WorldWideScience

Sample records for release insulin-mediated glucose

  1. Caffeine's impairment of insulin-mediated glucose disposal cannot be solely attributed to adrenaline in humans

    DEFF Research Database (Denmark)

    Battram, D S; Graham, T E; Dela, F

    2007-01-01

    Caffeine (CAF) impedes insulin-mediated glucose disposal (IMGD) and increases plasma adrenaline concentrations ([ADR]; 0.6 nm). While the antagonism of ADR abolishes the CAF effect, infusion of ADR (0.75 nm) has no effect on IMGD. We have now examined CAF and ADR in concert to determine whether...

  2. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling

    Directory of Open Access Journals (Sweden)

    Nigel Beaton

    2015-11-01

    Conclusions: Collectively, these findings establish TUSC5 as an adipose tissue-specific protein that enables proper protein recycling, linking the ubiquitous vesicle traffic machinery with tissue-specific insulin-mediated glucose uptake into adipose tissue and the maintenance of a healthy metabolic phenotype in mice and humans.

  3. Rates and tissue sites of non-insulin- and insulin-mediated glucose uptake in humans

    International Nuclear Information System (INIS)

    Baron, A.D.; Brechtel, G.; Wallace, P.; Edelman, S.V.

    1988-01-01

    In vivo glucose uptake can occur via two mechanisms, namely, insulin-mediated glucose uptake (IMGU) and non-insulin-mediated glucose uptake (NIMGU). Although the principal tissue sites for IMGU are skeletal muscle, the tissue sites for NIMGU at a given serum glucose concentration are not known. To examine this issue, rates of whole body glucose uptake (Rd) were measured at basal and during glucose clamp studies performed at euglycemia (approximately 90 mg/dl) and hyperglycemia (approximately 220 mg/dl) in six lean healthy men. Studies were performed during hyperinsulinemia (approximately 70 microU/ml) and during somatostatin-induced insulinopenia to measure IMGU and NIMGU, respectively. During each study, leg glucose balance (arteriovenous catheter technique) was also measured. With this approach, rates of whole body skeletal muscle IMGU and NIMGU can be estimated, and the difference between overall Rd and skeletal muscle glucose uptake represents non-skeletal muscle Rd. The results indicate that approximately 20% of basal Rd is into skeletal muscle. During insulinopenia approximately 86% of body NIMGU occurs in non-skeletal muscle tissues at euglycemia. When hyperglycemia was created, whole body NIMGU increased from 128 +/- 6 to 213 +/- 18 mg/min (P less than 0.01); NIMGU into non-skeletal muscle tissues was 134 +/- 11 and 111 +/- 6 mg/min at hyperglycemia and euglycemia, respectively, P = NS. Therefore, virtually all the hyperglycemia induced increment in NIMGU occurred in skeletal muscle. During hyperinsulinemia, IMGU in skeletal muscle represented 75 and 95% of body Rd, at euglycemia and hyperglycemia, respectively

  4. Hyperlipidaemia is associated with increased insulin-mediated glucose metabolism, reduced fatty acid metabolism and normal blood pressure in transgenic mice overexpressing human apolipoprotein C1

    NARCIS (Netherlands)

    Koopmans, S.J.; Jong, M.C.; Que, I.; Dahlmans, V.E.H.; Pijl, H.; Radder, J.K.; Frölich, M.; Havekes, L.M.

    2001-01-01

    Aims/hypothesis. Insulin resistance for glucose metabolism is associated with hyperlipidaemia and high blood pressure. In this study we investigated the effect of primary hyperlipidaemia on basal and insulin-mediated glucose and on non-esterified fatty acid (NEFA) metabolism and mean arterial

  5. The PPARα/γ Agonist, Tesaglitazar, Improves Insulin Mediated Switching of Tissue Glucose and Free Fatty Acid Utilization In Vivo in the Obese Zucker Rat

    Directory of Open Access Journals (Sweden)

    Kristina Wallenius

    2013-01-01

    Full Text Available Metabolic flexibility was assessed in male Zucker rats: lean controls, obese controls, and obese rats treated with the dual peroxisome proliferator activated receptor (PPAR agonist, tesaglitazar, 3 μmol/kg/day for 3 weeks. Whole body glucose disposal rate ( and hepatic glucose output (HGO were assessed under basal fasting and hyperinsulinemic isoglycemic clamp conditions using [3,3H]glucose. Indices of tissue specific glucose utilization ( were measured at basal, physiological, and supraphysiological levels of insulinemia using 2-deoxy-D-[2,6-3H]glucose. Finally, whole body and tissue specific FFA and glucose utilization and metabolic fate were evaluated under basal and hyperinsulinemic conditions using a combination of [U-13C]glucose, 2-deoxy-D-[U-14C]glucose, [U-14C]palmitate, and [9,10-3H]-(R-bromopalmitate. Tesaglitazar improved whole body insulin action by greater suppression of HGO and stimulation of compared to obese controls. This involved increased insulin stimulation of in fat and skeletal muscle as well as increased glycogen synthesis. Tesaglitazar dramatically improved insulin mediated suppression of plasma FFA level, whole body turnover (, and muscle, liver, and fat utilization. At basal insulin levels, tesaglitazar failed to lower HGO or compared to obese controls. In conclusion, the results demonstrate that tesaglitazar has a remarkable ability to improve insulin mediated control of glucose and FFA fluxes in obese Zucker rats.

  6. Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

    Science.gov (United States)

    Everman, Sarah; Mandarino, Lawrence J; Carroll, Chad C; Katsanos, Christos S

    2015-01-01

    Plasma branched-chain amino acids (BCAA) are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity. To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans. Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U) during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5) to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5). In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U) in association with the above BCAA infusion (N = 4) or under the same conditions without BCAA infusion (N = 3). Plasma glucose turnover was measured prior to and during insulin infusion. Insulin infusion completely suppressed the endogenous glucose production (EGP) across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05). Insulin infusion stimulated whole-body glucose disposal rate (GDR) across all groups. However, the increase (%) in GDR was not different [median (1st quartile - 3rd quartile)] between Control and BCAA in either the 40U ([199 (167-278) vs. 186 (94-308)] or 80 U ([491 (414-548) vs. 478 (409-857)] experiments (P > 0.05). Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P BCAA in either of the experiments (P > 0.05). Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

  7. Effects of acute exposure to increased plasma branched-chain amino acid concentrations on insulin-mediated plasma glucose turnover in healthy young subjects.

    Directory of Open Access Journals (Sweden)

    Sarah Everman

    Full Text Available Plasma branched-chain amino acids (BCAA are inversely related to insulin sensitivity of glucose metabolism in humans. However, currently, it is not known whether there is a cause-and-effect relationship between increased plasma BCAA concentrations and decreased insulin sensitivity.To determine the effects of acute exposure to increased plasma BCAA concentrations on insulin-mediated plasma glucose turnover in humans.Ten healthy subjects were randomly assigned to an experiment where insulin was infused at 40 mU/m2/min (40U during the second half of a 6-hour intravenous infusion of a BCAA mixture (i.e., BCAA; N = 5 to stimulate plasma glucose turnover or under the same conditions without BCAA infusion (Control; N = 5. In a separate experiment, seven healthy subjects were randomly assigned to receive insulin infusion at 80 mU/m2/min (80U in association with the above BCAA infusion (N = 4 or under the same conditions without BCAA infusion (N = 3. Plasma glucose turnover was measured prior to and during insulin infusion.Insulin infusion completely suppressed the endogenous glucose production (EGP across all groups. The percent suppression of EGP was not different between Control and BCAA in either the 40U or 80U experiments (P > 0.05. Insulin infusion stimulated whole-body glucose disposal rate (GDR across all groups. However, the increase (% in GDR was not different [median (1st quartile - 3rd quartile] between Control and BCAA in either the 40U ([199 (167-278 vs. 186 (94-308] or 80 U ([491 (414-548 vs. 478 (409-857] experiments (P > 0.05. Likewise, insulin stimulated the glucose metabolic clearance in all experiments (P 0.05.Short-term exposure of young healthy subjects to increased plasma BCAA concentrations does not alter the insulin sensitivity of glucose metabolism.

  8. Effects of Endogenous Androgens and Abdominal Fat Distribution on the Interrelationship Between Insulin and Non-Insulin-Mediated Glucose Uptake in Females

    Science.gov (United States)

    Ezeh, Uche; Pall, Marita; Mathur, Ruchi; Dey, Damini; Berman, Daniel; Chen, Ida Y.; Dumesic, Daniel A.

    2013-01-01

    Background: Polycystic ovary syndrome (PCOS) is associated with hyperandrogenism and insulin resistance. Glucose disposal occurs via noninsulin-mediated glucose uptake (NIMGU) and insulin-mediated glucose uptake (IMGU). It is unknown whether in PCOS NIMGU increases to compensate for declining IMGU and whether androgens and fat distribution influence this relationship. Objectives: The objective of the study was to compare in women with PCOS and controls the interrelationship between NIMGU [ie, glucose effectiveness (Sg)] and IMGU [ie, the insulin sensitivity index (Si)] and the role of androgens and fat distribution. Participants: Twenty-eight PCOS (by National Institutes of Health 1990 criteria) and 28 control (age, race, and body mass index matched) women were prospectively studied. A subset of 16 PCOS subjects and 16 matched controls also underwent abdominal computed tomography. Main Outcome Measures: Glucose disposal (by a frequently sampled iv glucose tolerance test), circulating androgens, and abdominal fat distribution [by waist to hip ratio and visceral (VAT) and sc (SAT) adipose tissue content] were measured. Results: PCOS women had lower mean Si and similar Sg and abdominal fat distribution compared with controls. PCOS women with Si below the PCOS median (more insulin resistant) had a lower mean Sg than controls with Si above the control median (more insulin sensitive). In PCOS only, body mass index, free T, modified Ferriman-Gallwey score, and waist to hip ratio independently predicted Sg, whereas Si did not. In PCOS, VAT and SAT independently and negatively predicted Si and Sg, respectively. Conclusion: The decreased IMGU in PCOS is not accompanied by a compensatory increase in NIMGU or associated with excessive VAT accumulation. Increased general obesity, SAT, and hyperandrogenism are primary predictors of the deterioration of NIMGU in PCOS. PMID:23450052

  9. Diminished insulin-mediated forearm blood flow and muscle glucose uptake in young men with low birth weight

    DEFF Research Database (Denmark)

    Sonne, M P; Højbjerre, L; Alibegovic, A C

    2009-01-01

    BACKGROUND: Low birth weight (LBW) is associated with increased risk of type 2 diabetes and cardiovascular disease. We studied endothelial function and insulin sensitivity in young men with LBW (n = 22) and controls (n = 22). METHODS: Insulin sensitivity and endothelial function was studied...... with venous occlusion plethysmography and intra-arterial infusions of adenosine and acetylcholine, before and during a hyperinsulinemic isoglycemic clamp. RESULTS: Forearm blood flow response to systemic hyperinsulinemia was diminished in LBW compared to controls (p ... extraction was similar, and consequently insulin-stimulated forearm glucose clearance was diminished in LBW compared with controls (0.8 +/- 0.09 vs. 1.4 +/- 0.36 ml x 100 ml(-1) x min(-1), respectively, p

  10. Maltitol inhibits small intestinal glucose absorption and increases insulin mediated muscle glucose uptake ex vivo but not in normal and type 2 diabetic rats.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2017-02-01

    This study investigated the effects of maltitol on intestinal glucose absorption and muscle glucose uptake using ex vivo and in vivo experimental models. The ex vivo experiment was conducted in isolated jejunum and psoas muscle from normal rats. The in vivo study investigated the effects of a single bolus dose of maltitol on gastric emptying, intestinal glucose absorption and digesta transit in normal and type 2 diabetic rats. Maltitol inhibited glucose absorption in isolated rat jejunum and increased glucose uptake in isolated rat psoas muscle in the presence of insulin but not in the absence of insulin. In contrast, maltitol did not significantly (p > 0.05) alter small intestinal glucose absorption or blood glucose levels as well as gastric emptying and digesta transit in normal or type 2 diabetic rats. The results suggest that maltitol may not be a suitable dietary supplement for anti-diabetic food and food products to improve glycemic control.

  11. Reduced insulin-mediated citrate synthase activity in cultured skeletal muscle cells from patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Mogensen, Martin; Petersen, Ingrid

    2005-01-01

    In myotubes established from patients with type 2 diabetes (T2D), lipid oxidation and insulin-mediated glucose oxidation are reduced, whereas in myotubes from obese non-diabetic subjects, exposure to palmitate impairs insulin-mediated glucose oxidation. To determine the underlying mechanisms...

  12. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    Energy Technology Data Exchange (ETDEWEB)

    Das, Joydeep; Vasan, Vandana; Sil, Parames C., E-mail: parames@bosemain.boseinst.ac.in

    2012-01-15

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

  13. Taurine exerts hypoglycemic effect in alloxan-induced diabetic rats, improves insulin-mediated glucose transport signaling pathway in heart and ameliorates cardiac oxidative stress and apoptosis

    International Nuclear Information System (INIS)

    Das, Joydeep; Vasan, Vandana; Sil, Parames C.

    2012-01-01

    Hyperlipidemia, inflammation and altered antioxidant profiles are the usual complications in diabetes mellitus. In the present study, we investigated the therapeutic potential of taurine in diabetes associated cardiac complications using a rat model. Rats were made diabetic by alloxan (ALX) (single i.p. dose of 120 mg/kg body weight) and left untreated or treated with taurine (1% w/v, orally, in water) for three weeks either from the day of ALX exposure or after the onset of diabetes. Animals were euthanized after three weeks. ALX-induced diabetes decreased body weight, increased glucose level, decreased insulin content, enhanced the levels of cardiac damage markers and altered lipid profile in the plasma. Moreover, it increased oxidative stress (decreased antioxidant enzyme activities and GSH/GSSG ratio, increased xanthine oxidase enzyme activity, lipid peroxidation, protein carbonylation and ROS generation) and enhanced the proinflammatory cytokines levels, activity of myeloperoxidase and nuclear translocation of NFκB in the cardiac tissue of the experimental animals. Taurine treatment could, however, result to a decrease in the elevated blood glucose and proinflammatory cytokine levels, diabetes-evoked oxidative stress, lipid profiles and NFκB translocation. In addition, taurine increased GLUT 4 translocation to the cardiac membrane by enhanced phosphorylation of IR and IRS1 at tyrosine and Akt at serine residue in the heart. Results also suggest that taurine could protect cardiac tissue from ALX induced apoptosis via the regulation of Bcl2 family and caspase 9/3 proteins. Taken together, taurine supplementation in regular diet could play a beneficial role in regulating diabetes and its associated complications in the heart. Highlights: ► Taurine controls blood glucose via protection of pancreatic β cells in diabetic rat. ► Taurine controls blood glucose via increasing the insulin level in diabetic rat. ► Taurine improves cardiac AKT/GLUT4 signaling

  14. An aqueous extract of Curcuma longa (turmeric) rhizomes stimulates insulin release and mimics insulin action on tissues involved in glucose homeostasis in vitro.

    Science.gov (United States)

    Mohankumar, Sureshkumar; McFarlane, James R

    2011-03-01

    Curcuma longa (turmeric) has been used widely as a spice, particularly in Asian countries. It is also used in the Ayurvedic system of medicine as an antiinflammatory and antimicrobial agent and for numerous other curative properties. The aim of this study was to investigate the effects of an aqueous extract of Curcuma longa (AEC) on tissues involved in glucose homeostasis. The extract was prepared by soaking 100 g of ground turmeric in 1 L of water, which was filtered and stored at -20°C prior to use. Pancreas and muscle tissues of adult mice were cultured in DMEM with 5 or 12 mmol/L glucose and varying doses of extract. The AEC stimulated insulin secretion from mouse pancreatic tissues under both basal and hyperglycaemic conditions, although the maximum effect was only 68% of that of tolbutamide. The AEC induced stepwise stimulation of glucose uptake from abdominal muscle tissues in the presence and absence of insulin, and the combination of AEC and insulin significantly potentiated the glucose uptake into abdominal muscle tissue. However, this effect was attenuated by wortmannin, suggesting that AEC possibly acts via the insulin-mediated glucose uptake pathway. In summary, water soluble compounds of turmeric exhibit insulin releasing and mimicking actions within in vitro tissue culture conditions. Copyright © 2010 John Wiley & Sons, Ltd.

  15. Regulation of gonadotropin-releasing hormone neurons by glucose

    Science.gov (United States)

    Roland, Alison V.; Moenter, Suzanne M.

    2011-01-01

    Reproduction is influenced by energy balance, but the physiological pathways mediating their relationship have not been fully elucidated. As the central regulators of fertility, gonadotropin-releasing hormone (GnRH) neurons integrate numerous physiological signals, including metabolic cues. Circulating glucose levels regulate GnRH release and may in part mediate the effects of negative energy balance on fertility. Existing evidence suggests that neural pathways originating in the hindbrain, as well as in the hypothalamic feeding nuclei, transmit information concerning glucose availability to GnRH neurons. Here we review recent evidence suggesting that GnRH neurons may directly sense changes in glucose availability by a mechanism involving adenosine monophosphate-activated protein kinase (AMPK). These findings expand our understanding of how metabolic signaling in the brain regulates reproduction. PMID:21855365

  16. Interleukin 6 stimulates hepatic glucose release from prelabeled glycogen pools

    International Nuclear Information System (INIS)

    Ritchie, D.G.

    1990-01-01

    Cytokines, derived from a wide variety of cell types, are now believed to initiate many of the physiological responses accompanying the inflammatory phase that follows either Gram-negative septicemia or thermal injury. Because hypoglycemia (after endotoxic challenge) and hyperglycemia (after thermal injury) represent well-characterized responses to these injuries, we sought to determine whether hepatic glycogen metabolism could be altered by specific cytokines. Cultured adult rat hepatocytes were prelabeled with [ 14 C]glucose for 24 h, a procedure that resulted in the labeling of hepatic glycogen pools that subsequently could be depleted (with concomitant [ 14 C]glucose release) by either glucagon or norepinephrine. After the addition of a highly concentrated human monocyte-conditioned medium (MCM) or various cytokines to these prelabeled cells, [ 14 C]glucose release was stimulated by MCM and recombinant human interleukin 6 (IL-6) but was not stimulated by other cytokines tested. Furthermore, only antisera to IL-6 were capable of reducing the glucose-releasing factor activity found in MCM. These data therefore suggest a novel glucoregulatory role for IL-6

  17. Sourcing and bioprocessing of brown seaweed for maximizing glucose release

    DEFF Research Database (Denmark)

    Manns, Dirk Martin

    maximum levels of glucose. The first requirement was to develop a robust methodology, including acid hydrolysis and analytical composition analysis, to quantitatively estimate the carbohydrate composition of the brown seaweeds. The monosaccharide composition of four different samples of brown seaweeds...... with lower enzyme loading. Simple application of only the cellulase preparation enabled the release of only half of the present glucose after 8 h. Analysis after the enzymatic treatment indicated a potential extraction of proteins from the solid residue and the sulfated polysaccharide fucoidan solubilized...

  18. Glucose-mediated control of ghrelin release from primary cultures of gastric mucosal cells

    Science.gov (United States)

    Sakata, Ichiro; Park, Won-Mee; Walker, Angela K.; Piper, Paul K.; Chuang, Jen-Chieh; Osborne-Lawrence, Sherri

    2012-01-01

    The peptide hormone ghrelin is released from a distinct group of gastrointestinal cells in response to caloric restriction, whereas its levels fall after eating. The mechanisms by which ghrelin secretion is regulated remain largely unknown. Here, we have used primary cultures of mouse gastric mucosal cells to investigate ghrelin secretion, with an emphasis on the role of glucose. Ghrelin secretion from these cells upon exposure to different d-glucose concentrations, the glucose antimetabolite 2-deoxy-d-glucose, and other potential secretagogues was assessed. The expression profile of proteins involved in glucose transport, metabolism, and utilization within highly enriched pools of mouse ghrelin cells and within cultured ghrelinoma cells was also determined. Ghrelin release negatively correlated with d-glucose concentration. Insulin blocked ghrelin release, but only in a low d-glucose environment. 2-Deoxy-d-glucose prevented the inhibitory effect of high d-glucose exposure on ghrelin release. mRNAs encoding several facilitative glucose transporters, hexokinases, the ATP-sensitive potassium channel subunit Kir6.2, and sulfonylurea type 1 receptor were expressed highly within ghrelin cells, although neither tolbutamide nor diazoxide exerted direct effects on ghrelin secretion. These findings suggest that direct exposure of ghrelin cells to low ambient d-glucose stimulates ghrelin release, whereas high d-glucose and glucose metabolism within ghrelin cells block ghrelin release. Also, low d-glucose sensitizes ghrelin cells to insulin. Various glucose transporters, channels, and enzymes that mediate glucose responsiveness in other cell types may contribute to the ghrelin cell machinery involved in regulating ghrelin secretion under these different glucose environments, although their exact roles in ghrelin release remain uncertain. PMID:22414807

  19. Gastrin-Releasing Peptide and Glucose Metabolism Following Pancreatitis.

    Science.gov (United States)

    Pendharkar, Sayali A; Drury, Marie; Walia, Monika; Korc, Murray; Petrov, Maxim S

    2017-08-01

    Gastrin-releasing peptide (GRP) is a pluripotent peptide that has been implicated in both gastrointestinal inflammatory states and classical chronic metabolic diseases such as diabetes. Abnormal glucose metabolism (AGM) after pancreatitis, an exemplar inflammatory disease involving the gastrointestinal tract, is associated with persistent low-grade inflammation and altered secretion of pancreatic and gut hormones as well as cytokines. While GRP is involved in secretion of many of them, it is not known whether GRP has a role in AGM. Therefore, we aimed to investigate the association between GRP and AGM following pancreatitis. Fasting blood samples were collected to measure GRP, blood glucose, insulin, amylin, glucagon, pancreatic polypeptide (PP), somatostatin, cholecystokinin, gastric-inhibitory peptide (GIP), gastrin, ghrelin, glicentin, glucagon-like peptide-1 and 2, oxyntomodulin, peptide YY (PYY), secretin, vasoactive intestinal peptide, tumor necrosis factor-α (TNF-α), monocyte chemoattractant protein (MCP)-1, and interleukin-6. Modified Poisson regression analysis and linear regression analyses were conducted. Four statistical models were used to adjust for demographic, metabolic, and pancreatitis-related risk factors. A total of 83 individuals after an episode of pancreatitis were recruited. GRP was significantly associated with AGM, consistently in all four models (P -trend < 0.05), and fasting blood glucose contributed 17% to the variance of GRP. Further, GRP was significantly associated with glucagon (P < 0.003), MCP-1 (P < 0.025), and TNF-α (P < 0.025) - consistently in all four models. GRP was also significantly associated with PP and PYY in three models (P < 0.030 for both), and with GIP and glicentin in one model (P = 0.001 and 0.024, respectively). Associations between GRP and other pancreatic and gut hormones were not significant. GRP is significantly increased in patients with AGM after pancreatitis and is associated with increased levels of pro

  20. Impaired basal glucose effectiveness but unaltered fasting glucose release and gluconeogenesis during short-term hypercortisolemia in healthy subjects

    DEFF Research Database (Denmark)

    Nielsen, Michael F; Caumo, Andrea; Chandramouli, Visvanathan

    2004-01-01

    Excess cortisol has been demonstrated to impair hepatic and extrahepatic insulin action. To determine whether glucose effectiveness and, in terms of endogenous glucose release (EGR), gluconeogenesis, also are altered by hypercortisolemia, eight healthy subjects were studied after overnight infusion...... resistance. Postabsorptive glucose production (P = 0.64) and the fractional....... Hepatic GE was lower during cortisol than during saline infusion (2.39 +/- 0.24 vs. 3.82 +/- 0.51 ml.kg-1.min-1; P

  1. Uptake and release of glucose by the human kidney. Postabsorptive rates and responses to epinephrine.

    Science.gov (United States)

    Stumvoll, M; Chintalapudi, U; Perriello, G; Welle, S; Gutierrez, O; Gerich, J

    1995-11-01

    Despite ample evidence that the kidney can both produce and use appreciable amounts of glucose, the human kidney is generally regarded as playing a minor role in glucose homeostasis. This view is based on measurements of arteriorenal vein glucose concentrations indicating little or no net release of glucose. However, inferences from net balance measurements do not take into consideration the simultaneous release and uptake of glucose by the kidney. Therefore, to assess the contribution of release and uptake of glucose by the human kidney to overall entry and removal of plasma glucose, we used a combination of balance and isotope techniques to measure renal glucose net balance, fractional extraction, uptake and release as well as overall plasma glucose appearance and disposal in 10 normal volunteers under basal postabsorptive conditions and during a 3-h epinephrine infusion. In the basal postabsorptive state, there was small but significant net output of glucose by the kidney (66 +/- 22 mumol.min-1, P = 0.016). However, since renal glucose fractional extraction averaged 2.9 +/- 0.3%, there was considerable renal glucose uptake (2.3 +/- 0.2 mumol.kg-1.min-1) which accounted for 20.2 +/- 1.7% of systemic glucose disposal (11.4 +/- 0.5 mumol.kg-1.min-1). Renal glucose release (3.2 +/- 0.2 mumol.kg-1.min-1) accounted for 27.8 +/- 2.1% of systemic glucose appearance (11.4 +/- 0.5 mumol.kg-1.min-1). Epinephrine infusion, which increased plasma epinephrine to levels observed during hypoglycemia (3722 +/- 453 pmol/liter) increased renal glucose release nearly twofold (5.2 +/- 0.5 vs 2.8 +/- 0.1 mol.kg-1.min-1, P = 0.01) so that at the end of the infusion, renal glucose release accounted for 40.3 +/- 5.5% of systemic glucose appearance and essentially all of the increase in systemic glucose appearance. These observations suggest an important role for the human kidney in glucose homeostasis.

  2. Glucose tolerance, insulin release, and insulin binding to monocytes in kidney transplant recipients

    International Nuclear Information System (INIS)

    Briggs, W.A.; Wielechowski, K.S.; Mahajan, S.K.; Migdal, S.D.; McDonald, F.D.

    1982-01-01

    In order to evaluate glucose tolerance following renal transplantation, intravenous glucose tolerance tests (IVGTT), with evaluation of hormonal responses to the intravenous glucose load and percent specific 125 I-insulin binding to peripheral blood monocytes, were studied in eight clinically stable kidney transplant recipients. For comparison purposes, identical studies were done in eight control subjects and seven clinically stable hemodialysis patients. One transplant recipient was glucose intolerant, with fasting hyperglycemia, elevated HbA1C, and abnormal glucose decay constant. Impaired pancreatic insulin release appeared to be the major factor accounting for his glucose intolerance. The seven glucose-tolerant transplant recipients had significantly increased insulin release during IVGTT compared to control subjects, and significant correlations were found among insulin release, glucose decay constant, and fasting blood sugar in those patients. Insulin binding to monocytes was significantly greater in transplant recipients than control subjects due to an increase in insulin binding capacity per cell. A significant correlation was found between percent specific 125 I-insulin binding and steroid dose, expressed as mg/kg body weight/day, in those patients. Thus, chronic steroid administration does not cause glucose intolerance in transplant recipients who manifest steroid-associated increases in pancreatic insulin release and cellular insulin binding capacity

  3. Effect of glibenclamide on insulin release at moderate and high blood glucose levels in normal man

    NARCIS (Netherlands)

    Ligtenberg, JJM; Venker, CE; Sluiter, WJ; VanHaeften, TW

    Insulin release occurs in two phases; sulphonylurea derivatives may have different potencies in stimulating first-and second-phase insulin release. We studied the effect of glibenclamide on insulin secretion at submaximally and maximally stimulating blood glucose levels with a primed hyperglycaemic

  4. Fabrication of Glucose-Sensitive Layer-by-Layer Films for Potential Controlled Insulin Release Applications

    Directory of Open Access Journals (Sweden)

    Talusan Timothy Jemuel E.

    2015-01-01

    Full Text Available Self-regulated drug delivery systems (DDS are potential alternative to the conventional method of introducing insulin to the body due to their controlled drug release mechanism. In this study, Layer-by-Layer technique was utlized to manufacture drug loaded, pH responsive thin films. Insulin was alternated with pH-sensitive, [2-(dimethyl amino ethyl aminoacrylate] (PDMAEMA and topped of with polymer/glucose oxidase (GOD layers. Similarly, films using a different polymer, namely Poly(Acrylic Acid (PAA were also fabricated. Exposure of the films to glucose solutions resulted to the production of gluconic acid causing a polymer conformation change due to protonation, thus releasing the embedded insulin. The insulin release was monitored by subjecting the dipping glucose solutions to Bradford Assay. Films exhibited a reversal in drug release profile in the presence of glucose as compared to without glucose. PAA films were also found out to release more insulin compared to that of the PDMAEMA films.The difference in the profile of the two films were due to different polymer-GOD interactions, since both films exhibited almost identical profiles when embedded with Poly(sodium 4-styrenesulfonate (PSS instead of GOD.

  5. Nitric oxide agents impair insulin-mediated signal transduction in rat skeletal muscle

    Directory of Open Access Journals (Sweden)

    Ragoobirsingh Dalip

    2006-05-01

    Full Text Available Abstract Background Evidence demonstrates that exogenously administered nitric oxide (NO can induce insulin resistance in skeletal muscle. We have investigated the modulatory effects of two NO donors, S-nitroso-N-acetyl-D, L-penicillamine (SNAP and S-nitrosoglutathione (GSNO on the early events in insulin signaling in rat skeletal myocytes. Results Skeletal muscle cells from 6–8 week old Sprague-Dawley rats were treated with SNAP or GSNO (25 ng/ml in the presence or absence of glucose (25 mM and insulin (100 nM. Cellular insulin receptor-β levels and tyrosine phosphorylation in IRS-1 were significantly reduced, while serine phosphorylation in IRS-1 was significantly increased in these cells, when compared to the insulin-stimulated control. Reversal to near normal levels was achieved using the NO scavenger, 2-(4-carboxyphenyl-4, 4, 5, 5-tetramethylimidazoline-1-oxyl 3-oxide (carboxy-PTIO. Conclusion These data suggest that NO is a potent modulator of insulin-mediated signal transduction and may play a significant role in the pathogenesis of type 2 diabetes mellitus.

  6. Insulin-mediated increases in renal plasma flow are impaired in insulin-resistant normal subjects

    NARCIS (Netherlands)

    ter Maaten, JC; Bakker, SJL; Serne, EH; Moshage, HJ; Gans, ROB

    2000-01-01

    Background Impaired vasodilatation in skeletal muscle is a possible mechanism linking insulin resistance to blood pressure regulation. Increased renal vascular resistance has been demonstrated in the offspring of essential hypertensives. We assessed whether insulin-mediated renal vasodilatation is

  7. Analysis of results of oral glucose tolerance test (OGTT) and insulin releasing test in hepatogenic diabetics

    International Nuclear Information System (INIS)

    He Haoming; Fu Qiang; Tian Xiaoping; Su Cainu

    2001-01-01

    Objective: To explore the clinical values of OGTT and insulin releasing test in hepatogenic diabetics. Method: OGTT was performed by enzymes method and insulin releasing test by RIA in 30 patients with hepatogenic diabetes, 31 cases with II diabetes and 35 controls. Results: During OGTT, blood glucose levels at various time were about the same in hepatogenic diabetics and II diabetics (P < 0.05), except at 180 min (P < 0.01). Basal hyperinsulinemia was present is hepatogenic diabetics. Conclusion: OGTT and insulin releasing test had a definite clinical value in the differential diagnosis of hepatogenic diabetics

  8. Insulin sensitivity, insulin release and glucagon-like peptide-1 levels in persons with impaired fasting glucose and/or impaired glucose tolerance in the EUGENE2 study

    DEFF Research Database (Denmark)

    Laakso, M; Zilinskaite, J; Hansen, T

    2008-01-01

    AIMS/HYPOTHESIS: We examined the phenotype of individuals with impaired fasting glucose (IFG) and/or impaired glucose tolerance (IGT) with regard to insulin release and insulin resistance. METHODS: Non-diabetic offspring (n=874; mean age 40+/-10.4 years; BMI 26.6+/-4.9 kg/m(2)) of type 2 diabetic...

  9. Light Control of Insulin Release and Blood Glucose Using an Injectable Photoactivated Depot.

    Science.gov (United States)

    Sarode, Bhagyesh R; Kover, Karen; Tong, Pei Y; Zhang, Chaoying; Friedman, Simon H

    2016-11-07

    In this work we demonstrate that blood glucose can be controlled remotely through light stimulated release of insulin from an injected cutaneous depot. Human insulin was tethered to an insoluble but injectable polymer via a linker, which was based on the light cleavable di-methoxy nitrophenyl ethyl (DMNPE) group. This material was injected into the skin of streptozotocin-treated diabetic rats. We observed insulin being released into the bloodstream after a 2 min trans-cutaneous irradiation of this site by a compact LED light source. Control animals treated with the same material, but in which light was blocked from the site, showed no release of insulin into the bloodstream. We also demonstrate that additional pulses of light from the light source result in additional pulses of insulin being absorbed into circulation. A significant reduction in blood glucose was then observed. Together, these results demonstrate the feasibility of using light to allow for the continuously variable control of insulin release. This in turn has the potential to allow for the tight control of blood glucose without the invasiveness of insulin pumps and cannulas.

  10. Impact of PTBP1 rs11085226 on glucose-stimulated insulin release in adult Danes

    DEFF Research Database (Denmark)

    Hansen, Tue Haldor; Vestergaard, Henrik; Jørgensen, Torben

    2015-01-01

    ,641 glucose tolerant controls, respectively. Quantitative trait analyses were performed in up to 13,605 individuals subjected to an OGTT or blood samples obtained after an overnight fast, as well as in 596 individuals subjected to an IVGTT. Results: Analyses of fasting and OGTT-derived quantitative traits did.......024; P=0.01) assuming a dominant model of inheritance, but failed to replicate a previously reported association with area under the curve (AUC) for insulin. Case control analysis did not show an association of the PTBP1 rs11085226 variant with type 2 diabetes. Conclusions: Despite failure to replicate......Background: The variant rs11085226 (G) within the gene encoding polypyrimidine tract binding protein 1 (PTBP1) was reported to associate with reduced insulin release determined by an oral glucose tolerance test (OGTT) as well as an intravenous glucose tolerance test (IVGTT). The aim of the present...

  11. Detection of glutathione based on MnO2 nanosheet-gated mesoporous silica nanoparticles and target induced release of glucose measured with a portable glucose meter.

    Science.gov (United States)

    Tan, Qingqing; Zhang, Ruirui; Kong, Rongmei; Kong, Weisu; Zhao, Wenzhi; Qu, Fengli

    2017-12-08

    The authors describe a novel method for the determination of glutathione (GSH). Detection is based on target induced release of glucose from MnO 2 nanosheet-gated aminated mesoporous silica nanoparticles (MSNs). In detail, glucose is loaded into the pores of MSNs. Negatively charged MnO 2 nanosheets are assembled on the MSNs through electrostatic interactions. The nanosheets are reduced by GSH, and this results in the release of glucose which is quantified by using a commercial electrochemical glucose meter. GSH can be quantified by this method in the 100 nM to 10 μM concentration range, with a 34 nM limit of detection. Graphical abstract Glucose is loaded into the pores of mesoporous silica nanoparticles (MSNs). MnO 2 nanosheets are assembled on MSNs through electrostatic interactions. Glutathione (GSH) can reduce the nanosheets, and this results in the release of glucose which is quantified by using a commercial glucose meter.

  12. Extracellular Vesicles from Hypoxic Adipocytes and Obese Subjects Reduce Insulin‐Stimulated Glucose Uptake

    Science.gov (United States)

    Mleczko, Justyna; Ortega, Francisco J.; Falcon‐Perez, Juan Manuel; Wabitsch, Martin; Fernandez‐Real, Jose Manuel

    2018-01-01

    Scope We investigate the effects of extracellular vesicles (EVs) obtained from in vitro adipocyte cell models and from obese subjects on glucose transport and insulin responsiveness. Methods and results EVs are isolated from the culture supernatant of adipocytes cultured under normoxia, hypoxia (1% oxygen), or exposed to macrophage conditioned media (15% v/v). EVs are isolated from the plasma of lean individuals and subjects with obesity. Cultured adipocytes are incubated with EVs and activation of insulin signalling cascades and insulin‐stimulated glucose transport are measured. EVs released from hypoxic adipocytes impair insulin‐stimulated 2‐deoxyglucose uptake and reduce insulin mediated phosphorylation of AKT. Insulin‐mediated phosphorylation of extracellular regulated kinases (ERK1/2) is not affected. EVs from individuals with obesity decrease insulin stimulated 2‐deoxyglucose uptake in adipocytes (p = 0.0159). Conclusion EVs released by stressed adipocytes impair insulin action in neighboring adipocytes. PMID:29292863

  13. Dietary fat content alters insulin-mediated glucose metabolism in healthy men

    NARCIS (Netherlands)

    Bisschop, PH; de Metz, J; Ackermans, MT; Endert, E; Pijl, H; Kuipers, F; Meijer, AJ; Sauerwein, HP; Romijn, JA

    Background: A high dietary fat intake is involved in the pathogenesis of insulin resistance. Objective: The aim was to compare the effect of different amounts of dietary fat on hepatic and peripheral insulin sensitivity. Design: Six healthy men were studied on 3 occasions after consuming for 11 d

  14. Controlled release of D-glucose from starch granules containing 29% free D-glucose and Eudragit L100-55 as a binding and coating agent.

