essential to ensure the newly acquired functions demanded by central nervous system signaling. We also review the role of NO in this microglial energy commitment that positions cytotoxic microglia within the energetics of the astrocyte-neuron lactate shuttle. Copyright © 2014 Wiley Periodicals, Inc.

Glucose Regulates Hypothalamic Long-chain Fatty Acid Metabolism via AMP-activated Kinase (AMPK) in Neurons and Astrocytes*

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Taïb, Bouchra; Bouyakdan, Khalil; Hryhorczuk, Cécile; Rodaros, Demetra; Fulton, Stephanie; Alquier, Thierry

2013-01-01

Hypothalamic controls of energy balance rely on the detection of circulating nutrients such as glucose and long-chain fatty acids (LCFA) by the mediobasal hypothalamus (MBH). LCFA metabolism in the MBH plays a key role in the control of food intake and glucose homeostasis, yet it is not known if glucose regulates LCFA oxidation and esterification in the MBH and, if so, which hypothalamic cell type(s) and intracellular signaling mechanisms are involved. The aim of this study was to determine the impact of glucose on LCFA metabolism, assess the role of AMP-activated Kinase (AMPK), and to establish if changes in LCFA metabolism and its regulation by glucose vary as a function of the kind of LCFA, cell type, and brain region. We show that glucose inhibits palmitate oxidation via AMPK in hypothalamic neuronal cell lines, primary hypothalamic astrocyte cultures, and MBH slices ex vivo but not in cortical astrocytes and slice preparations. In contrast, oleate oxidation was not affected by glucose or AMPK inhibition in MBH slices. In addition, our results show that glucose increases palmitate, but not oleate, esterification into neutral lipids in neurons and MBH slices but not in hypothalamic astrocytes. These findings reveal for the first time the metabolic fate of different LCFA in the MBH, demonstrate AMPK-dependent glucose regulation of LCFA oxidation in both astrocytes and neurons, and establish metabolic coupling of glucose and LCFA as a distinguishing feature of hypothalamic nuclei critical for the control of energy balance. PMID:24240094

Antidiabetic activities of aqueous and ethanolic extracts of Piper betle leaves in rats.

Science.gov (United States)

Arambewela, L S R; Arawwawala, L D A M; Ratnasooriya, W D

2005-11-14

Leaves of Piper betle (Piperaceae) possess several bioactivities and are used in traditional medicinal systems. However, its antidiabetic activity has not been scientifically investigated so far. The aim of this study therefore, was to investigate the antidiabetic activity of Piper betle leaves. This was tested in normoglycaemic and strepozotocin (STZ)-induced diabetic rats using oral administration of hot water extract (HWE) and cold ethanolic extract (CEE). In normoglycaemic rats, both HWE and CEE significantly lowered the blood glucose level in a dose-dependent manner. In glucose tolerance test, both extracts markedly reduced the external glucose load. The antidiabetic activity of HWE is comparable to that of CEE. Moreover, HWE failed to inhibit the glucose absorption from the small intestine of rats. Both extracts were found to be non-toxic and well tolerated after following chronic oral administration (no overt signs of toxicity, hepatotoxicity or renotoxicity). However, the weight of the spleen had increased in treated groups possibly indicating lymphoproliferative activity. It is concluded that HWE and CEE of Piper betle leaves possess safe and strong antidiabetic activity.

Glucose turnover, oxidation, and indices of recycling in severely traumatized patients

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Jeevanandam, M.; Young, D.H.; Schiller, W.R. (St. Joseph' s Hospital Medical Center, Phoenix, AZ (USA))

1990-05-01

Hyperglycemia is often seen in trauma patients and its etiology is not clearly understood. We have determined parameters of glucose metabolism by using simultaneous primed-constant intravenous infusion of both (6-3H) glucose and (U-14C) glucose in ten severely traumatized hypermetabolic subjects during the early flow phase of injury and in six post-absorptive normal volunteers. The mean rate of glucose production (determined by means of (6-3H) glucose) was 3.96 +/- 0.40 mg/kg/min in trauma patients, which was significantly (p = 0.025) higher than the value of 2.75 +/- 0.13 observed in normal volunteers. Glucose turnover rates determined with (U-14C) glucose as tracer were lower in all subjects. The difference between the turnover rates determined by the two tracers represents an index of recycling of glucose through three-carbon fragments. This recycling index was similar in both groups of subjects in amount (0.24 +/- 0.07 vs. 0.26 +/- 0.08 mg glucose/kg/min) but different when expressed as percentage of total glucose turnover (5.6 +/- 1.4% vs. 9.8 +/- 1.7%; p = 0.05). The absolute rates of glucose clearance, oxidation, and recycling were similar in stressed trauma patients and unstressed controls although the rate of production was increased by 44% due to injury. Post-trauma hyperglycemia was mainly due to an increased hepatic output of glucose and not due to a decreased ability of the tissue to extract glucose from the plasma. Hyperglycemia may be the driving force in the metabolic effects of injury.

Glucose turnover, oxidation, and indices of recycling in severely traumatized patients

International Nuclear Information System (INIS)

Jeevanandam, M.; Young, D.H.; Schiller, W.R.

1990-01-01

Hyperglycemia is often seen in trauma patients and its etiology is not clearly understood. We have determined parameters of glucose metabolism by using simultaneous primed-constant intravenous infusion of both [6-3H] glucose and [U-14C] glucose in ten severely traumatized hypermetabolic subjects during the early flow phase of injury and in six post-absorptive normal volunteers. The mean rate of glucose production (determined by means of [6-3H] glucose) was 3.96 +/- 0.40 mg/kg/min in trauma patients, which was significantly (p = 0.025) higher than the value of 2.75 +/- 0.13 observed in normal volunteers. Glucose turnover rates determined with [U-14C] glucose as tracer were lower in all subjects. The difference between the turnover rates determined by the two tracers represents an index of recycling of glucose through three-carbon fragments. This recycling index was similar in both groups of subjects in amount (0.24 +/- 0.07 vs. 0.26 +/- 0.08 mg glucose/kg/min) but different when expressed as percentage of total glucose turnover (5.6 +/- 1.4% vs. 9.8 +/- 1.7%; p = 0.05). The absolute rates of glucose clearance, oxidation, and recycling were similar in stressed trauma patients and unstressed controls although the rate of production was increased by 44% due to injury. Post-trauma hyperglycemia was mainly due to an increased hepatic output of glucose and not due to a decreased ability of the tissue to extract glucose from the plasma. Hyperglycemia may be the driving force in the metabolic effects of injury

A glucose-centric perspective of hyperglycemia.

Science.gov (United States)

Ramasarma, T; Rafi, M

2016-02-01

Digestion of food in the intestines converts the compacted storage carbohydrates, starch and glycogen, to glucose. After each meal, a flux of glucose (> 200 g) passes through the blood pool (4-6 g) in a short period of 2 h, keeping its concentration ideally in the range of 80-120 mg/100 mL. Tissue-specific glucose transporters (GLUTs) aid in the distribution of glucose to all tissues. The balance glucose after meeting the immediate energy needs is converted into glycogen and stored in liver (up to 100 g) and skeletal muscle (up to 300 g) for later use. High blood glucose gives the signal for increased release of insulin from pancreas. Insulin binds to insulin receptor on the plasma membrane and activates its autophosphorylation. This initiates the post-insulin-receptor signal cascade that accelerates synthesis of glycogen and triglyceride. Parallel control by phos-dephos and redox regulation of proteins exists for some of these steps. A major action of insulin is to inhibit gluconeogensis in the liver decreasing glucose output into blood. Cases with failed control of blood glucose have alarmingly increased since 1960 coinciding with changed life-styles and large scale food processing. Many of these turned out to be resistant to insulin, usually accompanied by dysfunctional glycogen storage. Glucose has an extended stay in blood at 8 mM and above and then indiscriminately adds on to surface protein-amino groups. Fructose in common sugar is 10-fold more active. This random glycation process interferes with the functions of many proteins (e.g., hemoglobin, eye lens proteins) and causes progressive damage to heart, kidneys, eyes and nerves. Some compounds are known to act as insulin mimics. Vanadium-peroxide complexes act at post-receptor level but are toxic. The fungus-derived 2,5-dihydroxybenzoquinone derivative is the first one known to act on the insulin receptor. The safe herbal products in use for centuries for glucose control have multiple active principles and

Galanin enhances systemic glucose metabolism through enteric Nitric Oxide Synthase-expressed neurons

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Anne Abot

2018-04-01

Full Text Available Objective: Decreasing duodenal contraction is now considered as a major focus for the treatment of type 2 diabetes. Therefore, identifying bioactive molecules able to target the enteric nervous system, which controls the motility of intestinal smooth muscle cells, represents a new therapeutic avenue. For this reason, we chose to study the impact of oral galanin on this system in diabetic mice. Methods: Enteric neurotransmission, duodenal contraction, glucose absorption, modification of gut–brain axis, and glucose metabolism (glucose tolerance, insulinemia, glucose entry in tissue, hepatic glucose metabolism were assessed. Results: We show that galanin, a neuropeptide expressed in the small intestine, decreases duodenal contraction by stimulating nitric oxide release from enteric neurons. This is associated with modification of hypothalamic nitric oxide release that favors glucose uptake in metabolic tissues such as skeletal muscle, liver, and adipose tissue. Oral chronic gavage with galanin in diabetic mice increases insulin sensitivity, which is associated with an improvement of several metabolic parameters such as glucose tolerance, fasting blood glucose, and insulin. Conclusion: Here, we demonstrate that oral galanin administration improves glucose homeostasis via the enteric nervous system and could be considered a therapeutic potential for the treatment of T2D. Keywords: Galanin, Enteric nervous system, Diabetes

Novel fungal FAD glucose dehydrogenase derived from Aspergillus niger for glucose enzyme sensor strips.

Science.gov (United States)

Sode, Koji; Loew, Noya; Ohnishi, Yosuke; Tsuruta, Hayato; Mori, Kazushige; Kojima, Katsuhiro; Tsugawa, Wakako; LaBelle, Jeffrey T; Klonoff, David C

2017-01-15

In this study, a novel fungus FAD dependent glucose dehydrogenase, derived from Aspergillus niger (AnGDH), was characterized. This enzyme's potential for the use as the enzyme for blood glucose monitor enzyme sensor strips was evaluated, especially by investigating the effect of the presence of xylose during glucose measurements. The substrate specificity of AnGDH towards glucose was investigated, and only xylose was found as a competing substrate. The specific catalytic efficiency for xylose compared to glucose was 1.8%. The specific activity of AnGDH for xylose at 5mM concentration compared to glucose was 3.5%. No other sugars were used as substrate by this enzyme. The superior substrate specificity of AnGDH was also demonstrated in the performance of enzyme sensor strips. The impact of spiking xylose in a sample with physiological glucose concentrations on the sensor signals was investigated, and it was found that enzyme sensor strips using AnGDH were not affected at all by 5mM (75mg/dL) xylose. This is the first report of an enzyme sensor strip using a fungus derived FADGDH, which did not show any positive bias at a therapeutic level xylose concentration on the signal for a glucose sample. This clearly indicates the superiority of AnGDH over other conventionally used fungi derived FADGDHs in the application for SMBG sensor strips. The negligible activity of AnGDH towards xylose was also explained on the basis of a 3D structural model, which was compared to the 3D structures of A. flavus derived FADGDH and of two glucose oxidases. Copyright © 2016 Elsevier B.V. All rights reserved.

Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture

DEFF Research Database (Denmark)

Benrick, Anna; Kokosar, Milana; Hu, Min

2017-01-01

was higher after EA in controls and women with PCOS. Plasma serotonin levels and homovanillic acid, markers of vagal activity, decreased in both controls and patients with PCOS. Adipose tissue expression of pro-nerve growth factor (proNGF) decreased, and the mature NGF/proNGF ratio increased after EA in PCOS...... of EA increases whole-body glucose uptake by activation of the sympathetic and partly the parasympathetic nervous systems, which could have important clinical implications for the treatment of insulin resistance.-Benrick, A., Kokosar, M., Hu, M., Larsson, M., Maliqueo, M., Marcondes, R. R., Soligo, M......., Protto, V., Jerlhag, E., Sazonova, A., Behre, C. J., Højlund, K., Thorén, P., Stener-Victorin, E. Autonomic nervous system activation mediates the increase in whole-body glucose uptake in response to electroacupuncture....

Colorimetric detection of glucose based on ficin with peroxidase-like activity

Science.gov (United States)

Pang, Yanjiao; Huang, Zili; Yang, Yufang; Long, Yijuan; Zheng, Huzhi

2018-01-01

In this work, we developed a colorimetric biosensing system for glucose detection by coupling the peroxidase-like of ficin and the glucose oxidase (GOx). GOx can catalyze the oxidation of glucose to produce H2O2, then, ficin catalyzes the oxidation of peroxidase substrate 3,3‧,5,5‧-tetramethylbenzidine (TMB) by H2O2 to produce a blue color reaction. The present sensing system showed a linear response toward glucose detection over range of 2.0-100 μM with a detection limit of 0.5 μM. This system is simple, low cost, highly sensitive and selective for glucose detection, and was also applied to measuring glucose in human serum. Furthermore, in order to expand the application of ficin in biological sensing, we immobilized ficin onto the SiO2@Fe3O4 NPs, which exhibited the merits of recycling as well as allowing the repeated detection of glucose. Thus it may provide great potential applications in biomedicine, biotechnology and environmental chemistry.

Dysregulated hepatic expression of glucose transporters in chronic disease: contribution of semicarbazide-sensitive amine oxidase to hepatic glucose uptake.

Science.gov (United States)

Karim, Sumera; Liaskou, Evaggelia; Fear, Janine; Garg, Abhilok; Reynolds, Gary; Claridge, Lee; Adams, David H; Newsome, Philip N; Lalor, Patricia F

2014-12-15

Insulin resistance is common in patients with chronic liver disease (CLD). Serum levels of soluble vascular adhesion protein-1 (VAP-1) are also increased in these patients. The amine oxidase activity of VAP-1 stimulates glucose uptake via translocation of transporters to the cell membrane in adipocytes and smooth muscle cells. We aimed to document human hepatocellular expression of glucose transporters (GLUTs) and to determine if VAP-1 activity influences receptor expression and hepatic glucose uptake. Quantitative PCR and immunocytochemistry were used to study human liver tissue and cultured cells. We also used tissue slices from humans and VAP-1-deficient mice to assay glucose uptake and measure hepatocellular responses to stimulation. We report upregulation of GLUT1, -3, -5, -6, -7, -8, -9, -10, -11, -12, and -13 in CLD. VAP-1 expression and enzyme activity increased in disease, and provision of substrate to hepatic VAP-1 drives hepatic glucose uptake. This effect was sensitive to inhibition of VAP-1 and could be recapitulated by H2O2. VAP-1 activity also altered expression and subcellular localization of GLUT2, -4, -9, -10, and -13. Therefore, we show, for the first time, alterations in hepatocellular expression of glucose and fructose transporters in CLD and provide evidence that the semicarbazide-sensitive amine oxidase activity of VAP-1 modifies hepatic glucose homeostasis and may contribute to patterns of GLUT expression in chronic disease. Copyright © 2014 the American Physiological Society.

Calcineurin Aβ regulates NADPH oxidase (Nox) expression and activity via nuclear factor of activated T cells (NFAT) in response to high glucose.

Science.gov (United States)

Williams, Clintoria R; Gooch, Jennifer L

2014-02-21

Hypertrophy is an adaptive response that enables organs to appropriately meet increased functional demands. Previously, we reported that calcineurin (Cn) is required for glomerular and whole kidney hypertrophy in diabetic rodents (Gooch, J. L., Barnes, J. L., Garcia, S., and Abboud, H. E. (2003). Calcineurin is activated in diabetes and is required for glomerular hypertrophy and ECM accumulation. Am. J. Physiol. Renal Physiol. 284, F144-F154; Reddy, R. N., Knotts, T. L., Roberts, B. R., Molkentin, J. D., Price, S. R., and Gooch, J. L. (2011). Calcineurin Aβ is required for hypertrophy but not matrix expansion in the diabetic kidney. J. Cell Mol. Med. 15, 414-422). Because studies have also implicated the reactive oxygen species-generating enzymes NADPH oxidases (Nox) in diabetic kidney responses, we tested the hypothesis that Nox and Cn cooperate in a common signaling pathway. First, we examined the role of the two main isoforms of Cn in hypertrophic signaling. Using primary kidney cells lacking a catalytic subunit of Cn (CnAα(-/-) or CnAβ(-/-)), we found that high glucose selectively activates CnAβ, whereas CnAα is constitutively active. Furthermore, CnAβ but not CnAα mediates hypertrophy. Next, we found that chronic reactive oxygen species generation in response to high glucose is attenuated in CnAβ(-/-) cells, suggesting that Cn is upstream of Nox. Consistent with this, loss of CnAβ reduces basal expression and blocks high glucose induction of Nox2 and Nox4. Inhibition of nuclear factor of activated T cells (NFAT), a CnAβ-regulated transcription factor, decreases Nox2 and Nox4 expression, whereas NFAT overexpression increases Nox2 and Nox4, indicating that the CnAβ/NFAT pathway modulates Nox. These data reveal that the CnAβ/NFAT pathway regulates Nox and plays an important role in high glucose-mediated hypertrophic responses in the kidney.

Novel Glucose-1-Phosphatase with High Phytase Activity and Unusual Metal Ion Activation from Soil Bacterium Pantoea sp. Strain 3.5.1.

Science.gov (United States)

Suleimanova, Aliya D; Beinhauer, Astrid; Valeeva, Liia R; Chastukhina, Inna B; Balaban, Nelly P; Shakirov, Eugene V; Greiner, Ralf; Sharipova, Margarita R

2015-10-01

Phosphorus is an important macronutrient, but its availability in soil is limited. Many soil microorganisms improve the bioavailability of phosphate by releasing it from various organic compounds, including phytate. To investigate the diversity of phytate-hydrolyzing bacteria in soil, we sampled soils of various ecological habitats, including forest, private homesteads, large agricultural complexes, and urban landscapes. Bacterial isolate Pantoea sp. strain 3.5.1 with the highest level of phytase activity was isolated from forest soil and investigated further. The Pantoea sp. 3.5.1 agpP gene encoding a novel glucose-1-phosphatase with high phytase activity was identified, and the corresponding protein was purified to apparent homogeneity, sequenced by mass spectroscopy, and biochemically characterized. The AgpP enzyme exhibits maximum activity and stability at pH 4.5 and at 37°C. The enzyme belongs to a group of histidine acid phosphatases and has the lowest Km values toward phytate, glucose-6-phosphate, and glucose-1-phosphate. Unexpectedly, stimulation of enzymatic activity by several divalent metal ions was observed for the AgpP enzyme. High-performance liquid chromatography (HPLC) and high-performance ion chromatography (HPIC) analyses of phytate hydrolysis products identify dl-myo-inositol 1,2,4,5,6-pentakisphosphate as the final product of the reaction, indicating that the Pantoea sp. AgpP glucose-1-phosphatase can be classified as a 3-phytase. The identification of the Pantoea sp. AgpP phytase and its unusual regulation by metal ions highlight the remarkable diversity of phosphorus metabolism regulation in soil bacteria. Furthermore, our data indicate that natural forest soils harbor rich reservoirs of novel phytate-hydrolyzing enzymes with unique biochemical features. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

Effects of MDMA on blood glucose levels and brain glucose metabolism

Energy Technology Data Exchange (ETDEWEB)

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

2007-06-15

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

Effects of MDMA on blood glucose levels and brain glucose metabolism

International Nuclear Information System (INIS)

Soto-Montenegro, M.L.; Vaquero, J.J.; Garcia-Barreno, P.; Desco, M.; Arango, C.; Ricaurte, G.

2007-01-01

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

Exercising Tactically for Taming Postmeal Glucose Surges

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Elsamma Chacko

2016-01-01

Full Text Available This review seeks to synthesize data on the timing, intensity, and duration of exercise found scattered over some 39 studies spanning 3+ decades into optimal exercise conditions for controlling postmeal glucose surges. The results show that a light aerobic exercise for 60 min or moderate activity for 20–30 min starting 30 min after meal can efficiently blunt the glucose surge, with minimal risk of hypoglycemia. Exercising at other times could lead to glucose elevation caused by counterregulation. Adding a short bout of resistance exercise of moderate intensity (60%–80%  VO2max to the aerobic activity, 2 or 3 times a week as recommended by the current guidelines, may also help with the lowering of glucose surges. On the other hand, high-intensity exercise (>80%  VO2max causes wide glucose fluctuations and its feasibility and efficacy for glucose regulation remain to be ascertained. Promoting the kind of physical activity that best counters postmeal hyperglycemia is crucial because hundreds of millions of diabetes patients living in developing countries and in the pockets of poverty in the West must do without medicines, supplies, and special diets. Physical activity is the one tool they may readily utilize to tame postmeal glucose surges. Exercising in this manner does not violate any of the current guidelines, which encourage exercise any time.

Exercising Tactically for Taming Postmeal Glucose Surges.

Science.gov (United States)

Chacko, Elsamma

2016-01-01

This review seeks to synthesize data on the timing, intensity, and duration of exercise found scattered over some 39 studies spanning 3+ decades into optimal exercise conditions for controlling postmeal glucose surges. The results show that a light aerobic exercise for 60 min or moderate activity for 20-30 min starting 30 min after meal can efficiently blunt the glucose surge, with minimal risk of hypoglycemia. Exercising at other times could lead to glucose elevation caused by counterregulation. Adding a short bout of resistance exercise of moderate intensity (60%-80%  VO2max) to the aerobic activity, 2 or 3 times a week as recommended by the current guidelines, may also help with the lowering of glucose surges. On the other hand, high-intensity exercise (>80%  VO2max) causes wide glucose fluctuations and its feasibility and efficacy for glucose regulation remain to be ascertained. Promoting the kind of physical activity that best counters postmeal hyperglycemia is crucial because hundreds of millions of diabetes patients living in developing countries and in the pockets of poverty in the West must do without medicines, supplies, and special diets. Physical activity is the one tool they may readily utilize to tame postmeal glucose surges. Exercising in this manner does not violate any of the current guidelines, which encourage exercise any time.

Glucose oxidase probe as a surface-enhanced Raman scattering sensor for glucose.

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Qi, Guohua; Wang, Yi; Zhang, Biying; Sun, Dan; Fu, Cuicui; Xu, Weiqing; Xu, Shuping

2016-10-01

Glucose oxidase (GOx) possessing a Raman-active chromophore (flavin adenine dinucleotide) is used as a signal reporter for constructing a highly specific "turn off" surface-enhanced Raman scattering (SERS) sensor for glucose. This sensing chip is made by the electrostatic assembly of GOx over silver nanoparticle (Ag NP)-functionalized SERS substrate through a positively charged polyelectrolyte linker under the pH of 6.86. To trace glucose in blood serum, owing to the reduced pH value caused by the production of gluconic acid in the GOx-catalyzed oxidation reaction, the bonding force between GOx and polyelectrolyte weakens, making GOx drop off from the sensing chip. As a result, the SERS intensity of GOx on the chip decreases along with the concentration of glucose. This glucose SERS sensor exhibits excellent selectivity based on the specific GOx/glucose catalysis reaction and high sensitivity to 1.0 μM. The linear sensing range is 2.0-14.0 mM, which also meets the requirement on the working range of the human blood glucose detection. Using GOx as a probe shows superiority over other organic probes because GOx almost has no toxicity to the biological system. This sensing mechanism can be applied for intracellular in vivo SERS monitoring of glucose in the future. Graphical abstract Glucose oxidase is used as a Raman signal reporter for constructing a highly specific glucose surface-enhanced Raman scattering (SERS) sensor.

Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.

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McDougal, David H; Hermann, Gerlinda E; Rogers, Richard C

2013-01-01

Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST) in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.

Astrocytes in the nucleus of the solitary tract are activated by low glucose or glucoprivation: evidence for glial involvement in glucose homeostasis.

Directory of Open Access Journals (Sweden)

David Harry McDougal

2013-12-01

Full Text Available Glucose homeostasis is maintained through interplay between central and peripheral control mechanisms which are aimed at storing excess glucose following meals and mobilizing these same stores during periods of fasting. The nucleus of the solitary tract (NST in the dorsal medulla has long been associated with the central detection of glucose availability and the control of glucose homeostasis. Recent evidence has emerged which supports the involvement of astrocytes in glucose homeostasis. The aim of the present study was to investigate whether NST-astrocytes respond to physiologically relevant decreases in glucose availability, in vitro, as well as to the presence of the glucoprivic compound 2-deoxy-D-Glucose. This report demonstrates that some NST-astrocytes are capable of responding to low glucose or glucoprivation by increasing cytoplasmic calcium; a change that reverses with restoration of normal glucose availability. While some NST-neurons also demonstrate an increase in calcium signaling during low glucose availability, this effect is smaller and somewhat delayed compared to those observed in adjacent astrocytes. TTX did not abolish these hypoglycemia mediated responses of astrocytes, suggesting that NST-astrocytes may be directly sensing low glucose levels as opposed to responding to neuronal detection of hypoglycemia. Thus, chemodetection of low glucose by NST-astrocytes may play an important role in the autonomic regulation of glucose homeostasis.

Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle.

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Santiago, Ammy M; Clegg, Deborah J; Routh, Vanessa H

2016-12-01

17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. These data suggest that physiological

Ventromedial hypothalamic glucose sensing and glucose homeostasis vary throughout the estrous cycle

Science.gov (United States)

Santiago, Ammy M.; Clegg, Deborah J.; Routh, Vanessa H.

2016-01-01

Objective 17β-Estradiol (17βE) regulates glucose homeostasis in part by centrally mediated mechanisms. In female rodents, the influence of the ovarian cycle on hypoglycemia counterregulation and glucose tolerance is unclear. We found previously that in prepubertal females, 17βE modulates glucose sensing in nonadapting glucose-inhibited (GI) and adapting GI (AdGI) neurons within the ventrolateral portion of the ventromedial nucleus (VL-VMN). Nonadapting GI neurons persistently decrease their activity as glucose increases while AdGI neurons transiently respond to a glucose increase. To begin to understand if endogenous fluctuations in estrogen levels across the estrous cycle impact hypothalamic glucose sensing and glucose homeostasis, we assessed whether hypoglycemia counterregulation and glucose tolerance differed across the phases of the estrous cycle. We hypothesized that the response to insulin-induced hypoglycemia (IIH) and/or glucose tolerance would vary throughout the estrous cycle according to changes in 17βE availability. Moreover, that these changes would correlate with estrous-dependent changes in the glucose sensitivity of VL-VMN glucose-sensing neurons (GSNs). Methods These hypotheses were tested in female mice by measuring the response to IIH, glucose tolerance and the glucose sensitivity of VL-VMN GSNs during each phase of the estrous cycle. Furthermore, a physiological brain concentration of 17βE seen during proestrus was acutely applied to brain slices isolated on the day of diestrous and the response to low glucose in VL-VMN GSNs was assayed. Results The response to IIH was strongest during diestrous. The response of nonadapting GI and AdGI neurons to a glucose decrease from 2.5 to 0.5mM also peaked during diestrous; an effect which was blunted by the addition of 17βE. In contrast, the glucose sensitivity of the subpopulation of GSNs which are excited by glucose (GE) was not affected by estrous phase or exogenous 17βE application. Conclusion

The inability of phosphatidylinositol 3-kinase activation to stimulate GLUT4 translocation indicates additional signaling pathways are required for insulin-stimulated glucose uptake.

Science.gov (United States)

Isakoff, S J; Taha, C; Rose, E; Marcusohn, J; Klip, A; Skolnik, E Y

1995-10-24

Recent experimental evidence has focused attention to the role of two molecules, insulin receptor substrate 1 (IRS-1) and phosphatidylinositol 3-kinase (PI3-kinase), in linking the insulin receptor to glucose uptake; IRS-1 knockout mice are insulin resistant, and pharmacological inhibitors of PI3-kinase block insulin-stimulated glucose uptake. To investigate the role of PI3-kinase and IRS-1 in insulin-stimulated glucose uptake we examined whether stimulation of insulin-sensitive cells with platelet-derived growth factor (PDGF) or with interleukin 4 (IL-4) stimulates glucose uptake; the activated PDGF receptor (PDGFR) directly binds and activates PI3-kinase, whereas the IL-4 receptor (IL-4R) activates PI3-kinase via IRS-1 or the IRS-1-related molecule 4PS. We found that stimulation of 3T3-L1 adipocytes with PDGF resulted in tyrosine phosphorylation of the PDGFR and activation of PI3-kinase in these cells. To examine whether IL-4 stimulates glucose uptake, L6 myoblasts were engineered to overexpress GLUT4 as well as both chains of the IL-4R (L6/IL-4R/GLUT4); when these L6/IL-4R/GLUT4 myoblasts were stimulated with IL-4, IRS-1 became tyrosine phosphorylated and associated with PI3-kinase. Although PDGF and IL-4 can activate PI3-kinase in the respective cell lines, they do not possess insulin's ability to stimulate glucose uptake and GLUT4 translocation to the plasma membrane. These findings indicate that activation of PI3-kinase is not sufficient to stimulate GLUT4 translocation to the plasma membrane. We postulate that activation of a second signaling pathway by insulin, distinct from PI3-kinase, is necessary for the stimulation of glucose uptake in insulin-sensitive cells.

MAP17 Is a Necessary Activator of Renal Na+/Glucose Cotransporter SGLT2

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Coady, Michael J.; El Tarazi, Abdulah; Santer, René; Bissonnette, Pierre; Sasseville, Louis J.; Calado, Joaquim; Lussier, Yoann; Dumayne, Christopher; Bichet, Daniel G.

2017-01-01

The renal proximal tubule reabsorbs 90% of the filtered glucose load through the Na+-coupled glucose transporter SGLT2, and specific inhibitors of SGLT2 are now available to patients with diabetes to increase urinary glucose excretion. Using expression cloning, we identified an accessory protein, 17 kDa membrane-associated protein (MAP17), that increased SGLT2 activity in RNA-injected Xenopus oocytes by two orders of magnitude. Significant stimulation of SGLT2 activity also occurred in opossum kidney cells cotransfected with SGLT2 and MAP17. Notably, transfection with MAP17 did not change the quantity of SGLT2 protein at the cell surface in either cell type. To confirm the physiologic relevance of the MAP17–SGLT2 interaction, we studied a cohort of 60 individuals with familial renal glucosuria. One patient without any identifiable mutation in the SGLT2 coding gene (SLC5A2) displayed homozygosity for a splicing mutation (c.176+1G>A) in the MAP17 coding gene (PDZK1IP1). In the proximal tubule and in other tissues, MAP17 is known to interact with PDZK1, a scaffolding protein linked to other transporters, including Na+/H+ exchanger 3, and to signaling pathways, such as the A-kinase anchor protein 2/protein kinase A pathway. Thus, these results provide the basis for a more thorough characterization of SGLT2 which would include the possible effects of its inhibition on colocalized renal transporters. PMID:27288013

Method of preparing uridine-diphospho-/sup 14/C-D-glucose of high molar activity and radiochemical purity by enzyme synthesis

Energy Technology Data Exchange (ETDEWEB)

Farkas, V; Biely, P; Koelbl, J

1980-06-15

A new method is described of enzyme synthesis of uridine-diphospho-/sup 14/C-D-glucose of high molar activity. After conversion of the initial /sup 14/C-D-glucose, the accompanying sugar phosphates and nucleoside-5'-phosphates are selectively hydrolyzed by the action of alkaline phosphatase in the presence of phenolphthalein as an indicator. Uridine-diphospho-/sup 14/C-D-glucose is separated by paper chromatography from the reaction mixture thus modified. Synthesis yields range within 75% and 85% relative to the starting /sup 14/C-D-glucose.

Experience-dependent escalation of glucose drinking and the development of glucose preference over fructose - association with glucose entry into the brain.

Science.gov (United States)

Wakabayashi, Ken T; Spekterman, Laurence; Kiyatkin, Eugene A

2016-06-01

Glucose, a primary metabolic substrate for cellular activity, must be delivered to the brain for normal neural functions. Glucose is also a unique reinforcer; in addition to its rewarding sensory properties and metabolic effects, which all natural sugars have, glucose crosses the blood-brain barrier and acts on glucoreceptors expressed on multiple brain cells. To clarify the role of this direct glucose action in the brain, we compared the neural and behavioural effects of glucose with those induced by fructose, a sweeter yet metabolically equivalent sugar. First, by using enzyme-based biosensors in freely moving rats, we confirmed that glucose rapidly increased in the nucleus accumbens in a dose-dependent manner after its intravenous delivery. In contrast, fructose induced a minimal response only after a large-dose injection. Second, we showed that naive rats during unrestricted access consumed larger volumes of glucose than fructose solution; the difference appeared with a definite latency during the initial exposure and strongly increased during subsequent tests. When rats with equal sugar experience were presented with either glucose or fructose in alternating order, the consumption of both substances was initially equal, but only the consumption of glucose increased during subsequent sessions. Finally, rats with equal glucose-fructose experience developed a strong preference for glucose over fructose during a two-bottle choice procedure; the effect appeared with a definite latency during the initial test and greatly amplified during subsequent tests. Our results suggest that direct entry of glucose in the brain and its subsequent effects on brain cells could be critical for the experience-dependent escalation of glucose consumption and the development of glucose preference over fructose. Published 2015. This article is a U.S. Government work and is in the public domain in the USA.

Fluctuations in nucleus accumbens extracellular glutamate and glucose during motivated glucose-drinking behavior: dissecting the neurochemistry of reward.

Science.gov (United States)

Wakabayashi, Ken T; Myal, Stephanie E; Kiyatkin, Eugene A

2015-02-01

While motivated behavior involves multiple neurochemical systems, few studies have focused on the role of glutamate, the brain's excitatory neurotransmitter, and glucose, the energetic substrate of neural activity in reward-related neural processes. Here, we used high-speed amperometry with enzyme-based substrate-sensitive and control, enzyme-free biosensors to examine second-scale fluctuations in the extracellular levels of these substances in the nucleus accumbens shell during glucose-drinking behavior in trained rats. Glutamate rose rapidly after the presentation of a glucose-containing cup and before the initiation of drinking (reward seeking), decreased more slowly to levels below baseline during consumption (sensory reward), and returned to baseline when the ingested glucose reached the brain (metabolic reward). When water was substituted for glucose, glutamate rapidly increased with cup presentation and in contrast to glucose drinking, increased above baseline after rats tasted the water and refused to drink further. Therefore, extracellular glutamate show distinct changes associated with key events of motivated drinking behavior and opposite dynamics during sensory and metabolic components of reward. In contrast to glutamate, glucose increased at each stimulus and behavioral event, showing a sustained elevation during the entire behavior and a robust post-ingestion rise that correlated with the gradual return of glutamate levels to their baseline. By comparing active drinking with passive intra-gastric glucose delivery, we revealed that fluctuations in extracellular glucose are highly dynamic, reflecting a balance between rapid delivery because of neural activity, intense metabolism, and the influence of ingested glucose reaching the brain. Published 2014. This article is a U.S. Government work and is in the public domain in the USA.