    Science.gov (United States)

    Kim, Yeon-Kye; Mukerjea, Rupendra; Robyt, John F

    2010-05-27

    Waxy maize starch (100% amylopectin) granules were modified by reaction of the granules with glucoamylase in a minimum amount of water to give 29% (w/w) D-glucose inside the granules [Kim, Y.-K.; Robyt, J. F. Carbohydr. Res.1999, 318, 129-134]. These granules were made into beads by dropping an ethanol slurry of starch and different amounts of Eudragit L100-55 in a constant ratio of 100:1 from a pipette onto Whatman 3MM filter paper. The starch beads were air dried and then repeatedly sprayed 0-12 times with 2.0% (w/v) Eudragit L100-55 in ethanol, with drying between each spraying, to coat the surface of the starch beads, giving different amounts of Eudragit L100-55 coating. Seven different kinds of beads, with different amounts of Eudragit L100-55 binding and coating agent, were obtained. The rates of release of D-glucose into water from the seven kinds of beads were inversely proportional to the amount of binding and coating agent. Bead type I, which was without any binding and coating gave a fast 100% release of D-glucose in 30 min. Beads II and III also gave a fast 100% release in 60 min and 90 min, respectively. Bead IV gave a near linear release of 97% D-glucose in 150 min; Bead V gave a 50% release in 120 min followed by the remaining 50% in 60 min; and Beads VI and VII gave a slow release of 10% and 4%, respectively, from 0 to 120 min, followed by a rapid 100% release from 120 to 180 min. (c) 2010 Elsevier Ltd. All rights reserved.

  15. Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release.

    LENUS (Irish Health Repository)

    Huber, Heinrich J

    2011-03-01

    Many anticancer drugs activate caspases via the mitochondrial apoptosis pathway. Activation of this pathway triggers a concomitant bioenergetic crisis caused by the release of cytochrome-c (cyt-c). Cancer cells are able to evade these processes by altering metabolic and caspase activation pathways. In this study, we provide the first integrated system study of mitochondrial bioenergetics and apoptosis signalling and examine the role of mitochondrial cyt-c release in these events. In accordance with single-cell experiments, our model showed that loss of cyt-c decreased mitochondrial respiration by 95% and depolarised mitochondrial membrane potential ΔΨ(m) from -142 to -88 mV, with active caspase-3 potentiating this decrease. ATP synthase was reversed under such conditions, consuming ATP and stabilising ΔΨ(m). However, the direction and level of ATP synthase activity showed significant heterogeneity in individual cancer cells, which the model explained by variations in (i) accessible cyt-c after release and (ii) the cell\\'s glycolytic capacity. Our results provide a quantitative and mechanistic explanation for the protective role of enhanced glucose utilisation for cancer cells to avert the otherwise lethal bioenergetic crisis associated with apoptosis initiation.

  16. Potentiation of glucose-induced insulin release in islets by desHis1[Glu9]glucagon amide

    DEFF Research Database (Denmark)

    Kofod, Hans; Unson, C G; Merrifield, R B

    1988-01-01

    Glucagon and secretin and some of their hybrid analogs potentiate glucose-induced release of insulin from isolated mouse pancreatic islets. It was recently shown that the synthetic glucagon analog, desHis1[Glu9]glucagon amide, does not stimulate the formation of cyclic adenosine monophosphate...... in the rat hepatocyte membrane, but binds well to the glucagon receptor and is a good competitive antagonist of glucagon. In the present study the effect of this analog on isolated islets was examined. desHis1-[Glu9]glucagon amide at 3 x 10(-7) M, in the presence of 0.01 M D-glucose, increased the release...

  17. Postprandial interleukin-6 release from skeletal muscle in men with impaired glucose tolerance can be reduced by weight loss

    NARCIS (Netherlands)

    Corpeleijn, E.; Saris, W.H.; Jansen, E.H.; Roekaerts, P.M.; Feskens, E.J.M.; Blaak, E.E.

    2005-01-01

    Context: Obesity and type 2 diabetes mellitus are associated with increased levels of IL-6, a marker of inflammation. Objective: This study addressed the question of whether IL-6 was released from skeletal muscle after a high-fat meal in men with impaired glucose tolerance (IGT), a prediabetic

  18. Liver glycogen in type 2 diabetic mice is randomly branched as enlarged aggregates with blunted glucose release.

    Science.gov (United States)

    Besford, Quinn Alexander; Zeng, Xiao-Yi; Ye, Ji-Ming; Gray-Weale, Angus

    2016-02-01

    Glycogen is a vital highly branched polymer of glucose that is essential for blood glucose homeostasis. In this article, the structure of liver glycogen from mice is investigated with respect to size distributions, degradation kinetics, and branching structure, complemented by a comparison of normal and diabetic liver glycogen. This is done to screen for differences that may result from disease. Glycogen α-particle (diameter ∼ 150 nm) and β-particle (diameter ∼ 25 nm) size distributions are reported, along with in vitro γ-amylase degradation experiments, and a small angle X-ray scattering analysis of mouse β-particles. Type 2 diabetic liver glycogen upon extraction was found to be present as large loosely bound, aggregates, not present in normal livers. Liver glycogen was found to aggregate in vitro over a period of 20 h, and particle size is shown to be related to rate of glucose release, allowing a structure-function relationship to be inferred for the tissue specific distribution of particle types. Application of branching theories to small angle X-ray scattering data for mouse β-particles revealed these particles to be randomly branched polymers, not fractal polymers. Together, this article shows that type 2 diabetic liver glycogen is present as large aggregates in mice, which may contribute to the inflexibility of interconversion between glucose and glycogen in type 2 diabetes, and further that glycogen particles are randomly branched with a size that is related to the rate of glucose release.

  19. Monomeric adiponectin modulates nitric oxide release and calcium movements in porcine aortic endothelial cells in normal/high glucose conditions.

    Science.gov (United States)

    Grossini, Elena; Farruggio, Serena; Qoqaiche, Fatima; Raina, Giulia; Camillo, Lara; Sigaudo, Lorenzo; Mary, David; Surico, Nicola; Surico, Daniela

    2016-09-15

    Perivascular adipose tissue can be involved in the process of cardiovascular pathology through the release of adipokines, namely adiponectins. Monomeric adiponectin has been shown to increase coronary blood flow in anesthetized pigs through increased nitric oxide (NO) release and the involvement of adiponectin receptor 1 (AdipoR1). The present study was therefore planned to examine the effects of monomeric adiponectin on NO release and Ca(2+) transients in porcine aortic endothelial cells (PAEs) in normal/high glucose conditions and the related mechanisms. PAEs were treated with monomeric adiponectin alone or in the presence of intracellular kinases blocker, AdipoR1 and Ca(2+)-ATPase pump inhibitors. The role of Na(+)/Ca(2+) exchanger was examined in experiments performed in zero Na(+) medium. NO release and intracellular Ca(2+) were measured through specific probes. In PAE cultured in normal glucose conditions, monomeric adiponectin elevated NO production and [Ca(2+)]c. Similar effects were observed in high glucose conditions, although the response was lower and not transient. The Ca(2+) mobilized by monomeric adiponectin originated from an intracellular pool thapsigargin- and ATP-sensitive and from the extracellular space. Moreover, the effects of monomeric adiponectin were prevented by kinase blockers and AdipoR1 inhibitor. Finally, in normal glucose condition, a role for Na(+)/Ca(2+) exchanger and Ca(2+)-ATPase pump in restoring Ca(2+) was found. Our results add new information about the control of endothelial function elicited by monomeric adiponectin, which would be achieved by modulation of NO release and Ca(2+) transients. A signalling related to Akt, ERK1/2 and p38MAPK downstream AdipoR1 would be involved. Copyright © 2016 Elsevier Inc. All rights reserved.

  20. Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

    Directory of Open Access Journals (Sweden)

    Annamaria Morelli

    2013-01-01

    Full Text Available Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose effects in the human GnRH-secreting FNC-B4 cells. Gene expression profiling by qRT-PCR, confirmed that FNC-B4 cells express GnRH and several genes relevant for GnRH neuron function (KISS1R, KISS1, sex steroid and leptin receptors, FGFR1, neuropilin 2, and semaphorins, along with glucose transporters (GLUT1, GLUT3, and GLUT4. High glucose exposure (22 mM; 40 mM significantly reduced gene and protein expression of GnRH, KISS1R, KISS1, and leptin receptor, as compared to normal glucose (5 mM. Consistent with previous studies, leptin treatment significantly induced GnRH mRNA expression at 5 mM glucose, but not in the presence of high glucose concentrations. In conclusion, our findings demonstrate a deleterious direct contribution of high glucose on human GnRH neurons, thus providing new insights into pathogenic mechanisms linking metabolic disorders to reproductive dysfunctions.

  1. Xylitol vs glucose: Effect on the rate of gastric emptying and motilin, insulin, and gastric inhibitory polypeptide release

    International Nuclear Information System (INIS)

    Salminen, E.K.; Salminen, S.J.; Porkka, L.; Kwasowski, P.; Marks, V.; Koivistoinen, P.E.

    1989-01-01

    The effect of xylitol and glucose on the rate of gastric emptying and intestinal transit and on motilin, gastric inhibitory polypeptide (GIP), and insulin release were studied in human volunteers. A single oral dose of 200 mL water containing 30 g glucose or 30 g xylitol, mixed with a 99m technetium-tin (99mTc-Sn) colloid, was used. Similar dosing without the label was used in motilin, GIP, and insulin studies. Xylitol decreased the rate of gastric emptying but concomitantly accelerated intestinal transit compared with glucose. The half-times for gastric emptying were 77.5 +/- 4.6 and 39.8 +/- 3.4 min after ingestion of xylitol and glucose solutions, respectively. Glucose suppressed motilin and stimulated GIP secretion; xylitol stimulated motilin secretion but had no effect on GIP, which is currently the main candidate for the role of enterogastrone. The accelerated intestinal transit and increase in plasma motilin observed after xylitol ingestion were thought to be causally related to the diarrhea and gastrointestinal discomfort produced by it

  2. Negative Effects of High Glucose Exposure in Human Gonadotropin-Releasing Hormone Neurons

    OpenAIRE

    Morelli, Annamaria; Comeglio, Paolo; Sarchielli, Erica; Cellai, Ilaria; Vignozzi, Linda; Vannelli, Gabriella B.; Maggi, Mario

    2013-01-01

    Metabolic disorders are often associated with male hypogonadotropic hypogonadism, suggesting that hypothalamic defects involving GnRH neurons may impair the reproductive function. Among metabolic factors hyperglycemia has been implicated in the control of the reproductive axis at central level, both in humans and in animal models. To date, little is known about the direct effects of pathological high glucose concentrations on human GnRH neurons. In this study, we investigated the high glucose...

  3. 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

  4. Exaggerated release and preserved insulinotropic action of glucagon-like peptide-1 underlie insulin hypersecretion in glucose-tolerant individuals after Roux-en-Y gastric bypass

    DEFF Research Database (Denmark)

    Dirksen, Carsten; Bojsen-Møller, Kirstine N; Jørgensen, Nils Bruun

    2013-01-01

    Roux-en-Y gastric bypass (RYGB) improves glycaemic control in part by increasing postprandial insulin secretion through exaggerated glucagon-like peptide (GLP)-1 release. However, it is unknown whether islet cell responsiveness to i.v. glucose, non-glucose (arginine) and incretin hormones...

  5. Mitochondrial Dynamics Mediated by Mitofusin 1 Is Required for POMC Neuron Glucose-Sensing and Insulin Release Control.

    Science.gov (United States)

    Ramírez, Sara; Gómez-Valadés, Alicia G; Schneeberger, Marc; Varela, Luis; Haddad-Tóvolli, Roberta; Altirriba, Jordi; Noguera, Eduard; Drougard, Anne; Flores-Martínez, Álvaro; Imbernón, Mónica; Chivite, Iñigo; Pozo, Macarena; Vidal-Itriago, Andrés; Garcia, Ainhoa; Cervantes, Sara; Gasa, Rosa; Nogueiras, Ruben; Gama-Pérez, Pau; Garcia-Roves, Pablo M; Cano, David A; Knauf, Claude; Servitja, Joan-Marc; Horvath, Tamas L; Gomis, Ramon; Zorzano, Antonio; Claret, Marc

    2017-06-06

    Proopiomelanocortin (POMC) neurons are critical sensors of nutrient availability implicated in energy balance and glucose metabolism control. However, the precise mechanisms underlying nutrient sensing in POMC neurons remain incompletely understood. We show that mitochondrial dynamics mediated by Mitofusin 1 (MFN1) in POMC neurons couple nutrient sensing with systemic glucose metabolism. Mice lacking MFN1 in POMC neurons exhibited defective mitochondrial architecture remodeling and attenuated hypothalamic gene expression programs during the fast-to-fed transition. This loss of mitochondrial flexibility in POMC neurons bidirectionally altered glucose sensing, causing abnormal glucose homeostasis due to defective insulin secretion by pancreatic β cells. Fed mice lacking MFN1 in POMC neurons displayed enhanced hypothalamic mitochondrial oxygen flux and reactive oxygen species generation. Central delivery of antioxidants was able to normalize the phenotype. Collectively, our data posit MFN1-mediated mitochondrial dynamics in POMC neurons as an intrinsic nutrient-sensing mechanism and unveil an unrecognized link between this subset of neurons and insulin release. Copyright © 2017 Elsevier Inc. All rights reserved.

  6. The Type 2 Diabetes Associated Minor Allele of rs2237895 KCNQ1 Associates with Reduced Insulin Release Following an Oral Glucose Load

    DEFF Research Database (Denmark)

    Brunak, Søren; Holmkvist, J; Banasik, K

    2009-01-01

    , and rs2237897) on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT) in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin...... release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean......,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified...

  7. Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Sylow, Lykke; Rose, Adam John

    2014-01-01

    signals through proteins such as AMPK. Here, we demonstrate in incubated mouse muscle that Ca(2+) release is neither sufficient nor strictly necessary to increase glucose transport. Rather, the glucose transport response is associated with metabolic feedback signals through AMPK, and mechanical stress......-activated signals. Furthermore, artificial stimulation of AMPK combined with passive stretch of muscle is additive and sufficient to elicit the full contraction glucose transport response. These results suggest that ATP-turnover and mechanical stress feedback are sufficient to fully increase glucose transport...

  8. Fabrication, characterization, in vitro drug release and glucose uptake activity of 14-deoxy, 11, 12-didehydroandrographolide loaded polycaprolactone nanoparticles

    Directory of Open Access Journals (Sweden)

    Nagalakshmi Kamaraj

    2017-07-01

    Full Text Available Biodegradable polymer based novel drug delivery systems brought a considerable attention in enhancing the therapeutic efficacy and bioavailability of various drugs. 14-deoxy 11, 12-didehydro andrographolide (poorly water soluble compound loaded polycaprolactone (nano-DDA was synthesized using the solvent evaporation technique. Nano-DDA was characterized by scanning electron microscopy (SEM and dynamic light scattering (DLS studies. Fourier Transform InfraRed Spectroscopy (FTIR was used to investigate the structural interaction between the drug and the polymer. Functional characterization of the formulation was determined using drug content, cellular uptake and in vitro drug release. 2-deoxy-D-[1-3H] glucose uptake assay was carried out to assess the antidiabetic potential of nano-DDA in L6 myotubes. The nano-DDA displayed spherical shape with a smooth surface (252.898 nm diameter, zeta potential, encapsulation and loading efficiencies of −38.9 mV, 91.98 ± 0.13% and 15.09 ± 0.18% respectively. No structural alteration between the drug and the polymer was evidenced (FTIR analysis. Confocal microscopy studies with rhodamine 123 loaded polycaprolactone nanoparticles (Rh123-PCL NPs revealed the internalization of Rh123-PCL NPs in a time dependent manner in L6 myoblasts. A dose dependent increase in glucose uptake was observed for nano-DDA with a maximal uptake of 108.54 ± 1.42% at 100 nM on L6 myotubes, thereby proving its anti-diabetic efficacy. A biphasic pattern of in vitro drug release demonstrated an initial burst release at 24 h followed by a sustained release for up to 11 days. To conclude, our results revealed that nano-DDA formulation can be a potent candidate for antidiabetic drug delivery.

  9. Contraction-stimulated glucose transport in muscle is controlled by AMPK and mechanical stress but not sarcoplasmatic reticulum Ca2+ release

    Directory of Open Access Journals (Sweden)

    Thomas E. Jensen

    2014-10-01

    Full Text Available Understanding how muscle contraction orchestrates insulin-independent muscle glucose transport may enable development of hyperglycemia-treating drugs. The prevailing concept implicates Ca2+ as a key feed forward regulator of glucose transport with secondary fine-tuning by metabolic feedback signals through proteins such as AMPK. Here, we demonstrate in incubated mouse muscle that Ca2+ release is neither sufficient nor strictly necessary to increase glucose transport. Rather, the glucose transport response is associated with metabolic feedback signals through AMPK, and mechanical stress-activated signals. Furthermore, artificial stimulation of AMPK combined with passive stretch of muscle is additive and sufficient to elicit the full contraction glucose transport response. These results suggest that ATP-turnover and mechanical stress feedback are sufficient to fully increase glucose transport during muscle contraction, and call for a major reconsideration of the established Ca2+ centric paradigm.

  10. Glucose-Dependent Insulin Secretion in Pancreatic β-Cell Islets from Male Rats Requires Ca2+ Release via ROS-Stimulated Ryanodine Receptors.

    Directory of Open Access Journals (Sweden)

    Paola Llanos

    Full Text Available Glucose-stimulated insulin secretion (GSIS from pancreatic β-cells requires an increase in intracellular free Ca2+ concentration ([Ca2+]. Glucose uptake into β-cells promotes Ca2+ influx and reactive oxygen species (ROS generation. In other cell types, Ca2+ and ROS jointly induce Ca2+ release mediated by ryanodine receptor (RyR channels. Therefore, we explored here if RyR-mediated Ca2+ release contributes to GSIS in β-cell islets isolated from male rats. Stimulatory glucose increased islet insulin secretion, and promoted ROS generation in islets and dissociated β-cells. Conventional PCR assays and immunostaining confirmed that β-cells express RyR2, the cardiac RyR isoform. Extended incubation of β-cell islets with inhibitory ryanodine suppressed GSIS; so did the antioxidant N-acetyl cysteine (NAC, which also decreased insulin secretion induced by glucose plus caffeine. Inhibitory ryanodine or NAC did not affect insulin secretion induced by glucose plus carbachol, which engages inositol 1,4,5-trisphosphate receptors. Incubation of islets with H2O2 in basal glucose increased insulin secretion 2-fold. Inhibitory ryanodine significantly decreased H2O2-stimulated insulin secretion and prevented the 4.5-fold increase of cytoplasmic [Ca2+] produced by incubation of dissociated β-cells with H2O2. Addition of stimulatory glucose or H2O2 (in basal glucose to β-cells disaggregated from islets increased RyR2 S-glutathionylation to similar levels, measured by a proximity ligation assay; in contrast, NAC significantly reduced the RyR2 S-glutathionylation increase produced by stimulatory glucose. We propose that RyR2-mediated Ca2+ release, induced by the concomitant increases in [Ca2+] and ROS produced by stimulatory glucose, is an essential step in GSIS.

  11. Glucose metabolism determines resistance of cancer cells to bioenergetic crisis after cytochrome-c release

    OpenAIRE

    Huber, Heinrich J.; Dussmann, Heiko; Kilbride, Sean M.; Rehm, Markus; Prehn, Jochen H. M.

    2011-01-01

    How can cells cope with a bioenergetic crisis? In particular, how can cancer cells survive the bioenergetic consequences of cyt-c release that are often induced by chemotherapeutic agents, and that lead to depolarisation of the mitochondrial membrane potential ΔΨm, result in loss of ionic homeostasis and induce cell death? Is there an inherent population heterogeneity that can lead to a non-synchronous response to above cell death stimuli, thereby aggravating treatment and contributing to cli...

  12. Glucagon-like peptide-2, but not glucose-dependent insulinotropic polypeptide, stimulates glucagon release in patients with type 1 diabetes

    DEFF Research Database (Denmark)

    Christensen, Mikkel; Knop, Filip K; Vilsbøll, Tina

    2010-01-01

    This study investigated the glucagon-releasing properties of the hormones glucagon-like peptide-2 (GLP-2) and glucose-dependent insulinotropic polypeptide (GIP) in 8 patients with type 1 diabetes mellitus (T1DM) without paracrine intraislet influence of insulin (C-peptide negative following a 5 g...... intravenous arginine stimulation; on study days only treated with basal insulin substitution). On 3 study days, 180-minute two-step glucose clamps were performed. Plasma glucose (PG) was clamped at fasting values, with a mean of 7.4+/-0.5 mM in the first 90 min (period 1) and raised 1.5 times the fasting...

  13. Sustained Na+/H+ exchanger activation promotes gliotransmitter release from reactive hippocampal astrocytes following oxygen-glucose deprivation.

    Directory of Open Access Journals (Sweden)

    Pelin Cengiz

    Full Text Available Hypoxia ischemia (HI-related brain injury is the major cause of long-term morbidity in neonates. One characteristic hallmark of neonatal HI is the development of reactive astrogliosis in the hippocampus. However, the impact of reactive astrogliosis in hippocampal damage after neonatal HI is not fully understood. In the current study, we investigated the role of Na(+/H(+ exchanger isoform 1 (NHE1 protein in mouse reactive hippocampal astrocyte function in an in vitro ischemia model (oxygen/glucose deprivation and reoxygenation, OGD/REOX. 2 h OGD significantly increased NHE1 protein expression and NHE1-mediated H(+ efflux in hippocampal astrocytes. NHE1 activity remained stimulated during 1-5 h REOX and returned to the basal level at 24 h REOX. NHE1 activation in hippocampal astrocytes resulted in intracellular Na(+ and Ca(2+ overload. The latter was mediated by reversal of Na(+/Ca(2+ exchange. Hippocampal astrocytes also exhibited a robust release of gliotransmitters (glutamate and pro-inflammatory cytokines IL-6 and TNFα during 1-24 h REOX. Interestingly, inhibition of NHE1 activity with its potent inhibitor HOE 642 not only reduced Na(+ overload but also gliotransmitter release from hippocampal astrocytes. The noncompetitive excitatory amino acid transporter inhibitor TBOA showed a similar effect on blocking the glutamate release. Taken together, we concluded that NHE1 plays an essential role in maintaining H(+ homeostasis in hippocampal astrocytes. Over-stimulation of NHE1 activity following in vitro ischemia disrupts Na(+ and Ca(2+ homeostasis, which reduces Na(+-dependent glutamate uptake and promotes release of glutamate and cytokines from reactive astrocytes. Therefore, blocking sustained NHE1 activation in reactive astrocytes may provide neuroprotection following HI.

  14. Glucose tolerance, insulin sensitivity and insulin release in European non-diabetic carriers of a polymorphism upstream of CDKN2A and CDKN2B

    DEFF Research Database (Denmark)

    Hribal, M L; Presta, I; Procopio, T

    2011-01-01

    The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry.......The aim of this study was to investigate the association of the rs10811661 polymorphism near the CDKN2B/CDKN2A genes with glucose tolerance, insulin sensitivity and insulin release in three samples of white people with European ancestry....

  15. Effect of exercise training on in vivo insulin-stimulated glucose uptake in intra-abdominal adipose tissue in rats

    DEFF Research Database (Denmark)

    Enevoldsen, L H; Stallknecht, B; Fluckey, J D

    2000-01-01

    Intra-abdominal obesity may be crucial in the pathogenesis of the insulin-resistance syndrome, and training may alleviate this condition. We compared insulin-mediated glucose uptake in vivo in three intra-abdominal adipose tissues (ATs; retroperitoneal, parametrial, and mesenteric) and in subcuta......Intra-abdominal obesity may be crucial in the pathogenesis of the insulin-resistance syndrome, and training may alleviate this condition. We compared insulin-mediated glucose uptake in vivo in three intra-abdominal adipose tissues (ATs; retroperitoneal, parametrial, and mesenteric...

  16. Differential effects of glucagon-like peptide-1 on microvascular recruitment and glucose metabolism in short- and long-term Insulin resistance

    DEFF Research Database (Denmark)

    Sjøberg, Kim Anker; Rattigan, Stephen; Jeppesen, Jacob Fuglsbjerg

    2015-01-01

    Acute infusion of glucagon-like-peptide-1 (GLP-1) has potent effects on blood flow distribution through the microcirculation in healthy humans and rats. High fat diet induces impairments in insulin-mediated microvascular recruitment (MVR) and muscle glucose uptake, and here we examined whether......-mediated glucose uptake in skeletal muscle by 90% (Prights...

  17. Alizarin Complexone Functionalized Mesoporous Silica Nanoparticles: A Smart System Integrating Glucose-Responsive Double-Drugs Release and Real-Time Monitoring Capabilities.

    Science.gov (United States)

    Zou, Zhen; He, Dinggeng; Cai, Linli; He, Xiaoxiao; Wang, Kemin; Yang, Xue; Li, Liling; Li, Siqi; Su, Xiaoya

    2016-04-06

    The outstanding progress of nanoparticles-based delivery systems capable of releasing hypoglycemic drugs in response to glucose has dramatically changed the outlook of diabetes management. However, the developed glucose-responsive systems have not offered real-time monitoring capabilities for accurate quantifying hypoglycemic drugs released. In this study, we present a multifunctional delivery system that integrates both delivery and monitoring issues using glucose-triggered competitive binding scheme on alizarin complexone (ALC) functionalized mesoporous silica nanoparticles (MSN). In this system, ALC is modified on the surface of MSN as the signal reporter. Gluconated insulin (G-Ins) is then introduced onto MSN-ALC via benzene-1,4-diboronic acid (BA) mediated esterification reaction, where G-Ins not only blocks drugs inside the mesopores but also works as a hypoglycemic drug. In the absence of glucose, the sandwich-type boronate ester structure formed by BA binding to the diols of ALC and G-Ins remains intact, resulting in an fluorescence emission peak at 570 nm and blockage of pores. Following a competitive binding, the presence of glucose cause the dissociation of boronate ester between ALC and BA, which lead to the pores opening and disappearance of fluorescence. As proof of concept, rosiglitazone maleate (RSM), an insulin-sensitizing agent, was doped into the MSN to form a multifunctional MSN (RSM@MSN-ALC-BA-Ins), integrating with double-drugs loading, glucose-responsive performance, and real-time monitoring capability. It has been demonstrated that the glucose-responsive release behaviors of insulin and RSM in buffer or in human serum can be quantified in real-time through evaluating the changes of fluorescence signal. We believe that this developed multifunctional system can shed light on the invention of a new generation of smart nanoformulations for optical diagnosis, individualized treatment, and noninvasive monitoring of diabetes management.

  18. Modeling of glucose release from native and modified wheat starch gels during in vitro gastrointestinal digestion using artificial intelligence methods.

    Science.gov (United States)

    Yousefi, A R; Razavi, Seyed M A

    2017-04-01

    Estimation of the amounts of glucose release (AGR) during gastrointestinal digestion can be useful to identify food of potential use in the diet of individuals with diabetes. In this work, adaptive neuro-fuzzy inference system (ANFIS), genetic algorithm-artificial neural network (GA-ANN) and group method of data handling (GMDH) models were applied to estimate the AGR from native (NWS), cross-linked (CLWS) and hydroxypropylated wheat starch (HPWS) gels during digestion under simulated gastrointestinal conditions. The GA-ANN and ANFIS were fed with 3 inputs of digestion time (1-120min), gel volume (7.5 and 15ml) and concentration (8 and 12%, w/w) for prediction of the AGR. The developed ANFIS predictions were close to the experimental data (r=0.977-0.996 and RMSE=0.225-0.619). The optimized GA-ANN, which included 6-7 hidden neurons, predicted the AGR with a good precision (r=0.984-0.993 and RMSE=0.338-0.588). Also, a three layers GMDH model with 3 neurons accurately predicted the AGR (r=0.979-0.986 and RMSE=0.339-0.443). Sensitivity analysis data demonstrated that the gel concentration was the most sensitive factor for prediction of the AGR. The results dedicated that the AGR will be accurately predictable through such soft computing methods providing less computational cost and time. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Downregulation of cinnamyl-alcohol dehydrogenase in switchgrass by RNA silencing results in enhanced glucose release after cellulase treatment.

    Directory of Open Access Journals (Sweden)

    Aaron J Saathoff

    Full Text Available Cinnamyl alcohol dehydrogenase (CAD catalyzes the last step in monolignol biosynthesis and genetic evidence indicates CAD deficiency in grasses both decreases overall lignin, alters lignin structure and increases enzymatic recovery of sugars. To ascertain the effect of CAD downregulation in switchgrass, RNA mediated silencing of CAD was induced through Agrobacterium mediated transformation of cv. "Alamo" with an inverted repeat construct containing a fragment derived from the coding sequence of PviCAD2. The resulting primary transformants accumulated less CAD RNA transcript and protein than control transformants and were demonstrated to be stably transformed with between 1 and 5 copies of the T-DNA. CAD activity against coniferaldehyde, and sinapaldehyde in stems of silenced lines was significantly reduced as was overall lignin and cutin. Glucose release from ground samples pretreated with ammonium hydroxide and digested with cellulases was greater than in control transformants. When stained with the lignin and cutin specific stain phloroglucinol-HCl the staining intensity of one line indicated greater incorporation of hydroxycinnamyl aldehydes in the lignin.

  20. Downregulation of cinnamyl-alcohol dehydrogenase in switchgrass by RNA silencing results in enhanced glucose release after cellulase treatment.

    Science.gov (United States)

    Saathoff, Aaron J; Sarath, Gautam; Chow, Elaine K; Dien, Bruce S; Tobias, Christian M

    2011-01-27

    Cinnamyl alcohol dehydrogenase (CAD) catalyzes the last step in monolignol biosynthesis and genetic evidence indicates CAD deficiency in grasses both decreases overall lignin, alters lignin structure and increases enzymatic recovery of sugars. To ascertain the effect of CAD downregulation in switchgrass, RNA mediated silencing of CAD was induced through Agrobacterium mediated transformation of cv. "Alamo" with an inverted repeat construct containing a fragment derived from the coding sequence of PviCAD2. The resulting primary transformants accumulated less CAD RNA transcript and protein than control transformants and were demonstrated to be stably transformed with between 1 and 5 copies of the T-DNA. CAD activity against coniferaldehyde, and sinapaldehyde in stems of silenced lines was significantly reduced as was overall lignin and cutin. Glucose release from ground samples pretreated with ammonium hydroxide and digested with cellulases was greater than in control transformants. When stained with the lignin and cutin specific stain phloroglucinol-HCl the staining intensity of one line indicated greater incorporation of hydroxycinnamyl aldehydes in the lignin.

  1. Glucose deprivation stimulates Cu(2+) toxicity in cultured cerebellar granule neurons and Cu(2+)-dependent zinc release.

    Science.gov (United States)

    Isaev, Nickolay K; Genrikhs, Elisaveta E; Aleksandrova, Olga P; Zelenova, Elena A; Stelmashook, Elena V

    2016-05-27

    Copper chloride (0.01mM, 2h) did not have significant influence on the survival of cerebellar granule neurons (CGNs) incubated in balanced salt solution. However, CuCl2 caused severe neuronal damage by glucose deprivation (GD). The glutamate NMDA-receptors blocker MK-801 partially and antioxidant N-acetyl-l-cysteine (NAC) or Zn(2+) chelator, N,N,N',N'-tetrakis(2-pyridylmethyl)ethylenediamine (TPEN) almost entirely protected CGNs from this toxic effect. Measurements of intracellular calcium ions using Fluo-4 AM, or zinc ions with FluoZin-3 AM demonstrated that 1 h-exposure to GD induced intensive increase of Fluo-4 but not FluoZin-3 fluorescence in neurons. The supplementation of solution with CuCl2 caused an increase of FluoZin-3, Fluo-4 and CellROX Green (reactive oxygen species probe) fluorescence by GD. The stimulation of Fluo-4 but not FluoZin-3 fluorescence by copper could be prevented partially by MK-801 and as well as CellROX Green fluorescence by NAC at GD. This data imply that during GD copper ions induce intense displacement zinc ions from intracellular stores, in addition free radical production, glutamate release and Ca(2+) overload of CGNs, that causes death of neurons as a result. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. Effect of thyrotropin-releasing hormone (TRH) on local cerebral glucose utilization, by the autoradiographic 2-deoxy [14C] glucose method, in conscious and pentobarbitalized rats

    International Nuclear Information System (INIS)

    Nagai, Y.; Narumi, S.; Nagawa, Y.; Sakurada, O.; Ueno, H.; Ishii, S.

    1980-01-01

    Effects of TRH and pentobarbital alone, and in combination, on local cerebral glucose utilization of rats were studied by the autoradiographic 2-deoxy[ 14 C] glucose method. TRH (5 mg/kg i.v.) reduced the rate of cerebral glucose utilization slightly in the whole brain. Locally, significant depression was observed in the following structures: frontal and visual cortices, hippocampus Ammon's horn and dentate gyrus, medial and lateral geniculate bodies, nucleus accumbens, caudate-putamen, substantia nigra, pontine gray matter, superior colliculus, superior olivary nucleus, vestibular nucleus, lateral lemniscus and cerebellar cortex. Pentobarbital (30 mg/kg i.v.) produced a marked and diffuse reduction in the rate of glucose utilization throughout the brain. TRH given 15 min after the administration of pentobarbital markedly shortened the pentobarbital sleeping time and caused some reversal of the depression in local cerebral glucose utilization produced by pentobarbital., These effects were almost completely abolished by pretreatment with intracerebroventricular injection of atropine methyl bromide (20 μg/rat). These results indicate that although TRH acts to cause a reduction in the rate of cerebral glucose utilization, it reverses the depression induced by pentobarbital, via a cholinergic mechanism, in a number of structures, some of which are related to monoaminergic systems and the reticulo-thalamo-cortical activating system. (author)

  3. A variant in the G6PC2/ABCB11 locus is associated with increased fasting plasma glucose, increased basal hepatic glucose production and increased insulin release after oral and intravenous glucose loads

    DEFF Research Database (Denmark)

    Rose, C S; Grarup, N; Krarup, N T

    2009-01-01

    An association between elevated fasting plasma glucose and the common rs560887 G allele in the G6PC2/ABCB11 locus has been reported. In Danes we aimed to examine rs560887 in relation to plasma glucose and serum insulin responses following oral and i.v. glucose loads and in relation to hepatic...... glucose production during a hyperinsulinaemic-euglycaemic clamp. Furthermore, we examined rs560887 for association with impaired fasting glycaemia (IFG), impaired glucose tolerance (IGT), type 2 diabetes and components of the metabolic syndrome....

  4. Long-term effects of rapamycin treatment on insulin mediated phosphorylation of Akt/PKB and glycogen synthase activity

    International Nuclear Information System (INIS)

    Varma, Shailly; Shrivastav, Anuraag; Changela, Sheena; Khandelwal, Ramji L.

    2008-01-01

    Protein kinase B (Akt/PKB) is a Ser/Thr kinase that is involved in the regulation of cell proliferation/survival through mammalian target of rapamycin (mTOR) and the regulation of glycogen metabolism through glycogen synthase kinase 3β (GSK-3β) and glycogen synthase (GS). Rapamycin is an inhibitor of mTOR. The objective of this study was to investigate the effects of rapamycin pretreatment on the insulin mediated phosphorylation of Akt/PKB phosphorylation and GS activity in parental HepG2 and HepG2 cells with overexpression of constitutively active Akt1/PKB-α (HepG2-CA-Akt/PKB). Rapamycin pretreatment resulted in a decrease (20-30%) in the insulin mediated phosphorylation of Akt1 (Ser 473) in parental HepG2 cells but showed an upregulation of phosphorylation in HepG2-CA-Akt/PKB cells. Rictor levels were decreased (20-50%) in parental HepG2 cells but were not significantly altered in the HepG2-CA-Akt/PKB cells. Furthermore, rictor knockdown decreased the phosphorylation of Akt (Ser 473) by 40-60% upon rapamycin pretreatment. GS activity followed similar trends as that of phosphorylated Akt and so with rictor levels in these cells pretreated with rapamycin; parental HepG2 cells showed a decrease in GS activity, whereas as HepG2-CA-Akt/PKB cells showed an increase in GS activity. The changes in the levels of phosphorylated Akt/PKB (Ser 473) correlated with GS and protein phoshatase-1 activity

  5. The type 2 diabetes associated minor allele of rs2237895 KCNQ1 associates with reduced insulin release following an oral glucose load.

    Directory of Open Access Journals (Sweden)

    Johan Holmkvist

    Full Text Available BACKGROUND: Polymorphisms in the potassium channel, voltage-gated, KQT-like subfamily, member 1 (KCNQ1 have recently been reported to associate with type 2 diabetes. The primary aim of the present study was to investigate the putative impact of these KCNQ1 polymorphisms (rs2283228, rs2237892, rs2237895, and rs2237897 on estimates of glucose stimulated insulin release. METHODOLOGY/PRINCIPAL FINDINGS: Genotypes were examined for associations with serum insulin levels following an oral glucose tolerance test (OGTT in a population-based sample of 6,039 middle-aged and treatment-naïve individuals. Insulin release indices estimated from the OGTT and the interplay between insulin sensitivity and insulin release were investigated using linear regression and Hotelling T2 analyses. Applying an additive genetic model the minor C-allele of rs2237895 was associated with reduced serum insulin levels 30 min (mean+/-SD: (CC 277+/-160 vs. (AC 280+/-164 vs. (AA 299+/-200 pmol/l, p = 0.008 after an oral glucose load, insulinogenic index (29.6+/-17.4 vs. 30.2+/-18.7vs. 32.2+/-22.1, p = 0.007, incremental area under the insulin curve (20,477+/-12,491 vs. 20,503+/-12,386 vs. 21,810+/-14,685, p = 0.02 among the 4,568 individuals who were glucose tolerant. Adjustment for the degree of insulin sensitivity had no effect on the measures of reduced insulin release. The rs2237895 genotype had a similar impact in the total sample of treatment-naïve individuals. No association with measures of insulin release were identified for the less common diabetes risk alleles of rs2237892, rs2237897, or rs2283228. CONCLUSION: The minor C-allele of rs2237895 of KCNQ1, which has a prevalence of about 42% among Caucasians was associated with reduced measures of insulin release following an oral glucose load suggesting that the increased risk of type 2 diabetes, previously reported for this variant, likely is mediated through an impaired beta cell function.

  6. The impact of blood glucose levels on stimulated adrenocorticotropin hormone and growth hormone release in healthy subjects

    NARCIS (Netherlands)

    Jakobsdottir, S.; Twisk, J.W.R.; Drent, M.L.