Selective conversion of plasma glucose into CO2 by Saccharomyces cerevisiae for the measurement of C-13 abundance by isotope ratio mass spectrometry : proof of principle

NARCIS (Netherlands)

Rembacz, Krzysztof P.; Faber, Klaas Nico; Stellaard, Frans

2007-01-01

To study carbohydrate digestion and glucose absorption, time-dependent C-13 enrichment in plasma glucose is measured after oral administration of naturally occurring C-13-enriched carbohydrates. The isotope enrichment of the administered carbohydrate is low (APE <0.1%) and plasma C-13 glucose

Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

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de Mello Maria

2002-04-01

Full Text Available Abstract Background It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. Methods To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein: pregnant (N, tumor-bearing (WN, pair-fed rats (Np. Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine: leucine (L, tumor-bearing (WL and pair-fed with leucine (Lp. Non pregnant rats (C, which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Results Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Conclusions Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones.

Effects of leucine supplemented diet on intestinal absorption in tumor bearing pregnant rats

International Nuclear Information System (INIS)

Ventrucci, Gislaine; Mello, Maria Alice Roston de; Gomes-Marcondes, Maria Cristina Cintra

2002-01-01

It is known that amino acid oxidation is increased in tumor-bearing rat muscles and that leucine is an important ketogenic amino acid that provides energy to the skeletal muscle. To evaluate the effects of a leucine supplemented diet on the intestinal absorption alterations produced by Walker 256, growing pregnant rats were distributed into six groups. Three pregnant groups received a normal protein diet (18% protein): pregnant (N), tumor-bearing (WN), pair-fed rats (Np). Three other pregnant groups were fed a diet supplemented with 3% leucine (15% protein plus 3% leucine): leucine (L), tumor-bearing (WL) and pair-fed with leucine (Lp). Non pregnant rats (C), which received a normal protein diet, were used as a control group. After 20 days, the animals were submitted to intestinal perfusion to measure leucine, methionine and glucose absorption. Tumor-bearing pregnant rats showed impairment in food intake, body weight gain and muscle protein content, which were less accentuated in WL than in WN rats. These metabolic changes led to reduction in both fetal and tumor development. Leucine absorption slightly increased in WN group. In spite of having a significant decrease in leucine and methionine absorption compared to L, the WL group has shown a higher absorption rate of methionine than WN group, probably due to the ingestion of the leucine supplemented diet inducing this amino acid uptake. Glucose absorption was reduced in both tumor-bearing groups. Leucine supplementation during pregnancy in tumor-bearing rats promoted high leucine absorption, increasing the availability of the amino acid for neoplasic cells and, mainly, for fetus and host utilization. This may have contributed to the better preservation of body weight gain, food intake and muscle protein observed in the supplemented rats in relation to the non-supplemented ones

Estimation of endogenous glucose production during hyperinsulinemic-euglycemic glucose clamps. Comparison of unlabeled and labeled exogenous glucose infusates

International Nuclear Information System (INIS)

Finegood, D.T.; Bergman, R.N.; Vranic, M.

1987-01-01

Tracer methodology has been applied extensively to the estimation of endogenous glucose production (Ra) during euglycemic glucose clamps. The accuracy of this approach has been questioned due to the observation of significantly negative estimates for Ra when insulin levels are high. We performed hyperinsulinemic (300 microU/ml)-euglycemic glucose clamps for 180 min in normal dogs and compared the standard approach, an unlabeled exogenous glucose infusate (cold GINF protocol, n = 12), to a new approach in which a tracer (D-[3- 3 H]glucose) was added to the exogenous glucose used for clamping (hot GINF protocol, n = 10). Plasma glucose, insulin and glucagon concentrations, and glucose infusion rates were similar for the two protocols. Plasma glucose specific activity was 20 +/- 1% of basal (at 120-180 min) in the cold GINF studies, and 44 +/- 3 to 187 +/- 5% of basal in the hot GINF studies. With the one-compartment, fixed pool volume model of Steele, Ra for the cold GINF studies was -2.4 +/- 0.7 mg X min-1 X kg-1 at 25 min and remained significantly negative until 110 min (P less than .05). For the hot GINF studies, Ra was never significantly less than zero (P greater than .05) and was greater than in the cold GINF studies at 20-90 min (P less than .05). There was substantially less between-(78%) and within- (40%) experiment variation for the hot GINF studies compared with the cold GINF studies. An alternate approach (regression method) to the application of the one-compartment model, which allows for a variable and estimable effective distribution volume, yielded Ra estimates that were suppressed 60-100% from basal

A study of the tyramine/glucose Maillard reaction: Variables, characterization, cytotoxicity and preliminary application.

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Jiang, Wei; Chen, Yaxin; He, Xiaoxia; Hu, Shiwei; Li, Shijie; Liu, Yu

2018-01-15

The tyramine/glucose Maillard reaction was proposed as an emerging tool for tyramine reduction in a model system and two commercial soy sauce samples. The model system was composed of tyramine and glucose in buffer solutions with or without NaCl. The results showed that tyramine was reduced in the model system, and the reduction rate was affected by temperature, heating time, initial pH value, NaCl concentration, initial glucose concentration and initial tyramine concentration. Changes in fluorescence intensity and ultraviolet-visible (UV-vis) absorption spectra showed three stages of the Maillard reaction between tyramine and glucose. Cytotoxicity assay demonstrated that tyramine/glucose Maillard reaction products (MRPs) were significantly less toxic than that of tyramine (pMaillard reaction is a promising method for tyramine reduction in foods. Copyright © 2017 Elsevier Ltd. All rights reserved.

Zero net flux estimates of septal extracellular glucose levels and the effects of glucose on septal extracellular GABA levels

OpenAIRE

Krebs-Kraft, Desiree L.; Rauw, Gail; Baker, Glen B.; Parent, Marise B.

2009-01-01

Although hippocampal infusions of glucose enhance memory, we have found repeatedly that septal glucose infusions impair memory when γ-aminobutyric acid (GABA) receptors are activated. For instance, hippocampal glucose infusions reverse the memory-impairing effects of co-infusions of the GABA agonist muscimol, whereas septal glucose infusions exacerbate memory deficits produced by muscimol. One potential explanation for these deleterious effects of glucose in the septum is that there are highe...

Effects of temperature on the near-infrared spectroscopic measurement of glucose

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Jung, Byungjo; McShane, Michael J.; Rastegar, Sohi; Cote, Gerard L.

1998-05-01

The noninvasive monitoring of sugars, and in particular, glucose using near-IR (NIR) spectroscopy would be useful for a number of applications including regulating the nutrients in cell culture medium, monitoring on-line processes in the food industry, and in vivo monitoring for control of glucose in DIabetic patients. The focus of this research was the investigation of the temperature effects across a 10.6 to 40.4 degrees C range on Fourier filtered and unfiltered single-beam as well as absorbance glucose and water NIR spectra. It is known that the positions of water absorption bands centered at 1.923 and 2.623 micrometers depend heavily on temperature effects while the glucose bands are temperature insensitive across this range. The water absorption bands were shown to shift to lower wavelengths while the distance between these bands increased with increasing temperatures. Partial least squares (PLS) calibration models were constructed at five separate temperatures, 15.7, 20.5, 25.5, 35.6, and 40.4 degrees C. When absorbance spectra were used with reference scans taken at the same temperature and PLS models were used, no significant difference in the standard error of prediction (SEP) was noted with temperature. Using PLS calibration with single-beam spectra at one temperature showed large SEPs at the other temperatures. The use of Fourier filtered single-beam spectra reduced the SEP but still showed an increase as large temperature differences were produced and the filtered single beam approach did not reduce the SEP to the level achieved with the absorbance spectra.

A novel Alaska pollack-derived peptide, which increases glucose uptake in skeletal muscle cells, lowers the blood glucose level in diabetic mice.

Science.gov (United States)

Ayabe, Tatsuhiro; Mizushige, Takafumi; Ota, Wakana; Kawabata, Fuminori; Hayamizu, Kohsuke; Han, Li; Tsuji, Tomoko; Kanamoto, Ryuhei; Ohinata, Kousaku

2015-08-01

We found that the tryptic digest of Alaska pollack protein exhibits a glucose-lowering effect in KK-Ay mice, a type II diabetic model. We then searched for glucose-lowering peptides in the digest. Ala-Asn-Gly-Glu-Val-Ala-Gln-Trp-Arg (ANGEVAQWR) was identified from a peak of the HPLC fraction selected based on the glucose-lowering activity in an insulin resistance test using ddY mice. ANGEVAQWR (3 mg kg(-1)) decreased the blood glucose level after intraperitoneal administration. Among its fragment peptides, the C-terminal tripeptide, Gln-Trp-Arg (QWR, 1 mg kg(-1)), lowered the blood glucose level, suggesting that the C-terminal is critical for glucose-lowering activity. QWR also enhanced glucose uptake into C2C12, a mouse skeletal muscle cell line. QWR did not induce the phosphorylation of serine/threonine protein kinase B (Akt) and adenosine monophosphate-activated protein kinase (AMPK). We also demonstrated that QWR lowered the blood glucose level in NSY and KK-Ay, type II diabetic models.

Glucose metabolism regulates T cell activation, differentiation and functions

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Clovis Steve Palmer

2015-01-01

Full Text Available The adaptive immune system is equipped to eliminate both tumors and pathogenic microorganisms. It requires a series of complex and coordinated signals to drive the activation, proliferation and differentiation of appropriate T cell subsets. It is now established that changes in cellular activation are coupled to profound changes in cellular metabolism. In addition, emerging evidence now suggest that specific metabolic alterations associated with distinct T cell subsets may be ancillary to their differentiation and influential in their immune functions. The Warburg effect originally used to describe a phenomenon in which most cancer cells relied on aerobic glycolysis for their growth is a key process that sustain T cell activation and differentiation. Here we review how different aspects of metabolism in T cells influence their functions, focusing on the emerging role of key regulators of glucose metabolism such as HIF-1α. A thorough understanding of the role of metabolism in T cell function could provide insights into mechanisms involved in inflammatory-mediated conditions, with the potential for developing novel therapeutic approaches to treat these diseases.

Estimation of gluconeogenesis and glucose utilization in carbohydate deficient growing rats

International Nuclear Information System (INIS)

Hill, F.W.; Egtesadi, S.; Rucker, R.B.

1986-01-01

A carbohydrate deficient diet based on food grade oleic acid and soybean oil and a minimally adequate level of casein protein was supplemented with graded levels of glucose (0, 4, 10, 65%), and casein protein (12% basal level plus 4, 6, 20%). Weanling rats were fed the respective diets for 28 days. Under anesthesia in fed state, the right jugular vein and left carotid artery were cannulated. NaH 14 CO 3 and 3 H-glucose labelled on C 6 were injected into aorta via carotid and blood samples taken from vena cava via jugular over a period of 30 minutes. Rate of increase of blood 14 C-glucose was the indicator of gluconeogenesis (GLNG). Disappearance of blood 3 H-glucose was the measure of glucose flux. Relative rate of GLNG was very high in basal unsupplemented rats, and glucose flux was very low. Rats growing rapidly with minimum supplementation (4% glucose or 6% casein) showed the lowest relative rate of GLNG and maximum glucose flux, of the order of 10 mg min -1 kg -1 . GLNG increased with higher levels of glucose and casein, but flux did not increase. The fed state glucose flux extrapolated to 24 hour basis was approximately 2X greater than the dietary intake of glucose and its equivalent of glucogenic precursors in rats fed the basal diet and low levels of supplements. Adjustment for lower flux in post absorptive state, based on flux in fasted rats, reduced the differences between observed flux and intake

Glucose homeostasis in mice is transglutaminase 2 independent.