    2009-01-01

    Objective In studies investigating the influence of glucose levels on the pituitary function the methods used have been variable and mainly focused on the change in function as a reaction to unphysiological low or high blood glucose levels. In the present study the impact of physiological and

  7. Evaluation of fasting state-/oral glucose tolerance test-derived measures of insulin release for the detection of genetically impaired β-cell function.

    Directory of Open Access Journals (Sweden)

    Silke A Herzberg-Schäfer

    Full Text Available BACKGROUND: To date, fasting state- and different oral glucose tolerance test (OGTT-derived measures are used to estimate insulin release with reasonable effort in large human cohorts required, e.g., for genetic studies. Here, we evaluated twelve common (or recently introduced fasting state-/OGTT-derived indices for their suitability to detect genetically determined β-cell dysfunction. METHODOLOGY/PRINCIPAL FINDINGS: A cohort of 1364 White European individuals at increased risk for type 2 diabetes was characterized by OGTT with glucose, insulin, and C-peptide measurements and genotyped for single nucleotide polymorphisms (SNPs known to affect glucose- and incretin-stimulated insulin secretion. One fasting state- and eleven OGTT-derived indices were calculated and statistically evaluated. After adjustment for confounding variables, all tested SNPs were significantly associated with at least two insulin secretion measures (p≤0.05. The indices were ranked according to their associations' statistical power, and the ranks an index obtained for its associations with all the tested SNPs (or a subset were summed up resulting in a final ranking. This approach revealed area under the curve (AUC(Insulin(0-30/AUC(Glucose(0-30 as the best-ranked index to detect SNP-dependent differences in insulin release. Moreover, AUC(Insulin(0-30/AUC(Glucose(0-30, corrected insulin response (CIR, AUC(C-Peptide(0-30/AUC(Glucose(0-30, AUC(C-Peptide(0-120/AUC(Glucose(0-120, two different formulas for the incremental insulin response from 0-30 min, i.e., the insulinogenic indices (IGI(2 and IGI(1, and insulin 30 min were significantly higher-ranked than homeostasis model assessment of β-cell function (HOMA-B; p<0.05. AUC(C-Peptide(0-120/AUC(Glucose(0-120 was best-ranked for the detection of SNPs involved in incretin-stimulated insulin secretion. In all analyses, HOMA-β displayed the highest rank sums and, thus, scored last. CONCLUSIONS/SIGNIFICANCE: With AUC(Insulin(0

  8. PKB/Akt phosphorylation of ERRγ contributes to insulin-mediated inhibition of hepatic gluconeogenesis.

    Science.gov (United States)

    Kim, Don-Kyu; Kim, Yong-Hoon; Hynx, Debby; Wang, Yanning; Yang, Keum-Jin; Ryu, Dongryeol; Kim, Kyung Seok; Yoo, Eun-Kyung; Kim, Jeong-Sun; Koo, Seung-Hoi; Lee, In-Kyu; Chae, Ho-Zoon; Park, Jongsun; Lee, Chul-Ho; Biddinger, Sudha B; Hemmings, Brian A; Choi, Hueng-Sik

    2014-12-01

    Insulin resistance, a major contributor to the pathogenesis of type 2 diabetes, leads to increased hepatic glucose production (HGP) owing to an impaired ability of insulin to suppress hepatic gluconeogenesis. Nuclear receptor oestrogen-related receptor γ (ERRγ) is a major transcriptional regulator of hepatic gluconeogenesis. In this study, we investigated insulin-dependent post-translational modifications (PTMs) altering the transcriptional activity of ERRγ for the regulation of hepatic gluconeogenesis. We examined insulin-dependent phosphorylation and subcellular localisation of ERRγ in cultured cells and in the liver of C57/BL6, leptin receptor-deficient (db/db), liver-specific insulin receptor knockout (LIRKO) and protein kinase B (PKB) β-deficient (Pkbβ (-/-)) mice. To demonstrate the role of ERRγ in the inhibitory action of insulin on hepatic gluconeogenesis, we carried out an insulin tolerance test in C57/BL6 mice expressing wild-type or phosphorylation-deficient mutant ERRγ. We demonstrated that insulin suppressed the transcriptional activity of ERRγ by promoting PKB/Akt-mediated phosphorylation of ERRγ at S179 and by eliciting translocation of ERRγ from the nucleus to the cytoplasm through interaction with 14-3-3, impairing its ability to promote hepatic gluconeogenesis. In addition, db/db, LIRKO and Pkbβ (-/-) mice displayed enhanced ERRγ transcriptional activity due to a block in PKBβ-mediated ERRγ phosphorylation during refeeding. Finally, the phosphorylation-deficient mutant ERRγ S179A was resistant to the inhibitory action of insulin on HGP. These results suggest that ERRγ is a major contributor to insulin action in maintaining hepatic glucose homeostasis.

  9. Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in patients with type 2 diabetes.

    Science.gov (United States)

    Temizkan, S; Deyneli, O; Yasar, M; Arpa, M; Gunes, M; Yazici, D; Sirikci, O; Haklar, G; Imeryuz, N; Yavuz, D G

    2015-02-01

    Artificial sweeteners were thought to be metabolically inactive, but after demonstrating that the gustatory mechanism was also localized in the small intestine, suspicions about the metabolic effects of artificial sweeteners have emerged. The objective of this study was to determine the effect of artificial sweeteners (aspartame and sucralose) on blood glucose, insulin, c-peptide and glucagon-like peptide-1 (GLP-1) levels. Eight newly diagnosed drug-naive type 2 diabetic patients (mean age 51.5±9.2 years; F/M: 4/4) and eight healthy subjects (mean age 45.0±4.1 years; F/M: 4/4) underwent 75 g oral glucose tolerance test (OGTT). During OGTT, glucose, insulin, c-peptide and GLP-1 were measured at 15- min intervals for 120 min. The OGTTs were performed at three settings on different days, where subjects were given 72 mg of aspartame and 24 mg of sucralose in 200 ml of water or 200 ml of water alone 15 min before OGTT in a single-blinded randomized order. In healthy subjects, the total area under the curve (AUC) of glucose was statistically significantly lower in the sucralose setting than in the water setting (P=0.002). There was no difference between the aspartame setting and the water setting (P=0.53). Total AUC of insulin and c-peptide was similar in aspartame, sucralose and water settings. Total AUC of GLP-1 was significantly higher in the sucralose setting than in the water setting (P=0.04). Total AUC values of glucose, insulin, c-peptide and GLP-1 were not statistically different in three settings in type 2 diabetic patients. Sucralose enhances GLP-1 release and lowers blood glucose in the presence of carbohydrate in healthy subjects but not in newly diagnosed type 2 diabetic patients.

  10. Release Profile and Inhibition Test of The Nanoparticles A. Paniculata Extract as Inhibitor of α-Glucosidase in The Process of Carbohydrates Breakdown Into Glucose Diabetes Mellitus

    Science.gov (United States)

    Imansari, Farisa; Sahlan, Muhammad; Arbianti, Rita

    2017-07-01

    Andrographis paniculata (A.paniculata) contain the main active substances Andrographolide which helps lower glucose levels in diabetics by inhibiting the enzyme α-glucosidase. The ability of the extract A.paniculata in lowering glucose levels will increase with the technique encapsulation with a coating of composition Chitosan-STPP as a drug delivery to the target organ. This study aimed to get an overview of A.paniculata release profile of nanoparticles in a synthetic fluid media with various concentrations of coating and inhibition testing nasty shard extract in inhibiting the enzyme α-glucosidase. This research resulted in nanoparticles by coating efficiency and loading capacity of chitosan greatest variation of 2% and 1% STPP 60% and 46.29%. chitosan greatest variation of 2% and 1% STPP 60% and 46.29%. The ability of A.paniculata extracts as α-glucosidase enzyme inhibitors has been demonstrated in this study, the percent inhibition of 33.17%.

  11. Biosynthesis and release of thyrotropin-releasing hormone immunoreactivity in rat pancreatic islets in organ culture. Effects of age, glucose, and streptozotocin

    DEFF Research Database (Denmark)

    Dolva, L O; Welinder, B S; Hanssen, K F

    1983-01-01

    Thyrotropin-releasing hormone immunoreactivity (TRH-IR) was measured in isolated islets and in medium from rat pancreatic islets maintained in organ culture. TRH-IR in methanol extracts of both islets and culture medium was eluted in the same position as synthetic TRH by ion-exchange and gel...... chromatography and exhibited dilution curves parallel with synthetic TRH in radioimmunoassay. [3H]Histidine was incorporated into a component that reacted with TRH antiserum and had the same retention time as synthetic TRH on reversed-phase high-performance liquid chromatography. A continuous release of TRH...

  12. Glucose-induced incretin hormone release and inactivation are differently modulated by oral fat and protein in mice

    DEFF Research Database (Denmark)

    Gunnarsson, P Thomas; Winzell, Maria Sörhede; Deacon, Carolyn F

    2006-01-01

    Monounsaturated fatty acids, such as oleic acid (OA), and certain milk proteins, especially whey protein (WP), have insulinotropic effects and can reduce postprandial glycemia. This effect may involve the incretin hormones glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like pepti...

  13. The glucose oxidase-peroxidase assay for glucose

    Science.gov (United States)

    The glucose oxidase-peroxidase assay for glucose has served as a very specific, sensitive, and repeatable assay for detection of glucose in biological samples. It has been used successfully for analysis of glucose in samples from blood and urine, to analysis of glucose released from starch or glycog...

  14. Type 2 diabetes risk allele near CENTD2 is associated with decreased glucose-stimulated insulin release

    DEFF Research Database (Denmark)

    Nielsen, Trine; Sparsø, T; Grarup, N

    2011-01-01

    By combining multiple genome-wide association (GWA) studies and comprehensive replication efforts, 12 novel type 2 diabetes associated loci have recently been discovered. Here we evaluate the effect of lead variants of these loci on estimates of insulin release and insulin resistance derived from...

  15. Piracetam ameliorated oxygen and glucose deprivation-induced injury in rat cortical neurons via inhibition of oxidative stress, excitatory amino acids release and P53/Bax.

    Science.gov (United States)

    He, Zhi; Hu, Min; Zha, Yun-hong; Li, Zi-cheng; Zhao, Bo; Yu, Ling-ling; Yu, Min; Qian, Ying

    2014-05-01

    Our previous work has demonstrated that piracetam inhibited the decrease in amino acid content induced by chronic hypoperfusion, ameliorated the dysfunction of learning and memory in a hypoperfusion rat model, down-regulated P53, and BAX protein, facilitated the synaptic plasticity, and may be helpful in the treatment of vascular dementia. To explore the precise mechanism, the present study further evaluated effects of piracetam on Oxygen and glucose deprivation (OGD)-induced neuronal damage in rat primary cortical cells. The addition of piracetam to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and lactate dehydrogenase release experiments. Piracetam also lowered the levels of malondialdehyde, nitrogen monoxidum, and xanthine oxidase which was increased in the OGD cells, and enhanced the activities of superoxide dismutase and glutathione peroxidase, which were decreased in the OGD cells. We also demonstrated that piracetam could decrease glutamate and aspartate release when cortical cells were subjected to OGD. Furthermore, Western blot study demonstrated that piracetam attenuated the increased expression of P53 and BAX protein in OGD cells. These observations demonstrated that piracetam reduced OGD-induced neuronal damage by inhibiting the oxidative stress and decreasing excitatory amino acids release and lowering P53/Bax protein expression in OGD cells.

  16. 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)

  17. The effect of endogenously released glucose, insulin, glucagon-like peptide 1, ghrelin on cardiac output, heart rate, stroke volume, and blood pressure.

    Science.gov (United States)

    Hlebowicz, Joanna; Lindstedt, Sandra; Björgell, Ola; Dencker, Magnus

    2011-12-29

    Ingestion of a meal increases the blood flow to the gastrointestinal organs and affects the heart rate (HR), blood pressure and cardiac output (CO), although the mechanisms are not known. The aim of this study was to evaluate the effect of endogenously released glucose, insulin, glucagon-like peptide 1 (GLP-1), ghrelin on CO, HR, stroke volume (SV), and blood pressure. Eleven healthy men and twelve healthy women ((mean ± SEM) aged: 26 ± 0.2 y; body mass index: 21.8 ± 0.1 kg/m(2))) were included in this study. The CO, HR, SV, systolic and diastolic blood pressure, antral area, gastric emptying rate, and glucose, insulin, GLP-1 and ghrelin levels were measured. The CO and SV at 30 min were significantly higher, and the diastolic blood pressure was significantly lower, than the fasting in both men and women (P blood pressure (P = 0.021, r = -0.681), and the change in SV (P = 0.008, r = -0.748) relative to the fasting in men. The insulin 0-30 min AUC was significantly correlated to the CO 0-30 min AUC (P = 0.002, r = 0.814) in men. Significant correlations were also found between the 0-120 min ghrelin and HR AUCs (P = 0.007, r = 0.966) in men. No statistically significant correlations were seen in women. Physiological changes in the levels of glucose, insulin, GLP-1 and ghrelin may influence the activity of the heart and the blood pressure. There may also be gender-related differences in the haemodynamic responses to postprandial changes in hormone levels. The results of this study show that subjects should not eat immediately prior to, or during, the evaluation of cardiovascular interventions as postprandial affects may affect the results, leading to erroneous interpretation of the cardiovascular effects of the primary intervention. NCT01027507.

  18. Inclusion of Whole Flour from Latin-American Crops into Bread Formulations as Substitute of Wheat Delays Glucose Release and Uptake.

    Science.gov (United States)

    Laparra, José Moisés; Haros, Monika

    2018-03-01

    Bakery formulations limiting glucose availability for uptake without compromising product quality are required. Herein, bread formulations containing whole flour from Amaranthus hypochondriacus (AB), Chenopodium quinoa (QB), Salvia hispanica L (ChB) or wheat (WWB) were compared to white bread (WB) for glycaemic index (GI) in fasted animals. The hepatic expression (mRNA) of PPAR-γ receptor as key regulator in substrate fractionation towards energy expenditure was monitored. GIs were associated to fluxes of glucose release (F Gluc ) and metabolic response (MTT assay) of HepG2 cells. ChB (19.7%) and AB (13.5%) decreased GI to a higher extent than QB (2.7%), but all increased expression of PPARγ in relation to WB. F Gluc (AB> > ChB, WWB, WB > QB) showed a reciprocal relationship with the area under curve (AUC) in vivo, and decreased MTT conversion values (WB > WWB, ChB, AB, QB) by HepG2 cells. Thus, inclusion of latin-american crops (LAcs) reducing GI, without compromising bread quality, could help preventing metabolic diseases.

  19. Effects of Higher Dietary Protein and Fiber Intakes at Breakfast on Postprandial Glucose, Insulin, and 24-h Interstitial Glucose in Overweight Adults.

    Science.gov (United States)

    Amankwaah, Akua F; Sayer, R Drew; Wright, Amy J; Chen, Ningning; McCrory, Megan A; Campbell, Wayne W

    2017-04-02

    Dietary protein and fiber independently influence insulin-mediated glucose control. However, potential additive effects are not well-known. Men and women ( n = 20; age: 26 ± 5 years; body mass index: 26.1 ± 0.2 kg/m²; mean ± standard deviation) consumed normal protein and fiber (NPNF; NP = 12.5 g, NF = 2 g), normal protein and high fiber (NPHF; NP = 12.5 g, HF = 8 g), high protein and normal fiber (HPNF; HP = 25 g, NF = 2 g), or high protein and fiber (HPHF; HP = 25 g, HF = 8 g) breakfast treatments during four 2-week interventions in a randomized crossover fashion. On the last day of each intervention, meal tolerance tests were completed to assess postprandial (every 60 min for 240 min) serum glucose and insulin concentrations. Continuous glucose monitoring was used to measure 24-h interstitial glucose during five days of the second week of each intervention. Repeated-measures ANOVA was applied for data analyses. The HPHF treatment did not affect postprandial glucose and insulin responses or 24-h glucose total area under the curve (AUC). Higher fiber intake reduced 240-min insulin AUC. Doubling the amount of protein from 12.5 g to 25 g/meal and quadrupling fiber from 2 to 8 g/meal at breakfast was not an effective strategy for modulating insulin-mediated glucose responses in these young, overweight adults.

  20. The effect of endogenously released glucose, insulin, glucagon-like peptide 1, ghrelin on cardiac output, heart rate, stroke volume, and blood pressure

    Directory of Open Access Journals (Sweden)

    Hlebowicz Joanna

    2011-12-01

    Full Text Available Abstract Background Ingestion of a meal increases the blood flow to the gastrointestinal organs and affects the heart rate (HR, blood pressure and cardiac output (CO, although the mechanisms are not known. The aim of this study was to evaluate the effect of endogenously released glucose, insulin, glucagon-like peptide 1 (GLP-1, ghrelin on CO, HR, stroke volume (SV, and blood pressure. Methods Eleven healthy men and twelve healthy women ((mean ± SEM aged: 26 ± 0.2 y; body mass index: 21.8 ± 0.1 kg/m2 were included in this study. The CO, HR, SV, systolic and diastolic blood pressure, antral area, gastric emptying rate, and glucose, insulin, GLP-1 and ghrelin levels were measured. Results The CO and SV at 30 min were significantly higher, and the diastolic blood pressure was significantly lower, than the fasting in both men and women (P P = 0.015, r = 0.946, and between ghrelin levels and HR (P = 0.013, r = 0.951 at 110 min. Significant correlations were also found between the change in glucose level at 30 min and the change in systolic blood pressure (P = 0.021, r = -0.681, and the change in SV (P = 0.008, r = -0.748 relative to the fasting in men. The insulin 0-30 min AUC was significantly correlated to the CO 0-30 min AUC (P = 0.002, r = 0.814 in men. Significant correlations were also found between the 0-120 min ghrelin and HR AUCs (P = 0.007, r = 0.966 in men. No statistically significant correlations were seen in women. Conclusions Physiological changes in the levels of glucose, insulin, GLP-1 and ghrelin may influence the activity of the heart and the blood pressure. There may also be gender-related differences in the haemodynamic responses to postprandial changes in hormone levels. The results of this study show that subjects should not eat immediately prior to, or during, the evaluation of cardiovascular interventions as postprandial affects may affect the results, leading to erroneous interpretation of the cardiovascular effects of the

  1. DDPH ameliorated oxygen and glucose deprivation-induced injury in rat hippocampal neurons via interrupting Ca2+ overload and glutamate release.

    Science.gov (United States)

    He, Zhi; Lu, Qing; Xu, Xulin; Huang, Lin; Chen, Jianguo; Guo, Lianjun

    2009-01-28

    Our previous work has demonstrated that DDPH (1-(2, 6-dimethylphenoxy)-2-(3, 4-dimethoxyphenylethylamino) propane hydrochloride), a competitive alpha(1)-adrenoceptor antagonist, could improve cognitive deficits, reduce histopathological damage and facilitate synaptic plasticity in vivo possibly via increasing NR2B (NMDA receptor 2B) expression and antioxidation of DDPH itself. The present study further evaluated effects of DDPH on OGD (Oxygen and glucose deprivation)-induced neuronal damage in rat primary hippocampal cells. The addition of DDPH to the cultured cells 12 h before OGD for 4 h significantly reduced neuronal damage as determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay and LDH (lactate dehydrogenase) release experiments. The effects of DDPH on intracellular calcium concentration were explored by Fura-2 based calcium imaging techniques and results showed that DDPH at the dosages of 5 microM and 10 microM suppressed the increase of intracellular calcium ([Ca(2+)](i)) stimulated by 50 mM KCl in Ca(2+)-containing extracellular solutions. However, DDPH couldn't suppress the increase of [Ca(2+)](i) induced by both 50 microM glutamate in Ca(2+)-containing extracellular solutions and 20 microM ATP (Adenosine Triphosphate) in Ca(2+)-free solution. These results indicated that DDPH prevented [Ca(2+)](i) overload in hippocampal neurons by blocking Ca(2+) influx (voltage-dependent calcium channel) but not Ca(2+) mobilization from the intracellular Ca(2+) store in endoplasm reticulum (ER). We also demonstrated that DDPH could decrease glutamate release when hippocampal cells were subjected to OGD. These observations demonstrated that DDPH protected hippocampal neurons against OGD-induced damage by preventing the Ca(2+) influx and decreasing glutamate release.

  2. Glucagon-Like Peptide-1 Secreting Cell Function as well as Production of Inflammatory Reactive Oxygen Species Is Differently Regulated by Glycated Serum and High Levels of Glucose

    Directory of Open Access Journals (Sweden)

    Alessandra Puddu

    2014-01-01

    Full Text Available Glucagon-like peptide-1 (GLP-1, an intestinal hormone contributing to glucose homeostasis, is synthesized by proglucagon and secreted from intestinal neuroendocrine cells in response to nutrients. GLP-1 secretion is impaired in type 2 diabetes patients. Here, we aimed at investigating whether diabetic toxic products (glycated serum (GS or high levels of glucose (HG may affect viability, function, and insulin sensitivity of the GLP-1 secreting cell line GLUTag. Cells were cultured for 5 days in presence or absence of different dilutions of GS or HG. GS and HG (alone or in combination increased reactive oxygen species (ROS production and upregulated proglucagon mRNA expression as compared to control medium. Only HG increased total production and release of active GLP-1, while GS alone abrogated secretion of active GLP-1. HG-mediated effects were associated with the increased cell content of the prohormone convertase 1/3 (PC 1/3, while GS alone downregulated this enzyme. HG upregulated Glucokinase (GK and downregulated SYNTHAXIN-1. GS abrogated SYNTHAXIN-1 and SNAP-25. Finally, high doses of GS alone or in combination with HG reduced insulin-mediated IRS-1 phosphorylation. In conclusion, we showed that GS and HG might regulate different pathways of GLP-1 production in diabetes, directly altering the function of neuroendocrine cells secreting this hormone.

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

    Energy Technology Data Exchange (ETDEWEB)

    Mathew, Jasmin; Loranger, Anne; Gilbert, Stéphane [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada); Faure, Robert [Département de Pédiatrie, Université Laval and Centre de recherche du CHUQ (Centre Mère-Enfant), Québec, Qc, Canada G1V 4G2 (Canada); Marceau, Normand, E-mail: normand.marceau@crhdq.ulaval.ca [Centre de recherche en cancérologie de l' Université Laval and Centre de recherche du CHUQ (L' Hôtel-Dieu de Québec), 9 McMahon, Québec, Qc, Canada G1R 2J6 (Canada)

    2013-02-15

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

  4. Experimental evaluation and computational modeling of the effects of encapsulation on the time-profile of glucose-stimulated insulin release of pancreatic islets.

    Science.gov (United States)

    Buchwald, Peter; Cechin, Sirlene R; Weaver, Jessica D; Stabler, Cherie L

    2015-03-28

    In type 1 diabetic patients, who have lost their ability to produce insulin, transplantation of pancreatic islet cells can normalize metabolic control in a manner that is not achievable with exogenous insulin. To be successful, this procedure has to address the problems caused by the immune and autoimmune responses to the graft. Islet encapsulation using various techniques and materials has been and is being extensively explored as a possible approach. Within this framework, it is of considerable interest to characterize the effect encapsulation has on the insulin response of pancreatic islets. To improve our ability to quantitatively describe the glucose-stimulated insulin release (GSIR) of pancreatic islets in general and of micro-encapsulated islets in particular, we performed dynamic perifusion experiments with frequent sampling. We used unencapsulated and microencapsulated murine islets in parallel and fitted the results with a complex local concentration-based finite element method (FEM) computational model. The high-resolution dynamic perifusion experiments allowed good characterization of the first-phase and second-phase insulin secretion, and we observed a slightly delayed and blunted first-phase insulin response for microencapsulated islets when compared to free islets. Insulin secretion profiles of both free and encapsulated islets could be fitted well by a COMSOL Multiphysics model that couples hormone secretion and nutrient consumption kinetics with diffusive and convective transport. This model, which was further validated and calibrated here, can be used for arbitrary geometries and glucose stimulation sequences and is well suited for the quantitative characterization of the insulin response of cultured, perifused, transplanted, or encapsulated islets. The present high-resolution GSIR experiments allowed for direct characterization of the effect microencapsulation has on the time-profile of insulin secretion. The multiphysics model, further validated

  5. 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...

  6. Oenothera paradoxa defatted seeds extract and its bioactive component penta-O-galloyl-β-D-glucose decreased production of reactive oxygen species and inhibited release of leukotriene B4, interleukin-8, elastase, and myeloperoxidase in human neutrophils.

    Science.gov (United States)

    Kiss, Anna K; Filipek, Agnieszka; Czerwińska, Monika; Naruszewicz, Marek

    2010-09-22

    In this study, we analyzed ex vivo the effect of an aqueous extract of Oenothera paradoxa defatted seeds on the formation of neutrophil-derived oxidants. For defining active compounds, we also tested lypophilic extract constituents such as gallic acid, (+)-catechin, ellagic acid, and penta-O-galloyl-β-D-glucose and a hydrophilic fraction containing polymeric procyanidins. The anti-inflammatory potential of the extract and compounds was tested by determining the release from activated neutrophils of elastase, myeloperoxidase, interleukin-8 (IL-8), and leukotriene B4 (LTB4), which are considered relevant for the pathogenesis of cardiovascular diseases. The extract of O. paradoxa defatted seeds displays potent antioxidant effects against both 4β-phorbol-12β-myristate-α13-acetate- and formyl-met-leu-phenylalanine-induced reactive oxygen species production in neutrophils with IC50 values around 0.2 μg/mL. All types of polyphenolics present in the extract contributed to the extract antioxidant activity. According to their IC50 values, penta-O-galloyl-β-D-glucose was the more potent constituent of the extract. In cell-free assays, we demonstrated that this effect is partially due to the scavenging of O2- and H2O2 oxygen species. The extract and especially penta-O-galloyl-β-D-glucose significantly inhibit elastase, myeloperoxidase IL-8, and LTB4 release with an IC50 for penta-O-galloyl-β-D-glucose of 17±1, 15±1, 6.5±2.5, and around 20 μM, respectively. The inhibition of penta-O-galloyl-β-D-glucose on reactive oxygen species and especially on O2- production, myeloperoxidase, and chemoattractant release may reduce the interaction of polymorphonuclear leukocyte with the vascular endothelium and by that potentially diminish the risk of progression of atherosclerosis development.

  7. Enhanced muscle glucose metabolism after exercise

    DEFF Research Database (Denmark)

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

    1984-01-01

    Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase in the pr......Studies in the rat suggest that after voluntary exercise there are two phases of glycogen repletion in skeletal muscle (preceding study). In phase I glucose utilization and glycogen synthesis are enhanced both in the presence and absence of insulin, whereas in phase II only the increase...... in the stimulated leg closely mimicked that observed previously after voluntary exercise on a treadmill. With no insulin added to the perfusate, glucose incorporation into glycogen was markedly enhanced in muscles that were glycogen depleted as were the uptake of 2-deoxyglucose and 3-O-methylglucose. Likewise......, the stimulation of these processes by insulin was enhanced and continued to be so 2 h later when the muscles of the stimulated leg had substantially repleted their glycogen stores. The results suggest that the increases in insulin-mediated glucose utilization and glycogen synthesis in muscle after exercise...

  8. Effect of prior immobilization on muscular glucose clearance in resting and running rats

    International Nuclear Information System (INIS)

    Vissing, J.; Ohkuwa, Tetsuo; Ploug, T.; Galbo, H.

    1988-01-01

    In vitro studies have shown that prior disuse impairs the glucose clearance of red skeletal muscle because of a developed insensitivity to insulin. We studied whether an impaired glucose clearance is present in vivo in 42-h immobilized muscles of resting rats and, furthermore, whether the exercise-induced increase in glucose clearance of red muscles is affected by prior immobilization. The 2-[ 3 H]deoxy-D-glucose (2DG) bolus injection method was used to determine glucose clearance of individual muscles. At rest, glucose clearance was markedly impaired in rats with previously immobilized red muscles compared with nonimmobilized control rats. During running, glucose clearance did not differ between muscles in previously immobilized and control rats. Insulin levels were always similar in the two groups and decreased during exercise. Intracellular nonphosphorylated 2DG was present in tissues with high glucose clearances. In conclusion, 42 h of immobilization markedly impairs glucose clearance of resting red muscle fibers in vivo. Apparently, physical inactivity in particular affects steps involved in insulin-mediated action that are not part of contraction-induced glucose uptake and metabolism. Presence of intracellular 2DG shows that separate determination of phosphorylated 2DG is necessary for accurate estimates of glucose metabolism and that accumulation of phosphorylated 2DG does not accurately reflect glucose transport

  9. The effect of caffeine on glucose kinetics in humans - influence of adrenaline

    DEFF Research Database (Denmark)

    Battram, Danielle S.; Graham, Terry E.; Richter, Erik

    2005-01-01

    While caffeine impedes insulin-mediated glucose disposal in humans, its effect on endo-genous glucose production (EGP) remains unknown. In addition, the mechanism involved in these effects is unclear, but may be due to the accompanying increase in adrenaline concentration. We studied the effect...... of caffeine on EGP and glucose infusion rates (GIR), and whether or not adrenaline can account for all of caffeine's effects. Subjects completed three isoglycaemic-hyperinsulinaemic clamps (with 3-[3H]glucose infusion) 30 min after ingesting: (1) placebo capsules (n= 12); (2) caffeine capsules (5 mg kg-1) (n......= 12); and either (3) placebo plus a high-dose adrenaline infusion (HAdr; adrenaline concentration, 1.2 nM; n= 8) or (4) placebo plus a low-dose adrenaline infusion (LAdr; adrenaline concentration, 0.75 nM; n= 6). With caffeine, adrenaline increased to 0.6 nM but no effect on EGP was observed. While...

  10. Hypothalamic and Striatal Insulin Action Suppresses Endogenous Glucose Production and May Stimulate Glucose Uptake During Hyperinsulinemia in Lean but Not in Overweight Men.

    Science.gov (United States)

    Heni, Martin; Wagner, Robert; Kullmann, Stephanie; Gancheva, Sofiya; Roden, Michael; Peter, Andreas; Stefan, Norbert; Preissl, Hubert; Häring, Hans-Ulrich; Fritsche, Andreas

    2017-07-01

    Intranasal spray application facilitates insulin delivery to the human brain. Although brain insulin modulates peripheral metabolism, the mechanisms involved remain elusive. Twenty-one men underwent two hyperinsulinemic-euglycemic clamps with d-[6,6- 2 H 2 ]glucose infusion to measure endogenous glucose production and glucose disappearance. On two separate days, participants received intranasal insulin or placebo. Insulin spillover into circulation after intranasal insulin application was mimicked by an intravenous insulin bolus on placebo day. On a different day, brain insulin sensitivity was assessed by functional MRI. Glucose infusion rates (GIRs) had to be increased more after nasal insulin than after placebo to maintain euglycemia in lean but not in overweight people. The increase in GIRs was associated with regional brain insulin action in hypothalamus and striatum. Suppression of endogenous glucose production by circulating insulin was more pronounced after administration of nasal insulin than after placebo. Furthermore, glucose uptake into tissue tended to be higher after nasal insulin application. No such effects were detected in overweight participants. By increasing insulin-mediated suppression of endogenous glucose production and stimulating peripheral glucose uptake, brain insulin may improve glucose metabolism during systemic hyperinsulinemia. Obese people appear to lack these mechanisms. Therefore, brain insulin resistance in obesity may have unfavorable consequences for whole-body glucose homeostasis. © 2017 by the American Diabetes Association.

  11. Effects of SH-reagents of different molecular size upon glucose metabolism in isolated rat fat cells

    International Nuclear Information System (INIS)

    Kather, H.; Simon, B.

    1975-01-01

    To study the role of membrane SH-groups in glucose transport of isolated rat fat cells we compared the effects of a small organic mercurial reagent p-CMB with those of a large p-CMB-derivative - p-CMB-Dextran, MW approximately 10,000 -. It could be shown that both compounds were of almost identical reactivity on fat cell homogenate metabolism. When applied to intact fat cells uncoupled p-CMB showed an 1) insulin-like enhancement of 14 C incorporation from (U- 14 C) glucose into CO 2 and triglyceride, 2) inhibition of the insulin-stimulatory effect on these parameters and 3) inhibition of basal glucose uptake dependent on the concentrations used. Identical concentrations of p-CMB-Dextran, however, failed to influence basal glucose uptake as well as the insulin mediated increase in glucose metabolism. (orig.) [de

  12. Effects of SH-reagents of different molecular size upon glucose metabolism in isolated rat fat cells

    Energy Technology Data Exchange (ETDEWEB)

    Kather, H; Simon, B [Heidelberg Univ. (F.R. Germany). Klinisches Inst. fuer Herzinfarktforschung

    1975-09-01

    To study the role of membrane SH-groups in glucose transport of isolated rat fat cells we compared the effects of a small organic mercurial reagent p-CMB with those of a large p-CMB-derivative - p-CMB-Dextran, MW approximately 10,000 -. It could be shown that both compounds were of almost identical reactivity on fat cell homogenate metabolism. When applied to intact fat cells uncoupled p-CMB showed an 1) insulin-like enhancement of /sup 14/C incorporation from (U-/sup 14/C) glucose into CO/sub 2/ and triglyceride, 2) inhibition of the insulin-stimulatory effect on these parameters and 3) inhibition of basal glucose uptake dependent on the concentrations used. Identical concentrations of p-CMB-Dextran, however, failed to influence basal glucose uptake as well as the insulin mediated increase in glucose metabolism.

  13. G-allele of intronic rs10830963 in MTNR1B confers increased risk of impaired fasting glycemia and type 2 diabetes through an impaired glucose-stimulated insulin release: studies involving 19,605 Europeans

    DEFF Research Database (Denmark)

    Sparsø, Thomas; Bonnefond, Amélie; Andersson, Ehm

    2009-01-01

    independent effect on FPG with isolated impaired fasting glycemia (i-IFG), isolated impaired glucose tolerance (i-IGT), type 2 diabetes, and measures of insulin release and peripheral and hepatic insulin sensitivity. RESEARCH DESIGN AND METHODS: We examined European-descent participants in the Inter99 study...... (n = 5,553), in a sample of young healthy Danes (n = 372), in Danish twins (n = 77 elderly and n = 97 young), in additional Danish type 2 diabetic patients (n = 1,626) and control subjects (n = 505), in the Data from the Epidemiological Study on the Insulin Resistance Syndrome (DESIR) study (n = 4...

  14. The Birth Weight Lowering C-Allele of rs900400 Near LEKR1 and CCNL1 Associates with Elevated Insulin Release following an Oral Glucose Challenge

    DEFF Research Database (Denmark)

    Andersson, Ehm A; Harder, Marie N; Pilgaard, Kasper

    2011-01-01

    participants, midwife journals were traced through the Danish State Archives and association of rs900400 with birth weight was examined. Associations between rs900400 and fasting serum insulin, fasting plasma glucose, insulinogenic index, homeostasis model assessment of insulin resistance (HOMA-IR...

  15. Comparison of two methods using plasma triglyceride concentration as a surrogate estimate of insulin action in nondiabetic subjects: triglycerides × glucose versus triglyceride/high-density lipoprotein cholesterol.

    Science.gov (United States)

    Abbasi, Fahim; Reaven, Gerald M

    2011-12-01

    The objective was to compare relationships between insulin-mediated glucose uptake and surrogate estimates of insulin action, particularly those using fasting triglyceride (TG) and high-density lipoprotein cholesterol (HDL-C) concentrations. Insulin-mediated glucose uptake was quantified by determining the steady-state plasma glucose (SSPG) concentration during the insulin suppression test in 455 nondiabetic subjects. Fasting TG, HDL-C, glucose, and insulin concentrations were measured; and calculations were made of the following: (1) plasma concentration ratio of TG/HDL-C, (2) TG × fasting glucose (TyG index), (3) homeostasis model assessment of insulin resistance, and (4) insulin area under the curve (insulin-AUC) during a glucose tolerance test. Insulin-AUC correlated most closely with SSPG (r ∼ 0.75, P index, homeostasis model assessment of insulin resistance, and fasting TG and insulin (r ∼ 0.60, P index correlated with SSPG concentration to a similar degree, and the relationships were comparable to estimates using fasting insulin. The strongest relationship was between SSPG and insulin-AUC. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. The minor C-allele of rs2014355 in ACADS is associated with reduced insulin release following an oral glucose load

    DEFF Research Database (Denmark)

    Hornbak, Malene; Banasik, Karina; Justesen, Johanne Marie

    2011-01-01

    -aged Danish individuals (nACADS=4,324; nACADM=4,337). The T2D-case-control study involved a total of ~8,300 Danish individuals (nACADS=8,313; nACADM=8,344). Results In glucose-tolerant individuals the minor C-allele of rs2014355 of ACADS associated with reduced measures of serum insulin at 30 min following...... an oral glucose load (per allele effect (beta)=-3.8% (-6.3%;-1.3%), P=0.003), reduced incremental area under the insulin curve (beta=-3.6% (-6.3%;-0.9%), P=0.009), reduced acute insulin response (beta=-2.2% (-4.2%;0.2%), P=0.03), and with increased insulin sensitivity ISIMatsuda (beta= 2.9% (0.5%;5.2%), P...

  17. Evaluation of efficient glucose release using sodium hydroxide and phosphoric acid as pretreating agents from the biomass of Sesbania grandiflora (L.) Pers.: A fast growing tree legume.

    Science.gov (United States)

    Mund, Nitesh K; Dash, Debabrata; Barik, Chitta R; Goud, Vaibhav V; Sahoo, Lingaraj; Mishra, Prasannajit; Nayak, Nihar R

    2017-07-01

    Sesbania grandiflora (L.) Pers. is one of the fast growing tree legumes having the efficiency to produce around 50tha -1 above ground dry matters in a year. In this study, biomass of 2years old S. grandiflora was selected for the chemical composition, pretreatments and enzymatic hydrolysis studies. The stem biomass with a wood density of 3.89±0.01gmcm -3 contains about 38% cellulose, 12% hemicellulose and 28% lignin. Enzymatic hydrolysis of pretreated biomass revealed that phosphoric acid (H 3 PO 4 ) pretreated samples even at lower cellulase loadings [1 Filter Paper Units (FPU)], could efficiently convert about 86% glucose, while, even at higher cellulase loadings (60FPU) alkali pretreated biomass could convert only about 58% glucose. The effectiveness of phosphoric acid pretreatment was also supported by X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM) and Fourier transform infrared spectroscopy (FTIR) analysis. Copyright © 2017 Elsevier Ltd. All rights reserved.

  18. Prediction of net hepatic release of glucose using a “hybrid” mechanistic model in ruminants applied to positive energy balance

    OpenAIRE

    Bahloul, Lahlou; Ortigues, Isabelle; Vernet, Jean; Lapierre, Helène; Noziere, Pierre; Sauvant, Daniel

    2013-01-01

    Ruminants depend on hepatic gluconeogenesis to meet most of their metabolic demand for glucose which relies on availability of precursors from diet supply and animal requirements (Loncke et al., 2010). Several mechanistic models of the metabolic fate of nutrients across the liver exist that have been parameterized for dairy cows. They cannot be directly used to predict hepatic gluconeogenesis in all types of ruminants in different physiological status. A hybrid mechanistic model of nutrient f...

  19. DEFECTS IN INSULIN-SECRETION IN NIDDM - B-CELL GLUCOSE INSENSITIVITY OR GLUCOSE TOXICITY

    NARCIS (Netherlands)

    VANHAEFTEN, TW

    In NIDDM, first-phase insulin release to glucose is (almost) absent. However, in contrast to older studies which suggested that in NIDDM the B-cell is ''blind'' for glucose, recent evidence indicates that the B-cell is not insensitive for glucose as far as second phase release is concerned. This

  20. Distribution of glucose transporters in renal diseases

    OpenAIRE

    Szablewski, Leszek

    2017-01-01

    Kidneys play an important role in glucose homeostasis. Renal gluconeogenesis prevents hypoglycemia by releasing glucose into the blood stream. Glucose homeostasis is also due, in part, to reabsorption and excretion of hexose in the kidney. Lipid bilayer of plasma membrane is impermeable for glucose, which is hydrophilic and soluble in water. Therefore, transport of glucose across the plasma membrane depends on carrier proteins expressed in the plasma membrane. In humans, there are three famil...

  1. Glucose Sensing

    CERN Document Server

    Geddes, Chris D

    2006-01-01

    Topics in Fluorescence Spectroscopy, Glucose Sensing is the eleventh volume in the popular series Topics in Fluorescence Spectroscopy, edited by Drs. Chris D. Geddes and Joseph R. Lakowicz. This volume incorporates authoritative analytical fluorescence-based glucose sensing reviews specialized enough to be attractive to professional researchers, yet also appealing to the wider audience of scientists in related disciplines of fluorescence. Glucose Sensing is an essential reference for any lab working in the analytical fluorescence glucose sensing field. All academics, bench scientists, and industry professionals wishing to take advantage of the latest and greatest in the continuously emerging field of glucose sensing, and diabetes care & management, will find this volume an invaluable resource. Topics in Fluorescence Spectroscopy Volume 11, Glucose Sensing Chapters include: Implantable Sensors for Interstitial Fluid Smart Tattoo Glucose Sensors Optical Enzyme-based Glucose Biosensors Plasmonic Glucose Sens...

  2. FOXO1 and GSK-3β Are Main Targets of Insulin-Mediated Myogenesis in C2C12 Muscle Cells.

    Science.gov (United States)

    Litwiniuk, Anna; Pijet, Barbara; Pijet-Kucicka, Maja; Gajewska, Małgorzata; Pająk, Beata; Orzechowski, Arkadiusz

    2016-01-01

    , inhibition of GSK-3β activity by insulin alone or together with LiCl raised the expression of genes and some proteins central to the metabolic activity of mitochondria resulting in higher ATP synthesis and accelerated myogenesis. The results of this study indicate that there are at least two main targets in insulin-mediated myogenesis: notably FOXO1 and GSK-3β both playing apparent negative role in muscle fiber formation.

  3. FOXO1 and GSK-3β Are Main Targets of Insulin-Mediated Myogenesis in C2C12 Muscle Cells.

    Directory of Open Access Journals (Sweden)

    Anna Litwiniuk

    . Thus, inhibition of GSK-3β activity by insulin alone or together with LiCl raised the expression of genes and some proteins central to the metabolic activity of mitochondria resulting in higher ATP synthesis and accelerated myogenesis. The results of this study indicate that there are at least two main targets in insulin-mediated myogenesis: notably FOXO1 and GSK-3β both playing apparent negative role in muscle fiber formation.

  4. A randomized controlled trial to compare the effects of sulphonylurea gliclazide MR (modified release) and the DPP-4 inhibitor vildagliptin on glycemic variability and control measured by continuous glucose monitoring (CGM) in Brazilian women with type 2 diabetes.

    Science.gov (United States)

    Vianna, Andre Gustavo Daher; Lacerda, Claudio Silva; Pechmann, Luciana Muniz; Polesel, Michelle Garcia; Marino, Emerson Cestari; Faria-Neto, Jose Rocha

    2018-05-01

    This study aims to evaluate whether there is a difference between the effects of vildagliptin and gliclazide MR (modified release) on glycemic variability (GV) in women with type 2 diabetes (T2DM) as evaluated by continuous glucose monitoring (CGM). An open-label, randomized study was conducted in T2DM women on steady-dose metformin monotherapy which were treated with 50 mg vildagliptin twice daily or 60-120 mg of gliclazide MR once daily. CGM and GV indices calculation were performed at baseline and after 24 weeks. In total, 42 patients (age: 61.9 ± 5.9 years, baseline glycated hemoglobin (HbA1c): 7.3 ± 0.56) were selected and 37 completed the 24-week protocol. Vildagliptin and gliclazide MR reduced GV, as measured by the mean amplitude of glycemic excursions (MAGE, p = 0.007 and 0.034, respectively). The difference between the groups did not reach statistical significance. Vildagliptin also significantly decreased the standard deviation of the mean glucose (SD) and the mean of the daily differences (MODD) (p = 0.007 and 0.030). Vildagliptin and gliclazide MR similarly reduced the MAGE in women with T2DM after 24 weeks of treatment. Further studies are required to attest differences between vildagliptin and gliclazide MR regarding glycemic variability. Copyright © 2018 Elsevier B.V. All rights reserved.

  5. Exogenous thyroxine improves glucose intolerance in insulin-resistant rats.

    Science.gov (United States)

    Vazquez-Anaya, Guillermo; Martinez, Bridget; Soñanez-Organis, José G; Nakano, Daisuke; Nishiyama, Akira; Ortiz, Rudy M

    2017-03-01

    Both hypothyroidism and hyperthyroidism are associated with glucose intolerance, calling into question the contribution of thyroid hormones (TH) on glucose regulation. TH analogues and derivatives may be effective treatment options for glucose intolerance and insulin resistance (IR), but their potential glucoregulatory effects during conditions of impaired metabolism are not well described. To assess the effects of thyroxine (T 4 ) on glucose intolerance in a model of insulin resistance, an oral glucose tolerance test (oGTT) was performed on three groups of rats (n = 8): (1) lean, Long Evans Tokushima Otsuka (LETO), (2) obese, Otsuka Long Evans Tokushima Fatty (OLETF) and (3) OLETF + T 4 (8.0 µg/100 g BM/day × 5 weeks). T 4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T 4 -treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T 4 increased the mRNA expressions of muscle monocarboxylate transporter 10 (Mct10), deiodinase type 2 (Di2), sirtuin 1 (Sirt1) and uncoupling protein 2 (Ucp2) by 1.8-, 2.2-, 2.7- and 1.4-fold, respectively, compared to OLETF. Activation of AMP-activated protein kinase (AMPK) and insulin receptor were not significantly altered suggesting that the improvements in glucose intolerance and IR were independent of enhanced insulin-mediated signaling. The results suggest that T 4 treatment increased the influx of T 4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T 3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis. © 2017 Society for Endocrinology.

  6. Detoxification of ammonia in mouse cortical GABAergic cell cultures increases neuronal oxidative metabolism and reveals an emerging role for release of glucose-derived alanine.

    Science.gov (United States)

    Leke, Renata; Bak, Lasse K; Anker, Malene; Melø, Torun M; Sørensen, Michael; Keiding, Susanne; Vilstrup, Hendrik; Ott, Peter; Portela, Luis V; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2011-04-01

    Cerebral hyperammonemia is believed to play a pivotal role in the development of hepatic encephalopathy (HE), a debilitating condition arising due to acute or chronic liver disease. In the brain, ammonia is thought to be detoxified via the activity of glutamine synthetase, an astrocytic enzyme. Moreover, it has been suggested that cerebral tricarboxylic acid (TCA) cycle metabolism is inhibited and glycolysis enhanced during hyperammonemia. The aim of this study was to characterize the ammonia-detoxifying mechanisms as well as the effects of ammonia on energy-generating metabolic pathways in a mouse neuronal-astrocytic co-culture model of the GABAergic system. We found that 5 mM ammonium chloride affected energy metabolism by increasing the neuronal TCA cycle activity and switching the astrocytic TCA cycle toward synthesis of substrate for glutamine synthesis. Furthermore, ammonia exposure enhanced the synthesis and release of alanine. Collectively, our results demonstrate that (1) formation of glutamine is seminal for detoxification of ammonia; (2) neuronal oxidative metabolism is increased in the presence of ammonia; and (3) synthesis and release of alanine is likely to be important for ammonia detoxification as a supplement to formation of glutamine.

  7. One-week glucose control via zero-order release kinetics from an injectable depot of glucagon-like peptide-1 fused to a thermosensitive biopolymer.

    Science.gov (United States)

    Luginbuhl, Kelli M; Schaal, Jeffrey L; Umstead, Bret; Mastria, Eric M; Li, Xinghai; Banskota, Samagya; Arnold, Susan; Feinglos, Mark; D'Alessio, David; Chilkoti, Ashutosh

    2017-01-01

    Stimulation of the glucagon-like peptide-1 (GLP1) receptor is a useful treatment strategy for type 2 diabetes because of pleiotropic effects, including the regulation of islet hormones and the induction of satiety. However, the native ligand for the GLP1 receptor has a short half-live owing to enzymatic inactivation and rapid clearance. Here, we show that a subcutaneous depot formed after a single injection of GLP1 recombinantly fused to a thermosensitive elastin-like polypeptide results in zero-order release kinetics and circulation times of up to 10 days in mice and 17 days in monkeys. The optimized pharmacokinetics leads to 10 days of glycemic control in three different mouse models of diabetes, as well as to the reduction of glycosylated hemoglobin levels and weight gain in ob/ob mice treated once weekly for 8 weeks. Our results suggest that the optimized GLP1 formulation could enhance therapeutic outcomes by eliminating peak-and-valley pharmacokinetics and improving overall safety and tolerability. The design principles that we established should be broadly applicable for improving the pharmacological performance of other peptide and protein therapeutics.

  8. Glucose allostasis

    DEFF Research Database (Denmark)

    Stumvoll, Michael; Tataranni, P Antonio; Stefan, Norbert

    2003-01-01

    individuals with normal glucose tolerance, normoglycemia can always be maintained by compensatorily increasing AIR in response to decreasing M (and vice versa). This has been mathematically described by the hyperbolic relationship between AIR and M and referred to as glucose homeostasis, with glucose......In many organisms, normoglycemia is achieved by a tight coupling of nutrient-stimulated insulin secretion in the pancreatic beta-cell (acute insulin response [AIR]) and the metabolic action of insulin to stimulate glucose disposal (insulin action [M]). It is widely accepted that in healthy...... concentration assumed to remain constant along the hyperbola. Conceivably, glucose is one of the signals stimulating AIR in response to decreasing M. Hypothetically, as with any normally functioning feed-forward system, AIR should not fully compensate for worsening M, since this would remove the stimulus...

  9. Ginsenoside Rb1 Attenuates Oxygen-Glucose Deprivation-Induced Apoptosis in SH-SY5Y Cells via Protection of Mitochondria and Inhibition of AIF and Cytochrome c Release

    Directory of Open Access Journals (Sweden)

    Pengfei Ge

    2013-10-01

    Full Text Available To investigate the role of mitochondria in the protective effects of ginsenoside Rb1 on cellular apoptosis caused by oxygen-glucose deprivation, in this study, MTT assay, TUNEL staining, flow cytometry, immunocytochemistry and western blotting were used to examine the cellular viability, apoptosis, ROS level, mitochondrial membrane potential, and the distribution of apoptosis inducing factor, cytochrome c, Bax and Bcl-2 in nucleus, mitochondria and cytoplasm. We found that pretreatment with GRb1 improved the cellular viability damaged by OGD. Moreover, GRb1 inhibited apoptosis in SH-SY5Y cells induced by OGD. Further studies showed that the elevation of cellular reactive oxygen species levels and the reduction of mitochondrial membrane potential caused by OGD were both counteracted by GRb1. Additionally, GRb1 not only suppressed the translocation of apoptosis inducing factor into nucleus and cytochrome c into cytoplasm, but also inhibited the increase of Bax within mitochondria and alleviated the decrease of mitochondrial Bcl-2. Our study indicates that the protection of GRb1 on OGD-induced apoptosis in SH-SY5Y cells is associated with its protection on mitochondrial function and inhibition of release of AIF and cytochrome c.

  10. Low whole-body insulin sensitivity in patients with ischaemic heart disease is associated with impaired myocardial glucose uptake predictive of poor outcome after revascularisation

    DEFF Research Database (Denmark)

    Kofoed, Klaus F; Carstensen, Steen; Hove, Jens D

    2002-01-01

    patients with ischaemic heart disease and impaired LV ejection fraction (EF) and age-matched healthy volunteers ( n = 30). As assessed by euglycaemic glucose-insulin clamp, 15 patients had a low and 14 a normal whole-body insulin sensitivity. Using positron emission tomography, patterns of fluorine-18......We tested the hypothesis that low whole-body insulin sensitivity in patients with ischaemic heart disease and impaired left ventricular (LV) function is associated with abnormalities of insulin-mediated myocardial glucose uptake affecting outcome after coronary bypass surgery (CABG). We studied 29......-normal myocardium was found to be higher in patients with normal whole-body insulin sensitivity ( P body insulin sensitivity more segments displayed a pattern of reduced glucose uptake in normoperfused myocardium (PET-reverse mismatch) ( P

  11. 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...

  12. Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats.

    Science.gov (United States)

    Farese, R V; Standaert, M L; Yamada, K; Huang, L C; Zhang, C; Cooper, D R; Wang, Z; Yang, Y; Suzuki, S; Toyota, T

    1994-11-08

    Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosphoglycan (IPG) mediator, prepared from beef liver, bypassed this defect and comparably activated G3PAT in cell-free adipocyte preparations of both diabetic GK and control rats. A myo-inositol-containing IPG mediator did not activate G3PAT. Relative to control adipocytes, labeling of GPI by [3H]glucosamine was diminished by 50% and insulin failed to stimulate GPI hydrolysis in GK adipocytes. In contrast to GPI-dependent G3PAT activation, insulin-stimulated hexose transport was intact in adipocytes and soleus and gastrocnemius muscles of the GK rat, as was insulin-induced activation of mitogen-activated protein kinase and protein kinase C. We conclude that (i) chiro-inositol-containing IPG mediator activates G3PAT during insulin action, (ii) diabetic GK rats have a defect in synthesizing or releasing functional chiro-inositol-containing IPG, and (iii) defective IPG-regulated intracellular glucose metabolism contributes importantly to insulin resistance in diabetic GK rats.

  13. Meal-stimulated glucagon release is associated with postprandial blood glucose level and does not interfere with glycemic control in children and adolescents with new-onset type 1 diabetes

    DEFF Research Database (Denmark)

    Pörksen, Sven; Nielsen, Lotte B; Kaas, Anne

    2007-01-01

    The role of glucagon in hyperglycemia in type 1 diabetes is unresolved, and in vitro studies suggest that increasing blood glucose might stimulate glucagon secretion.......The role of glucagon in hyperglycemia in type 1 diabetes is unresolved, and in vitro studies suggest that increasing blood glucose might stimulate glucagon secretion....

  14. 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.

  15. Curcuma longa polyphenols improve insulin-mediated lipid accumulation and attenuate proinflammatory response of 3T3-L1 adipose cells during oxidative stress through regulation of key adipokines and antioxidant enzymes.

    Science.gov (United States)

    Septembre-Malaterre, Axelle; Le Sage, Fanny; Hatia, Sarah; Catan, Aurélie; Janci, Laurent; Gonthier, Marie-Paule

    2016-07-08

    Plant polyphenols may exert beneficial action against obesity-related oxidative stress and inflammation which promote insulin resistance. This study evaluated the effect of polyphenols extracted from French Curcuma longa on 3T3-L1 adipose cells exposed to H2 O2 -mediated oxidative stress. We found that Curcuma longa extract exhibited high amounts of curcuminoids identified as curcumin, demethoxycurcumin, and bisdemethoxycurcumin, which exerted free radical-scavenging activities. Curcuma longa polyphenols improved insulin-mediated lipid accumulation and upregulated peroxisome proliferator-activated receptor-gamma gene expression and adiponectin secretion which decreased in H2 O2 -treated cells. Curcuminoids attenuated H2 O2 -enhanced production of pro-inflammatory molecules such as interleukin-6, tumor necrosis factor-alpha, monocyte chemoattractant protein-1, and nuclear factor κappa B. Moreover, they reduced intracellular levels of reactive oxygen species elevated by H2 O2 and modulated the expression of genes encoding superoxide dismutase and catalase antioxidant enzymes. Collectively, these findings highlight that Curcuma longa polyphenols protect adipose cells against oxidative stress and may improve obesity-related metabolic disorders. © 2016 BioFactors, 42(4):418-430, 2016. © 2016 International Union of Biochemistry and Molecular Biology.

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

    Science.gov (United States)

    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.

  17. Increased VLDL-triglyceride secretion precedes impaired control of endogenous glucose production in obese, normoglycemic men.

    Science.gov (United States)

    Sørensen, Lars P; Søndergaard, Esben; Nellemann, Birgitte; Christiansen, Jens S; Gormsen, Lars C; Nielsen, Søren

    2011-09-01

    To assess basal and insulin-mediated VLDL-triglyceride (TG) kinetics and the relationship between VLDL-TG secretion and hepatic insulin resistance assessed by endogenous glucose production (EGP) in obese and lean men. A total of 12 normoglycemic, obese (waist-to-hip ratio >0.9, BMI >30 kg/m(2)) and 12 lean (BMI 20-25 kg/m(2)) age-matched men were included. Ex vivo-labeled [1-(14)C]VLDL-TGs and [3-(3)H]glucose were infused postabsorptively and during a hyperinsulinemic-euglycemic clamp to determine VLDL-TG kinetics and EGP. Body composition was determined by dual X-ray absorptiometry and computed tomography scanning. Energy expenditure and substrate oxidation rates were measured by indirect calorimetry. Basal VLDL-TG secretion rates were increased in obese compared with lean men (1.25 ± 0.34 vs. 0.86 ± 0.34 μmol/kg fat-free mass [FFM]/min; P = 0.011), whereas there was no difference in clearance rates (150 ± 56 vs. 162 ± 77 mL/min; P = NS), resulting in greater VLDL-TG concentrations (0.74 ± 0.40 vs. 0.38 ± 0.20 mmol/L; P = 0.011). The absolute insulin-mediated suppression of VLDL-TG secretion was similar in the groups. However, the percentage reduction (-36 ± 18 vs. -54 ± 10%; P = 0.008) and achieved VLDL-TG secretion rates (0.76 ± 0.20 vs. 0.41 ± 0.19 μmol/kg FFM/min; P lean men (-17 ± 18 vs. 7 ± 20%; P = 0.007), resulting in less percentage reduction of VLDL-TG concentrations in obese men (-22 ± 20 vs. -56 ± 11%; P < 0.001). Insulin-suppressed EGP was similar (0.4 [0.0-0.8] vs. 0.1 [0.0-1.2] mg/kg FFM/min (median [range]); P = NS), and the percentage reduction was equivalent (-80% [57-98] vs. -98% [49-100], P = NS). Insulin-mediated glucose disposal was significantly reduced in obese men. Basal VLDL-TG secretion rates are increased in normoglycemic but insulin-resistant, obese men, resulting in hypertriglyceridemia. Insulin-mediated suppression of EGP is preserved in obese men, whereas suppression of VLDL-TG secretion is less pronounced in obese

  18. Neuroscience of glucose homeostasis

    NARCIS (Netherlands)

    La Fleur, S E; Fliers, E; Kalsbeek, A

    2014-01-01

    Plasma glucose concentrations are homeostatically regulated and maintained within strict boundaries. Several mechanisms are in place to increase glucose output when glucose levels in the circulation drop as a result of glucose utilization, or to decrease glucose output and increase tissue glucose

  19. Insulin release by glucagon and secretin

    DEFF Research Database (Denmark)

    Kofod, Hans; Andreu, D; Thams, P

    1988-01-01

    Secretin and glucagon potentiate glucose-induced insulin release. We have compared the effects of secretin and glucagon with that of four hybrid molecules of the two hormones on insulin release and formation of cyclic AMP (cAMP) in isolated mouse pancreatic islets. All six peptides potentiated...... the release of insulin at 10 mM D-glucose, and their effects were indistinguishable with respect to the dynamics of release, dose-response relationship, and glucose dependency. However, measurements of cAMP accumulation in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine (10(-4) M...... potentiating effects of secretin and glucagon on glucose-induced insulin release, their modes of action may be different....

  20. Transcriptional evidence for the role of chronic venlafaxine treatment in neurotrophic signaling and neuroplasticity including also Glutamatergic [corrected] - and insulin-mediated neuronal processes.

    Directory of Open Access Journals (Sweden)

    Viola Tamási

    Full Text Available Venlafaxine (VLX, a serotonine-noradrenaline reuptake inhibitor, is one of the most commonly used antidepressant drugs in clinical practice for the treatment of major depressive disorder (MDD. Despite being more potent than its predecessors, similarly to them, the therapeutical effect of VLX is visible only 3-4 weeks after the beginning of treatment. Furthermore, recent papers show that antidepressants, including also VLX, enhance the motor recovery after stroke even in non depressed persons. In the present, transcriptomic-based study we looked for changes in gene expressions after a long-term VLX administration.Osmotic minipumps were implanted subcutaneously into Dark Agouti rats providing a continuous (40 mg/kg/day VLX delivery for three weeks. Frontal regions of the cerebral cortex were isolated and analyzed using Illumina bead arrays to detect genes showing significant chances in expression. Gene set enrichment analysis was performed to identify specific regulatory networks significantly affected by long term VLX treatment.Chronic VLX administration may have an effect on neurotransmitter release via the regulation of genes involved in vesicular exocytosis and receptor endocytosis (such as Kif proteins, Myo5a, Sv2b, Syn2 or Synj2. Simultaneously, VLX activated the expression of genes involved in neurotrophic signaling (Ntrk2, Ntrk3, glutamatergic transmission (Gria3, Grin2b and Grin2a, neuroplasticity (Camk2g/b, Cd47, synaptogenesis (Epha5a, Gad2 and cognitive processes (Clstn2. Interestingly, VLX increased the expression of genes involved in mitochondrial antioxidant activity (Bcl2 and Prdx1. Additionally, VLX administration also modulated genes related to insulin signaling pathway (Negr1, Ppp3r1, Slc2a4 and Enpp1, a mechanism that has recently been linked to neuroprotection, learning and memory.Our results strongly suggest that chronic VLX treatment improves functional reorganization and brain plasticity by influencing gene expression in

  1. Insulin modulates hippocampally-mediated spatial working memory via glucose transporter-4.

    Science.gov (United States)

    Pearson-Leary, J; Jahagirdar, V; Sage, J; McNay, E C

    2018-02-15

    The insulin-regulated glucose transporter, GluT4, is a key molecule in peripheral insulin signaling. Although GluT4 is abundantly expressed in neurons of specific brain regions such as the hippocampus, the functional role of neuronal GluT4 is unclear. Here, we used pharmacological inhibition of GluT4-mediated glucose uptake to determine whether GluT4 mediates insulin-mediated glucose uptake in the hippocampus. Consistent with previous reports, we found that glucose utilization increased in the dorsal hippocampus of male rats during spontaneous alternation (SA), a hippocampally-mediated spatial working memory task. We previously showed that insulin signaling within the hippocampus is required for processing this task, and that administration of exogenous insulin enhances performance. At baseline levels of hippocampal insulin, inhibition of GluT4-mediated glucose uptake did not affect SA performance. However, inhibition of an upstream regulator of GluT4, Akt, did impair SA performance. Conversely, when a memory-enhancing dose of insulin was delivered to the hippocampus prior to SA-testing, inhibition of GluT4-mediated glucose transport prevented cognitive enhancement. These data suggest that baseline hippocampal cognitive processing does not require functional hippocampal GluT4, but that cognitive enhancement by supra-baseline insulin does. Consistent with these findings, we found that in neuronal cell culture, insulin increases glucose utilization in a GluT4-dependent manner. Collectively, these data demonstrate a key role for GluT4 in transducing the procognitive effects of elevated hippocampal insulin. Copyright © 2017 Elsevier B.V. All rights reserved.

  2. Effect of glucose and insulin infusion on the myocardial extraction of a radioiodinated methyl-substituted fatty acid

    International Nuclear Information System (INIS)

    Bianco, J.A.; Elmaleh, D.R.; Leppo, J.A.; King, M.A.; Moring, A.; Livni, E.; Espinoza, E.; Alpert, J.S.; Strauss, H.W.; Massachusetts General Hospital, Boston

    1986-01-01

    We investigated the one-way. An extraction of 14-iodophenyl-tetradecanoic acid (BMTDA) in the canine heart under fasting conditions and during infusion of glucose plus insulin in eight an esthetized greyhound dogs. Myocardial extraction measurements were made with dual tracer approach, using Tc-99m albumin as reference tracer. Prior to, and during, infusion of 10% glucose and 25 units of regular insulin, heart rate, blood pressure, plasma glucose, insulin and free fatty acid levels were measured. Myocardial blood flow was determined using Sn-113 and Ru-103 radioactive microspheres. The mean extraction fraction of BMTDA was 0.38+-SEM 0.06 at baseline and increased to 0.44+-0.06 during hyperglycemia plus insulin (P<0.025). Plasma glucose and insulin were higher during the infusion (P<0.01) while plasma free fatty acids significantly declined (P<0.01). There were no changes in hemodynamics or myocardial blood flow during the infusion. We conclude that glucose and insulin infusion result in increased first-pass extraction fraction of radioiodinated BMTDA unaccompanied by changes in coronary flow or hemodynamics, implying an insulin-mediated augmented transport of BMTDA. (orig.)

  3. Underestimation of glucose turnover corrected with high-performance liquid chromatography purification of [6-3H]glucose

    International Nuclear Information System (INIS)

    Schwenk, W.F.; Butler, P.C.; Haymond, M.W.; Rizza, R.A.

    1990-01-01

    We have recently reported that during infusion of commercially available [6-3H]glucose, a radioactive nonglucose contaminant may accumulate in plasma causing errors in the measurement of glucose turnover. To determine whether purification of this tracer by HPLC (high-performance liquid chromatography) before infusion would eliminate the contaminant in plasma and remove the underestimation of glucose turnover reported during hyperinsulinemia, four normal subjects each underwent two 5-h euglycemic clamps during infusion of insulin (1 mU.kg-1.min-1). Glucose turnover was measured with either commercially available [6-3H]glucose or with HPLC-purified [6-3H]glucose. HPLC analysis of samples from the clamps done with commercially available [6-3H]glucose showed that 9.7% of the infused tracer and 26% of the plasma glucose 3H radioactivity were contaminants. In contrast, no contaminant was observed in the plasma during infusion of HPLC-purified [6-3H]glucose. During the last hour of the clamp, mean glucose turnover using commercially available [6-3H]glucose was less (P less than 0.01) than the mean glucose infusion rate (7.6 +/- 0.3 vs. 10.5 +/- 0.3 mg.kg-1.min-1) yielding apparent negative (P less than 0.001) hepatic glucose release. In contrast, when HPLC-purified [6-3H]glucose was employed, glucose turnover equaled the glucose infusion rate (10.4 +/- 0.9 vs. 10.2 +/- 0.9 mg.kg-1.min-1) and hepatic glucose release was no longer negative. We conclude that removal of a tritiated nonglucose contaminant in [6-3H]glucose by HPLC yields correct estimations of glucose turnover at steady state

  4. Glucose and cardiovascular risk

    NARCIS (Netherlands)

    Fuchs, M.; Hoekstra, J. B. L.; Mudde, A. H.

    2002-01-01

    The American Diabetes Association and the World Health Organisation have recently redefined the spectrum of abnormal glucose tolerance. The criteria for diabetes mellitus were sharpened and impaired fasting glucose (IFG) and impaired glucose tolerance (IGT) were classified as intermediate stages

  5. Effect and Modeling of Glucose Inhibition and In Situ Glucose Removal During Enzymatic Hydrolysis of Pretreated Wheat Straw

    DEFF Research Database (Denmark)

    Andric, Pavle; Meyer, Anne S.; Jensen, Peter Arendt

    2010-01-01

    The enzymatic hydrolysis of lignocellulosic biomass is known to be product-inhibited by glucose. In this study, the effects on cellulolytic glucose yields of glucose inhibition and in situ glucose removal were examined and modeled during extended treatment of heat-pretreated wheat straw......, during 96 h of reaction. When glucose was removed by dialysis during the enzymatic hydrolysis, the cellulose conversion rates and glucose yields increased. In fact, with dialytic in situ glucose removal, the rate of enzyme-catalyzed glucose release during 48-72 h of reaction recovered from 20......-40% to become approximate to 70% of the rate recorded during 6-24 h of reaction. Although Michaelis-Menten kinetics do not suffice to model the kinetics of the complex multi-enzymatic degradation of cellulose, the data for the glucose inhibition were surprisingly well described by simple Michaelis...

  6. Comprehensive enzymatic analysis of the cellulolytic system in digestive fluid of the Sea Hare Aplysia kurodai. Efficient glucose release from sea lettuce by synergistic action of 45 kDa endoglucanase and 210 kDa ß-glucosidase.

    Directory of Open Access Journals (Sweden)

    Akihiko Tsuji

    Full Text Available Although many endo-ß-1,4-glucanases have been isolated in invertebrates, their cellulolytic systems are not fully understood. In particular, gastropod feeding on seaweed is considered an excellent model system for production of bioethanol and renewable bioenergy from third-generation feedstocks (microalgae and seaweeds. In this study, enzymes involved in the conversion of cellulose and other polysaccharides to glucose in digestive fluids of the sea hare (Aplysia kurodai were screened and characterized to determine how the sea hare obtains glucose from sea lettuce (Ulva pertusa. Four endo-ß-1,4-glucanases (21K, 45K, 65K, and 95K cellulase and 2 ß-glucosidases (110K and 210K were purified to a homogeneous state, and the synergistic action of these enzymes during cellulose digestion was analyzed. All cellulases exhibited cellulase and lichenase activities and showed distinct cleavage specificities against cellooligosaccharides and filter paper. Filter paper was digested to cellobiose, cellotriose, and cellotetraose by 21K cellulase, whereas 45K and 65K enzymes hydrolyzed the filter paper to cellobiose and glucose. 210K ß-glucosidase showed unique substrate specificity against synthetic and natural substrates, and 4-methylumbelliferyl (4MU-ß-glucoside, 4MU-ß-galactoside, cello-oligosaccharides, laminarin, and lichenan were suitable substrates. Furthermore, 210K ß-glucosidase possesses lactase activity. Although ß-glucosidase and cellulase are necessary for efficient hydrolysis of carboxymethylcellulose to glucose, laminarin is hydrolyzed to glucose only by 210K ß-glucosidase. Kinetic analysis of the inhibition of 210K ß-glucosidase by D-glucono-1,5-lactone suggested the presence of 2 active sites similar to those of mammalian lactase-phlorizin hydrolase. Saccharification of sea lettuce was considerably stimulated by the synergistic action of 45K cellulase and 210K ß-glucosidase. Our results indicate that 45K cellulase and 210K

  7. 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

  8. Beta2- and beta3-adrenoceptors activate glucose uptake in chick astrocytes by distinct mechanisms: a mechanism for memory enhancement?

    Science.gov (United States)

    Hutchinson, Dana S; Summers, Roger J; Gibbs, Marie E

    2007-11-01

    Isoprenaline, acting at beta-adrenoceptors (ARs), enhances memory formation in single trial discriminated avoidance learning in day-old chicks by mechanisms involving alterations in glucose and glycogen metabolism. Earlier studies of memory consolidation in chicks indicated that beta3-ARs enhanced memory by increasing glucose uptake, whereas beta2-ARs enhance memory by increasing glycogenolysis. This study examines the ability of beta-ARs to increase glucose uptake in chick forebrain astrocytes. The beta-AR agonist isoprenaline increased glucose uptake in a concentration-dependent manner, as did insulin. Glucose uptake was increased by the beta2-AR agonist zinterol and the beta3-AR agonist CL316243, but not by the beta1-AR agonist RO363. In chick astrocytes, reverse transcription-polymerase chain reaction studies showed that beta1-, beta2-, and beta3-AR mRNA were present, whereas radioligand-binding studies showed the presence of only beta2- and beta3-ARs. beta-AR or insulin-mediated glucose uptake was inhibited by phosphatidylinositol-3 kinase and protein kinase C inhibitors, suggesting a possible interaction between the beta-AR and insulin pathways. However beta2- and beta3-ARs increase glucose uptake by two different mechanisms: beta2-ARs via a Gs-cAMP-protein kinase A-dependent pathway, while beta3-ARs via interactions with Gi. These results indicate that activation of beta2- and beta3-ARs causes glucose uptake in chick astrocytes by distinct mechanisms, which may be relevant for memory enhancement.

  9. Glucokinase, the pancreatic glucose sensor, is not the gut glucose sensor

    DEFF Research Database (Denmark)

    Murphy, R; Tura, A; Clark, P M

    2008-01-01

    AIMS/HYPOTHESIS: The incretin hormones glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotrophic peptide (GIP) are released from intestinal endocrine cells in response to luminal glucose. Glucokinase is present in these cells and has been proposed as a glucose sensor. The physiological...... role of glucokinase can be tested using individuals with heterozygous glucokinase gene (GCK) mutations. If glucokinase is the gut glucose sensor, GLP-1 and GIP secretion during a 75 g OGTT would be lower in GCK mutation carriers compared with controls. METHODS: We compared GLP-1 and GIP concentrations...... measured at five time-points during a 75 g OGTT in 49 participants having GCK mutations with those of 28 familial controls. Mathematical modelling of glucose, insulin and C-peptide was used to estimate basal insulin secretion rate (BSR), total insulin secretion (TIS), beta cell glucose sensitivity...

  10. Estimation of glucose carbon recycling in children with glycogen storage disease: A 13C NMR study using [U-13C]glucose

    International Nuclear Information System (INIS)

    Kalderon, B.; Korman, S.H.; Gutman, A.; Lapidot, A.

    1989-01-01

    A stable isotope procedure to estimate hepatic glucose carbon recycling and thereby elucidate the mechanism by which glucose is produced in patients lacking glucose 6-phosphatase is described. A total of 10 studies was performed in children with glycogen storage disease type I (GSD-I) and type III (GSD-III) and control subjects. A primed dose-constant nasogastric infusion of D-[U- 13 C]glucose or an infusion diluted with nonlabeled glucose solution was administered following different periods of fasting. Hepatic glucose carbon recycling was estimated from 13 C NMR spectra. The values obtained for GSD-I patients coincided with the standard [U- 13 C]glucose dilution curve. These results indicate that the plasma glucose of GSD-I subjects comprises only a mixture of 99% 13 C-enriched D-[U- 13 C]glucose and unlabeled glucose but lacks any recycled glucose. Significantly different glucose carbon recycling values were obtained for two GSD-III patients in comparison to GSD-I patients. The results eliminate a mechanism for glucose production in GSD-I children involving gluconeogenesis. However, glucose release by amylo-1,6-glucosidase activity would result in endogenous glucose production of non- 13 C-labeled and nonrecycled glucose carbon, as was found in this study. In GSD-III patients gluconeogenesis is suggested as the major route for endogenous glucose synthesis. The contribution of the triose-phosphate pathway in these patients has been determined

  11. Interaction Between the Central and Peripheral Effects of Insulin in Controlling Hepatic Glucose Metabolism in the Conscious Dog

    Science.gov (United States)

    Ramnanan, Christopher J.; Kraft, Guillaume; Smith, Marta S.; Farmer, Ben; Neal, Doss; Williams, Phillip E.; Lautz, Margaret; Farmer, Tiffany; Donahue, E. Patrick; Cherrington, Alan D.; Edgerton, Dale S.

    2013-01-01

    The importance of hypothalamic insulin action to the regulation of hepatic glucose metabolism in the presence of a normal liver/brain insulin ratio (3:1) is unknown. Thus, we assessed the role of central insulin action in the response of the liver to normal physiologic hyperinsulinemia over 4 h. Using a pancreatic clamp, hepatic portal vein insulin delivery was increased three- or eightfold in the conscious dog. Insulin action was studied in the presence or absence of intracerebroventricularly mediated blockade of hypothalamic insulin action. Euglycemia was maintained, and glucagon was clamped at basal. Both the molecular and metabolic aspects of insulin action were assessed. Blockade of hypothalamic insulin signaling did not alter the insulin-mediated suppression of hepatic gluconeogenic gene transcription but blunted the induction of glucokinase gene transcription and completely blocked the inhibition of glycogen synthase kinase-3β gene transcription. Thus, central and peripheral insulin action combined to control some, but not other, hepatic enzyme programs. Nevertheless, inhibition of hypothalamic insulin action did not alter the effects of the hormone on hepatic glucose flux (production or uptake). These data indicate that brain insulin action is not a determinant of the rapid (<4 h) inhibition of hepatic glucose metabolism caused by normal physiologic hyperinsulinemia in this large animal model. PMID:23011594

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

    Science.gov (United States)

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

    2016-06-01

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

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ... you should check and what your blood glucose levels should be. Checking your blood and then treating ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... blood glucose High levels of sugar in the urine Frequent urination Increased thirst Part of managing your ... glucose is above 240 mg/dl, check your urine for ketones. If you have ketones, do not ...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... can often lower your blood glucose level by exercising. However, if your blood glucose is above 240 ... ketones. If you have ketones, do not exercise. Exercising when ketones are present may make your blood ...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- A Future Without Diabetes - a-future- ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high blood glucose (blood sugar). High ... We Are Research Leaders We Support Your Doctor Student Resources Patient Access to Research Research Resources Practice ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    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 ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your Carbs Count Glycemic Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get ... the technical term for high blood glucose (blood sugar). High blood glucose happens when the body has ...