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Siiri E Iismaa

Full Text Available Transglutaminase type 2 (TG2 has been reported to be a candidate gene for maturity onset diabetes of the young (MODY because three different mutations that impair TG2 transamidase activity have been found in 3 families with MODY. TG2 null (TG2(-/- mice have been reported to be glucose intolerant and have impaired glucose-stimulated insulin secretion (GSIS. Here we rigorously evaluated the role of TG2 in glucose metabolism using independently generated murine models of genetic TG2 disruption, which show no compensatory enhanced expression of other TGs in pancreatic islets or other tissues. First, we subjected chow- or fat-fed congenic SV129 or C57BL/6 wild type (WT and TG2(-/- littermates, to oral glucose gavage. Blood glucose and serum insulin levels were similar for both genotypes. Pancreatic islets isolated from these animals and analysed in vitro for GSIS and cholinergic potentiation of GSIS, showed no significant difference between genotypes. Results from intraperitoneal glucose tolerance tests (GTTs and insulin tolerance tests (ITTs were similar for both genotypes. Second, we directly investigated the role of TG2 transamidase activity in insulin secretion using a coisogenic model that expresses a mutant form of TG2 (TG2(R579A, which is constitutively active for transamidase activity. Intraperitoneal GTTs and ITTs revealed no significant differences between WT and TG2(R579A/R579A mice. Given that neither deletion nor constitutive activation of TG2 transamidase activity altered basal responses, or responses to a glucose or insulin challenge, our data indicate that glucose homeostasis in mice is TG2 independent, and question a link between TG2 and diabetes.

Buddleja officinalis suppresses high glucose-induced vascular smooth muscle cell proliferation: role of mitogen-activated protein kinases, nuclear factor-kappaB and matrix metalloproteinases.

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Lee, Yun Jung; Kim, Jin Sook; Kang, Dae Gill; Lee, Ho Sub

2010-02-01

Diabetes mellitus is a well-established risk factor for vascular diseases caused by atherosclerosis. In the development of diabetic atherogenesis, vascular smooth muscle cell proliferation is recognized as a key event. Thus, we aimed to investigate whether an ethanol extract of Buddleja officinalis (EBO) suppresses high glucose-induced proliferation in primary cultured human aortic smooth muscle cells (HASMC). [(3)H]-thymidine incorporation revealed that incubation of HASMC with a high concentration of glucose (25 mmol/L) increased cell proliferation. The expression levels of cell cycle protein were also increased by treatment with high glucose concentration. Pretreatment of HASMC with EBO significantly attenuated the increase of high glucose-induced cell proliferation as well as p38 mitogen-activated protein kinases (MAPK) and JNK phosphorylation. EBO suppressed high glucose-induced matrix metalloproteinase (MMP)-9 activity in a dose-dependent manner. In addition, EBO suppressed nuclear factor-kappaB (NF-kappaB) nuclear translocation and transcriptional activity in high glucose conditions. Taken together, the present data suggest that EBO could suppress high glucose-induced atherosclerotic processes through inhibition of p38, JNK, NF-kappaB and MMP signal pathways in HASMC.

Glucose 6P binds and activates HlyIIR to repress Bacillus cereus haemolysin hlyII gene expression.

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Elisabeth Guillemet

Full Text Available Bacillus cereus is a Gram-positive spore-forming bacterium causing food poisoning and serious opportunistic infections. These infections are characterized by bacterial accumulation despite the recruitment of phagocytic cells. We have previously shown that B. cereus Haemolysin II (HlyII induces macrophage cell death by apoptosis. In this work, we investigated the regulation of the hlyII gene. We show that HlyIIR, the negative regulator of hlyII expression in B. cereus, is especially active during the early bacterial growth phase. We demonstrate that glucose 6P directly binds to HlyIIR and enhances its activity at a post-transcriptional level. Glucose 6P activates HlyIIR, increasing its capacity to bind to its DNA-box located upstream of the hlyII gene, inhibiting its expression. Thus, hlyII expression is modulated by the availability of glucose. As HlyII induces haemocyte and macrophage death, two cell types that play a role in the sequestration of nutrients upon infection, HlyII may induce host cell death to allow the bacteria to gain access to carbon sources that are essential components for bacterial growth.

ABSORPTION OF GASES INTO ACTIVATED CARBON WATER SLURRIES IN A STIRRED CELL

NARCIS (Netherlands)

TINGE, JT; DRINKENBURG, AAH

A surface-aerated stirred cell with a flat liquid surface was used to investigate the absorption of propane and ethene gas into slurries of activated carbon and water. Slurries with a solids concentration up to 4% by weight and particle diameters up to 565-mu-m were used. The experimental mass

Dynamic Changes in Cytosolic ATP Levels in Cultured Glutamatergic Neurons During NMDA-Induced Synaptic Activity Supported by Glucose or Lactate.

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Lange, Sofie C; Winkler, Ulrike; Andresen, Lars; Byhrø, Mathilde; Waagepetersen, Helle S; Hirrlinger, Johannes; Bak, Lasse K

2015-12-01

We have previously shown that synaptic transmission fails in cultured neurons in the presence of lactate as the sole substrate. Thus, to test the hypothesis that the failure of synaptic transmission is a consequence of insufficient energy supply, ATP levels were monitored employing the ATP biosensor Ateam1.03YEMK. While inducing synaptic activity by subjecting cultured neurons to two 30 s pulses of NMDA (30 µM) with a 4 min interval, changes in relative ATP levels were measured in the presence of lactate (1 mM), glucose (2.5 mM) or the combination of the two. ATP levels reversibly declined following NMDA-induced neurotransmission activity, as indicated by a reversible 10-20 % decrease in the response of the biosensor. The responses were absent when the NMDA receptor antagonist memantine was present. In the presence of lactate alone, the ATP response dropped significantly more than in the presence of glucose following the 2nd pulse of NMDA (approx. 10 vs. 20 %). Further, cytosolic Ca(2+) homeostasis during NMDA-induced synaptic transmission is partially inhibited by verapamil indicating that voltage-gated Ca(2+) channels are activated. Lastly, we showed that cytosolic Ca(2+) homeostasis is supported equally well by both glucose and lactate, and that a pulse of NMDA causes accumulation of Ca(2+) in the mitochondrial matrix. In summary, we have shown that ATP homeostasis during neurotransmission activity in cultured neurons is supported by both glucose and lactate. However, ATP homeostasis seems to be negatively affected by the presence of lactate alone, suggesting that glucose is needed to support neuronal energy metabolism during activation.

Glucose, other secretagogues, and nerve growth factor stimulate mitogen-activated protein kinase in the insulin-secreting beta-cell line, INS-1

DEFF Research Database (Denmark)

Frödin, M; Sekine, N; Roche, E

1995-01-01

The signaling pathways whereby glucose and hormonal secretagogues regulate insulin-secretory function, gene transcription, and proliferation of pancreatic beta-cells are not well defined. We show that in the glucose-responsive beta-cell line INS-1, major secretagogue-stimulated signaling pathways...... converge to activate 44-kDa mitogen-activated protein (MAP) kinase. Thus, glucose-induced insulin secretion was found to be associated with a small stimulatory effect on 44-kDa MAP kinase, which was synergistically enhanced by increased levels of intracellular cAMP and by the hormonal secretagogues......-1. Phorbol ester, an activator of protein kinase C, stimulated 44-kDa MAP kinase by both Ca(2+)-dependent and -independent pathways. Nerve growth factor, independently of changes in cytosolic Ca2+, efficiently stimulated 44-kDa MAP kinase without causing insulin release, indicating that activation...

Direct electrochemistry of glucose oxidase and glucose biosensing on a hydroxyl fullerenes modified glassy carbon electrode.

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Gao, Yun-Fei; Yang, Tian; Yang, Xiao-Lu; Zhang, Yu-Shuai; Xiao, Bao-Lin; Hong, Jun; Sheibani, Nader; Ghourchian, Hedayatollah; Hong, Tao; Moosavi-Movahedi, Ali Akbar

2014-10-15

Direct electrochemistry of glucose oxidase (GOD) was achieved when GOD-hydroxyl fullerenes (HFs) nano-complex was immobilized on a glassy carbon (GC) electrode and protected with a chitosan (Chit) membrane. The ultraviolet-visible absorption spectrometry (UV-vis), transmission electron microscopy (TEM), and circular dichroism spectropolarimeter (CD) methods were utilized for additional characterization of the GOD, GOD-HFs and Chit/GOD-HFs. Chit/HFs may preserve the secondary structure and catalytic properties of GOD. The cyclic voltammograms (CVs) of the modified GC electrode showed a pair of well-defined quasi-reversible redox peaks with the formal potential (E°') of 353 ± 2 mV versus Ag/AgCl at a scan rate of 0.05 V/s. The heterogeneous electron transfer constant (ks) was calculated to be 2.7 ± 0.2s(-1). The modified electrode response to glucose was linear in the concentrations ranging from 0.05 to 1.0mM, with a detection limit of 5 ± 1 μM. The apparent Michaelis-Menten constant (Km(app)) was 694 ± 8 μM. Thus, the modified electrode could be applied as a third generation biosensor for glucose with high sensitivity, selectivity and low detection limit. Copyright © 2014 Elsevier B.V. All rights reserved.

Gastrointestinal Transit Time, Glucose Homeostasis and Metabolic Health: Modulation by Dietary Fibers.

Science.gov (United States)

Müller, Mattea; Canfora, Emanuel E; Blaak, Ellen E

2018-02-28

Gastrointestinal transit time may be an important determinant of glucose homeostasis and metabolic health through effects on nutrient absorption and microbial composition, among other mechanisms. Modulation of gastrointestinal transit may be one of the mechanisms underlying the beneficial health effects of dietary fibers. These effects include improved glucose homeostasis and a reduced risk of developing metabolic diseases such as obesity and type 2 diabetes mellitus. In this review, we first discuss the regulation of gastric emptying rate, small intestinal transit and colonic transit as well as their relation to glucose homeostasis and metabolic health. Subsequently, we briefly address the reported health effects of different dietary fibers and discuss to what extent the fiber-induced health benefits may be mediated through modulation of gastrointestinal transit.

Small fluorescence-activating and absorption-shifting tag for tunable protein imaging in vivo.

Science.gov (United States)

Plamont, Marie-Aude; Billon-Denis, Emmanuelle; Maurin, Sylvie; Gauron, Carole; Pimenta, Frederico M; Specht, Christian G; Shi, Jian; Quérard, Jérôme; Pan, Buyan; Rossignol, Julien; Moncoq, Karine; Morellet, Nelly; Volovitch, Michel; Lescop, Ewen; Chen, Yong; Triller, Antoine; Vriz, Sophie; Le Saux, Thomas; Jullien, Ludovic; Gautier, Arnaud

2016-01-19

This paper presents Yellow Fluorescence-Activating and absorption-Shifting Tag (Y-FAST), a small monomeric protein tag, half as large as the green fluorescent protein, enabling fluorescent labeling of proteins in a reversible and specific manner through the reversible binding and activation of a cell-permeant and nontoxic fluorogenic ligand (a so-called fluorogen). A unique fluorogen activation mechanism based on two spectroscopic changes, increase of fluorescence quantum yield and absorption red shift, provides high labeling selectivity. Y-FAST was engineered from the 14-kDa photoactive yellow protein by directed evolution using yeast display and fluorescence-activated cell sorting. Y-FAST is as bright as common fluorescent proteins, exhibits good photostability, and allows the efficient labeling of proteins in various organelles and hosts. Upon fluorogen binding, fluorescence appears instantaneously, allowing monitoring of rapid processes in near real time. Y-FAST distinguishes itself from other tagging systems because the fluorogen binding is highly dynamic and fully reversible, which enables rapid labeling and unlabeling of proteins by addition and withdrawal of the fluorogen, opening new exciting prospects for the development of multiplexing imaging protocols based on sequential labeling.

Maternal insulin sensitivity is associated with oral glucose-induced changes in fetal brain activity.