  20. [Thromboresistance of glucose-containing hydrogels].

    Science.gov (United States)

    Valuev, I L; Valuev, L I; Vanchugova, L V; Obydennova, I V; Valueva, T A

    2013-01-01

    The thromboresistance of glucose-sensitive polymer hydrogels, modeling one of the functions of the pancreas, namely, the ability to secrete insulin in response to the introduction of glucose into the environment, has been studied. Hydrogels were synthesized by the copolymerization of hydroxyethyl methacrylate with N-acryloyl glucosamine in the presence of a cross-linking agent and subsequently treated with concanavalin A. Introduction of glucose residues into the hydrogel did not result in significant changes in either the number of trombocytes adhered to the hydrogel or the degree of denaturation of blood plasma proteins interacting with the hydrogel. Consequently, the biological activity of insulin did not change after release from the hydrogel. The use of glucose-sensitive hydrogels is supposed to contribute to the development of a novel strategy for the treatment of diabetes.

  1. [Blood glucose self monitoring].

    Science.gov (United States)

    Wascher, Thomas C; Stechemesser, Lars

    2016-04-01

    Self monitoring of blood glucose contributes to the integrated management of diabetes mellitus. It, thus, should be available for all patients with diabetes mellitus type-1 and type-2. Self monitoring of blood glucose improves patients safety, quality of life and glucose control. The current article represents the recommendations of the Austrian Diabetes Association for the use of blood glucose self monitoring according to current scientific evidence.

  2. 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.

  3. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Carbohydrate Counting Make Your Carbs Count Glycemic Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type ... Checking Your Blood Glucose A1C and eAG Hypoglycemia (Low blood glucose) Hyperglycemia (High blood glucose) Dawn Phenomenon ...

  4. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... how often you should check and what your blood glucose levels should be. Checking your blood and then treating ... I Treat Hyperglycemia? You can often lower your blood glucose level by exercising. However, if your blood glucose is ...

  5. Electrocatalytic glucose sensor

    Energy Technology Data Exchange (ETDEWEB)

    Gebhardt, U; Luft, G; Mund, K; Preidel, W; Richter, G J

    1983-01-01

    An artificial pancreas consists of an insulin depot, a dosage unit and a glucose sensor. The measurement of the actual glucose concentration in blood is still an unsolved problem. Two methods are described for an electrocatalytic glucose sensor. Under the interfering action of amino acids and urea in-vitro measurements show an error of between 10% and 20%.

  6. Vitamins and glucose metabolism: The role of static magnetic fields.

    Science.gov (United States)

    Lahbib, Aïda; Ghodbane, Soumaya; Sakly, Mohsen; Abdelmelek, Hafedh

    2014-12-01

    This review focuses on our own data and other data from the literature of static magnetic fields (SMF) bioeffects and vitamins and glucose metabolism. Three main areas of investigation have been covered: Static magnetic field and glucose metabolism, static magnetic field and vitamins and the role of vitamins on glucose metabolism. Considering these articles comprehensively, the conclusions are as follows: The primary cause of changes in cells after incubation in external SMF is disruption of free radical metabolism and elevation of their concentration. Such disruption causes oxidative stress leading to an unsteadiness of glucose level and insulin release. Moreover, based on available data, it was concluded that exposure to SMF alters plasma levels of vitamin A, C, D and E; these parameters can take part in disorder of glucose homeostasis and insulin release.

  7. The 78 kDa glucose-regulated protein (GRP78/BIP) is expressed on the cell membrane, is released into cell culture medium and is also present in human peripheral circulation.

    Science.gov (United States)

    Delpino, Andrea; Castelli, Mauro

    2002-01-01

    In human rabdomiosarcoma cells (TE671/RD) chronic exposure to 500 nM thapsigargin (a powerful inhibitor of the endoplasmic reticulum Ca2+-ATPases) resulted in the induction of the stress protein GRP78/BIP. Making use of the surface biotinylation method, followed by the isolation of the GRP78 using ATP-agarose affinity chromatography, it was found that a fraction of the thapsigargin-induced GRP78 is expressed on the cell surface. The presence of GRP78 on the membrane of thapsigargin-treated cells was confirmed by fractionation of cell lysates into a soluble and a membrane fraction, followed by Western blot analysis with an anti-GRP78 antibody. It was also found that conspicuous amounts of GRP78 are present in the culture medium collected from thapsigargin-treated cultures. This extracellular GRP78 originates mostly by an active release from intact cells and does not result solely from the leakage of proteins from dead cells. Moreover, small amounts of circulating, free GRP78 and naturally-occurring anti-GRP78 autoantibodies were detected in the peripheral circulation of healthy human individuals.

  8. Measuring brain glucose phosphorylation with labeled glucose

    International Nuclear Information System (INIS)

    Brondsted, H.E.; Gjedde, A.

    1988-01-01

    This study tested whether glucose labeled at the C-6 position generates metabolites that leave brain so rapidly that C-6-labeled glucose cannot be used to measure brain glucose phosphorylation (CMRGlc). In pentobarbital-anesthetized rats, the parietal cortex uptake of [ 14 C]glucose labeled in the C-6 position was followed for times ranging from 10 s to 60 min. We subtracted the observed radioactivity from the radioactivity expected with no loss of labeled metabolites from brain by extrapolation of glucose uptake in an initial period when loss was negligible. The observed radioactivity was a monoexponentially declining function of the total radioactivity expected in the absence of metabolite loss. The constant of decline was 0.0077.min-1 for parietal cortex. Metabolites were lost from the beginning of the experiment. However, with correction for the loss of labeled metabolites, it was possible to determine an average CMRGlc between 4 and 60 min of circulation of 64 +/- 4 (SE; n = 49) mumol.hg-1.min-1

  9. Carbon Nanotube Yarn-Based Glucose Sensing Artificial Muscle.

    Science.gov (United States)

    Lee, Junghan; Ko, Sachan; Kwon, Cheong Hoon; Lima, Márcio D; Baughman, Ray H; Kim, Seon Jeong

    2016-04-01

    Boronic acid (BA), known to be a reversible glucose-sensing material, is conjugated to a nanogel (NG) derived from hyaluronic acid biopolymer and used as a guest material for a carbon multiwalled nanotube (MWNT) yarn. By exploiting the swelling/deswelling of the NG that originates from the internal anionic charge changes resulting from BA binding to glucose, a NG MWNT yarn artificial muscle is obtained that provides reversible torsional actuation that can be used for glucose sensing. This actuator shows a short response time and high sensitivity (in the 5-100 × 10(-3) m range) for monitoring changes in glucose concentration in physiological buffer, without using any additional auxiliary substances or an electrical power source. It may be possible to apply the glucose-sensing MWNT yarn muscles as implantable glucose sensors that automatically release drugs when needed or as an artificial pancreas. © 2016 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications Neuropathy Foot Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ...

  11. Biostable glucose permeable polymer

    DEFF Research Database (Denmark)

    2017-01-01

    A new biostable glucose permeable polymer has been developed which is useful, for example, in implantable glucose sensors. This biostable glucose permeable polymer has a number of advantageous characteristics and, for example, does not undergo hydrolytic cleavage and degradation, thereby providing...... a composition that facilitates long term sensor stability in vivo. The versatile characteristics of this polymer allow it to be used in a variety of contexts, for example to form the body of an implantable glucose sensor. The invention includes the polymer composition, sensor systems formed from this polymer...

  12. Bifurcate effects of glucose on caspase-independent cell death during hypoxia

    International Nuclear Information System (INIS)

    Aki, Toshihiko; Nara, Akina; Funakoshi, Takeshi; Uemura, Koichi

    2010-01-01

    We investigated the effect of glucose on hypoxic death of rat cardiomyocyte-derived H9c2 cells and found that there is an optimal glucose concentration for protection against hypoxic cell death. Hypoxic cell death in the absence of glucose is accompanied by rapid ATP depletion, release of apoptosis-inducing factor from mitochondria, and nuclear chromatin condensation, all of which are inhibited by glucose in a dose-dependent manner. In contrast, excessive glucose also induces hypoxic cell death that is not accompanied by these events, suggesting a change in the mode of cell death between hypoxic cells with and without glucose supplementation.

  13. Dissociation of the effects of epinephrine and insulin on glucose and protein metabolism

    International Nuclear Information System (INIS)

    Castellino, P.; Luzi, L.; Del Prato, S.; DeFronzo, R.A.

    1990-01-01

    The separate and combined effects of insulin and epinephrine on leucine metabolism were examined in healthy young volunteers. Subjects participated in four experimental protocols: (1) euglycemic insulin clamp (+80 microU/ml), (2) epinephrine infusion (50 ng.kg-1.min-1) plus somatostatin with basal replacement of insulin and glucagon, (3) combined epinephrine (50 ng.kg-1.min-1) plus insulin (+80 microU/ml) infusion, and (4) epinephrine and somatostatin as in study 2 plus basal amino acid replacement. Studies were performed with a prime-continuous infusion of [1-14C]leucine and indirect calorimetry. Our results indicate that (1) hyperinsulinemia causes a generalized decrease in plasma amino acid concentrations, including leucine; (2) the reduction in plasma leucine concentration is primarily due to an inhibition of endogenous leucine flux; nonoxidative leucine disposal decreases after insulin infusion; (3) epinephrine, without change in plasma insulin concentration, reduces plasma amino acid levels; (4) combined epinephrine-insulin infusion causes a greater decrease in plasma amino levels than observed with either hormone alone; this is because of a greater inhibition of endogenous leucine flux; and (5) when basal amino acid concentrations are maintained constant with a balanced amino acid infusion, epinephrine inhibits the endogenous leucine flux. In conclusion, the present results do not provide support for the concept that epinephrine is a catabolic hormone with respect to amino acid-protein metabolism. In contrast, epinephrine markedly inhibits insulin-mediated glucose metabolism

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... by Mail Close www.diabetes.org > Living With Diabetes > Treatment and Care > Blood Glucose Testing Share: Print Page ... and-how-tos, . In this section Living With Diabetes Treatment and Care Blood Glucose Testing Checking Your Blood ...

  15. Blood Glucose Determination

    DEFF Research Database (Denmark)

    Lippi, Giuseppe; Nybo, Mads; Cadamuro, Janne

    2018-01-01

    The measurement of fasting plasma glucose may be biased by a time-dependent decrease of glucose in blood tubes, mainly attributable to blood cell metabolism when glycolysis is not rapidly inhibited or blood cells cannot be rapidly separated from plasma. Although glycolysis inhibitors such as sodium...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for ... is checking your blood glucose often. Ask your doctor how often you should ... associated with hyperglycemia. How Do I Treat Hyperglycemia? ...

  17. Brain Glucose Metabolism Controls Hepatic Glucose and Lipid Production

    OpenAIRE

    Lam, Tony K.T.

    2007-01-01

    Brain glucose-sensing mechanisms are implicated in the regulation of feeding behavior and hypoglycemic-induced hormonal counter-regulation. This commentary discusses recent findings indicating that the brain senses glucose to regulate both hepatic glucose and lipid production.

  18. Nanomaterials in glucose sensing

    CERN Document Server

    Burugapalli, Krishna

    2013-01-01

    The smartness of nano-materials is attributed to their nanoscale and subsequently unique physicochemical properties and their use in glucose sensing has been aimed at improving performance, reducing cost and miniaturizing the sensor and its associated instrumentation. So far, portable (handheld) glucose analysers were introduced for hospital wards, emergency rooms and physicians' offices; single-use strip systems achieved nanolitre sampling for painless and accurate home glucose monitoring; advanced continuous monitoring devices having 2 to 7 days operating life are in clinical and home use; and continued research efforts are being made to develop and introduce increasingly advanced glucose monitoring systems for health as well as food, biotechnology, cell and tissue culture industries. Nanomaterials have touched every aspect of biosensor design and this chapter reviews their role in the development of advanced technologies for glucose sensing, and especially for diabetes. Research shows that overall, nanomat...

  19. Carbon balance studies of glucose metabolism in rat cerebral cortical synaptosomes

    Energy Technology Data Exchange (ETDEWEB)

    Bauer, U; Brand, K

    1982-07-01

    Synaptosomes were isolated from rat cerebral cortex and incubated with (U-/sup 14/C)-, (1-/sup 14/C)- or (6-/sup 14/C)glucose. Glucose utilization and the metabolic partitioning of glucose carbon in products were determined by isotopic methods. From the data obtained a carbon balance was constructed, showing lactate to be the main product of glucose metabolism, followed by CO/sup 2/, amino acids and pyruvate. Measuring the release of /sup 14/CO/sup 2/ from glucose labelled in three different positions allowed the construction of a flow diagram of glucose carbon atoms in synaptosomes, which provides information about the contribution of the various pathways of glucose metabolism. Some 2% of glucose utilized was calculated to be degraded via the pentose phosphate pathway. Addition of chlorpromazine, imipramine or haloperidol at concentrations of 10(-5) M reduced glucose utilisation by 30% without changing the distribution pattern of radioactivity in the various products.

  20. Glucose screening tests during pregnancy

    Science.gov (United States)

    Oral glucose tolerance test - pregnancy; OGTT - pregnancy; Glucose challenge test - pregnancy; Gestational diabetes - glucose screening ... screening test between 24 and 28 weeks of pregnancy. The test may be done earlier if you ...

  1. 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

  2. Association of SSTR2 Polymorphisms and Glucose Homeostasis Phenotypes

    OpenAIRE

    Sutton, Beth S.; Palmer, Nicholette D.; Langefeld, Carl D.; Xue, Bingzhong; Proctor, Alexandria; Ziegler, Julie T.; Haffner, Steven M.; Norris, Jill M.; Bowden, Donald W.

    2009-01-01

    OBJECTIVE This study evaluated the influence of somatostatin receptor type 2 (SSTR2) polymorphisms on measures of glucose homeostasis in the Insulin Resistance Atherosclerosis Family Study (IRASFS). SSTR2 is a G-protein?coupled receptor that, in response to somatostatin, mediates inhibition of insulin, glucagon, and growth hormone release and thus may affect glucose homeostasis. RESEARCH DESIGN AND METHODS Ten single nucleotide polymorphisms (SNPs) spanning the gene were chosen using a SNP de...

  3. Glucose and age-related changes in memory.

    Science.gov (United States)

    Gold, Paul E

    2005-12-01

    Epinephrine, released from the adrenal medulla, enhances memory in young rats and mice and apparently does so, at least in part, by increasing blood glucose levels. Like epinephrine, administration of glucose enhances cognitive functions in humans and rodents, including reversing age-related impairments in learning and memory. Epinephrine responses to training are increased in aged rats but the subsequent increase in blood glucose levels is severely blunted. The absence of increases in blood glucose levels during training might contribute to age-related deficits in learning and memory. Also, extracellular glucose levels in the hippocampus are depleted during spontaneous alternation testing to a far greater extent in aged than in young rats. Importantly, systemic injections of glucose block the depletion in the hippocampus and also enhance performance on the alternation task. Thus, the extensive depletion of extracellular glucose during training in aged rats may be associated with age-related memory impairments, an effect that might be related to - or may exacerbate - the effects on learning and memory of an absence of the increases in blood glucose levels to training as seen in young rats. Together, these findings suggest that age-related changes in both peripheral and central glucose physiology contribute to age-related impairments in memory.

  4. Methane release

    International Nuclear Information System (INIS)

    Seifert, M.

    1999-01-01

    The Swiss Gas Industry has carried out a systematic, technical estimate of methane release from the complete supply chain from production to consumption for the years 1992/1993. The result of this survey provided a conservative value, amounting to 0.9% of the Swiss domestic output. A continuation of the study taking into account new findings with regard to emission factors and the effect of the climate is now available, which provides a value of 0.8% for the target year of 1996. These results show that the renovation of the network has brought about lower losses in the local gas supplies, particularly for the grey cast iron pipelines. (author)

  5. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... them through the urine. Unfortunately, the body cannot release all the ketones and they build up in ... Careers Contact Us Policies Corporate Support Newsroom Press Releases For Professionals En Español Online Community Walk Bike ...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools ...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics Home Symptoms Diagnosis America's Diabetes Challenge Type 1 Type 2 Facts About Type 2 Enroll ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... to Give Close Are You at Risk? Home Prevention Diagnosing Diabetes and Learning About Prediabetes Type 2 ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ...

  9. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication ... Learning at Camp Find a Camp Fundraising Events Step Out Walk to Stop Diabetes Tour de Cure ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... EXPO Volunteer Opportunities Sponsorship and Exhibit Opportunities Camp ... when ketones are present may make your blood glucose level go even higher. You'll need to work with your doctor ...

  11. CSF glucose test

    Science.gov (United States)

    ... in the space surrounding the spinal cord and brain. ... Abnormal results include higher and lower glucose levels. Abnormal results may be due to: Infection (bacterial or fungus) Inflammation of the central nervous system Tumor

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... Clinical Practice Guidelines Patient Education Materials Scientific Sessions Journals for Professionals Professional Books Patient Access to Research ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... Diabetes Meal Plans Create Your Plate Gluten Free Diets Meal Planning for Vegetarian Diets Cook with Heart- ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... Index Low-Calorie Sweeteners Sugar and Desserts Fitness Exercise & Type 1 Diabetes Get Started Safely Get And ...

  15. Nocturnal continuous glucose monitoring

    DEFF Research Database (Denmark)

    Bay, Christiane; Kristensen, Peter Lommer; Pedersen-Bjergaard, Ulrik

    2013-01-01

    Abstract Background: A reliable method to detect biochemical nocturnal hypoglycemia is highly needed, especially in patients with recurrent severe hypoglycemia. We evaluated reliability of nocturnal continuous glucose monitoring (CGM) in patients with type 1 diabetes at high risk of severe...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More ... us get closer to curing diabetes and better treatments for those living with diabetes. Other Ways to ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... for energy. When your body breaks down fats, waste products called ketones are produced. Your body cannot ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- A Future Without Diabetes - a-future- ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... breast cancer and AIDS combined. Your gift today will help us get closer to curing diabetes and ... blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. How ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers ... updated, this is the "take-you-by-the-hand" guide that will become a trusted friend and ...

  20. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics Home Symptoms Diagnosis America's Diabetes Challenge Type ...

  1. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Know Your Rights Employment Discrimination Health Care Professionals Law Enforcement Driver's License For Lawyers Food & Fitness Home ... symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ...

  2. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ... Day in the Life of Diabetes Famous People Working to Stop Diabetes Common Terms Diabetes Statistics Infographics ...

  3. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Superfoods Non-starchy Vegetables Grains and Starchy Vegetables Fats Alcohol What Can I Drink? Fruit Dairy Food ... glucose for fuel, so your body breaks down fats to use for energy. When your body breaks ...

  4. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Care Blood Glucose Testing Medication Doctors, Nurses & More Oral ... someone new is diagnosed. Diabetes causes more deaths a year than breast cancer and AIDS combined. Your gift today will help ...

  5. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Care > Blood Glucose Testing Share: Print Page Text Size: A A A Listen En Español Hyperglycemia ( ... compact USB drives that can carry a person's full medical record for use in an emergency. How ...

  6. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... for Association Events Messaging Tools Recruiting Advocates Local Market Planning Training Webinars News & Events Advocacy News Call ... Care > Blood Glucose Testing Share: Print Page Text Size: A A A Listen En Español Hyperglycemia (High ...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral ... 2 Diabetes Know Your Rights Employment Discrimination Health Care Professionals Law Enforcement Driver's License For Lawyers Food & ...

  9. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers Health ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... blood glucose level go even higher. You'll need to work with your doctor to find the ... lead to ketoacidosis. Ketoacidosis is life-threatening and needs immediate treatment. Symptoms include: Shortness of breath Breath ...

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... your blood and then treating high blood glucose early will help you avoid problems associated with hyperglycemia. ... to detect hyperglycemia so you can treat it early — before it gets worse. If you're new ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To ... Email: Sign Up Thank you for signing up ' + ' '); $('.survey-form').show(); }, success: function (data) { $('#survey-errors').remove(); $('. ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ... Living With Diabetes Recently Diagnosed Treatment & Care Complications Health ... EXPOs Awareness Programs Wellness Lives Here Become a Member American ...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Your best bet is to practice good diabetes management and learn to detect hyperglycemia so you can ... glucose) Dawn Phenomenon Checking for Ketones Tight Diabetes Control donate en -- A Future Without Diabetes - a-future- ...

  16. Muscle glucose metabolism following exercise in the rat

    DEFF Research Database (Denmark)

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

    1982-01-01

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

  17. Glucose-lowering effect of BTS 67 582.

    Science.gov (United States)

    Page, T; Bailey, C J

    1997-12-01

    1. The hypoglycaemic effect of BTS 67 582 (1,1-dimethyl-2(2-morpholinophenyl) guanidine fumarate) was studied in normal rats. 2. BTS 67 582 (100 mg kg(-1), p.o.) acutely lowered basal plasma glucose concentrations: onset within 1 h, maximum decrease of >40% at 2-3 h, and partial return to euglycaemia by 5 h. Plasma insulin concentrations were increased: onset within 30 min, maximum increase 3 fold at 1-2 h; returning to normal by 5 h. 3. BTS 67 582 (100 mg kg(-1)) increased (by 56%) the rate of disappearance of plasma glucose during an intravenous glucose tolerance test, accompanied by a 51% increase in insulin concentrations. 4. During hyperglycaemic clamp studies BTS 67 582 (100 mg kg(-1)) increased glucose utilization 3 fold. This was associated with a 3 fold increase in insulin concentrations, even in the presence of adrenaline at a dosage which inhibits glucose-induced insulin release. 5. When the insulin-releasing effect of BTS 67 582 (100 mg kg(-1)) was inhibited by infusion of somatostatin, there was no effect on glycaemia. 6. Insulin-dependent diabetic BB/S rats, which do not produce endogenous insulin, showed no effect of BTS 67 582 (100 mg kg(-1)) on plasma glucose concentrations in the presence or absence of exogenous insulin. 7. The results demonstrate an acute hypoglycaemic effect of BTS 67 582 which appears to result mainly from its potent insulin-releasing action.

  18. Insulin-induced activation of glycerol-3-phosphate acyltransferase by a chiro-inositol-containing insulin mediator is defective in adipocytes of insulin-resistant, type II diabetic, Goto-Kakizaki rats.

    OpenAIRE

    Farese, R V; Standaert, M L; Yamada, K; Huang, L C; Zhang, C; Cooper, D R; Wang, Z; Yang, Y; Suzuki, S; Toyota, T

    1994-01-01

    Type II diabetic Goto-Kakizaki (GK) rats were insulin-resistant in euglycemic-hyperinsulinemic clamp studies. We therefore examined insulin signaling systems in control Wistar and diabetic GK rats. Glycerol-3-phosphate acyltransferase (G3PAT), which is activated by headgroup mediators released from glycosyl-phosphatidylinositol (GPI), was activated by insulin in intact and cell-free adipocyte preparations of control, but not diabetic, rats. A specific chiro-inositol-containing inositol phosph...

  19. Lack of change in glucose metabolism in eszopiclone-treated primary insomnia patients

    Directory of Open Access Journals (Sweden)

    Buxton OM

    2017-07-01

    to changes in IVGTT-derived glucose effectiveness, or non-insulin-mediated glucose uptake.Conclusion: Treatment with 3 mg eszopiclone for 2 months, compared with placebo, did not significantly influence either sleep or measures of diabetes risk in this preliminary study. Keywords: primary insomnia, sleep duration, metabolism, IVGTT, insulin sensitivity, diabetes, eszopiclone, wake after sleep onset

  20. Gibbs Free-Energy Gradient along the Path of Glucose Transport through Human Glucose Transporter 3.

    Science.gov (United States)

    Liang, Huiyun; Bourdon, Allen K; Chen, Liao Y; Phelix, Clyde F; Perry, George

    2018-06-11

    Fourteen glucose transporters (GLUTs) play essential roles in human physiology by facilitating glucose diffusion across the cell membrane. Due to its central role in the energy metabolism of the central nervous system, GLUT3 has been thoroughly investigated. However, the Gibbs free-energy gradient (what drives the facilitated diffusion of glucose) has not been mapped out along the transport path. Some fundamental questions remain. Here we present a molecular dynamics study of GLUT3 embedded in a lipid bilayer to quantify the free-energy profile along the entire transport path of attracting a β-d-glucose from the interstitium to the inside of GLUT3 and, from there, releasing it to the cytoplasm by Arrhenius thermal activation. From the free-energy profile, we elucidate the unique Michaelis-Menten characteristics of GLUT3, low K M and high V MAX , specifically suitable for neurons' high and constant demand of energy from their low-glucose environments. We compute GLUT3's binding free energy for β-d-glucose to be -4.6 kcal/mol in agreement with the experimental value of -4.4 kcal/mol ( K M = 1.4 mM). We also compute the hydration energy of β-d-glucose, -18.0 kcal/mol vs the experimental data, -17.8 kcal/mol. In this, we establish a dynamics-based connection from GLUT3's crystal structure to its cellular thermodynamics with quantitative accuracy. We predict equal Arrhenius barriers for glucose uptake and efflux through GLUT3 to be tested in future experiments.

  1. Phosphatidylcholine biosynthesis and insulin release in rat islets of Langerhans

    International Nuclear Information System (INIS)

    Hoffman, J.M.

    1988-01-01

    Turnover of phosphatidylcholine (PC) has been demonstrated to play a role in glucose stimulation of insulin release by pancreatic islets of Langerhans. The activity of the islet CDP-choline pathway of PC synthesis was determined by measuring the incorporation of radiolabeled choline or 32 PO 4 into PC, phosphorylcholine and CDP-choline. Concurrently, insulin release was measured by radioimmunoassay to correlate insulin release and PC synthesis. Glucose concentrations greater than 8.5 mM stimulated CDP-choline pathway activity. However, measurement of PC lipid phosphorus tended to decrease, suggesting that stimulation of the CDP-choline pathway was a means of replenishing PC pools diminished by hydrolysis of PC. Inhibition of glucose oxidation by mannoheptulose or incubations under hypoxic conditions prevented stimulation of the CDP-choline pathway, while inhibition of phospholipase A 2 (PLA 2 ) and secretion by the removal of extracellular Ca 2+ potentiated the stimulation seen with glucose

  2. 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.

  3. Release from the Crabtree effect by hypoxic cell radiosensitizers

    International Nuclear Information System (INIS)

    Mustea, I.; Bara, A.

    1979-01-01

    The Crabtree effect can be observed when the 0 2 consumption of tumour cells or of mammalian cells grown in culture is measured in physiological medium containing glucose. The effect of 2 hypoxic cell radiosensitizers, misonidazole and NDPP, on the 0 2 consumption of Ehrlich ascites tumour cells was compared in media with and without glucose. A stimulatory effect on 0 2 consumption was found for 5-20 mM misonidazole as well as for 0.5mM NDPP, both in media containing 10 -2 M glucose. Thus glucose induced a Crabtree effect in Ehrlich tumour cells, expressed as 38-45% inhibition of 0 2 consumption relative to that in the same medium without glucose. The stimulatory effect of misonidazole and NDPP on 0 2 utilization in medium with glucose undoubtedly appeared as a release from the Crabtree effect. (author)

  4. Association testing of novel type 2 diabetes risk alleles in the JAZF1, CDC123/CAMK1D, TSPAN8, THADA, ADAMTS9, and NOTCH2 loci with insulin release, insulin sensitivity, and obesity in a population-based sample of 4,516 glucose-tolerant middle-aged Danes

    DEFF Research Database (Denmark)

    Grarup, Niels; Andersen, Gitte; Krarup, Nikolaj Thure

    2008-01-01

    identified by meta-analysis of genome-wide association data. RESEARCH DESIGN AND METHODS: We genotyped the six variants in 4,516 middle-aged glucose-tolerant individuals of the population-based Inter99 cohort who were all characterized by an oral glucose tolerance test (OGTT). RESULTS: Homozygous carriers...

  5. The modulatory role of alpha-melanocyte stimulating hormone administered spinally in the regulation of blood glucose level in d-glucose-fed and restraint stress mouse models.

    Science.gov (United States)

    Sim, Yun-Beom; Park, Soo-Hyun; Kim, Sung-Su; Lim, Su-Min; Jung, Jun-Sub; Suh, Hong-Won

    2014-08-01

    Alpha-melanocyte stimulating hormone (α-MSH) is known as a regulator of the blood glucose homeostasis and food intake. In the present study, the possible roles of α-MSH located in the spinal cord in the regulation of the blood glucose level were investigated in d-glucose-fed and immobilization stress (IMO) mouse models. We found in the present study that intrathecal (i.t.) injection with α-MSH alone did not affect the blood glucose level. However, i.t. administration with α-MSH reduced the blood glucose level in d-glucose-fed model. The plasma insulin level was increased in d-glucose-fed model and was further increased by α-MSH, whereas α-MSH did not affect plasma corticosterone level in d-glucose-fed model. In addition, i.t. administration with glucagon alone enhanced blood glucose level and, i.t. injection with glucagon also increased the blood glucose level in d-glucose-fed model. In contrasted to results observed in d-glucose-fed model, i.t. treatment with α-MSH caused enhancement of the blood glucose level in IMO model. The plasma insulin level was increased in IMO model. The increased plasma insulin level by IMO was reduced by i.t. treatment with α-MSH, whereas i.t. pretreatment with α-MSH did not affect plasma corticosterone level in IMO model. Taken together, although spinally located α-MSH itself does not alter the blood glucose level, our results suggest that the activation of α-MSH system located in the spinal cord play important modulatory roles for the reduction of the blood glucose level in d-glucose fed model whereas α-MSH is responsible for the up-regulation of the blood glucose level in IMO model. The enhancement of insulin release may be responsible for modulatory action of α-MSH in down-regulation of the blood glucose in d-glucose fed model whereas reduction of insulin release may be responsible for modulatory action of α-MSH in up-regulation of the blood glucose in IMO model. Copyright © 2014 Elsevier Ltd. All rights reserved.

  6. Glucagon-like-peptide-1 secretion from canine L-cells is increased by glucose-dependent-insulinotropic peptide but unaffected by glucose

    DEFF Research Database (Denmark)

    Damholt, A B; Buchan, A M; Kofod, Hans

    1998-01-01

    dependently stimulated the release of GLP-1 and resulted in a 2-fold increase at 100 nM GIP. This effect was fully inhibited by 10 nM somatostatin. However, neither basal or GIP stimulated GLP-1 secretion were affected by ambient glucose concentrations from 5-25 mM. The receptor-independent secretagogues beta...... but not by staurosporine. These results indicate that glucose does not directly stimulate canine L-cells. It is more probable that glucose releases GIP from the upper intestine that in turn stimulates GLP-1 secretion. The ability of GIP to stimulate GLP-1 secretion is probably mediated through activation of protein kinase...

  7. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... around 4:00 a.m. to 5:00 a.m.). What are the Symptoms of Hyperglycemia? The signs and symptoms include the following: High blood glucose High levels of sugar in the urine Frequent urination Increased ...

  8. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... In Memory In Honor Become a Member En Español Type 1 Type 2 About Us Online Community ... Page Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical ...

  9. Low Blood Glucose (Hypoglycemia)

    Science.gov (United States)

    ... 24 hours after the activity. Drinking too much alcohol without enough food Alcohol makes it harder for your body to keep ... t eaten in a while. The effects of alcohol can also keep you from feeling the ... able to eat as much or keep food down, which can cause low blood glucose. Learn ...

  10. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term for high ... function (data) { $('#survey-errors').remove(); $('.survey-form .form-group .survey-alert-wrap').remove(); if (data.submitSurveyResponse.success == ' ...

  11. Blood Glucose Monitoring Devices

    Science.gov (United States)

    ... are below 100 mg/dL before meals and fasting and are less than 140 mg/dL two hours after meals. People with diabetes should consult their doctor or health care provider to set appropriate blood glucose goals. ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor ... Chat Closed engagement en -- Have Type 2 Diabetes? - 2017-03-lwt2d-en.html Have Type 2 Diabetes? ...

  13. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease (Nephropathy) Gastroparesis Mental Health Step On Up Treatment & Care Blood Glucose Testing ... Pinterest Youtube Instagram Diabetes Stops Here Blog Online Community Site ... Day Prediabetes My Health Advisor Tools to Know Your Risk Diabetes Basics ...

  14. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Up Treatment & Care Blood Glucose Testing Medication Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy ... de Cure Women's Series Do-It-Yourself Fundraising Become a Volunteer American Diabetes Month® American Diabetes Association ...

  15. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Text Size: A A A Listen En Español Hyperglycemia (High Blood Glucose) Hyperglycemia is the technical term ... body can't use insulin properly. What Causes Hyperglycemia? A number of things can cause hyperglycemia: If ...

  16. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Research & Practice Ways to Give Close Are You at Risk? Home Prevention Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose ...

  17. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... You At Risk? Diabetes Basics Living with Diabetes Food & Fitness In My Community Advocacy Research & Practice Ways to Give Close Are You at Risk? Home ... work with your doctor to find the safest way for you to lower your blood glucose ... down on the amount of food you eat might also help. Work with your ...

  18. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... You at Risk? Home Prevention Diagnosing Diabetes and Learning About Prediabetes Type 2 Diabetes Risk Test Lower Your Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools To Know Your Risk Alert Day Diabetes Basics ...

  19. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Risk Healthy Eating Overweight Smoking High Blood Pressure Physical Activity High Blood Glucose My Health Advisor Tools ... Complications DKA (Ketoacidosis) & Ketones Kidney Disease ... than planned or exercised less than planned. You have stress from an illness, such as a cold or flu. You have ...

  20. Role of fibroblast growth factor 19 in the control of glucose homeostasis

    NARCIS (Netherlands)

    Schaap, Frank G.

    2012-01-01

    Purpose of review Fibroblast growth factor 19 (FGF19) is a postprandial hormone released from the small intestine. FGF19 improves glucose tolerance when overexpressed in mice with impaired glucose tolerance or diabetes. This review summarizes the recent advances in our understanding of the biology

  1. 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.

  2. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors.

    Science.gov (United States)

    Song, Zhilin; Levin, Barry E; Stevens, Wanida; Sladek, Celia D

    2014-04-01

    Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca(2+)]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating K ATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P neurons functioning as glucose and "metabolic" sensors to participate in appetite regulation.

  3. Supraoptic oxytocin and vasopressin neurons function as glucose and metabolic sensors

    Science.gov (United States)

    Song, Zhilin; Levin, Barry E.; Stevens, Wanida

    2014-01-01

    Neurons in the supraoptic nuclei (SON) produce oxytocin and vasopressin and express insulin receptors (InsR) and glucokinase. Since oxytocin is an anorexigenic agent and glucokinase and InsR are hallmarks of cells that function as glucose and/or metabolic sensors, we evaluated the effect of glucose, insulin, and their downstream effector ATP-sensitive potassium (KATP) channels on calcium signaling in SON neurons and on oxytocin and vasopressin release from explants of the rat hypothalamo-neurohypophyseal system. We also evaluated the effect of blocking glucokinase and phosphatidylinositol 3 kinase (PI3K; mediates insulin-induced mobilization of glucose transporter, GLUT4) on responses to glucose and insulin. Glucose and insulin increased intracellular calcium ([Ca2+]i). The responses were glucokinase and PI3K dependent, respectively. Insulin and glucose alone increased vasopressin release (P glucose in the presence of insulin. The oxytocin (OT) and vasopressin (VP) responses to insulin+glucose were blocked by the glucokinase inhibitor alloxan (4 mM; P ≤ 0.002) and the PI3K inhibitor wortmannin (50 nM; OT: P = 0.03; VP: P ≤ 0.002). Inactivating KATP channels with 200 nM glibenclamide increased oxytocin and vasopressin release (OT: P neurons functioning as glucose and “metabolic” sensors to participate in appetite regulation. PMID:24477542

  4. Glucose metabolism in critically ill patients

    DEFF Research Database (Denmark)

    Nielsen, Signe Tellerup; Krogh-Madsen, Rikke; Møller, Kirsten

    2015-01-01

    glucose (BG). This is taken advantage of in the treatment of patients with T2DM, for whom GLP-1 analogs have been introduced during the recent years. Infusion of GLP-1 also lowers the BG level in critically ill patients without causing severe hypoglycemia. The T2DM and critical illness share similar......, stimulates insulin secretion and inhibits glucagon release both in healthy individuals and in patients with type 2 diabetes (T2DM). Compared to insulin, GLP-1 appears to be associated with a lower risk of severe hypoglycemia, probably because the magnitude of its insulinotropic action is dependent on blood...

  5. Ambient but not local lactate underlies neuronal tolerance to prolonged glucose deprivation

    Science.gov (United States)

    Sobieski, Courtney; Shu, Hong-Jin

    2018-01-01

    Neurons require a nearly constant supply of ATP. Glucose is the predominant source of brain ATP, but the direct effects of prolonged glucose deprivation on neuronal viability and function remain unclear. In sparse rat hippocampal microcultures, neurons were surprisingly resilient to 16 h glucose removal in the absence of secondary excitotoxicity. Neuronal survival and synaptic transmission were unaffected by prolonged removal of exogenous glucose. Inhibition of lactate transport decreased microculture neuronal survival during concurrent glucose deprivation, suggesting that endogenously released lactate is important for tolerance to glucose deprivation. Tandem depolarization and glucose deprivation also reduced neuronal survival, and trace glucose concentrations afforded neuroprotection. Mass cultures, in contrast to microcultures, were insensitive to depolarizing glucose deprivation, a difference attributable to increased extracellular lactate levels. Removal of local astrocyte support did not reduce survival in response to glucose deprivation or alter evoked excitatory transmission, suggesting that on-demand, local lactate shuttling is not necessary for neuronal tolerance to prolonged glucose removal. Taken together, these data suggest that endogenously produced lactate available globally in the extracellular milieu sustains neurons in the absence of glucose. A better understanding of resilience mechanisms in reduced preparations could lead to therapeutic strategies aimed to bolster these mechanisms in vulnerable neuronal populations. PMID:29617444

  6. 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.

  7. 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

  8. Glucose effectiveness in nondiabetic relatives

    DEFF Research Database (Denmark)

    Egede, M B; Henriksen, J-E; Durck, T T

    2014-01-01

    AIMS: Reduced glucose effectiveness is a predictor of future glucose tolerance in individuals with a family history of type 2 diabetes. We examined retrospectively at 10 years in normoglycemic relatives of diabetic subjects (RELs) the pathophysiological role of glucose effectiveness in the develo...

  9. Effect of glucocorticoid therapy upon glucose metabolism in COPD patients with acute exacerbation

    International Nuclear Information System (INIS)

    Wu Sihai; Wei Zhenggan; Huang Ming'an; Yao Jianguo; Li Hongsheng

    2002-01-01

    Objective: To study the effect of glucocorticoids therapy upon glucose metabolism in COPD patients with acute exacerbation. Methods: Plasma glucose and insulin levels in COPD patients after intravenous administration of 10 mg dexamethasone daily for 5 days were determined oral with glucose tolerance test (OGTT) and insulin release test (IRT). Results: 1) The levels of basal plasma glucose and insulin were significantly higher in severe hypoxemic group than those in moderate hypoxemic group (p 2 (r = -0.5242, p < 0.05). 2) The levels of plasma glucose in intermediate and severe hypoxemic groups were remarkable higher (p < 0.05) than those in mild group. The two peak times of glucose curve were observed at one and two hour after oral glucose load. 3) After the administration of glucocorticoids, at half an hour and one hour plasma glucose levels were significantly higher than those before, the peak time of glucose levels appeared earlier and the insulin release levels were higher than they were before therapy (p < 0.05). Conclusion: COPD patients with acute exacerbation complicated with hypoxemia had problems of impaired glucose tolerance. The administration of glucocorticoids made the impairment worse

  10. Dietary fructose and glucose differentially affect lipid and glucose homeostasis.

    Science.gov (United States)

    Schaefer, Ernst J; Gleason, Joi A; Dansinger, Michael L

    2009-06-01

    Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these 2 monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial triglyceride (TG) levels and has little effect on serum glucose concentrations, whereas dietary glucose has the opposite effects. When dietary glucose and fructose have been directly compared at approximately 20-25% of energy over a 4- to 6-wk period, dietary fructose caused significant increases in fasting TG and LDL cholesterol concentrations, whereas dietary glucose did not, but dietary glucose did increase serum glucose and insulin concentrations in the postprandial state whereas dietary fructose did not. When fructose at 30-60 g ( approximately 4-12% of energy) was added to the diet in the free-living state, there were no significant effects on lipid or glucose biomarkers. Sucrose and high-fructose corn syrup (HFCS) contain approximately equal amounts of fructose and glucose and no metabolic differences between them have been noted. Controlled feeding studies at more physiologic dietary intakes of fructose and glucose need to be conducted. In our view, to decrease the current high prevalence of obesity, dyslipidemia, insulin resistance, and diabetes, the focus should be on restricting the intake of excess energy, sucrose, HFCS, and animal and trans fats and increasing exercise and the intake of vegetables, vegetable oils, fish, fruit, whole grains, and fiber.

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... Fund Research Funding the Next Generation of Brilliant Researchers Diabetes Pro: Professional Resources Online We Support Your ... Collectibles Donate Stocks About Us Who We Are Careers Contact Us Policies Corporate Support Newsroom Press Releases ...

  12. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... About Us Who We Are Careers Contact Us Policies Corporate Support Newsroom Press Releases For Professionals En Español Online Community Walk Bike Shop Sign in American Diabetes Association ...

  13. Continued glucose output after re-feeding contributes to glucose intolerance in hyperthyroidism.

    OpenAIRE

    Holness, M J; Sugden, M C

    1987-01-01

    The effects of hyperthyroidism to elicit glucose intolerance after glucose administration were decreased under conditions where hepatic glucose output was suppressed. It is concluded that continued hepatic glucose output contributes to abnormal glucose tolerance in hyperthyroidism.

  14. Glucose production for cellulose

    Energy Technology Data Exchange (ETDEWEB)

    Suzuki, S; Karube, I

    1977-04-16

    Glucose was produced from cellulose by passing a cellulose solution through a column of an immobilized cellulase which was prepared by coating an inorganic carrier such as macadam or stainless steel beads with collagen containing the cellulase. Thus, 4 mL of 5% cellulase T-AP (60,000 units/g) solution was dissolved in 100 g of 0.9% collagen solution and the solution mixed with 60 g of macadam (diam. = 0.5 to 1.5 mm) and stirred for 10 min. The treated beads were dried in air at 10/sup 0/ to yield an immobilized enzyme retaining 64% of its activity. Through a column (0.8 x 20 cm) packed with 3 g of the immobilized enzyme, 100 mL of 0.33% Avicel SF solution was circulated at 26.4 mL/min at 30/sup 0/ for 60 h. The Avicel SF conversion to glucose was 23%.

  15. Chapter 10: Glucose control: insulin therapy*

    African Journals Online (AJOL)

    Insulin and its analogues lower blood glucose by stimulating peripheral glucose uptake, especially by skeletal muscle and fat, and by inhibiting hepatic glucose production. Insulin inhibits ... control on 2 or 3 oral glucose lowering drugs.

  16. Is Low Blood Glucose (Hypoglycemia) Dangerous?

    Science.gov (United States)

    ... pills. In general, hypoglycemia is defined as a blood glucose level below 70 mg/dl. Low blood glucose is ... glucose. Always carry carbohydrate foods for treatment. Check blood glucose levels again in 15 minutes, and repeat treatment if ...

  17. 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.

  18. Glucose-dependent insulinotropic polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel Bring

    2016-01-01

    was to investigate how the blood glucose level affects the glucagon and insulin responses to GIP in healthy subjects (Study 1) and patients with Type 2 diabetes (Study 2), and more specifically to investigate the effects of GIP and GLP-1 at low blood glucose in patients with Type 1 diabetes without endogenous...... as his own control. Interventions were intravenous administration of hormones GIP, GLP-1 and placebo (saline) during different blood glucose levels maintained (clamped) at a certain level. The end-points were plasma concentrations of glucagon and insulin as well as the amount of glucose used to clamp...... the blood glucose levels. In Study 3, we also used stable glucose isotopes to estimate the endogenous glucose production and assessed symptoms and cognitive function during hypoglycaemia. The results from the three studies indicate that GIP has effects on insulin and glucagon responses highly dependent upon...

  19. Glucose-dependent Insulinotropic Polypeptide

    DEFF Research Database (Denmark)

    Christensen, Mikkel B; Calanna, Salvatore; Holst, Jens Juul

    2014-01-01

    CONTEXT: Patients with type 2 diabetes mellitus (T2DM) have clinically relevant disturbances in the effects of the hormone glucose-dependent insulinotropic polypeptide (GIP). OBJECTIVE: We aimed to evaluate the importance of the prevailing plasma glucose levels for the effect of GIP on responses......: During fasting glycemia (plasma glucose ∼8 mmol/L), GIP elicited significant increments in both insulin and glucagon levels, resulting in neutral effects on plasma glucose. During insulin-induced hypoglycemia (plasma glucose ∼3 mmol/L), GIP elicited a minor early-phase insulin response and increased...... glucagon levels during the initial 30 minutes, resulting in less glucose needed to be infused to maintain the clamp (29 ± 8 vs 49 ± 12 mg × kg(-1), P glucose ∼12 mmol/L), GIP augmented insulin secretion throughout the clamp, with slightly less glucagon...

  20. News/Press Releases

    Data.gov (United States)

    Office of Personnel Management — A press release, news release, media release, press statement is written communication directed at members of the news media for the purpose of announcing programs...

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

    Directory of Open Access Journals (Sweden)

    H.G. Padilha

    2011-10-01

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

  2. CNC-bZIP protein Nrf1-dependent regulation of glucose-stimulated insulin secretion.

    Science.gov (United States)

    Zheng, Hongzhi; Fu, Jingqi; Xue, Peng; Zhao, Rui; Dong, Jian; Liu, Dianxin; Yamamoto, Masayuki; Tong, Qingchun; Teng, Weiping; Qu, Weidong; Zhang, Qiang; Andersen, Melvin E; Pi, Jingbo

    2015-04-01

    The inability of pancreatic β-cells to secrete sufficient insulin in response to glucose stimulation is a major contributing factor to the development of type 2 diabetes (T2D). We investigated both the in vitro and in vivo effects of deficiency of nuclear factor-erythroid 2-related factor 1 (Nrf1) in β-cells on β-cell function and glucose homeostasis. Silencing of Nrf1 in β-cells leads to a pre-T2D phenotype with disrupted glucose metabolism and impaired insulin secretion. Specifically, MIN6 β-cells with stable knockdown of Nrf1 (Nrf1-KD) and isolated islets from β-cell-specific Nrf1-knockout [Nrf1(b)-KO] mice displayed impaired glucose responsiveness, including elevated basal insulin release and decreased glucose-stimulated insulin secretion (GSIS). Nrf1(b)-KO mice exhibited severe fasting hyperinsulinemia, reduced GSIS, and glucose intolerance. Silencing of Nrf1 in MIN6 cells resulted in oxidative stress and altered glucose metabolism, with increases in both glucose uptake and aerobic glycolysis, which is associated with the elevated basal insulin release and reduced glucose responsiveness. The elevated glycolysis and reduced glucose responsiveness due to Nrf1 silencing likely result from altered expression of glucose metabolic enzymes, with induction of high-affinity hexokinase 1 and suppression of low-affinity glucokinase. Our study demonstrated a novel role of Nrf1 in regulating glucose metabolism and insulin secretion in β-cells and characterized Nrf1 as a key transcription factor that regulates the coupling of glycolysis and mitochondrial metabolism and GSIS. Nrf1 plays critical roles in regulating glucose metabolism, mitochondrial function, and insulin secretion, suggesting that Nrf1 may be a novel target to improve the function of insulin-secreting β-cells.

  3. 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.

  4. "Smart tattoo" glucose biosensors and effect of coencapsulated anti-inflammatory agents.

    Science.gov (United States)

    Srivastava, Rohit; Jayant, Rahul Dev; Chaudhary, Ayesha; McShane, Michael J

    2011-01-01

    Minimally invasive glucose biosensors with increased functional longevity form one of the most promising techniques for continuous glucose monitoring. In the present study, we developed a novel nanoengineered microsphere formulation comprising alginate microsphere glucose sensors and anti-inflammatory-drug-loaded alginate microspheres. The formulation was prepared and characterized for size, shape, in vitro drug release, biocompatibility, and in vivo acceptability. Glucose oxidase (GOx)- and Apo-GOx-based glucose sensors were prepared and characterized. Sensing was performed both in distilled water and simulated interstitial body fluid. Layer-by-layer self-assembly techniques were used for preventing drug and sensing chemistry release. Finally, in vivo studies, involving histopathologic examination of subcutaneous tissue surrounding the implanted sensors using Sprague-Dawley rats, were performed to test the suppression of inflammation and fibrosis associated with glucose sensor implantation. The drug formulation showed 100% drug release with in 30 days with zero-order release kinetics. The GOx-based sensors showed good enzyme retention and enzyme activity over a period of 1 month. Apo-GOx-based visible and near-infrared sensors showed good sensitivity and analytical response range of 0-50 mM glucose, with linear range up to 12 mM glucose concentration. In vitro cell line studies proved biocompatibility of the material used. Finally, both anti-inflammatory drugs were successful in controlling the implant-tissue interface by suppressing inflammation at the implant site. The incorporation of anti-inflammatory drug with glucose biosensors shows promise in improving sensor biocompatibility, thereby suggesting potential application of alginate microspheres as "smart tattoo" glucose sensors with increased functional longevity. © 2010 Diabetes Technology Society.

  5. Glucose-dependent trafficking of 5-HT3 receptors in rat gastrointestinal vagal afferent neurons

    Science.gov (United States)

    Babic, Tanja; Troy, Amanda E; Fortna, Samuel R; Browning, Kirsteen N

    2012-01-01

    Background Intestinal glucose induces gastric relaxation via vagally mediated sensory-motor reflexes. Glucose can alter the activity of gastrointestinal (GI) vagal afferent (sensory) neurons directly, via closure of ATP-sensitive potassium channels, as well as indirectly, via the release of 5-hydroxytryptamine (5-HT) from mucosal enteroendocrine cells. We hypothesized that glucose may also be able to modulate the ability of GI vagal afferent neurons to respond to the released 5-HT, via regulation of neuronal 5-HT3 receptors. Methods Whole cell patch clamp recordings were made from acutely dissociated GI-projecting vagal afferent neurons exposed to equiosmolar Krebs’ solution containing different concentrations of D-glucose (1.25–20mM) and the response to picospritz application of 5-HT assessed. The distribution of 5-HT3 receptors in neurons exposed to different glucose concentrations was also assessed immunohistochemically. Key Results Increasing or decreasing extracellular D-glucose concentration increased or decreased, respectively, the 5-HT-induced inward current as well as the proportion of 5-HT3 receptors associated with the neuronal membrane. These responses were blocked by the Golgi-disrupting agent Brefeldin-A (5µM) suggesting involvement of a protein trafficking pathway. Furthermore, L-glucose did not mimic the response of D-glucose implying that metabolic events downstream of neuronal glucose uptake are required in order to observe the modulation of 5-HT3 receptor mediated responses. Conclusions & Inferences These results suggest that, in addition to inducing the release of 5-HT from enterochromaffin cells, glucose may also increase the ability of GI vagal sensory neurons to respond to the released 5-HT, providing a means by which the vagal afferent signal can be amplified or prolonged. PMID:22845622

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

    Directory of Open Access Journals (Sweden)

    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

  7. Gut-Brain Glucose Signaling in Energy Homeostasis.

    Science.gov (United States)

    Soty, Maud; Gautier-Stein, Amandine; Rajas, Fabienne; Mithieux, Gilles

    2017-06-06

    Intestinal gluconeogenesis is a recently identified function influencing energy homeostasis. Intestinal gluconeogenesis induced by specific nutrients releases glucose, which is sensed by the nervous system surrounding the portal vein. This initiates a signal positively influencing parameters involved in glucose control and energy management controlled by the brain. This knowledge has extended our vision of the gut-brain axis, classically ascribed to gastrointestinal hormones. Our work raises several questions relating to the conditions under which intestinal gluconeogenesis proceeds and may provide its metabolic benefits. It also leads to questions on the advantage conferred by its conservation through a process of natural selection. Copyright © 2017 Elsevier Inc. All rights reserved.

  8. Glucose metabolism in gamma-irradiated rice seeds

    International Nuclear Information System (INIS)

    Inoue, M.; Hasegawa, H.; Hori, S.

    1980-01-01

    Gamma-irradiation of 30 kR in rice seeds caused marked inhibition in seedling growth, and prevented the release of reduced sugar during the period of 25 to 76hr after soaking. The C 6 /C 1 ratio following irradiation continued to decrease up to the 76th hour of soaking; the control's ratio tended to increase with comparable soaking time. The percentage recovery of 14 C in carbon dioxide from glucose -1- 14 C was lower in irradiated than in control seeds. These results indicate that gamma-irradiation reduces the participation of the pentose phosphate pathway in glucose catabolism during an early period of germination. (author)

  9. Emotionally arousing pictures increase blood glucose levels and enhance recall.

    Science.gov (United States)

    Blake, T M; Varnhagen, C K; Parent, M B

    2001-05-01

    Arousal enhances memory in human participants and this enhancing effect is likely due to the release of peripheral epinephrine. As epinephrine does not readily enter the brain, one way that peripheral epinephrine may enhance memory is by increasing circulating blood glucose levels. The present study investigated the possibility that emotionally arousing color pictures would improve memory and elevate blood glucose levels in human participants. Blood glucose levels were measured before, 15 min, and 30 min after male university students viewed 60 emotionally arousing or relatively neutral pictures. Participants viewed each picture for 6 s and then had 10 s to rate the arousal (emotional intensity) and valence (pleasantness) of each picture. A free-recall memory test was given 30 min after the last picture was viewed. Although the emotionally arousing and neutral picture sets were given comparable valence ratings, participants who viewed the emotionally arousing pictures rated the pictures as being more arousing, recalled more pictures, and had higher blood glucose levels after viewing the pictures than did participants who viewed the neutral pictures. These findings indicate that emotionally arousing pictures increase blood glucose levels and enhance memory, and that this effect is not due to differences in the degree of pleasantness of the stimuli. These findings support the possibility that increases in circulating blood glucose levels in response to emotional arousal may be part of the biological mechanism that allows emotional arousal to enhance memory. Copyright 2001 Academic Press.

  10. 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.

  11. Hyperglycemia (High Blood Glucose)

    Medline Plus

    Full Text Available ... errors); $.each(surveyErrors, function () { if (this.errorField) { $('input[name="' + this.errorField + '"]').closest('.form-group') .prepend(' ' + ' ' + this.errorMessage + ' ' + ' '); } }); $('. ... Us Who We Are Careers Contact Us Policies Corporate Support Newsroom Press Releases For Professionals En Español ...

  12. Glucose metabolism in lactating reindeer

    Energy Technology Data Exchange (ETDEWEB)

    White, R G; Luick, J R

    1976-01-01

    Changes in glucose synthesis during the lactation cycle were estimated in pen-fed and grazing reindeer. The pool size, space, transfer rate, and irreversible loss of glucose were determined using simultaneous injections of (2-/sup 3/H)glucose and primed infusions of (U-/sup 14/C)glucose in reindeer lactating for 1-2, 4-5, 8-9, and 12-16 weeks. Glucose transfer rate and irreversible loss were higher during early to midlactation than at other times of the year; maximum estimates were at 8-9 week postpartum (July), and a decline was noted at 12-16 weeks (August). During the first 1-2 weeks in pen-fed and 4-5 weeks in grazing reindeer, glucose transfer rate and irreversible loss were almost twice the values reported for reindeer at maintenance. No difference in the irreversible loss of glucose was noted between lactating and non-lactating reindeer at 18-20 weeks postpartum (September), and there is evidence that this may occur as early as 12-16 weeks postpartum. No significant trend was noted in the glucose space throughout lactation; however, a significant increase in plasma glucose concentration and pool size was noted when glucose synthesis was highest (8-9 weeks postpartum). Glucose turnover time was consistently faster (78-88 min) in lactating than in non-lactating reindeer (107-140 min). Reindeer used a smaller proportion of plasma glucose-C for lactose synthesis than did other domestic species. This probably results from the low lactose content of reindeer milk and the relatively low rate of milk secretion. (auth)

  13. Intake of Lactobacillus reuteri Improves Incretin and Insulin Secretion in Glucose-Tolerant Humans

    DEFF Research Database (Denmark)

    Simon, Marie-Christine; Strassburger, Klaus; Nowotny, Bettina

    2015-01-01

    production. Muscle and hepatic lipid contents were assessed by (1)H-magnetic resonance spectroscopy, and immune status, cytokines, and endotoxin were measured with specific assays. RESULTS: In glucose-tolerant volunteers, daily administration of L. reuteri SD5865 increased glucose-stimulated GLP-1 and GLP-2....... reuteri SD5865 or placebo over 4 weeks. Oral glucose tolerance and isoglycemic glucose infusion tests were used to assess incretin effect and GLP-1 and GLP-2 secretion, and euglycemic-hyperinsulinemic clamps with [6,6-(2)H2]glucose were used to measure peripheral insulin sensitivity and endogenous glucose...... cytokines. CONCLUSIONS: Enrichment of gut microbiota with L. reuteri increases insulin secretion, possibly due to augmented incretin release, but does not directly affect insulin sensitivity or body fat distribution. This suggests that oral ingestion of one specific strain may serve as a novel therapeutic...

  14. Theophylline enhances glucose recovery after hypoglycemia in healthy man and in type I diabetic patients

    DEFF Research Database (Denmark)

    Hvidberg, A; Rasmussen, M H; Christensen, N J

    1994-01-01

    followed by IV infusion of 1 mg/kg/h) was administered from 1 hour before induction of hypoglycemia until the end of the study period. On the other day, NaCl was administered. Plasma glucose before induction of hypoglycemia was equal on the 2 study days. The plasma glucose area under the curve (AUC......). The incremental AUC for cAMP was larger with theophylline for diabetic patients (P = .01). For healthy subjects, cAMP was greater with theophylline 30 minutes after insulin (P = .03). In conclusion, glucose recovery after hypoglycemia is significantly increased when theophylline is administered in an asthma......The principal mediators of glucose counterregulation (glucagon and epinephrine) use intracellular cyclic adenosine monophosphate (cAMP) to mediate glucose release. Since theophylline increases cAMP (by inhibiting its decomposition), we investigated the effect of theophylline on glucose recovery...

  15. Is contraction-stimulated glucose transport feedforward regulated by Ca2+?

    DEFF Research Database (Denmark)

    Jensen, Thomas Elbenhardt; Angin, Yeliz; Sylow, Lykke

    2014-01-01

    cell types. The literature is contrasted against our recent findings suggesting that SR Ca(2+) release is neither essential nor adequate to stimulate glucose transport in muscle. Instead, feedback signals through AMPK and mechanical stress are likely to account for most of contraction......In many cell types, Ca(2+) signals to increase the movement and surface membrane insertion of vesicles. In skeletal muscle, Ca(2+) is predominantly released from the sarcoplasmic reticulum (SR) to initiate contraction. Sarcoplasmic reticulum Ca(2+) release is widely believed to be a direct......-stimulated glucose transport. A revised working model is proposed, in which muscle glucose transport during contraction is not directly regulated by SR Ca(2+) release but rather responds exclusively to feedback signals activated secondary to cross-bridge cycling and tension development....

  16. 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...

  17. Effects of high-fructose corn syrup and sucrose consumption on circulating glucose, insulin, leptin, and ghrelin and on appetite in normal-weight women.

    Science.gov (United States)

    Melanson, Kathleen J; Zukley, Linda; Lowndes, Joshua; Nguyen, Von; Angelopoulos, Theodore J; Rippe, James M

    2007-02-01

    Fructose has been implicated in obesity, partly due to lack of insulin-mediated leptin stimulation and ghrelin suppression. Most work has examined effects of pure fructose, rather than high-fructose corn syrup (HFCS), the most commonly consumed form of fructose. This study examined effects of beverages sweetened with HFCS or sucrose (Suc), when consumed with mixed meals, on blood glucose, insulin, leptin, ghrelin, and appetite. Thirty lean women were studied on two randomized 2-d visits during which HFCS- and Suc-sweetened beverages were consumed as 30% of energy on isocaloric diets during day 1 while blood was sampled. On day 2, food was eaten ad libitum. Subjects rated appetite at designated times throughout visits. No significant differences between the two sweeteners were seen in fasting plasma glucose, insulin, leptin, and ghrelin (P > 0.05). The within-day variation in all four items was not different between the two visits (P > 0.05). Net areas under the curve were similar for glucose, insulin, and leptin (P > 0.05). There were no differences in energy or macronutrient intake on day 2. The only appetite variable that differed between sweeteners was desire to eat, which had a higher area under the curve the day after Suc compared with HFCS. These short-term results suggest that, when fructose is consumed in the form of HFCS, the measured metabolic responses do not differ from Suc in lean women. Further research is required to examine appetite responses and to determine if these findings hold true for obese individuals, males, or longer periods.

  18. Effect of blood glucose level on acute stress response of grass carp Ctenopharyngodon idella.

    Science.gov (United States)

    Jiang, Danli; Wu, Yubo; Huang, Di; Ren, Xing; Wang, Yan

    2017-10-01

    Stress has a considerable impact on welfare and productivity of fish, and blood glucose level of fish may be a factor modulating stress response. This study evaluated the effect of blood glucose level and handling on acute stress response of grass carp Ctenopharyngodon idella. Fish were intraperitoneally injected with glucose at 0, 0.2, 0.5, and 1.0 mg g -1 body mass (BM) and then were exposed to handling for 5 min. Glucose injection resulted in increase of plasma glucose level and liver glycogen content and decrease of plasma lactate level. Handling resulted in increase of plasma levels of cortisol, glucose, and lactate and plasma lactic dehydrogenase (LDH) activity and decrease of liver glycogen content. At 1 h post-stress, the plasma cortisol level was lower in the stressed fish injected with glucose at 0.5 mg g -1 BM than the stressed fish injected with glucose at 0, 0.2, and 1.0 mg g -1 BM. No significant differences were found in the activities of phosphoenolpyruvate carboxykinase (PEPCK) and pyruvate kinase (PK) in the liver between the stressed and unstressed fish, regardless of the dose of glucose injection. At 1 h post-stress, the liver glucose-6-phosphatase (G6Pase) activity was higher in the fish without glucose injection than in the fish injected with glucose. This study reveals that blood glucose level can affect stress response of grass carp by modulating cortisol release and glucose homeostasis through glycogen metabolism and gluconeogenesis in the liver.

  19. Prediction of Glucose Tolerance without an Oral Glucose Tolerance Test

    Directory of Open Access Journals (Sweden)

    Rohit Babbar

    2018-03-01

    Full Text Available IntroductionImpaired glucose tolerance (IGT is diagnosed by a standardized oral glucose tolerance test (OGTT. However, the OGTT is laborious, and when not performed, glucose tolerance cannot be determined from fasting samples retrospectively. We tested if glucose tolerance status is reasonably predictable from a combination of demographic, anthropometric, and laboratory data assessed at one time point in a fasting state.MethodsGiven a set of 22 variables selected upon clinical feasibility such as sex, age, height, weight, waist circumference, blood pressure, fasting glucose, HbA1c, hemoglobin, mean corpuscular volume, serum potassium, fasting levels of insulin, C-peptide, triglyceride, non-esterified fatty acids (NEFA, proinsulin, prolactin, cholesterol, low-density lipoprotein, HDL, uric acid, liver transaminases, and ferritin, we used supervised machine learning to estimate glucose tolerance status in 2,337 participants of the TUEF study who were recruited before 2012. We tested the performance of 10 different machine learning classifiers on data from 929 participants in the test set who were recruited after 2012. In addition, reproducibility of IGT was analyzed in 78 participants who had 2 repeated OGTTs within 1 year.ResultsThe most accurate prediction of IGT was reached with the recursive partitioning method (accuracy = 0.78. For all classifiers, mean accuracy was 0.73 ± 0.04. The most important model variable was fasting glucose in all models. Using mean variable importance across all models, fasting glucose was followed by NEFA, triglycerides, HbA1c, and C-peptide. The accuracy of predicting IGT from a previous OGTT was 0.77.ConclusionMachine learning methods yield moderate accuracy in predicting glucose tolerance from a wide set of clinical and laboratory variables. A substitution of OGTT does not currently seem to be feasible. An important constraint could be the limited reproducibility of glucose tolerance status during a

  20. Stimulation of the endogenous incretin glucose-dependent insulinotropic peptide by enteral dextrose improves glucose homeostasis and inflammation in murine endotoxemia.

    Science.gov (United States)

    Shah, Faraaz Ali; Singamsetty, Srikanth; Guo, Lanping; Chuan, Byron W; McDonald, Sherie; Cooper, Bryce A; O'Donnell, Brett J; Stefanovski, Darko; Wice, Burton; Zhang, Yingze; O'Donnell, Christopher P; McVerry, Bryan J

    2018-03-01

    Loss of glucose homeostasis during sepsis is associated with increased organ dysfunction and higher mortality. Novel therapeutic strategies to promote euglycemia in sepsis are needed. We have previously shown that early low-level intravenous (IV) dextrose suppresses pancreatic insulin secretion and induces insulin resistance in septic mice, resulting in profound hyperglycemia and worsened systemic inflammation. In this study, we hypothesized that administration of low-level dextrose via the enteral route would stimulate intestinal incretin hormone production, potentiate insulin secretion in a glucose-dependent manner, and thereby improve glycemic control in the acute phase of sepsis. We administered IV or enteral dextrose to 10-week-old male C57BL/6J mice exposed to bacterial endotoxin and measured incretin hormone release, glucose disposal, and proinflammatory cytokine production. Compared with IV administration, enteral dextrose increased circulating levels of the incretin hormone glucose-dependent insulinotropic peptide (GIP) associated with increased insulin release and insulin sensitivity, improved mean arterial pressure, and decreased proinflammatory cytokines in endotoxemic mice. Exogenous GIP rescued glucose metabolism, improved blood pressure, and increased insulin release in endotoxemic mice receiving IV dextrose, whereas pharmacologic inhibition of GIP signaling abrogated the beneficial effects of enteral dextrose. Thus, stimulation of endogenous GIP secretion by early enteral dextrose maintains glucose homeostasis and attenuates the systemic inflammatory response in endotoxemic mice and may provide a therapeutic target for improving glycemic control and clinical outcomes in patients with sepsis. Published by Elsevier Inc.

  1. An ancestral role for the mitochondrial pyruvate carrier in glucose-stimulated insulin secretion

    Directory of Open Access Journals (Sweden)

    Kyle S. McCommis

    2016-08-01

    Full Text Available Objective: Transport of pyruvate into the mitochondrial matrix by the Mitochondrial Pyruvate Carrier (MPC is an important and rate-limiting step in its metabolism. In pancreatic β-cells, mitochondrial pyruvate metabolism is thought to be important for glucose sensing and glucose-stimulated insulin secretion. Methods: To evaluate the role that the MPC plays in maintaining systemic glucose homeostasis, we used genetically-engineered Drosophila and mice with loss of MPC activity in insulin-producing cells. Results: In both species, MPC deficiency results in elevated blood sugar concentrations and glucose intolerance accompanied by impaired glucose-stimulated insulin secretion. In mouse islets, β-cell MPC-deficiency resulted in decreased respiration with glucose, ATP-sensitive potassium (KATP channel hyperactivity, and impaired insulin release. Moreover, treatment of pancreas-specific MPC knockout mice with glibenclamide, a sulfonylurea KATP channel inhibitor, improved defects in islet insulin secretion and abnormalities in glucose homeostasis in vivo. Finally, using a recently-developed biosensor for MPC activity, we show that the MPC is rapidly stimulated by glucose treatment in INS-1 insulinoma cells suggesting that glucose sensing is coupled to mitochondrial pyruvate carrier activity. Conclusions: Altogether, these studies suggest that the MPC plays an important and ancestral role in insulin-secreting cells in mediating glucose sensing, regulating insulin secretion, and controlling systemic glycemia. Keywords: Stimulus-coupled secretion, Insulin, β-Cell, Diabetes, Pyruvate, Mitochondria, Drosophila

  2. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    OpenAIRE

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide...

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

    DEFF Research Database (Denmark)

    Sonne, David P; Hare, Kristine J; Martens, Pernille

    2013-01-01

    -rich liquid meal (2,200 kJ). Basal and postprandial plasma concentrations of glucose, insulin, C-peptide, glucagon, GLP-1, glucose-dependent insulinotropic polypeptide (GIP), glucagon-like peptide-2 (GLP-2), cholecystokinin (CCK), and gastrin were measured. Furthermore, gastric emptying and duodenal and serum......Preclinical studies suggest that gallbladder emptying, via bile acid-induced activation of the G protein-coupled receptor TGR5 in intestinal L cells, may play a significant role in the secretion of the incretin hormone glucagon-like peptide-1 (GLP-1) and, hence, postprandial glucose homeostasis. We...... examined the secretion of gut hormones in cholecystectomized subjects to test the hypothesis that gallbladder emptying potentiates postprandial release of GLP-1. Ten cholecystectomized subjects and 10 healthy, age-, gender-, and body mass index-matched control subjects received a standardized fat...

  4. Skeletal muscle glucose uptake during dynamic exercise in humans

    DEFF Research Database (Denmark)

    Richter, Erik; Kiens, Bente; Saltin, Bengt

    1988-01-01

    uptake was not compensated for by increased uptake of free fatty acids but was accompanied by decreases in plasma insulin and increases in plasma epinephrine and norepinephrine. During work with large muscle masses, arterial lactate increased to approximately 6 mM, and net leg lactate release reverted......To study the role of muscle mass in glucoregulation, six subjects worked with the knee extensors of one leg on a specially constructed cycle ergometer. The knee extensors of one leg worked either alone or in combination with the knee extensors of the other leg and/or with the arms. Substrate usage...... to net lactate uptake. Decreased glucose uptake could not be explained by decreased perfusion. It is concluded that thigh muscle glucose uptake is affected by the size of the total muscle mass engaged in exercise. The decrease in thigh glucose uptake, when arm cranking was added and O2 uptake...

  5. Intracellular ascorbic acid inhibits transport of glucose by neurons, but not by astrocytes.

    Science.gov (United States)

    Castro, Maite A; Pozo, Miguel; Cortés, Christian; García, María de Los Angeles; Concha, Ilona I; Nualart, Francisco

    2007-08-01

    It has been demonstrated that glutamatergic activity induces ascorbic acid (AA) depletion in astrocytes. Additionally, different data indicate that AA may inhibit glucose accumulation in primary cultures of rat hippocampal neurons. Thus, our hypothesis postulates that AA released from the astrocytes during glutamatergic synaptic activity may inhibit glucose uptake by neurons. We observed that cultured neurons express the sodium-vitamin C cotransporter 2 and the facilitative glucose transporters (GLUT) 1 and 3, however, in hippocampal brain slices GLUT3 was the main transporter detected. Functional activity of GLUTs was confirmed by means of kinetic analysis using 2-deoxy-d-glucose. Therefore, we showed that AA, once accumulated inside the cell, inhibits glucose transport in both cortical and hippocampal neurons in culture. Additionally, we showed that astrocytes are not affected by AA. Using hippocampal slices, we observed that upon blockade of monocarboxylate utilization by alpha-cyano-4-hydroxycinnamate and after glucose deprivation, glucose could rescue neuronal response to electrical stimulation only if AA uptake is prevented. Finally, using a transwell system of separated neuronal and astrocytic cultures, we observed that glutamate can reduce glucose transport in neurons only in presence of AA-loaded astrocytes, suggesting the essential role of astrocyte-released AA in this effect.

  6. Adipocyte glucose transport regulation by eicosanoid precursors and inhibitors

    International Nuclear Information System (INIS)

    Lee, H.C.C.

    1987-01-01

    Glucose uptake and free fatty acid release by adipocytes are increased by catecholamines. The mechanism of the stimulatory action of catecholamines on glucose uptake may be via eicosanoid production from release fatty acids. Rats were fed iso-nutrient diets with high or low safflower oil. After one month, 5 rats per diet group were fed diets with aspirin or without aspirin for 2 days. Isolated adipocytes from epididymal fat pads were incubated at 37 0 C, gassed with 95% O 2 -5% CO 2 in KRB buffer with 3% bovine serum albumin and with or without eicosanoid modifiers; a stimulator (10 -5 M norepinephrine, N), or inhibitors (167 μl of antiserum to prostaglandin E (AntiE) per 1600 μl or 23mM Asp), or combinations of these. At 2-, 5-, and 10-min incubation, samples of incubation mixtures were taken to measure 2-deoxy glucose transport using 3 H-2-deoxy glucose, 14 C-inulin, and liquid scintillation counter

  7. Glucose-stimulated acrolein production from unsaturated fatty acids.

    Science.gov (United States)

    Medina-Navarro, R; Duran-Reyes, G; Diaz-Flores, M; Hicks, J J; Kumate, J

    2004-02-01

    Glucose auto-oxidation may be a significant source of reactive oxygen species (ROS), and also be important in the lipid peroxidation process, accompanied by the release of toxic reactive products. We wanted to demonstrate that acrolein can be formed directly and actively from free fatty acids in a hyperglycemic environment. A suspension of linoleic and arachidonic acids (2.5 mM) was exposed to different glucose concentrations (5, 10 and 15 mmol/L) in vitro. The samples were extracted with organic solvents, partitioned, followed at 255-267 nm, and analysed using capillary electrophoresis and mass spectroscopy. The total release of aldehydes significantly (P products, acrolein (5% of total) and its condensing product, 4-hydroxy-hexenal, were identified. From the results presented here, it was possible to demonstrate the production of acrolein, probably as a fatty acid product, due to free radicals generated from the glucose auto-oxidation process. The results led us to propose that acrolein, which is one of the most toxic aldehydes, is produced during hyperglycemic states, and may lead to tissue injury, as one of the initial problems to be linked to high levels of glucose in vivo.

  8. Proton Transport Chains in Glucose Metabolism: Mind the Proton

    Directory of Open Access Journals (Sweden)

    Dirk Roosterman

    2018-06-01

    Full Text Available The Embden–Meyerhof–Parnas (EMP pathway comprises eleven cytosolic enzymes interacting to metabolize glucose to lactic acid [CH3CH(OHCOOH]. Glycolysis is largely considered as the conversion of glucose to pyruvate (CH3COCOO-. We consider glycolysis to be a cellular process and as such, transporters mediating glucose uptake and lactic acid release and enable the flow of metabolites through the cell, must be considered as part of the EMP pathway. In this review, we consider the flow of metabolites to be coupled to a flow of energy that is irreversible and sufficient to form ordered structures. This latter principle is highlighted by discussing that lactate dehydrogenase (LDH complexes irreversibly reduce pyruvate/H+ to lactate [CH3CH(OHCOO-], or irreversibly catalyze the opposite reaction, oxidation of lactate to pyruvate/H+. However, both LDH complexes are considered to be driven by postulated proton transport chains. Metabolism of glucose to two lactic acids is introduced as a unidirectional, continuously flowing pathway. In an organism, cell membrane-located proton-linked monocarboxylate transporters catalyze the final step of glycolysis, the release of lactic acid. Consequently, both pyruvate and lactate are discussed as intermediate products of glycolysis and substrates of regulated crosscuts of the glycolytic flow.