Science.gov (United States)

Linder, Katarzyna; Schleger, Franziska; Ketterer, Caroline; Fritsche, Louise; Kiefer-Schmidt, Isabelle; Hennige, Anita; Häring, Hans-Ulrich; Preissl, Hubert; Fritsche, Andreas

2014-06-01

Fetal programming plays an important role in the pathogenesis of type 2 diabetes. The aim of the present study was to investigate whether maternal metabolic changes during OGTT influence fetal brain activity. Thirteen healthy pregnant women underwent an OGTT (75 g). Insulin sensitivity was determined by glucose and insulin measurements at 0, 60 and 120 min. At each time point, fetal auditory evoked fields were recorded with a fetal magnetoencephalographic device and response latencies were determined. Maternal insulin increased from a fasting level of 67 ± 25 pmol/l (mean ± SD) to 918 ± 492 pmol/l 60 min after glucose ingestion and glucose levels increased from 4.4 ± 0.3 to 7.4 ± 1.1 mmol/l. Over the same time period, fetal response latencies decreased from 297 ± 99 to 235 ± 84 ms (p = 0.01) and then remained stable until 120 min (235 ± 84 vs 251 ± 91 ms, p = 0.39). There was a negative correlation between maternal insulin sensitivity and fetal response latencies 60 min after glucose ingestion (r = 0.68, p = 0.02). After a median split of the group based on maternal insulin sensitivity, fetuses of insulin-resistant mothers showed a slower response to auditory stimuli (283 ± 79 ms) than those of insulin-sensitive mothers (178 ± 46 ms, p = 0.03). Lower maternal insulin sensitivity is associated with slower fetal brain responses. These findings provide the first evidence of a direct effect of maternal metabolism on fetal brain activity and suggest that central insulin resistance may be programmed during fetal development.

Seeing diabetes: visual detection of glucose based on the intrinsic peroxidase-like activity of MoS2 nanosheets

Science.gov (United States)

Lin, Tianran; Zhong, Liangshuang; Guo, Liangqia; Fu, Fengfu; Chen, Guonan

2014-09-01

Molybdenum disulfide (MoS2) has attracted increasing research interest recently due to its unique physical, optical and electrical properties, correlated with its 2D ultrathin atomic-layered structure. Until now, however, great efforts have focused on its applications such as lithium ion batteries, transistors, and hydrogen evolution reactions. Herein, for the first time, MoS2 nanosheets are discovered to possess an intrinsic peroxidase-like activity and can catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a color reaction. The catalytic activity follows the typical Michaelis-Menten kinetics and is dependent on temperature, pH, H2O2 concentration, and reaction time. Based on this finding, a highly sensitive and selective colorimetric method for H2O2 and glucose detection is developed and applied to detect glucose in serum samples. Moreover, a simple, inexpensive, instrument-free and portable test kit for the visual detection of glucose in normal and diabetic serum samples is constructed by utilizing agarose hydrogel as a visual detection platform.Molybdenum disulfide (MoS2) has attracted increasing research interest recently due to its unique physical, optical and electrical properties, correlated with its 2D ultrathin atomic-layered structure. Until now, however, great efforts have focused on its applications such as lithium ion batteries, transistors, and hydrogen evolution reactions. Herein, for the first time, MoS2 nanosheets are discovered to possess an intrinsic peroxidase-like activity and can catalytically oxidize 3,3',5,5'-tetramethylbenzidine (TMB) by H2O2 to produce a color reaction. The catalytic activity follows the typical Michaelis-Menten kinetics and is dependent on temperature, pH, H2O2 concentration, and reaction time. Based on this finding, a highly sensitive and selective colorimetric method for H2O2 and glucose detection is developed and applied to detect glucose in serum samples. Moreover, a simple, inexpensive

Estrogens modulate ventrolateral ventromedial hypothalamic glucose-inhibited neurons

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Ammy M. Santiago

2016-10-01

Full Text Available Objective: Brain regulation of glucose homeostasis is sexually dimorphic; however, the impact sex hormones have on specific neuronal populations within the ventromedial hypothalamic nucleus (VMN, a metabolically sensitive brain region, has yet to be fully characterized. Glucose-excited (GE and -inhibited (GI neurons are located throughout the VMN and may play a critical role in glucose and energy homeostasis. Within the ventrolateral portion of the VMN (VL-VMN, glucose sensing neurons and estrogen receptor (ER distributions overlap. We therefore tested the hypothesis that VL-VMN glucose sensing neurons were sexually dimorphic and regulated by 17β-estradiol (17βE. Methods: Electrophysiological recordings of VL-VMN glucose sensing neurons in brain slices isolated from age- and weight-matched female and male mice were performed in the presence and absence of 17βE. Results: We found a new class of VL-VMN GI neurons whose response to low glucose was transient despite continued exposure to low glucose. Heretofore, we refer to these newly identified VL-VMN GI neurons as ‘adapting’ or AdGI neurons. We found a sexual dimorphic response to low glucose, with male nonadapting GI neurons, but not AdGI neurons, responding more robustly to low glucose than those from females. 17βE blunted the response of both nonadapting GI and AdGI neurons to low glucose in both males and females, which was mediated by activation of estrogen receptor β and inhibition of AMP-activated kinase. In contrast, 17βE had no impact on GE or non-glucose sensing neurons in either sex. Conclusion: These data suggest sex differences and estrogenic regulation of VMN hypothalamic glucose sensing may contribute to the sexual dimorphism in glucose homeostasis. Author Video: Author Video Watch what authors say about their articles Keywords: 17β-estradiol, AMP-activated kinase, Glucose excited neurons, Glucose inhibited neurons, Ventromedial hypothalamic nucleus, Sexual dimorphism

Stability of glucose oxidase and catalase adsorbed on variously activated 13X zeolite.

Science.gov (United States)

Pifferi, P G; Vaccari, A; Ricci, G; Poli, G; Ruggeri, O

1982-10-01

The use of 13X zeolite (0.1-0.4-mm granules), treated with 2N and 0.01N HCI, 0.01M citric acid, 0.1M citric-phosphate buffer (pH 3.6), and in untreated form to adsorb glucose oxidase of fungal origin and microbial catalase was examined. Physicochemical analysis of the support demonstrated that its crystalline structure, greatly altered by the HCl and buffer, could be partially maintained with citric acid. The specific adsorption of the enzymes increased with decreasing pH and proved to be considerable for all the supports. The stability with storage at 25 degrees C is strictly correlated with the titrable acidity of the activated zeolite expressed as meq NaOH/g and with pH value of the activation solution. It proved to be lower than 55 h for both enzymes if adsorbed on zeolite treated with 2N HCl, and 15-fold and 30-fold higher for glucose oxidase and catalase adsorbed, respectively, on zeolite treated with the 0.1M citric-phosphate buffer and 0.01M citric acid. The specific adsorption of glucose oxidase and catalase was, respectively, 1840 U/g at pH 3.0 and 6910 U/g at pH 5.0. Their half-life at 25 degrees C with storage at pH 3.5 for the former and at pH 5.0 for the latter was 800 and 1560 h vs. 40 and 110 h for the corresponding free enzymes.

Implementation of an integrating sphere for the enhancement of noninvasive glucose detection using quantum cascade laser spectroscopy

Science.gov (United States)

Werth, Alexandra; Liakat, Sabbir; Dong, Anqi; Woods, Callie M.; Gmachl, Claire F.

2018-05-01

An integrating sphere is used to enhance the collection of backscattered light in a noninvasive glucose sensor based on quantum cascade laser spectroscopy. The sphere enhances signal stability by roughly an order of magnitude, allowing us to use a thermoelectrically (TE) cooled detector while maintaining comparable glucose prediction accuracy levels. Using a smaller TE-cooled detector reduces form factor, creating a mobile sensor. Principal component analysis has predicted principal components of spectra taken from human subjects that closely match the absorption peaks of glucose. These principal components are used as regressors in a linear regression algorithm to make glucose concentration predictions, over 75% of which are clinically accurate.

Effect of steeping temperature on antioxidant and inhibitory activities of green tea extracts against α-amylase, α-glucosidase and intestinal glucose uptake.

Science.gov (United States)

Liu, Shuyuan; Ai, Zeyi; Qu, Fengfeng; Chen, Yuqiong; Ni, Dejiang

2017-11-01

The objective of the present study was to evaluate the effect of steeping temperature on the biological activities of green tea, including the 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging capacity, α-glucosidase and α-amylase inhibitory activities, and glucose uptake inhibitory activity in Caco-2 cells. Results showed that, with increasing extraction temperature, the polyphenol content increased, which contributed to enhance antioxidant activity and inhibitory effects on α-glucosidase and α-amylase. Green tea steeped at 100°C showed the highest DPPH radical-scavenging activity and inhibitory effects on α-glucosidase and α-amylase activities with EC 50 or IC 50 values of 6.15μg/mL, 0.09mg/mL, and 6.31mg/mL, respectively. However, the inhibitory potential on glucose uptake did not show an upward trend with increasing extraction temperature. Green tea steeped at 60°C had significantly stronger glucose uptake inhibitory activity (ptea. Copyright © 2017 Elsevier Ltd. All rights reserved.

Duodenal mucosal protein kinase C-δ regulates glucose production in rats.

Science.gov (United States)

Kokorovic, Andrea; Cheung, Grace W C; Breen, Danna M; Chari, Madhu; Lam, Carol K L; Lam, Tony K T

2011-11-01

Activation of protein kinase C (PKC) enzymes in liver and brain alters hepatic glucose metabolism, but little is known about their role in glucose regulation in the gastrointestinal tract. We investigated whether activation of PKC-δ in the duodenum is sufficient and necessary for duodenal nutrient sensing and regulates hepatic glucose production through a neuronal network in rats. In rats, we inhibited duodenal PKC and evaluated whether nutrient-sensing mechanisms, activated by refeeding, have disruptions in glucose regulation. We then performed gain- and loss-of-function pharmacologic and molecular experiments to target duodenal PKC-δ; we evaluated the impact on glucose production regulation during the pancreatic clamping, while basal levels of insulin were maintained. PKC-δ was detected in the mucosal layer of the duodenum; intraduodenal infusion of PKC inhibitors disrupted glucose homeostasis during refeeding, indicating that duodenal activation of PKC-δ is necessary and sufficient to regulate glucose homeostasis. Intraduodenal infusion of the PKC activator 1-oleoyl-2-acetyl-sn-glycerol (OAG) specifically activated duodenal mucosal PKC-δ and a gut-brain-liver neuronal pathway to reduce glucose production. Molecular and pharmacologic inhibition of duodenal mucosal PKC-δ negated the ability of duodenal OAG and lipids to reduce glucose production. In the duodenal mucosa, PKC-δ regulates glucose homeostasis. Copyright © 2011 AGA Institute. Published by Elsevier Inc. All rights reserved.

A highly sensitive electrochemical glucose sensor structuring with nickel hydroxide and enzyme glucose oxidase

International Nuclear Information System (INIS)

Mathew, Manjusha; Sandhyarani, N.