  9. Contribution of abnormal muscle and liver glucose metabolism to postprandial hyperglycemia in NIDDM

    International Nuclear Information System (INIS)

    Mitrakou, A.; Kelley, D.; Veneman, T.; Jenssen, T.; Pangburn, T.; Reilly, J.; Gerich, J.

    1990-01-01

    To assess the role of muscle and liver in the pathogenesis of postprandial hyperglycemia in non-insulin-dependent diabetes mellitus (NIDDM), we administered an oral glucose load enriched with [14C]glucose to 10 NIDDM subjects and 10 age- and weight-matched nondiabetic volunteers and compared muscle glucose disposal by measuring forearm balance of glucose, lactate, alanine, O2, and CO2. In addition, we used the dual-lable isotope method to compare overall rates of glucose appearance (Ra) and disappearance (Rd), suppression of endogenous glucose output, and splanchnic glucose sequestration. During the initial 1-1.5 h after glucose ingestion, plasma glucose increased by approximately 8 mM in NIDDM vs. approximately 3 mM in nondiabetic subjects (P less than 0.01); overall glucose Ra was nearly 11 g greater in NIDDM than nondiabetic subjects, but glucose Rd was not significantly different in NIDDM and nondiabetic subjects. The greater overall glucose Ra of NIDDM subjects was due to 6.8 g greater endogenous glucose output (13.7 +/- 1.1 vs. 6.8 +/- 1.0 g, P less than 0.01) and 3.8 g less oral glucose splanchnic sequestration of the oral load (31.4 +/- 1.5 vs. 27.5 +/- 0.9 g, P less than 0.05). Although glucose taken up by muscle was not significantly different in NIDDM and nondiabetic subjects (39.3 +/- 3.5 vs. 41.0 +/- 2.5 g/5 h), a greater amount of the glucose taken up by muscle in NIDDM was released as lactate and alanine (11.7 +/- 1.0 vs. 5.2 +/- 0.3 g in nondiabetic subjects, P less than 0.01), and less was stored (11.7 +/- 1.3 vs. 16.9 +/- 1.5 g, P less than 0.05). We conclude that increased systemic glucose delivery, due primarily to reduced suppression of endogenous hepatic glucose output and, to a lesser extent, reduced splanchnic glucose sequestration, is the predominant factor responsible for postprandial hyperglycemia in NIDDM

  10. Predicting Plasma Glucose From Interstitial Glucose Observations Using Bayesian Methods

    DEFF Research Database (Denmark)

    Hansen, Alexander Hildenbrand; Duun-Henriksen, Anne Katrine; Juhl, Rune

    2014-01-01

    One way of constructing a control algorithm for an artificial pancreas is to identify a model capable of predicting plasma glucose (PG) from interstitial glucose (IG) observations. Stochastic differential equations (SDEs) make it possible to account both for the unknown influence of the continuous...... glucose monitor (CGM) and for unknown physiological influences. Combined with prior knowledge about the measurement devices, this approach can be used to obtain a robust predictive model. A stochastic-differential-equation-based gray box (SDE-GB) model is formulated on the basis of an identifiable...

  11. Toxics Release Inventory (TRI)

    Data.gov (United States)

    U.S. Environmental Protection Agency — The Toxics Release Inventory (TRI) is a dataset compiled by the U.S. Environmental Protection Agency (EPA). It contains information on the release and waste...

  12. Continuous glucose monitoring, oral glucose tolerance, and insulin - glucose parameters in adolescents with simple obesity.

    Science.gov (United States)

    El Awwa, A; Soliman, A; Al-Ali, M; Yassin, M; De Sanctis, V

    2012-09-01

    In obese adolescents pancreatic beta-cells may not be able to cope with insulin resistance leading to hyperglycemia and type2 diabetes (T2DM To assess oral glucose tolerance, 72-h continuous blood glucose concentrations (CGM) and calculate homeostatic model assessment (HOMA), and the quantitative insulin sensitivity check index (QUICKI) in 13 adolescents with simple obesity (BMI SDS=4 ± 1.06). OGTT performed in 13 obese adolescents (13.47 ± 3 years) revealed 3 cases (23%) with impaired fasting glucose (IFG: fasting glucose >5.6 mmol/L), 4 cases (30%) with impaired glucose tolerance (IGT: 2h blood glucose >7.8 continuous glucose monitoring system ( CGMS), IFG was detected in 4 cases, the maximum serum blood glucose (BG : 2h or more after meal) was >7.8 and 11.1 mmol/L (diabetes) in one case (7.6%). Five cases had a minimum BG recorded of 2.6 and QUICKI values obese adolescents, CGMS is superior to OGTT and HbA1C in detecting glycemic abnormalities, which appears to be secondary to insulin resistance.

  13. Glucose-Responsive Implantable Polymeric Microdevices for "Smart" Insulin Therapy of Diabetes

    Science.gov (United States)

    Chu, Michael Kok Loon

    Diabetes mellitus is a chronic illness manifested by improper blood glucose management, affecting over 350 million worldwide. As a result, all type 1 patients and roughly 20% of type 2 patients require exogenous insulin therapy to survive. Typically, daily multiple injections are taken to maintain normal glucose levels in response glucose spikes from meals. However, patient compliance and dosing accuracy can fluctuate with variation in meals, exercise, glucose metabolism or stress, leading to poor clinical outcomes. A 'smart', closed-loop insulin delivery system providing on-demand release kinetics responding to circulating glucose levels would be a boon for diabetes patients, replacing constant self monitoring and insulin. This thesis focuses on the development of a novel, 'smart' insulin microdevice that can provide on-demand insulin release in response to blood glucose levels. In the early stage, the feasibility of integrating a composite membrane with pH-responsive nanoparticles embedded in ethylcellulose membrane to provide pH-responsive in vitro release was examined and confirmed using a model drug, vitamin B12. In the second microdevice, glucose oxidase for generating pH signals from glucose oxidation, catalase and manganese dioxide nanoparticles, as peroxide scavengers, were used in a bioinorganic, albumin-based membrane cross-linked with a polydimethylsiloxane (PDMS) grid-microdevice system. This prototype device demonstrated insulin release in response to glucose levels in vitro and regulating plasma glucose in type 1 diabetic rats when implanted intraperitoneally. Advancement allowing for subcutaneous implantation and improved biocompatibility was achieved with surface modification of PDMS microdevices grafted with activated 20 kDa polyethylene glycol (PEG) chains, dramatically reducing immune response and local inflammation. When implanted subcutaneously in diabetic rats, glucose-responsive insulin delivery microdevices showed short and long

  14. Skeletal muscle glucose uptake during exercise

    DEFF Research Database (Denmark)

    Rose, Adam John; Richter, Erik

    2005-01-01

    The increase in skeletal muscle glucose uptake during exercise results from a coordinated increase in rates of glucose delivery (higher capillary perfusion), surface membrane glucose transport, and intracellular substrate flux through glycolysis. The mechanism behind the movement of GLUT4...

  15. Lactate overrides central nervous but not beta-cell glucose sensing in humans.

    Science.gov (United States)

    Schmid, Sebastian M; Jauch-Chara, Kamila; Hallschmid, Manfred; Oltmanns, Kerstin M; Peters, Achim; Born, Jan; Schultes, Bernd

    2008-12-01

    Lactate has been shown to serve as an alternative energy substrate in the central nervous system and to interact with hypothalamic glucose sensors. On the background of marked similarities between central nervous and beta-cell glucose sensing, we examined whether lactate also interacts with pancreatic glucose-sensing mechanisms in vivo. The effects of intravenously infused lactate vs placebo (saline) on central nervous and pancreatic glucose sensing were assessed during euglycemic and hypoglycemic clamp experiments in 10 healthy men. The release of neuroendocrine counterregulatory hormones during hypoglycemia was considered to reflect central nervous glucose sensing, whereas endogenous insulin secretion as assessed by serum C-peptide levels served as an indicator of pancreatic beta-cell glucose sensing. Lactate infusion blunted the counterregulatory hormonal responses to hypoglycemia, in particular, the release of epinephrine (P = .007) and growth hormone (P = .004), so that higher glucose infusion rates (P = .012) were required to maintain the target blood glucose levels. In contrast, the decrease in C-peptide concentrations during the hypoglycemic clamp remained completely unaffected by lactate (P = .60). During euglycemic clamp conditions, lactate infusion did not affect the concentrations of C-peptide and of counterregulatory hormones, with the exception of norepinephrine levels that were lower during lactate than saline infusion (P = .049) independently of the glycemic condition. Data indicate that glucose sensing of beta-cells is specific to glucose, whereas glucose sensing at the central nervous level can be overridden by lactate, reflecting the brain's ability to rely on lactate as an alternative major energy source.

  16. Current concepts in blood glucose monitoring

    OpenAIRE

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-01-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on t...

  17. Osmotic load from glucose polymers.

    Science.gov (United States)

    Koo, W W; Poh, D; Leong, M; Tam, Y K; Succop, P; Checkland, E G

    1991-01-01

    Glucose polymer is a carbohydrate source with variable chain lengths of glucose units which may result in variable osmolality. The osmolality of two commercial glucose polymers was measured in reconstituted powder infant formulas, and the change in osmolality of infant milk formulas at the same increases in energy density (67 kcal/dL to 81 and 97 kcal/dL) from the use of additional milk powder or glucose polymers was compared. All samples were prepared from powders (to nearest 0.1 mg), and osmolality was measured by freezing point depression. For both glucose polymers the within-batch variability of the measured osmolality was less than 3.5%, and between-batch variability of the measured osmolality was less than 9.6%. The measured osmolality varies linearly with energy density (p less than 0.001) and was highest in infant formula reconstituted from milk powder alone. However, there exist significant differences in the measured osmolality between different glucose polymer preparations. At high energy densities (greater than or equal to 97 kcal/dL), infant milk formulas prepared with milk powder alone or with the addition of certain glucose polymer preparation may have high osmolality (greater than or equal to 450 mosm/kg) and theoretically predispose the infant to complications of hyperosmotic feeds.

  18. Glucose metabolism of lactobacillus divergens

    International Nuclear Information System (INIS)

    De Bruyn, I.N.

    1987-02-01

    The aim of this study was to compile an optimal growth and selective medium for Lactobacillus divergens and to determine the pathway by which it metabolised glucose. The optimum growth temperature is 25 o C which is lower than that of most other lactobacilli. Citrate stimulates growth up to a concentration of 1% while acetate inhibits the organism at neutral pH, but it stimulates growth at pH 8.5 up to a concentration of 0.8%. MRS medium was therefore modified in order to obtain maximum growth of the organism. The acetate was omitted, sucrose was substituted for glucose and the pH was adjusted to 8.5. Sucrose was used, since a neutral pH is obtained after sterilisation of glucose in alkaline (pH ≥ 7.5) solution due to the degradation of glucose by the Maillard reaction. Various inhibitors and dyes were tested in order to formulate a selective medium. In the present study differently labelled glucose precursors were fermented by L. divergens and the fermentation products isolated by HPLC. The concentrations of acetate and formate were determined by comparison to a standard while the concentration of lactate and glucose was determined by enzymic assay. The radioactivity was determined by liquid scintillation counting and the positional labelling in lactate and acetate by chemical degradation. Fermentation of D-[U- 14 C]-glucose was included to correct for endogenous product dilution

  19. Lipolytic response to glucose infusion in human subjects

    International Nuclear Information System (INIS)

    Wolfe, R.R.; Peters, E.J.

    1987-01-01

    The authors have determined the effect of various rates of glucose infusion on the rates of release of glycerol (R/sub a/ glycerol), free fatty acids (R/sub a/ FFA), and on energy metabolism in normal human volunteers. Plasma kinetics were determined with use of the stable isotopic tracers D-5-glycerol and [1- 13 C]palmitate, and energy metabolism was determined by indirect calorimetry. The effect of glucose infusion on R/sub a/ glycerol and R/sub a/ FFA was dose-dependent. At 4 mg x kg -1 x min -1 , both R/sub a/ glycerol and R/sub a/ FFA were suppressed; at 8 mg x kg -1 x min -1 , R/sub a/ FFA was even more depressed, but R/sub a/ glycerol was similar to the value during the 4 mg x kg -1 x min -1 infusion. At all infusion rates tested, the amount of potential energy available from the sum of the glucose infusion and endogenously mobilized fat was always greater than when no glucose was infused. Glucose decreased fat mobilization by both inhibiting lipolysis and stimulating reesterification, thus causing a significant increase in triglyceride-fatty acid substrate cycling within the adipose tissue. Plasma insulin was determined by radioimmunoassay

  20. Glucose Binding Protein as a Novel Optical Glucose Nanobiosensor

    Directory of Open Access Journals (Sweden)

    Majed DWEIK

    2009-11-01

    Full Text Available Development of an in vivo optical sensor requires the utilization of Near Infra Red (NIR fluorophores due to their ability to operate within the biological tissue window. Alexa Fluor 750 (AF750 and Alexa Fluor 680 (AF680 were examined as potential NIR fluorophores for an in vivo fluorescence resonance energy transfer (FRET glucose biosensor. AF680 and AF750 found to be a FRET pair and percent energy transfer was calculated. Next, the tested dye pair was utilized in a competitive binding assay in order to detect glucose. Concanavalin A (Con A and dextran have binding affinity, but in the presence of glucose, glucose displaces dextran due to its higher affinity to Con A than dextran. Finally, the percent signal transfer through porcine skin was examined. The results showed with approximately 4.0 mm porcine skin thickness, 1.98 % of the fluorescence was transmitted and captured by the detector.

  1. Limited effects of exogenous glucose during severe hypoxia and a lack of hypoxia-stimulated glucose uptake in isolated rainbow trout cardiac muscle

    Science.gov (United States)

    Becker, Tracy A.; DellaValle, Brian; Gesser, Hans; Rodnick, Kenneth J.

    2013-01-01

    SUMMARY We examined whether exogenous glucose affects contractile performance of electrically paced ventricle strips from rainbow trout under conditions known to alter cardiomyocyte performance, ion regulation and energy demands. Physiological levels of d-glucose did not influence twitch force development for aerobic preparations (1) paced at 0.5 or 1.1 Hz, (2) at 15 or 23°C, (3) receiving adrenergic stimulation or (4) during reoxygenation with or without adrenaline after severe hypoxia. Contractile responses to ryanodine, an inhibitor of Ca2+ release from the sarcoplasmic reticulum, were also not affected by exogenous glucose. However, glucose did attenuate the fall in twitch force during severe hypoxia. Glucose uptake was assayed in non-contracting ventricle strips using 2-[3H] deoxy-d-glucose (2-DG) under aerobic and hypoxic conditions, at different incubation temperatures and with different inhibitors. Based upon a lack of saturation of 2-DG uptake and incomplete inhibition of uptake by cytochalasin B and d-glucose, 2-DG uptake was mediated by a combination of facilitated transport and simple diffusion. Hypoxia stimulated lactate efflux sixfold to sevenfold with glucose present, but did not increase 2-DG uptake or reduce lactate efflux in the presence of cytochalasin B. Increasing temperature (14 to 24°C) also did not increase 2-DG uptake, but decreasing temperature (14 to 4°C) reduced 2-DG uptake by 45%. In conclusion, exogenous glucose improves mechanical performance under hypoxia but not under any of the aerobic conditions applied. The extracellular concentration of glucose and cold temperature appear to determine and limit cardiomyocyte glucose uptake, respectively, and together may help define a metabolic strategy that relies predominantly on intracellular energy stores. PMID:23685969

  2. 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...

  3. High pressure HC1 conversion of cellulose to glucose

    Energy Technology Data Exchange (ETDEWEB)

    Antonoplis, Robert Alexander [Univ. of California, Berkeley, CA (United States); Blanch, Harvey W. [Univ. of California, Berkeley, CA (United States); Wilke, Charles R. [Univ. of California, Berkeley, CA (United States)

    1981-08-01

    The production of ethanol from glucose by means of fermentation represents a potential long-range alternative to oil for use as a transportation fuel. Today's rising oil prices and the dwindling world supply of oil have made other fuels, such as ethanol, attractive alternatives. It has been shown that automobiles can operate, with minor alterations, on a 10% ethanol-gasoline mixture popularly known as gasohol. Wood has long been known as a potential source of glucose. Glucose may be obtained from wood following acid hydrolysis. In this research, it was found that saturating wood particles with HCl gas under pressure was an effective pretreatment before subjecting the wood to dilute acid hydrolysis. The pretreatment is necessary because of the tight lattice structure of cellulose, which inhibits dilute acid hydrolysis. HCl gas makes the cellulose more susceptible to hydrolysis and the glucose yield is doubled when dilute acid hydrolysis is preceded by HCl saturation at high pressure. The saturation was most effectively performed in a fluidized bed reactor, with pure HCl gas fluidizing equal volumes of ground wood and inert particles. The fluidized bed effectively dissipated the large amount of heat released upon HCl absorption into the wood. Batch reaction times of one hour at 314.7 p.s.i.a. gave glucose yields of 80% and xylose yields of 95% after dilute acid hydrolysis. A non-catalytic gas-solid reaction model, with gas diffusing through the solid limiting the reaction rate, was found to describe the HCl-wood reaction in the fluidized bed. HCl was found to form a stable adduct with the lignin residue in the wood, in a ratio of 3.33 moles per mole of lignin monomer. This resulted in a loss of 0.1453 lb. of HCl per pound of wood. The adduct was broken upon the addition of water. A process design and economic evaluation for a plant to produce 214 tons per day of glucose from air-dried ground Populus tristi gave an estimated glucose cost of 15.14 cents per pound

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

    Science.gov (United States)

    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.

  5. Glucose-6-phosphatase deficiency

    Directory of Open Access Journals (Sweden)

    Labrune Philippe

    2011-05-01

    Full Text Available Abstract Glucose-6-phosphatase deficiency (G6P deficiency, or glycogen storage disease type I (GSDI, is a group of inherited metabolic diseases, including types Ia and Ib, characterized by poor tolerance to fasting, growth retardation and hepatomegaly resulting from accumulation of glycogen and fat in the liver. Prevalence is unknown and annual incidence is around 1/100,000 births. GSDIa is the more frequent type, representing about 80% of GSDI patients. The disease commonly manifests, between the ages of 3 to 4 months by symptoms of hypoglycemia (tremors, seizures, cyanosis, apnea. Patients have poor tolerance to fasting, marked hepatomegaly, growth retardation (small stature and delayed puberty, generally improved by an appropriate diet, osteopenia and sometimes osteoporosis, full-cheeked round face, enlarged kydneys and platelet dysfunctions leading to frequent epistaxis. In addition, in GSDIb, neutropenia and neutrophil dysfunction are responsible for tendency towards infections, relapsing aphtous gingivostomatitis, and inflammatory bowel disease. Late complications are hepatic (adenomas with rare but possible transformation into hepatocarcinoma and renal (glomerular hyperfiltration leading to proteinuria and sometimes to renal insufficiency. GSDI is caused by a dysfunction in the G6P system, a key step in the regulation of glycemia. The deficit concerns the catalytic subunit G6P-alpha (type Ia which is restricted to expression in the liver, kidney and intestine, or the ubiquitously expressed G6P transporter (type Ib. Mutations in the genes G6PC (17q21 and SLC37A4 (11q23 respectively cause GSDIa and Ib. Many mutations have been identified in both genes,. Transmission is autosomal recessive. Diagnosis is based on clinical presentation, on abnormal basal values and absence of hyperglycemic response to glucagon. It can be confirmed by demonstrating a deficient activity of a G6P system component in a liver biopsy. To date, the diagnosis is most

  6. [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.

  7. Determination of the energetics of the UDP-glucose pyrophosphorylase reaction by positional isotope exchange inhibition

    International Nuclear Information System (INIS)

    Hester, L.S.; Raushel, F.M.

    1987-01-01

    A method has been developed for obtaining qualitative information about enzyme-catalyzed reactions by measuring the inhibitory effects of added substrates on positional isotope exchange rates. It has been demonstrated for ordered kinetic mechanisms that an increase in the concentration of the second substrate to add to the enzyme will result in a linear increase in the ratio of the chemical and positional isotope exchange rates. The slopes and intercepts from these plots can be used to determine the partitioning ratios of binary and ternary enzyme complexes. The method has been applied to the reaction catalyzed by UDP-glucose pyrophosphorylase. A positional isotope exchange reaction was measured within oxygen-18-labeled UTP as a function of variable glucose 1-phosphate concentration in the forward reaction. In the reverse reaction, a positional isotope exchange reaction was measured within oxygen-18-labeled UDP-glucose as a function of increasing pyrophosphate concentration. The results have been interpreted to indicate that the interconversion of the ternary central complexes is fast relative to product dissociation in either direction. In the forward direction, the release of UDP-glucose is slower than the release of pyrophosphate. The release of glucose 1-phosphate is slower than the release of UTP in the reverse reaction

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

    Science.gov (United States)

    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.

  9. Age-related memory impairments due to reduced blood glucose responses to epinephrine.

    Science.gov (United States)

    Morris, Ken A; Chang, Qing; Mohler, Eric G; Gold, Paul E

    2010-12-01

    Increases in blood glucose levels are an important component of the mechanisms by which epinephrine enhances memory formation. The present experiments addressed the hypothesis that a dysfunction in the blood glucose response to circulating epinephrine contributes to age-related memory impairments. Doses of epinephrine and glucagon that significantly increased blood glucose levels in young adult rats were far less effective at doing so in 2-year-old rats. In young rats, epinephrine and glucose were about equally effective in enhancing memory and in prolonging post-training release of acetylcholine in the hippocampus. However, glucose was more effective than epinephrine in enhancing both memory and acetylcholine release in aged rats. These results suggest that an uncoupling between circulating epinephrine and glucose levels in old rats may lead to an age-related reduction in the provision of glucose to the brain during training. This in turn may contribute to age-related changes in memory and neural plasticity. Copyright © 2008 Elsevier Inc. All rights reserved.

  10. Glucose impairs tamoxifen responsiveness modulating connective tissue growth factor in breast cancer cells.

    Science.gov (United States)

    Ambrosio, Maria Rosaria; D'Esposito, Vittoria; Costa, Valerio; Liguoro, Domenico; Collina, Francesca; Cantile, Monica; Prevete, Nella; Passaro, Carmela; Mosca, Giusy; De Laurentiis, Michelino; Di Bonito, Maurizio; Botti, Gerardo; Franco, Renato; Beguinot, Francesco; Ciccodicola, Alfredo; Formisano, Pietro

    2017-12-12

    Type 2 diabetes and obesity are negative prognostic factors in patients with breast cancer (BC). We found that sensitivity to tamoxifen was reduced by 2-fold by 25 mM glucose (High Glucose; HG) compared to 5.5 mM glucose (Low Glucose; LG) in MCF7 BC cells. Shifting from HG to LG ameliorated MCF7 cell responsiveness to tamoxifen. RNA-Sequencing of MCF7 BC cells revealed that cell cycle-related genes were mainly affected by glucose. Connective Tissue Growth Factor (CTGF) was identified as a glucose-induced modulator of cell sensitivity to tamoxifen. Co-culturing MCF7 cells with human adipocytes exposed to HG, enhanced CTGF mRNA levels and reduced tamoxifen responsiveness of BC cells. Inhibition of adipocyte-released IL8 reverted these effects. Interestingly, CTGF immuno-detection in bioptic specimens from women with estrogen receptor positive (ER + ) BC correlated with hormone therapy resistance, distant metastases, reduced overall and disease-free survival. Thus, glucose affects tamoxifen responsiveness directly modulating CTGF in BC cells, and indirectly promoting IL8 release by adipocytes.

  11. Growth hormone-releasing peptides.

    Science.gov (United States)

    Ghigo, E; Arvat, E; Muccioli, G; Camanni, F

    1997-05-01

    decreases thereafter. By the sixth decade of life, the activity of GHRPs is reduced but it is still marked and higher than that of GHRH. The GH-releasing activity of GHRPs is synergistic with that of GHRH, is not affected by opioid receptor antagonists, such as naloxone, and is only blunted by inhibitory influences, including neurotransmitters, glucose, free fatty acids, gluco corticoids, recombinant human GH and even exogenous somatostatin, which are known to almost abolish the effect of GHRH. GHRPs maintain their GH-releasing effect in somatotrope hypersecretory states such as in acromegaly, anorexia nervosa and hyperthyroidism. On the other hand, their good GH-releasing activity has been shown in some but not in other somatotrope hyposecretory states. In fact, reduced GH responses after GHRP administration have been reported in idiopathic GH deficiency as well as in idiopathic short stature, in obesity and in hypothyroidism, while in patients with pituitary stalk disconnection or Cushing's syndrome the somatotrope responsiveness to GHRPs is almost absent. In short children an increase in height velocity has also been reported during chronic GHRP treatment. Thus, based on their marked GH-releasing effect even after oral administration, GHRPs offer their own clinical usefulness for treatment of some GH hyposecretory states.

  12. Current concepts in blood glucose monitoring.

    Science.gov (United States)

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-12-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.

  13. Current concepts in blood glucose monitoring

    Science.gov (United States)

    Khadilkar, Kranti Shreesh; Bandgar, Tushar; Shivane, Vyankatesh; Lila, Anurag; Shah, Nalini

    2013-01-01

    Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG) and continuous glucose monitoring system (CGMS). It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus. PMID:24910827

  14. Current concepts in blood glucose monitoring

    Directory of Open Access Journals (Sweden)

    Kranti Shreesh Khadilkar

    2013-01-01

    Full Text Available Blood glucose monitoring has evolved over the last century. The concept of adequate glycemic control and minimum glycemic variability requires an ideal, accurate and reliable glucose monitoring system. The search for an ideal blood glucose monitoring system still continues. This review explains the various blood glucose monitoring systems with special focus on the monitoring systems like self- monitored blood glucose (SMBG and continuous glucose monitoring system (CGMS. It also focuses on the newer concepts of blood glucose monitoring and their incorporation in routine clinical management of diabetes mellitus.

  15. A review of metabolism of labeled glucoses for use in measuring glucose recycling

    International Nuclear Information System (INIS)

    Russell, R.W.; Young, J.W.

    1990-01-01

    The fate of tritium from each carbon of D-glucose and the metabolism of L-glucose and 2-deoxy-D-glucose are known. Differences in metabolism of labeled glucoses can be used to quantify physical and chemical recycling of glucose. Only physical recycling is measured by [1- 3 H]-L-glucose, whereas [U- 14 C]-D-glucose measures total recycling. The difference between [1- 3 H]-L-glucose and [U- 14 C]-D-glucose, therefore, is chemical recycling. Recycling from extracellular binding sites and hepatic glucose 6-phosphate can be measured by difference between [1,2- 3 H]-2-deoxy-D-glucose and [1- 3 H]-L-glucose, and the difference in irreversible loss of the two will measure extrahepatic uptake of D-glucose. Recycling via Cori-alanine cycle plus CO 2 is the difference in irreversible loss measured by using [6- 3 H]-glucose and [U- 14 C]-D-glucose. Recycling via the hexose monophosphate pathway can be determined by difference in irreversible loss between [1- 3 H]-D-glucose and [6- 3 H]-D-glucose. Recycling via CO 2 and glycerol must be measured directly with [U- 14 C]glucose, bicarbonate, and glycerol. Recycling via hepatic glycogen can be estimated by subtracting all other measured chemical recycling from total chemical recycling. This review describes means to quantify glucose recycling in vivo, enabling studies of mechanisms for conservation and utilization of glucose. 54 references

  16. 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...

  17. Sodium glucose co-transporter 2 inhibitors: blocking renal tubular reabsorption of glucose to improve glycaemic control in patients with diabetes.

    Science.gov (United States)

    Jabbour, S A; Goldstein, B J

    2008-08-01

    The kidney plays a central role in the regulation of plasma glucose levels, although until recently this has not been widely appreciated or considered a target for therapeutic intervention. The sodium glucose co-transporter type 2 (SGLT2) located in the plasma membrane of cells lining the proximal tubule mediates the majority of renal glucose reabsorption from the tubular fluid, which normally prevents the loss of glucose in the urine. Competitive inhibitors of SGLT2 that provoke the renal excretion of glucose have been discovered, thereby providing a unique mechanism to potentially lower the elevated blood glucose levels in patients with diabetes. To explore the physiology of SGLT2 action and discuss several SGLT2 inhibitors that have entered early clinical development. All publicly available data were identified by searching the internet for 'SGLT2' and 'SGLT2 inhibitor' through 1 November 2007. Published articles, press releases and abstracts presented at national and international meetings were considered. Sodium glucose co-transporter type 2 inhibition is a novel treatment option for diabetes, which has been studied in preclinical models and a few potent and selective SGLT2 inhibitors have been reported and are currently in clinical development. These agents appear to be safe and generally well tolerated, and will potentially be a beneficial addition to the growing battery of oral antihyperglycaemic agents.

  18. 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.

  19. Dichloroacetate effects on glucose and lactate oxidation by neurons and astroglia in vitro and on glucose utilization by brain in vivo.

    Science.gov (United States)

    Itoh, Yoshiaki; Esaki, Takanori; Shimoji, Kazuaki; Cook, Michelle; Law, Mona J; Kaufman, Elaine; Sokoloff, Louis

    2003-04-15

    Neuronal cultures in vitro readily oxidized both D-[(14)C]glucose and l-[(14)C]lactate to (14)CO(2), whereas astroglial cultures oxidized both substrates sparingly and metabolized glucose predominantly to lactate and released it into the medium. [(14)C]Glucose oxidation to (14)CO(2) varied inversely with unlabeled lactate concentration in the medium, particularly in neurons, and increased progressively with decreasing lactate concentration. Adding unlabeled glucose to the medium inhibited [(14)C]lactate oxidation to (14)CO(2) only in astroglia but not in neurons, indicating a kinetic preference in neurons for oxidation of extracellular lactate over intracellular pyruvatelactate produced by glycolysis. Protein kinase-catalyzed phosphorylation inactivates pyruvate dehydrogenase (PDH), which regulates pyruvate entry into the tricarboxylic acid cycle. Dichloroacetate inhibits this kinase, thus enhancing PDH activity. In vitro dichloroacetate stimulated glucose and lactate oxidation to CO(2) and reduced lactate release mainly in astroglia, indicating that limitations in glucose and lactate oxidation by astroglia may be due to a greater balance of PDH toward the inactive form. To assess the significance of astroglial export of lactate to neurons in vivo, we attempted to diminish this traffic in rats by administering dichloroacetate (50 mgkg) intravenously to stimulate astroglial lactate oxidation and then examined the effects on baseline and functionally activated local cerebral glucose utilization (lCMR(glc)). Dichloroacetate raised baseline lCMR(glc) throughout the brain and decreased the percent increases in lCMR(glc) evoked by functional activation. These studies provide evidence in support of the compartmentalization of glucose metabolism between astroglia and neurons but indicate that the compartmentalization may be neither complete nor entirely obligatory.

  20. 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...

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

    International Nuclear Information System (INIS)

    Finan, A.; Cleary, M.P.

    1986-01-01

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

  2. Large scientific releases

    International Nuclear Information System (INIS)

    Pongratz, M.B.

    1981-01-01

    The motivation for active experiments in space is considered, taking into account the use of active techniques to obtain a better understanding of the natural space environment, the utilization of the advantages of space as a laboratory to study fundamental plasma physics, and the employment of active techniques to determine the magnitude, degree, and consequences of artificial modification of the space environment. It is pointed out that mass-injection experiments in space plasmas began about twenty years ago with the Project Firefly releases. Attention is given to mass-release techniques and diagnostics, operational aspects of mass release active experiments, the active observation of mass release experiments, active perturbation mass release experiments, simulating an artificial modification of the space environment, and active experiments to study fundamental plasma physics

  3. Studies on the production of glucose isomerase by Bacillus licheniformis

    Directory of Open Access Journals (Sweden)

    Nwokoro Ogbonnaya

    2015-09-01

    Full Text Available This work reports the effects of some culture conditions on the production of glucose isomerase by Bacillus licheniformis. The bacterium was selected based on the release of 3.62 mg/mL fructose from the fermentation of glucose. Enzyme was produced using a variety of carbon substrates but the highest enzyme activity was detected in a medium containing 0.5% xylose and 1% glycerol (specific activity = 6.88 U/mg protein. Media containing only xylose or glucose gave lower enzyme productivies (specific activities= 4.60 and 2.35 U/mg protein respectively. The effects of nitrogen substrates on glucose isomerase production showed that yeast extract supported maximum enzyme activity (specific activity = 5.24 U/mg protein. Lowest enzyme activity was observed with sodium trioxonitrate (specific activity = 2.44 U/mg protein. In general, organic nitrogen substrates supported higher enzyme productivity than inorganic nitrogen substrates. Best enzyme activity was observed in the presence of Mg2+ (specific activity = 6.85 U/mg protein while Hg2+ was inhibitory (specific activity = 1.02 U/mg protein. The optimum pH for best enzyme activity was 6.0 while optimum temperature for enzyme production was 50ºC.

  4. Effects of tetracaine on insulin release and calcium handling by rat pancreatic islets

    International Nuclear Information System (INIS)

    Abdel El Motal, S.M.A.; Pian-Smith, M.C.M.; Sharp, G.W.G.

    1987-01-01

    The effects of tetracaine on insulin release and 45 Ca 2+ handling by rat pancreatic islets have been studied under basal, glucose-stimulated, and 3-isobutyl-1-methylxanthine (IBMX)-stimulated conditions. Islets were isolated by the use of collagenase and used either directly (freshly isolated islets) or after a period under tissue culture conditions. Tetracaine was found to stimulate insulin release under basal conditions, to inhibit glucose-stimulated insulin release, and to potentiate insulin release stimulated by IBMX. In studies on the mechanisms underlying these effects, tetracaine was found to decrease glucose-stimulated net retention of 45 Ca 2+ (by an action to block the voltage-dependent Ca channels) and to mobilize Ca 2+ from intracellular stores. These two actions form the basis for the inhibition of glucose-stimulated insulin release, which depends heavily on Ca 2+ entry via the voltage-dependent channels and the synergism with IBMX to potentiate release. No inhibition of IBMX-stimulated release occurs because IBMX does not use the voltage-dependent channels to raise intracellular Ca 2+

  5. Parsimonious model for blood glucose level monitoring in type 2 diabetes patients.

    Science.gov (United States)

    Zhao, Fang; Ma, Yan Fen; Wen, Jing Xiao; DU, Yan Fang; Li, Chun Lin; Li, Guang Wei

    2014-07-01

    To establish the parsimonious model for blood glucose monitoring in patients with type 2 diabetes receiving oral hypoglycemic agent treatment. One hundred and fifty-nine adult Chinese type 2 diabetes patients were randomized to receive rapid-acting or sustained-release gliclazide therapy for 12 weeks. Their blood glucose levels were measured at 10 time points in a 24 h period before and after treatment, and the 24 h mean blood glucose levels were measured. Contribution of blood glucose levels to the mean blood glucose level and HbA1c was assessed by multiple regression analysis. The correlation coefficients of blood glucose level measured at 10 time points to the daily MBG were 0.58-0.74 and 0.59-0.79, respectively, before and after treatment (Pblood glucose levels measured at 6 of the 10 time points could explain 95% and 97% of the changes in MBG before and after treatment. The three blood glucose levels, which were measured at fasting, 2 h after breakfast and before dinner, of the 10 time points could explain 84% and 86% of the changes in MBG before and after treatment, but could only explain 36% and 26% of the changes in HbA1c before and after treatment, and they had a poorer correlation with the HbA1c than with the 24 h MBG. The blood glucose levels measured at fasting, 2 h after breakfast and before dinner truly reflected the change 24 h blood glucose level, suggesting that they are appropriate for the self-monitoring of blood glucose levels in diabetes patients receiving oral anti-diabetes therapy. Copyright © 2014 The Editorial Board of Biomedical and Environmental Sciences. Published by China CDC. All rights reserved.