2013-01-01

Graphical abstract: A combination of Ni 2+ /Ni 3+ redox couple and glucose oxidase has successfully been exploited for the realization of a highly sensitive glucose sensor for the first time. -- Highlights: • A multilayered glucose biosensor with enhanced sensitivity was fabricated. • Combination of Ni 2+ /Ni 3+ redox couple and glucose oxidase has been exploited for the first time. • Exhibits a lower detection limit of 100 nM with a high sensitivity of 16,840 μA mM −1 cm −2 . • The surface shows a low Michaelis–Menten constant value of 2.4 μM. • Detailed mechanism of sensing was proposed and justified. -- Abstract: A multilayered glucose biosensor with enhanced electron transport was fabricated via the sequential electrodeposition of chitosan gold nanocomposite (CGNC) and nickel hydroxide (Ni(OH) 2 ) on a bare gold electrode and subsequent immobilization of glucose oxidase. A thin film of Ni(OH) 2 deposited on CGNC modified gold electrode serves as an electrochemical redox probe as well as a matrix for the immobilization of glucose oxidase retaining its activity. Electron transport property of CGNC has been exploited to enhance the electron transport between the analyte and electrode. Electrochemical characteristics of the biosensor were studied by cyclic voltammetry and chronoamperometry. Under optimal conditions the biosensor exhibits a linear range from 1 μM to 100 μM with a limit of detection (lod) down to 100 nM. The sensor shows a low Michaelis-Menten constant value of 2.4 μM indicates the high affinity of enzyme to the analyte points to the retained activity of enzyme after immobilization. The present glucose sensor with the high selectivity, sensitivity and stability is promising for practical clinical applications

Amino acids and carbohydrates absorption by Na+-dependent transporters in the pyloric ceca of Hoplias malabaricus (Erythrinidae

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Vieira Vania Lucia Pimentel

2001-01-01

Full Text Available Information about amino acids and carbohydrate absorption in fish is important to formulate an adequate diet to obtain optimal growth. Therefore, the objective of this study was to investigate if Na+-dependent transporters are involved on the absorption of glycine, L-glutamine, L-leucine, L-lysine, L-proline, L-alanine, and the carbohydrates fructose and glucose in the pyloric ceca of Hoplias malabaricus. The pyloric ceca were mounted in a system of continuous perfusion "in vitro". Amino acids and carbohydrates were placed on the mucosal side at concentrations of 10, 20, and 40mM. The serosal side of the pyloric ceca was positive in relation to the mucosal side. The addition of glycine, L-glutamine, L-leucine, L-lysine, L-proline (all tested concentrations, and glucose (at concentrations of 20 and 40mM increased the positivity of the serosal side, indicating the presence of Na+-dependent transporters in the absorption of these substances. L-alanine and fructose did not change the positivity of the serosal side. The pyloric ceca seem to be the main site of nutrient absorption in the digestive tract of H. malabaricus.

Field Measurements of Water Continuum and Water Dimer Absorption by Active Long Path Differential Optical Absorption Spectroscopy (DOAS)

OpenAIRE

Lotter, Andreas

2006-01-01

Water vapor plays an important role in Earth's radiative budget since water molecules strongly absorb the incoming solar shortwave and the outgoing thermal infrared radiation. Superimposed on the water monomer absorption, a water continuum absorption has long been recognized, but its true nature still remains controversial. On the one hand, this absorption is explained by a deformation of the line shape of the water monomer absorption lines as a consequence of a molecular collision. One the o...

A leptin-regulated circuit controls glucose mobilization during noxious stimuli.

Science.gov (United States)

Flak, Jonathan N; Arble, Deanna; Pan, Warren; Patterson, Christa; Lanigan, Thomas; Goforth, Paulette B; Sacksner, Jamie; Joosten, Maja; Morgan, Donald A; Allison, Margaret B; Hayes, John; Feldman, Eva; Seeley, Randy J; Olson, David P; Rahmouni, Kamal; Myers, Martin G

2017-08-01

Adipocytes secrete the hormone leptin to signal the sufficiency of energy stores. Reductions in circulating leptin concentrations reflect a negative energy balance, which augments sympathetic nervous system (SNS) activation in response to metabolically demanding emergencies. This process ensures adequate glucose mobilization despite low energy stores. We report that leptin receptor-expressing neurons (LepRb neurons) in the periaqueductal gray (PAG), the largest population of LepRb neurons in the brain stem, mediate this process. Application of noxious stimuli, which often signal the need to mobilize glucose to support an appropriate response, activated PAG LepRb neurons, which project to and activate parabrachial nucleus (PBN) neurons that control SNS activation and glucose mobilization. Furthermore, activating PAG LepRb neurons increased SNS activity and blood glucose concentrations, while ablating LepRb in PAG neurons augmented glucose mobilization in response to noxious stimuli. Thus, decreased leptin action on PAG LepRb neurons augments the autonomic response to noxious stimuli, ensuring sufficient glucose mobilization during periods of acute demand in the face of diminished energy stores.

Glucose transport in brain - effect of inflammation.

Science.gov (United States)

Jurcovicova, J

2014-01-01

Glucose is transported across the cell membrane by specific saturable transport system, which includes two types of glucose transporters: 1) sodium dependent glucose transporters (SGLTs) which transport glucose against its concentration gradient and 2) sodium independent glucose transporters (GLUTs), which transport glucose by facilitative diffusion in its concentration gradient. In the brain, both types of transporters are present with different function, affinity, capacity, and tissue distribution. GLUT1 occurs in brain in two isoforms. The more glycosylated GLUT1 is produced in brain microvasculature and ensures glucose transport across the blood brain barrier (BBB). The less glycosylated form is localized in astrocytic end-feet and cell bodies and is not present in axons, neuronal synapses or microglia. Glucose transported to astrocytes by GLUT1 is metabolized to lactate serving to neurons as energy source. Proinflammatory cytokine interleukin (IL)-1β upregulates GLUT1 in endothelial cells and astrocytes, whereas it induces neuronal death in neuronal cell culture. GLUT2 is present in hypothalamic neurons and serves as a glucose sensor in regulation of food intake. In neurons of the hippocampus, GLUT2 is supposed to regulate synaptic activity and neurotransmitter release. GLUT3 is the most abundant glucose transporter in the brain having five times higher transport capacity than GLUT1. It is present in neuropil, mostly in axons and dendrites. Its density and distribution correlate well with the local cerebral glucose demands. GLUT5 is predominantly fructose transporter. In brain, GLUT5 is the only hexose transporter in microglia, whose regulation is not yet clear. It is not present in neurons. GLUT4 and GLUT8 are insulin-regulated glucose transporters in neuronal cell bodies in the cortex and cerebellum, but mainly in the hippocampus and amygdala, where they maintain hippocampus-dependent cognitive functions. Insulin translocates GLUT4 from cytosol to plasma

Absolute activity determinations on large volume geological samples independent of self-absorption effects

International Nuclear Information System (INIS)

Wilson, W.E.

1980-01-01

This paper describes a method for measuring the absolute activity of large volume samples by γ-spectroscopy independent of self-absorption effects using Ge detectors. The method yields accurate matrix independent results at the expense of replicative counting of the unknown sample. (orig./HP)

Characterization of the biocontrol activity of pseudomonas fluorescens strain X reveals novel genes regulated by glucose.

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Gerasimos F Kremmydas

Full Text Available Pseudomonas fluorescens strain X, a bacterial isolate from the rhizosphere of bean seedlings, has the ability to suppress damping-off caused by the oomycete Pythium ultimum. To determine the genes controlling the biocontrol activity of strain X, transposon mutagenesis, sequencing and complementation was performed. Results indicate that, biocontrol ability of this isolate is attributed to gcd gene encoding glucose dehydrogenase, genes encoding its co-enzyme pyrroloquinoline quinone (PQQ, and two genes (sup5 and sup6 which seem to be organized in a putative operon. This operon (named supX consists of five genes, one of which encodes a non-ribosomal peptide synthase. A unique binding site for a GntR-type transcriptional factor is localized upstream of the supX putative operon. Synteny comparison of the genes in supX revealed that they are common in the genus Pseudomonas, but with a low degree of similarity. supX shows high similarity only to the mangotoxin operon of Ps. syringae pv. syringae UMAF0158. Quantitative real-time PCR analysis indicated that transcription of supX is strongly reduced in the gcd and PQQ-minus mutants of Ps. fluorescens strain X. On the contrary, transcription of supX in the wild type is enhanced by glucose and transcription levels that appear to be higher during the stationary phase. Gcd, which uses PQQ as a cofactor, catalyses the oxidation of glucose to gluconic acid, which controls the activity of the GntR family of transcriptional factors. The genes in the supX putative operon have not been implicated before in the biocontrol of plant pathogens by pseudomonads. They are involved in the biosynthesis of an antimicrobial compound by Ps. fluorescens strain X and their transcription is controlled by glucose, possibly through the activity of a GntR-type transcriptional factor binding upstream of this putative operon.

SCAPIS Pilot Study: Sitness, Fitness and Fatness - Is Sedentary Time Substitution by Physical Activity Equally Important for Everyone's Markers of Glucose Regulation?

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Ekblom-Bak, Elin; Ekblom, Örjan; Bolam, Kate A; Ekblom, Björn; Bergström, Göran; Börjesson, Mats

2016-07-01

Although moderate-to-vigorous physical activity (MVPA) is mainly recommended for glucose control, light physical activity (LIPA) may also have the potential to induce favorable changes. We investigated sedentary time (SED) substitution with equal time in LIPA and MVPA, and the association with markers of glucose regulation and insulin sensitivity after stratification by waist circumference, fitness and fasting glucose levels. A total of 654 men and women, 50 to 64 years, from the SCAPIS pilot study were included. Daily SED, LIPA and MVPA were assessed using hip-worn accelerometers. Fasting plasma glucose, insulin and HOMA-IR were determined. Substituting 30 min of SED with LIPA was significantly associated with 3.0% lower fasting insulin values and 3.1% lower HOMA-IR values, with even lower levels when substituting SED with MVPA. Participants with lower fitness and participants with high fasting glucose levels benefited significantly more from substituting 30 min of SED with LIPA compared with participants with normal to high fitness levels and participants with normal glucose levels, respectively. LIPA, and not only MVPA, may have beneficial associations with glucose regulation. This is of great clinical and public health importance, not least because it may confer a higher compliance rate to regular PA.

Phytopharmacological evaluation of Byesukar for hypoglycaemic activity and its effect on lipid profile and hepatic enzymes of glucose metabolism in diabetic rats.

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Guruvayoorappan, C; Sudha, G

2008-01-01

Many anti-diabetic herbal preparations have been recommended in alternative systems of medicine for the treatment of diabetes. No systematic study has been done on the anti-diabetic efficacy of Byesukar, a polyherbal formulation to treat diabetes. The anti-diabetic efficacy of byesukar ethanol extract was evaluated in an animal model of diabetes induced by alloxan. Male Wistar rats were divided in to four groups. Group 1 was normal control group; group 2 and 3 received alloxan. After inducing experimental diabetes group 2 served as diabetic control; group 3 received byesukar (500 mg/kg body weight) orally for 30 consecutive days. Group 4 were normal rats which received byesukar extract alone. The effect of byesukar on glucose level in diabetic rats was studied and the level of glucose metabolizing enzymes (Hexokinase, glucose-6-phosphatase and fructose 1, 6-bisphosphatase) in the liver and kidney were estimated. The effect of byesukar on the serum and tissue lipid profile (Cholesterol, triglycerides, phospholipids and free fatty acids) were also estimated in diabetic rats. Our results indicate that treatment with byesukar resulted in significant reduction of blood glucose, tissue glucose-6-phosphatase and fructose 1, 6- bisphosphatase activity. The decreased tissue hexokinase activity in diabetes state was found to be significantly increased by byesukar treatment. Also the byesukar treated diabetic rats showed a significant decrease in the tissue lipid profile compared to the diabetic rats. In conclusion the decreased blood glucose accompanied with decreased lipid profile and changes in the activities of the glucose metabolizing enzymes shows the antidiabetic effect of byesukar.

SREBP-1c regulates glucose-stimulated hepatic clusterin expression

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Kim, Gukhan [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Geun Hyang; Oh, Gyun-Sik; Yoon, Jin [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Hae Won [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Min-Seon [Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Seung-Whan, E-mail: swkim7@amc.seoul.kr [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

2011-05-20

Highlights: {yields} This is the first report to show nutrient-regulated clusterin expression. {yields} Clusterin expression in hepatocytes was increased by high glucose concentration. {yields} SREBP-1c is directly involved in the transcriptional activation of clusterin by glucose. {yields} This glucose-stimulated activation process is mediated through tandem E-box motifs. -- Abstract: Clusterin is a stress-response protein that is involved in diverse biological processes, including cell proliferation, apoptosis, tissue differentiation, inflammation, and lipid transport. Its expression is upregulated in a broad spectrum of diverse pathological states. Clusterin was recently reported to be associated with diabetes, metabolic syndrome, and their sequelae. However, the regulation of clusterin expression by metabolic signals was not addressed. In this study we evaluated the effects of glucose on hepatic clusterin expression. Interestingly, high glucose concentrations significantly increased clusterin expression in primary hepatocytes and hepatoma cell lines, but the conventional promoter region of the clusterin gene did not respond to glucose stimulation. In contrast, the first intronic region was transcriptionally activated by high glucose concentrations. We then defined a glucose response element (GlRE) of the clusterin gene, showing that it consists of two E-box motifs separated by five nucleotides and resembles carbohydrate response element (ChoRE). Unexpectedly, however, these E-box motifs were not activated by ChoRE binding protein (ChREBP), but were activated by sterol regulatory element binding protein-1c (SREBP-1c). Furthermore, we found that glucose induced recruitment of SREBP-1c to the E-box of the clusterin gene intronic region. Taken together, these results suggest that clusterin expression is increased by glucose stimulation, and SREBP-1c plays a crucial role in the metabolic regulation of clusterin.

Central serotonergic neurons activate and recruit thermogenic brown and beige fat and regulate glucose and lipid homeostasis.

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McGlashon, Jacob M; Gorecki, Michelle C; Kozlowski, Amanda E; Thirnbeck, Caitlin K; Markan, Kathleen R; Leslie, Kirstie L; Kotas, Maya E; Potthoff, Matthew J; Richerson, George B; Gillum, Matthew P

2015-05-05

Thermogenic brown and beige adipocytes convert chemical energy to heat by metabolizing glucose and lipids. Serotonin (5-HT) neurons in the CNS are essential for thermoregulation and accordingly may control metabolic activity of thermogenic fat. To test this, we generated mice in which the human diphtheria toxin receptor (DTR) was selectively expressed in central 5-HT neurons. Treatment with diphtheria toxin (DT) eliminated 5-HT neurons and caused loss of thermoregulation, brown adipose tissue (BAT) steatosis, and a >50% decrease in uncoupling protein 1 (Ucp1) expression in BAT and inguinal white adipose tissue (WAT). In parallel, blood glucose increased 3.5-fold, free fatty acids 13.4-fold, and triglycerides 6.5-fold. Similar BAT and beige fat defects occurred in Lmx1b(f/f)ePet1(Cre) mice in which 5-HT neurons fail to develop in utero. We conclude 5-HT neurons play a major role in regulating glucose and lipid homeostasis, in part through recruitment and metabolic activation of brown and beige adipocytes. Copyright © 2015 Elsevier Inc. All rights reserved.

Hepatic glucose output in humans measured with labeled glucose to reduce negative errors

International Nuclear Information System (INIS)

Levy, J.C.; Brown, G.; Matthews, D.R.; Turner, R.C.

1989-01-01

Steele and others have suggested that minimizing changes in glucose specific activity when estimating hepatic glucose output (HGO) during glucose infusions could reduce non-steady-state errors. This approach was assessed in nondiabetic and type II diabetic subjects during constant low dose [27 mumol.kg ideal body wt (IBW)-1.min-1] glucose infusion followed by a 12 mmol/l hyperglycemic clamp. Eight subjects had paired tests with and without labeled infusions. Labeled infusion was used to compare HGO in 11 nondiabetic and 15 diabetic subjects. Whereas unlabeled infusions produced negative values for endogenous glucose output, labeled infusions largely eliminated this error and reduced the dependence of the Steele model on the pool fraction in the paired tests. By use of labeled infusions, 11 nondiabetic subjects suppressed HGO from 10.2 +/- 0.6 (SE) fasting to 0.8 +/- 0.9 mumol.kg IBW-1.min-1 after 90 min of glucose infusion and to -1.9 +/- 0.5 mumol.kg IBW-1.min-1 after 90 min of a 12 mmol/l glucose clamp, but 15 diabetic subjects suppressed only partially from 13.0 +/- 0.9 fasting to 5.7 +/- 1.2 at the end of the glucose infusion and 5.6 +/- 1.0 mumol.kg IBW-1.min-1 in the clamp (P = 0.02, 0.002, and less than 0.001, respectively)

Production of rabbit antibodies against purified Glucose oxidase

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Muhammad Anjum Zia

2012-02-01

Full Text Available Glucose oxidase is an active oxygen species generating enzyme produced from Aspergillus niger grown in submerged fermentation. Disintegration of the mycelium resulted in high glucose oxidase activity that was subjected to ammonium sulfate precipitation at 60-85% saturation rates that resulted to 6.14 U mg -1 specific activity. Purification of enzyme by anion exchange column (DEAE-Cellulose resulted into 22.53 U mg-1 specific activity and 10.27 fold purification. This was applied to sephadex G-200 column for gel filtration chromatography. It was observed that enzyme achieved 59.37 U mg-1of specific activity with 27.08 fold purity and 64.36% recovery. Purified glucose oxidase was injected into rabbits through intravenous route, to raise the glucose oxidase antibodies. After 30 days incubation period, the rabbits were slaughtered and serum was separated from blood. The antibodies were isolated by ammonium sulfate precipitation and confirmed by agar gel precipitation test. This could be a convenient and low cost alternate assay for the estimation of glucose oxidase in biological fluids. Moreover, such antibodies against the said enzyme could be used in various therapeutic and diagnostic applications.

Protein kinase C is activated in glomeruli from streptozotocin diabetic rats. Possible mediation by glucose

International Nuclear Information System (INIS)

Craven, P.A.; DeRubertis, F.R.

1989-01-01

Glomerular inositol content and the turnover of polyphosphoinositides was reduced by 58% in 1-2 wk streptozotocin diabetic rats. Addition of inositol to the incubation medium increased polyphosphoinositide turnover in glomeruli from diabetic rats to control values. Despite the reduction in inositol content and polyphosphoinositide turnover, protein kinase C was activated in glomeruli from diabetic rats, as assessed by an increase in the percentage of enzyme activity associated with the particulate cell fraction. Total protein kinase C activity was not different between glomeruli from control and diabetic rats. Treatment of diabetic rats with insulin to achieve near euglycemia prevented the increase in particulate protein kinase C. Moreover, incubation of glomeruli from control rats with glucose (100-1,000 mg/dl) resulted in a progressive increase in labeled diacylglycerol production and in the percentage of protein kinase C activity which was associated with the particulate fraction. These results support a role for hyperglycemia per se in the enhanced state of activation of protein kinase C seen in glomeruli from diabetic rats. Glucose did not appear to increase diacylglycerol by stimulating inositol phospholipid hydrolysis in glomeruli. Other pathways for diacylglycerol production, including de novo synthesis and phospholipase C mediated hydrolysis of phosphatidylcholine or phosphatidyl-inositol-glycan are not excluded

Modeling error and apparent isotope discrimination confound estimation of endogenous glucose production during euglycemic glucose clamps

International Nuclear Information System (INIS)

Finegood, D.T.; Bergman, R.N.; Vranic, M.

1988-01-01

We previously demonstrated that conventional tracer methods applied to euglycemic-hyperinsulinemic glucose clamps result in substantially negative estimates for the rate of endogenous glucose production, particularly during the first half of 180-min clamps. We also showed that addition of tracer to the exogenous glucose infusate resulted in nonnegative endogenous glucose production (Ra) estimates. In this study, we investigated the underlying cause of negative estimates of Ra from conventional clamp/tracer methods and the reason for the difference in estimates when tracer is added to the exogenous glucose infusate. We performed euglycemic-hyperinsulinemic (300-microU/ml) clamps in normal dogs without (cold GINF protocol, n = 6) or with (hot GINF protocol, n = 6) tracer (D-[3-3H]glucose) added to the exogenous glucose infusate. In the hot GINF protocol, sufficient tracer was added to the exogenous glucose infusate such that arterial plasma specific activity (SAa) did not change from basal through the clamp period (P greater than .05). In the cold GINF studies, plasma SAa fell 81 +/- 2% from the basal level by the 3rd h of clamping. We observed a significant, transient, positive venous-arterial difference in specific activity (SAv-SAa difference) during the cold GINF studies. The SAv-SAa difference reached a peak of 27 +/- 6% at 30 min and diminished to a plateau of 7 +/- 1% between 70 and 180 min. We also observed a positive but constant SAv-SAa difference (4.6 +/- 0.2% between 10 and 180 min) during the hot GINF studies

Glucose ingestion stimulates atherothrombotic inflammation in polycystic ovary syndrome

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Kirwan, John P.; Rote, Neal S.; Minium, Judi

2013-01-01

Women with polycystic ovary syndrome (PCOS) have chronic low-grade inflammation that can increase the risk of atherothrombosis. We performed a cross-sectional study to examine the effect of glucose ingestion on markers of atherothrombotic inflammation in mononuclear cells (MNC) of 16 women with PCOS (8 lean, 8 obese) and 16 weight-matched controls. Activator protein-1 (AP-1) activation and the protein content of early growth response-1 (EGR-1), matrix matalloproteinases-2 (MMP2), and tissue factor (TF) were quantified from MNC obtained from blood drawn fasting and 2 h after glucose ingestion. Plasma MMP9 and C-reactive protein (CRP) were measured from fasting blood samples. Truncal fat was determined by DEXA. Lean women with PCOS exhibited greater AP-1 activation and MMP2 protein content after glucose ingestion and higher plasma MMP9 and CRP levels than lean controls. Obese women with PCOS exhibited greater EGR-1 and TF protein content after glucose ingestion, and plasma CRP levels were even higher compared with lean subjects regardless of PCOS status. Truncal fat correlated with MMP9 and CRP levels and glucose-stimulated increases in AP-1 activation and EGR-1 and TF protein content. Testosterone correlated with glucose-stimulated AP-1 activation, and androstenedione correlated with MMP9 and CRP levels and glucose-stimulated AP-1 activation. Thus, both PCOS and obesity contribute to an atherothrombotic state in which excess abdominal adiposity and hyperandrogenism may be specific risk factors for developing atherothrombosis. PMID:23249695

Effects of ketamine on glucose uptake by glucose transporter type 3 expressed in Xenopus oocytes: The role of protein kinase C

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Tomioka, Shigemasa, E-mail: tomioka@dent.tokushima-u.ac.jp [Department of Dental Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 18-15, Tokushima City, Tokushima 770-8504 (Japan); Kaneko, Miyuki [Department of Dental Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 18-15, Tokushima City, Tokushima 770-8504 (Japan); Satomura, Kazuhito [First Department of Oral and Maxillofacial Surgery, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 18-15, Tokushima City, Tokushima 770-8504 (Japan); Mikyu, Tomiko; Nakajo, Nobuyoshi [Department of Dental Anesthesiology, Institute of Health Biosciences, The University of Tokushima Graduate School, Kuramoto-cho 18-15, Tokushima City, Tokushima 770-8504 (Japan)

2009-10-09

We investigated the effects of ketamine on the type 3 facilitative glucose transporter (GLUT3), which plays a major role in glucose transport across the plasma membrane of neurons. Human-cloned GLUT3 was expressed in Xenopus oocytes by injection of GLUT3 mRNA. GLUT3-mediated glucose uptake was examined by measuring oocyte radioactivity following incubation with 2-deoxy-D-[1,2-{sup 3}H]glucose. While ketamine and S(+)-ketamine significantly increased GLUT3-mediated glucose uptake, this effect was biphasic such that higher concentrations of ketamine inhibited glucose uptake. Ketamine (10 {mu}M) significantly increased V{sub max} but not K{sub m} of GLUT3 for 2-deoxy-D-glucose. Although staurosporine (a protein kinase C inhibitor) increased glucose uptake, no additive or synergistic interactions were observed between staurosporine and racemic ketamine or S(+)-ketamine. Treatment with ketamine or S(+)-ketamine partially prevented GLUT3 inhibition by the protein kinase C activator phorbol-12-myrisate-13-acetate. Our results indicate that ketamine increases GLUT3 activity at clinically relevant doses through a mechanism involving PKC inhibition.