  6. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    Energy Technology Data Exchange (ETDEWEB)

    Ogawa, Eiichi [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Hosokawa, Masaya [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Faculty of Human Sciences, Tezukayama Gakuin University, Osaka (Japan); Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Tsukiyama, Katsushi; Yamada, Yuichiro [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Department of Internal Medicine, Division of Endocrinology, Diabetes and Geriatric Medicine, Akita University School of Medicine, Akita (Japan); Seino, Yutaka [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); Kansai Electric Power Hospital, Osaka (Japan); Inagaki, Nobuya, E-mail: inagaki@metab.kuhp.kyoto-u.ac.jp [Department of Diabetes and Clinical Nutrition, Graduate School of Medicine, Kyoto University (Japan); CREST of Japan Science and Technology Cooperation (JST), Kyoto (Japan)

    2011-01-07

    Research highlights: {yields} Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. {yields} Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. {yields} The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic {beta} cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [{sup 14}C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [{sup 14}C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin

  7. The effect of gastric inhibitory polypeptide on intestinal glucose absorption and intestinal motility in mice

    International Nuclear Information System (INIS)

    Ogawa, Eiichi; Hosokawa, Masaya; Harada, Norio; Yamane, Shunsuke; Hamasaki, Akihiro; Toyoda, Kentaro; Fujimoto, Shimpei; Fujita, Yoshihito; Fukuda, Kazuhito; Tsukiyama, Katsushi; Yamada, Yuichiro; Seino, Yutaka; Inagaki, Nobuya

    2011-01-01

    Research highlights: → Exogenous GIP inhibits intestinal motility through a somatostatin-mediated pathway. → Exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility. → The GIP-receptor-mediated action in intestine does not involve in GLP-1-mediated pathway. -- Abstract: Gastric inhibitory polypeptide (GIP) is released from the small intestine upon meal ingestion and increases insulin secretion from pancreatic β cells. Although the GIP receptor is known to be expressed in small intestine, the effects of GIP in small intestine are not fully understood. This study was designed to clarify the effect of GIP on intestinal glucose absorption and intestinal motility. Intestinal glucose absorption in vivo was measured by single-pass perfusion method. Incorporation of [ 14 C]-glucose into everted jejunal rings in vitro was used to evaluate the effect of GIP on sodium-glucose co-transporter (SGLT). Motility of small intestine was measured by intestinal transit after oral administration of a non-absorbed marker. Intraperitoneal administration of GIP inhibited glucose absorption in wild-type mice in a concentration-dependent manner, showing maximum decrease at the dosage of 50 nmol/kg body weight. In glucagon-like-peptide-1 (GLP-1) receptor-deficient mice, GIP inhibited glucose absorption as in wild-type mice. In vitro examination of [ 14 C]-glucose uptake revealed that 100 nM GIP did not change SGLT-dependent glucose uptake in wild-type mice. After intraperitoneal administration of GIP (50 nmol/kg body weight), small intestinal transit was inhibited to 40% in both wild-type and GLP-1 receptor-deficient mice. Furthermore, a somatostatin receptor antagonist, cyclosomatostatin, reduced the inhibitory effect of GIP on both intestinal transit and glucose absorption in wild-type mice. These results demonstrate that exogenous GIP inhibits intestinal glucose absorption by reducing intestinal motility through a somatostatin-mediated pathway rather

  8. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    Energy Technology Data Exchange (ETDEWEB)

    Kover, Karen, E-mail: kkover@cmh.edu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States); Tasch, James; Hager, Melissa [Kansas City University Medical Biosciences, Kansas City, MO (United States); Clements, Mark; Moore, Wayne V. [Division of Endocrine/Diabetes, Children' s Mercy Hospital & Clinics, Kansas City, MO 64108 (United States); University of Missouri-Kansas City School of Medicine, Kansas City, MO 64108 (United States)

    2015-06-19

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H{sub 2}O{sub 2} assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H{sub 2}O{sub 2} levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose

  9. Osteocalcin protects pancreatic beta cell function and survival under high glucose conditions

    International Nuclear Information System (INIS)

    Kover, Karen; Yan, Yun; Tong, Pei Ying; Watkins, Dara; Li, Xiaoyu; Tasch, James; Hager, Melissa; Clements, Mark; Moore, Wayne V.

    2015-01-01

    Diabetes is characterized by progressive beta cell dysfunction and loss due in part to oxidative stress that occurs from gluco/lipotoxicity. Treatments that directly protect beta cell function and survival in the diabetic milieu are of particular interest. A growing body of evidence suggests that osteocalcin, an abundant non-collagenous protein of bone, supports beta cell function and proliferation. Based on previous gene expression data by microarray, we hypothesized that osteocalcin protects beta cells from glucose-induced oxidative stress. To test our hypothesis we cultured isolated rat islets and INS-1E cells in the presence of normal, high, or high glucose ± osteocalcin for up to 72 h. Oxidative stress and viability/mitochondrial function were measured by H 2 O 2 assay and Alamar Blue assay, respectively. Caspase 3/7 activity was also measured as a marker of apoptosis. A functional test, glucose stimulated insulin release, was conducted and expression of genes/protein was measured by qRT-PCR/western blot/ELISA. Osteocalcin treatment significantly reduced high glucose-induced H 2 O 2 levels while maintaining viability/mitochondrial function. Osteocalcin also significantly improved glucose stimulated insulin secretion and insulin content in rat islets after 48 h of high glucose exposure compared to untreated islets. As expected sustained high glucose down-regulated gene/protein expression of INS1 and BCL2 while increasing TXNIP expression. Interestingly, osteocalcin treatment reversed the effects of high glucose on gene/protein expression. We conclude that osteocalcin can protect beta cells from the negative effects of glucose-induced oxidative stress, in part, by reducing TXNIP expression, thereby preserving beta cell function and survival. - Highlights: • Osteocalcin reduces glucose-induced oxidative stress in beta cells. • Osteocalcin preserves beta cell function and survival under stress conditions. • Osteocalcin reduces glucose-induced TXNIP

  10. 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.

  11. Biphasic insulin-releasing effect of BTS 67 582 in rats.

    Science.gov (United States)

    Storey, D A; Bailey, C J

    1998-12-01

    BTS 67 582 (1,1-dimethyl-2(2-morpholinophenyl)guanidine fumarate) is being developed as a short-acting anti-diabetic insulin secretagogue. The effect of BTS 67 582 on the phasic pattern of insulin release was assessed in anaesthetized normal rats by measuring arterial plasma insulin concentrations while arterial glucose concentrations were fixed at 6, 8.5 and 12.5 mM. Intravenous BTS 67 582 (10 mg kg(-1)) induced an immediate but transient increase in insulin concentrations which declined by 10 min (first phase). This was followed by a smaller but sustained increase in insulin concentrations (second phase). The increment from basal to peak insulin release (0-2 min) was independent of glucose, but the first phase was maintained for longer and the second phase was greater at the highest concentration of glucose (12.5 mM). BTS 67 582 also extended the first-phase insulin response to a standard intravenous glucose challenge and enhanced the rate of glucose disappearance by approximately 12%. Thus BTS 67 582 causes biphasic stimulation of insulin release and augments the insulin-releasing effect of glucose.

  12. Growth Hormone-Releasing Hormone in Diabetes

    Directory of Open Access Journals (Sweden)

    Leonid Evsey Fridlyand

    2016-10-01

    Full Text Available Growth hormone-releasing hormone (GHRH is produced by the hypothalamus and stimulates growth hormone synthesis and release in the anterior pituitary gland. In addition GHRH is an important regulator of cellular functions in many cells and organs. Expression of GHRH G-Protein Coupled Receptor (GHRHR has been demonstrated in different peripheral tissues and cell types including pancreatic islets. Among the peripheral activities, recent studies demonstrate a novel ability of GHRH analogs to increase and preserve insulin secretion by beta-cells in isolated pancreatic islets, which makes them potentially useful for diabetes treatment. This review considers the role of GHRHR in the beta-cell and addresses the unique engineered GHRH agonists and antagonists for treatment of Type 2 diabetes mellitus. We discuss the similarity of signaling pathways activated by GHRHR in pituitary somatotrophs and in pancreatic beta-cells and possible ways as to how the GHRHR pathway can interact with glucose and other secretagogues to stimulate insulin secretion. We also consider the hypothesis that novel GHRHR agonists can improve glucose metabolism in Type 2 diabetes by preserving the function and survival of pancreatic beta-cells. Wound healing and cardioprotective action with new GHRH agonists suggesting that they may prove useful in ameliorating certain diabetic complications. These findings highlight the future potential therapeutic effectiveness of modulators of GHRHR activity for the development of new therapeutic approaches in diabetes and its complications.

  13. Increased muscle glucose uptake after exercise

    DEFF Research Database (Denmark)

    Richter, Erik; Ploug, Thorkil; Galbo, Henrik

    1985-01-01

    responsiveness of glucose uptake was noted only in controls. Analysis of intracellular glucose-6-phosphate, glucose, glycogen synthesis, and glucose transport suggested that the exercise effect on responsiveness might be due to enhancement of glucose disposal. After electrical stimulation of diabetic...... of glucose. At maximal insulin concentrations, the enhancing effect of exercise on glucose uptake may involve enhancement of glucose disposal, an effect that is probably less in muscle from diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)......It has recently been shown that insulin sensitivity of skeletal muscle glucose uptake and glycogen synthesis is increased after a single exercise session. The present study was designed to determine whether insulin is necessary during exercise for development of these changes found after exercise...

  14. The Glucose-Insulin Control System

    DEFF Research Database (Denmark)

    Hallgreen, Christine Erikstrup; Korsgaard, Thomas Vagn; Hansen, RenéNormann N.

    2008-01-01

    This chapter reviews the glucose-insulin control system. First, classic control theory is described briefly and compared with biological control. The following analysis of the control system falls into two parts: a glucose-sensing part and a glucose-controlling part. The complex metabolic pathways...... are divided into smaller pieces and analyzed via several small biosimulation models that describe events in beta cells, liver, muscle and adipose tissue etc. In the glucose-sensing part, the beta cell are shown to have some characteristics of a classic PID controller, but with nonlinear properties...... control, the analysis shows that the system has many more facets than just keeping the glucose concentration within narrow limits. After glucose enters the cell and is phosphorylated to glucose-6-phosphate, the handling of glucose-6-phosphate is critical for glucose regulation. Also, this handling...

  15. 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.

  16. Interplay between glucose and leptin signalling determines the strength of GABAergic synapses at POMC neurons.

    Science.gov (United States)

    Lee, Dong Kun; Jeong, Jae Hoon; Chun, Sung-Kun; Chua, Streamson; Jo, Young-Hwan

    2015-03-26

    Regulation of GABAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals regulate energy and glucose homeostasis. Thus, understanding how POMC neurons integrate these two signal molecules at the synaptic level is important. Here we show that leptin's action on GABA release to POMC neurons is influenced by glucose levels. Leptin stimulates the JAK2-PI3K pathway in both presynaptic GABAergic terminals and postsynaptic POMC neurons. Inhibition of AMPK activity in presynaptic terminals decreases GABA release at 10 mM glucose. However, postsynaptic TRPC channel opening by the PI3K-PLC signalling pathway in POMC neurons enhances spontaneous GABA release via activation of presynaptic MC3/4 and mGlu receptors at 2.5 mM glucose. High-fat feeding blunts AMPK-dependent presynaptic inhibition, whereas PLC-mediated GABAergic feedback inhibition remains responsive to leptin. Our data indicate that the interplay between glucose and leptin signalling in glutamatergic POMC neurons is critical for determining the strength of inhibitory tone towards POMC neurons.

  17. Interplay between glucose and leptin signaling determines the strength of GABAergic synapses at POMC neurons

    Science.gov (United States)

    Lee, Dong Kun; Jeong, Jae Hoon; Chun, Sung-Kun; Chua, Streamson; Jo, Young-Hwan

    2015-01-01

    Regulation of GABAergic inhibitory inputs and alterations in POMC neuron activity by nutrients and adiposity signals regulate energy and glucose homeostasis. Thus, understanding how POMC neurons integrate these two signal molecules at the synaptic level is important. Here we show that leptin’s action on GABA release to POMC neurons is influenced by glucose levels. Leptin stimulates the JAK2-PI3K pathway in both presynaptic GABAergic terminals and postsynaptic POMC neurons. Inhibition of AMPK activity in presynaptic terminals decreases GABA release at 10 mM glucose. However, postsynaptic TRPC channel opening by the PI3K-PLC signaling pathway in POMC neurons enhances spontaneous GABA release via activation of presynaptic MC3/4 and mGlu receptors at 2.5 mM glucose. High-fat feeding blunts AMPK-dependent presynaptic inhibition, whereas PLC-mediated GABAergic feedback inhibition remains responsive to leptin. Our data indicate that the interplay between glucose and leptin signaling in glutamatergic POMC neurons is critical for determining the strength of inhibitory tone towards POMC neurons. PMID:25808323

  18. Relationship between insulin release and 65zinc efflux from rat pancreatic islets maintained in tissue culture

    International Nuclear Information System (INIS)

    Formby, B.; Schmid-Formby, F.; Grodsky, G.M.

    1984-01-01

    In short-term batch-incubation or perfusion experiments, we studied insulin release and associated 65 Zn efflux from rat pancreatic islets loaded with 65 Zn by 24-h tissue culture in low-glucose medium. The fractional basal insulin release and 65 Zn efflux were 0.4% and 3% of total content/h/islet, respectively. Thus, basal 65 Zn efflux was much greater than that to be accounted for if zinc was released proportionally with insulin release only; extragranular zinc flux was suggested. Two millimolar glucose, with or without 1 mM 3-isobutyl-1-methylxanthine (IBMX), affected neither insulin release nor associated 65 Zn efflux. Twenty-five millimolar glucose produced a significant threefold increase in insulin release above baseline, but somewhat decreased 65 Zn efflux at marginal significance. Glucose (25 mM) plus 1 mM IBMX provoked a high increase in insulin release and an associated 30% increase in fractional 65 Zn efflux over basal. Calculations based on previous estimations of 65 Zn distribution and equilibrium with islet zinc indicated that molar zinc efflux was more than sufficient to account for a 2-zinc-insulin hexamer. L-Leucine (2 or 20 mM) plus 1 mM IBMX caused far greater 65 Zn efflux for the amount of insulin released, indicating additional 65 Zn mobilization not directly related to insulin secretion. To evaluate 65 Zn efflux during inhibited insulin secretion, batch incubations were performed in 100% D 2 O or at 27 degrees C, conditions that inhibited insulin release stimulated by high glucose plus IBMX. These agents decreased the 65 Zn efflux far below the basal value (35% and 50%, respectively) and greater than could be accounted for by the attendent inhibition of insulin secretion.(ABSTRACT TRUNCATED AT 250 WORDS)

  19. Piracetam and TRH analogues antagonise inhibition by barbiturates, diazepam, melatonin and galanin of human erythrocyte D-glucose transport

    Science.gov (United States)

    Naftalin, Richard J; Cunningham, Philip; Afzal-Ahmed, Iram

    2004-01-01

    Nootropic drugs increase glucose uptake into anaesthetised brain and into Alzheimer's diseased brain. Thyrotropin-releasing hormone, TRH, which has a chemical structure similar to nootropics increases cerebellar uptake of glucose in murine rolling ataxia. This paper shows that nootropic drugs like piracetam (2-oxo 1 pyrrolidine acetamide) and levetiracetam and neuropeptides like TRH antagonise the inhibition of glucose transport by barbiturates, diazepam, melatonin and endogenous neuropeptide galanin in human erythrocytes in vitro. The potencies of nootropic drugs in opposing scopolamine-induced memory loss correlate with their potencies in antagonising pentobarbital inhibition of erythrocyte glucose transport in vitro (Pnootropics, D-levetiracetam and D-pyroglutamate, have higher antagonist Ki's against pentobarbital inhibition of glucose transport than more potent L-stereoisomers (Pnootropics, like aniracetam and levetiracetam, while antagonising pentobarbital action, also inhibit glucose transport. Analeptics like bemigride and methamphetamine are more potent inhibitors of glucose transport than antagonists of hypnotic action on glucose transport. There are similarities between amino-acid sequences in human glucose transport protein isoform 1 (GLUT1) and the benzodiazepine-binding domains of GABAA (gamma amino butyric acid) receptor subunits. Mapped on a 3D template of GLUT1, these homologies suggest that the site of diazepam and piracetam interaction is a pocket outside the central hydrophilic pore region. Nootropic pyrrolidone antagonism of hypnotic drug inhibition of glucose transport in vitro may be an analogue of TRH antagonism of galanin-induced narcosis. PMID:15148255

  20. 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

  1. Blood glucose in acute stroke

    DEFF Research Database (Denmark)

    Olsen, Tom Skyhøj

    2009-01-01

    of infarcts. For a number of years, tight glycemic control has been regarded as beneficial in critically illness, but recent research has been unable to support this notion. The only completed randomized study on glucose-lowering therapy in stroke has failed to demonstrate effect, and concerns relating...

  2. Hypothalamic neurones governing glucose homeostasis.

    Science.gov (United States)

    Coppari, R

    2015-06-01

    The notion that the brain directly controls the level of glucose in the blood (glycaemia) independent of its known action on food intake and body weight has been known ever since 1849. That year, the French physiologist Dr Claude Bernard reported that physical puncture of the floor of the fourth cerebral ventricle rapidly leads to an increased level of sugar in the blood (and urine) in rabbits. Despite this important discovery, it took approximately 150 years before significant efforts aimed at understanding the underlying mechanism of brain-mediated control of glucose metabolism were made. Technological developments allowing for genetically-mediated manipulation of selected molecular pathways in a neurone-type-specific fashion unravelled the importance of specific molecules in specific neuronal populations. These neuronal pathways govern glucose metabolism in the presence and even in the absence of insulin. Also, a peculiarity of these pathways is that certain biochemically-defined neurones govern glucose metabolism in a tissue-specific fashion. © 2015 British Society for Neuroendocrinology.

  3. Saccharification of ozonated sugarcane bagasse using enzymes from Myceliophthora thermophila JCP 1-4 for sugars release and ethanol production.

    Science.gov (United States)

    de Cassia Pereira, Josiani; Travaini, Rodolfo; Paganini Marques, Natalia; Bolado-Rodríguez, Silvia; Bocchini Martins, Daniela Alonso

    2016-03-01

    The saccharification of ozonated sugarcane bagasse (SCB) by enzymes from Myceliophthora thermophila JCP 1-4 was studied. Fungal enzymes provided slightly higher sugar release than commercial enzymes, working at 50°C. Sugar release increased with temperature increase. Kinetic studies showed remarkable glucose release (4.99 g/L, 3%w/w dry matter) at 60°C, 8 h of hydrolysis, using an enzyme load of 10 FPU (filter paper unit). FPase and β-glucosidase activities increased during saccharification (284% and 270%, respectively). No further significant improvement on glucose release was observed increasing the enzyme load above 7.5 FPU per g of cellulose. Higher dry matter contents increased sugars release, but not yields. The fermentation of hydrolysates by Saccharomyces cerevisiae provided glucose-to-ethanol conversions around to 63%. Copyright © 2015 Elsevier Ltd. All rights reserved.

  4. The 2017 Release Cloudy

    Science.gov (United States)

    Ferland, G. J.; Chatzikos, M.; Guzmán, F.; Lykins, M. L.; van Hoof, P. A. M.; Williams, R. J. R.; Abel, N. P.; Badnell, N. R.; Keenan, F. P.; Porter, R. L.; Stancil, P. C.

    2017-10-01

    We describe the 2017 release of the spectral synthesis code Cloudy, summarizing the many improvements to the scope and accuracy of the physics which have been made since the previous release. Exporting the atomic data into external data files has enabled many new large datasets to be incorporated into the code. The use of the complete datasets is not realistic for most calculations, so we describe the limited subset of data used by default, which predicts significantly more lines than the previous release of Cloudy. This version is nevertheless faster than the previous release, as a result of code optimizations. We give examples of the accuracy limits using small models, and the performance requirements of large complete models. We summarize several advances in the H- and He-like iso-electronic sequences and use our complete collisional-radiative models to establish the densities where the coronal and local thermodynamic equilibrium approximations work.

  5. EIA new releases

    International Nuclear Information System (INIS)

    1994-09-01

    This report is a compliation of news releases from the Energy Information Administration. The september-october report includes articles on energy conservation, energy consumption in commercial buildings, and a short term energy model for a personal computer

  6. Effects of intravenous glucose on Dopaminergic function in the human brain in vivo

    NARCIS (Netherlands)

    Haltia, Lauri T.; Rinne, Juha O.; Merisaari, Harri; Maguire, Ralph P.; Savontaus, Eriika; Helin, Semi; Nagren, Kjell; Kaasinen, Valtteri

    Dopamine is known to regulate food intake by modulating food reward via the mesolimbic circuitry of the brain. The objective of this study was to compare the effects of high energy input (i.v. glucose) on striatal and thalamic dopamine release in overweight and lean individuals. We hypothesized that

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

    DEFF Research Database (Denmark)

    Bülow, J; Simonsen, L; Wiggins, D

    1999-01-01

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

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

    Science.gov (United States)

    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 whethe...

  9. New approach to modulate retinal cellular toxic effects of high glucose using marine epa and dha

    Directory of Open Access Journals (Sweden)

    Fagon Roxane

    2011-06-01

    Full Text Available Abstract Background Protective effects of omega-3 fatty acids against cellular damages of high glucose were studied on retinal pigmented epithelial (RPE cells. Methods Retinal epithelial cells were incubated with omega-3 marine oils rich in EPA and DHA and then with high glucose (25 mM for 48 hours. Cellular responses were compared to normal glucose (5 mM: intracellular redox status, reactive oxygen species (ROS, mitochondrial succinate deshydrogenase activity, inflammatory cytokines release and caveolin-1 expression were evaluated using microplate cytometry, ELISA and flow cytometry techniques. Fatty acids incorporation in retinal cell membranes was analysed using chromatography. Results Preincubation of the cells with fish oil decreased ROS overproduction, mitochondrial alterations and TNFα release. These protective effects could be attributed to an increase in caveolin-1 expression induced by marine oil. Conclusion Marine formulations rich in omega-3 fatty acids represent a promising therapeutic approach for diabetic retinopathy.

  10. Sellafield (release of radioactivity)

    Energy Technology Data Exchange (ETDEWEB)

    Cunningham, J; Goodlad, A; Morris, M

    1986-02-06

    A government statement is reported, about the release of plutonium nitrate at the Sellafield site of British Nuclear Fuels plc on 5 February 1986. Matters raised included: details of accident; personnel monitoring; whether radioactive material was released from the site; need for public acceptance of BNFL activities; whether plant should be closed; need to reduce level of radioactive effluent; number of incidents at the plant.

  11. Glucose tolerance test - non-pregnant

    Science.gov (United States)

    ... for energy. People with untreated diabetes have high blood glucose levels. Most often, the first tests used to diagnose ... in people who are not pregnant are: Fasting blood glucose level: diabetes is diagnosed if it is higher than ...

  12. Methylphenidate increases glucose uptake in the brain of young and adult rats.

    Science.gov (United States)

    Réus, Gislaine Z; Scaini, Giselli; Titus, Stephanie E; Furlanetto, Camila B; Wessler, Leticia B; Ferreira, Gabriela K; Gonçalves, Cinara L; Jeremias, Gabriela C; Quevedo, João; Streck, Emilio L

    2015-10-01

    Methylphenidate (MPH) is the drug of choice for pharmacological treatment of attention deficit hyperactivity disorder. Studies have pointed to the role of glucose and lactate as well as in the action mechanisms of drugs used to treat these neuropsychiatric diseases. Thus, this study aims to evaluate the effects of MPH administration on lactate release and glucose uptake in the brains of young and adult rats. MPH (1.0, 2.0 and 10.0mg/kg) or saline was injected in young and adult Wistar male rats either acutely (once) or chronically (once daily for 28 days). Then, the levels of lactate release and glucose uptake were assessed in the prefrontal cortex, hippocampus, striatum, cerebellum and cerebral cortex. Chronic MPH treatment increased glucose uptake at the dose of 10.0mg/kg in the prefrontal cortex and striatum, and at the dose of 2.0mg/kg in the cerebral cortex of young rats. In adult rats, an increase in glucose uptake was observed after acute administration of MPH at the dose of 10.0mg/kg in the prefrontal cortex. After chronic treatment, there was an increase in glucose uptake with MPH doses of 2.0 and 10.0mg/kg in the prefrontal cortex, and at an MPH dose of 2.0mg/kg in the striatum of adult rats. The lactate release did not change with either acute or chronic treatments in young or adult rats. These findings indicate that MPH increases glucose consumption in the brain, and that these changes are dependent on age and posology. Copyright © 2015 Institute of Pharmacology, Polish Academy of Sciences. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

  13. Dopamine and glucose, obesity and Reward Deficiency Syndrome

    Directory of Open Access Journals (Sweden)

    Kenneth eBlum

    2014-09-01

    Full Text Available Obesity and many well described eating disorders are accurately considered a global epidemic. The consequences of Reward Deficiency Syndrome, a genetic and epigenetic phenomena that involves the interactions of powerful neurotransmitters, are impairments of brain reward circuitry, hypodopaminergic function and abnormal craving behavior. Numerous sound neurochemical and genetic studies provide strong evidence that food addiction is similar to psychoactive drug addiction. Important facts which could translate to potential therapeutic targets espoused in this review include: 1 brain dopamine (DA production and use is stimulated by consumption of alcohol in large quantities or carbohydrates bingeing; 2 in the mesolimbic system the enkephalinergic neurons are in close proximity, to glucose receptors; 3 highly concentrated glucose activates the calcium channel to stimulate dopamine release from P12 cells; 4 blood glucose and cerebrospinal fluid concentrations of homovanillic acid, the dopamine metabolite, are significantly correlated and 5 2-deoxyglucose the glucose analogue, in pharmacological doses associates with enhanced dopamine turnover and causes acute glucoprivation. Evidence from animal studies and human fMRI support the hypothesis that multiple, but similar brain circuits are disrupted in obesity and drug dependence and DA-modulated reward circuits are involved in pathologic eating behaviors. Treatment for addiction to glucose and drugs alike, based on a consensus of neuroscience research, should incorporate dopamine agonist therapy, in contrast to current theories and practices that use dopamine antagonists. Until now, powerful dopamine-D2 agonists have failed clinically, due to chronic down regulation of D2 receptors instead, consideration of novel less powerful D2 agonists that up-regulate D2 receptors seems prudent. We encourage new strategies targeted at improving DA function in the treatment and prevention of obesity a subtype of

  14. Impaired insulin secretion and glucose intolerance in synaptotagmin-7 null mutant mice

    DEFF Research Database (Denmark)

    Gustavsson, Natalia; Lao, Ye; Maximov, Anton

    2008-01-01

    and insulin release. Here, we show that synaptotagmin-7 is required for the maintenance of systemic glucose tolerance and glucose-stimulated insulin secretion. Mutant mice have normal insulin sensitivity, insulin production, islet architecture and ultrastructural organization, and metabolic and calcium...... secretion in pancreatic beta-cells. Of these other synaptotagmins, synaptotagmin-7 is one of the most abundant and is present in pancreatic beta-cells. To determine whether synaptotagmin-7 regulates Ca(2+)-dependent insulin secretion, we analyzed synaptotagmin-7 null mutant mice for glucose tolerance...... responses but exhibit impaired glucose-induced insulin secretion, indicating a calcium-sensing defect during insulin-containing secretory granule exocytosis. Taken together, our findings show that synaptotagmin-7 functions as a positive regulator of insulin secretion and may serve as a calcium sensor...

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

    DEFF Research Database (Denmark)

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

    2015-01-01

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

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

    Directory of Open Access Journals (Sweden)

    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.

  17. Autonomic regulation of hepatic glucose production

    NARCIS (Netherlands)

    Bisschop, Peter H.; Fliers, Eric; Kalsbeek, Andries

    2015-01-01

    Glucose produced by the liver is a major energy source for the brain. Considering its critical dependence on glucose, it seems only natural that the brain is capable of monitoring and controlling glucose homeostasis. In addition to neuroendocrine pathways, the brain uses the autonomic nervous system

  18. Estimation of liver glucose metabolism after refeeding

    International Nuclear Information System (INIS)

    Rognstad, R.

    1987-01-01

    Refeeding or infusing glucose to rats fasted for 24 hr or more causes rapid liver glycogen synthesis, the carbon source now considered to be largely from gluconeogenesis. While substrate cycling between plasma glucose and liver glucose-6P is known to occur, this cycling has apparently been ignored when calculations are made of % contribution of direct and indirect pathways to liver glycogen synthesis, or when hepatic glucose output is calculated from glucose turnover minus the glucose infusion rate. They show that, isotopically, an estimate of the fluxes of liver glucokinase and glucose-6-phosphatase is required to quantitate sources of carbon for liver glycogen synthesis, and to measure hepatic glucose output (or uptake). They propose a method to estimate these fluxes, involving a short infusion of a 14 C labelled gluconeogenic precursor plus (6T)glucose, with determination of isotopic yields in liver glycogen and total glucose. Given also the rate of liver glycogen synthesis, this procedure permits the estimation of net gluconeogenesis and hepatic glucose output or uptake. Also, in vitro evidence against the notion of a drastic zonation of liver carbohydrate metabolism is presented, e.g. raising the glucose concentration from 10 to 25 mM increases the 14 C yield from H 14 CO 3 - in lactate, with the increased pyruvate kinase flux and decreased gluconeogenesis occurring in the same cell type, not opposing pathways in different hepatocyte types (as has been postulated by some to occur in vivo after refeeding

  19. 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…

  20. Brain glucose sensing, counterregulation, and energy homeostasis.

    Science.gov (United States)

    Marty, Nell; Dallaporta, Michel; Thorens, Bernard

    2007-08-01

    Neuronal circuits in the central nervous system play a critical role in orchestrating the control of glucose and energy homeostasis. Glucose, beside being a nutrient, is also a signal detected by several glucose-sensing units that are located at different anatomical sites and converge to the hypothalamus to cooperate with leptin and insulin in controlling the melanocortin pathway.

  1. Glucose transport machinery reconstituted in cell models.

    Science.gov (United States)

    Hansen, Jesper S; Elbing, Karin; Thompson, James R; Malmstadt, Noah; Lindkvist-Petersson, Karin

    2015-02-11

    Here we demonstrate the production of a functioning cell model by formation of giant vesicles reconstituted with the GLUT1 glucose transporter and a glucose oxidase and hydrogen peroxidase linked fluorescent reporter internally. Hence, a simplified artificial cell is formed that is able to take up glucose and process it.

  2. The Effects of High Glucose on Adipogenic and Osteogenic Differentiation of Gestational Tissue-Derived MSCs

    Directory of Open Access Journals (Sweden)

    Weerawan Hankamolsiri

    2016-01-01

    Full Text Available Most type 2 diabetic patients are obese who have increased number of visceral adipocytes. Those visceral adipocytes release several factors that enhance insulin resistance making diabetic treatment ineffective. It is known that significant percentages of visceral adipocytes are derived from mesenchymal stem cells and high glucose enhances adipogenic differentiation of mouse bone marrow-derived MSCs (BM-MSCs. However, the effect of high glucose on adipogenic differentiation of human bone marrow and gestational tissue-derived MSCs is still poorly characterized. This study aims to investigate the effects of high glucose on proliferation as well as adipogenic and osteogenic differentiation of human MSCs derived from bone marrow and several gestational tissues including chorion, placenta, and umbilical cord. We found that high glucose reduced proliferation but enhanced adipogenic differentiation of all MSCs examined. The expression levels of some adipogenic genes were also upregulated when MSCs were cultured in high glucose. Although high glucose transiently downregulated the expression levels of some osteogenic genes examined, its effect on the osteogenic differentiation levels of the MSCs is not clearly demonstrated. The knowledge gained from this study will increase our understanding about the effect of high glucose on adipogenic differentiation of MSCs and might lead to an improvement in the diabetic treatment in the future.

  3. Effects of intravenous glucose on dopaminergic function in the human brain in vivo.

    Science.gov (United States)

    Haltia, Lauri T; Rinne, Juha O; Merisaari, Harri; Maguire, Ralph P; Savontaus, Eriika; Helin, Semi; Någren, Kjell; Kaasinen, Valtteri

    2007-09-01

    Dopamine is known to regulate food intake by modulating food reward via the mesolimbic circuitry of the brain. The objective of this study was to compare the effects of high energy input (i.v. glucose) on striatal and thalamic dopamine release in overweight and lean individuals. We hypothesized that glucose would induce dopamine release and positive ratings (e.g., satiety) in Behavioral Analog Scales, particularly in food-deprived lean subjects. [(11)C]raclopride PET was performed for 12 lean (mean BMI = 22 kg/m(2)) and 12 overweight (mean BMI = 33 kg/m(2)) healthy subjects. Each subject was imaged twice in a blinded counter-balanced setting, after 300 mg/kg i.v. glucose and after i.v. placebo. Dopamine D2 receptor binding potentials (BPs) were estimated. The voxel-based analysis of the baseline scans indicated lower striatal BPs in the overweight group and a negative correlation between BMIs and BPs. Intravenous glucose did not have a significant effect on BPs in overweight or lean subjects (male and female groups combined). However, BP changes were opposite in the two gender groups. In male subjects, significant BP reductions after glucose were seen in the right and left caudate nucleus, left putamen, and right thalamus. In female subjects, increases in BP secondary to glucose were seen in the right caudate nucleus and right and left putamen. The sexually dimorphic effect of glucose was seen in both overweight and lean subjects. Although gender differences were not among the a priori hypotheses of the present study and, therefore, they must be considered to be preliminary findings, we postulate that this observation is a reflection of an interaction between glucose, sex steroids (estrogen), leptin, and dopamine.

  4. 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

  5. ATP Release Channels

    Directory of Open Access Journals (Sweden)

    Akiyuki Taruno

    2018-03-01

    Full Text Available Adenosine triphosphate (ATP has been well established as an important extracellular ligand of autocrine signaling, intercellular communication, and neurotransmission with numerous physiological and pathophysiological roles. In addition to the classical exocytosis, non-vesicular mechanisms of cellular ATP release have been demonstrated in many cell types. Although large and negatively charged ATP molecules cannot diffuse across the lipid bilayer of the plasma membrane, conductive ATP release from the cytosol into the extracellular space is possible through ATP-permeable channels. Such channels must possess two minimum qualifications for ATP permeation: anion permeability and a large ion-conducting pore. Currently, five groups of channels are acknowledged as ATP-release channels: connexin hemichannels, pannexin 1, calcium homeostasis modulator 1 (CALHM1, volume-regulated anion channels (VRACs, also known as volume-sensitive outwardly rectifying (VSOR anion channels, and maxi-anion channels (MACs. Recently, major breakthroughs have been made in the field by molecular identification of CALHM1 as the action potential-dependent ATP-release channel in taste bud cells, LRRC8s as components of VRACs, and SLCO2A1 as a core subunit of MACs. Here, the function and physiological roles of these five groups of ATP-release channels are summarized, along with a discussion on the future implications of understanding these channels.

  6. A mathematical model of brain glucose homeostasis

    Directory of Open Access Journals (Sweden)

    Kimura Hidenori

    2009-11-01

    Full Text Available Abstract Background The physiological fact that a stable level of brain glucose is more important than that of blood glucose suggests that the ultimate goal of the glucose-insulin-glucagon (GIG regulatory system may be homeostasis of glucose concentration in the brain rather than in the circulation. Methods In order to demonstrate the relationship between brain glucose homeostasis and blood hyperglycemia in diabetes, a brain-oriented mathematical model was developed by considering the brain as the controlled object while the remaining body as the actuator. After approximating the body compartmentally, the concentration dynamics of glucose, as well as those of insulin and glucagon, are described in each compartment. The brain-endocrine crosstalk, which regulates blood glucose level for brain glucose homeostasis together with the peripheral interactions among glucose, insulin and glucagon, is modeled as a proportional feedback control of brain glucose. Correlated to the brain, long-term effects of psychological stress and effects of blood-brain-barrier (BBB adaptation to dysglycemia on the generation of hyperglycemia are also taken into account in the model. Results It is shown that simulation profiles obtained from the model are qualitatively or partially quantitatively consistent with clinical data, concerning the GIG regulatory system responses to bolus glucose, stepwise and continuous glucose infusion. Simulations also revealed that both stress and BBB adaptation contribute to the generation of hyperglycemia. Conclusion Simulations of the model of a healthy person under long-term severe stress demonstrated that feedback control of brain glucose concentration results in elevation of blood glucose level. In this paper, we try to suggest that hyperglycemia in diabetes may be a normal outcome of brain glucose homeostasis.

  7. Effect of whey on blood glucose and insulin responses to composite breakfast and lunch meals in type 2 diabetic subjects

    DEFF Research Database (Denmark)

    Frid, Anders H; Nilsson, Mikael; Holst, Jens Juul

    2005-01-01

    glycemic index (GI) with whey proteins may increase insulin secretion and improve blood glucose control in type 2 diabetic subjects. DESIGN: Fourteen diet-treated subjects with type 2 diabetes were served a high-GI breakfast (white bread) and subsequent high-GI lunch (mashed potatoes with meatballs...... insulin release and reduces postprandial blood glucose excursion after a lunch meal consisting of mashed potatoes and meatballs in type 2 diabetic subjects....

  8. RAVEN Beta Release

    International Nuclear Information System (INIS)

    Rabiti, Cristian; Alfonsi, Andrea; Cogliati, Joshua Joseph; Mandelli, Diego; Kinoshita, Robert Arthur; Wang, Congjian; Maljovec, Daniel Patrick; Talbot, Paul William

    2016-01-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  9. RAVEN Beta Release

    Energy Technology Data Exchange (ETDEWEB)

    Rabiti, Cristian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Alfonsi, Andrea [Idaho National Lab. (INL), Idaho Falls, ID (United States); Cogliati, Joshua Joseph [Idaho National Lab. (INL), Idaho Falls, ID (United States); Mandelli, Diego [Idaho National Lab. (INL), Idaho Falls, ID (United States); Kinoshita, Robert Arthur [Idaho National Lab. (INL), Idaho Falls, ID (United States); Wang, Congjian [Idaho National Lab. (INL), Idaho Falls, ID (United States); Maljovec, Daniel Patrick [Idaho National Lab. (INL), Idaho Falls, ID (United States); Talbot, Paul William [Idaho National Lab. (INL), Idaho Falls, ID (United States)

    2016-02-01

    This documents the release of the Risk Analysis Virtual Environment (RAVEN) code. A description of the RAVEN code is provided, and discussion of the release process for the M2LW-16IN0704045 milestone. The RAVEN code is a generic software framework to perform parametric and probabilistic analysis based on the response of complex system codes. RAVEN is capable of investigating the system response as well as the input space using Monte Carlo, Grid, or Latin Hyper Cube sampling schemes, but its strength is focused toward system feature discovery, such as limit surfaces, separating regions of the input space leading to system failure, using dynamic supervised learning techniques. RAVEN has now increased in maturity enough for the Beta 1.0 release.

  10. Lifestyle, glucose regulation and the cognitive effects of glucose load in middle-aged adults

    OpenAIRE

    Riby, Leigh; McLaughlin, Jennifer; Riby, Deborah

    2008-01-01

    Interventions aimed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly. In particular, previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia (after a glucose drink) or after improvements in glucose regulation. The present study aimed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition. In addit...

  11. Dietary Fructose and Glucose Differentially Affect Lipid and Glucose Homeostasis1–3

    OpenAIRE

    Schaefer, Ernst J.; Gleason, Joi A.; Dansinger, Michael L.

    2009-01-01

    Absorbed glucose and fructose differ in that glucose largely escapes first-pass removal by the liver, whereas fructose does not, resulting in different metabolic effects of these 2 monosaccharides. In short-term controlled feeding studies, dietary fructose significantly increases postprandial triglyceride (TG) levels and has little effect on serum glucose concentrations, whereas dietary glucose has the opposite effects. When dietary glucose and fructose have been directly compared at ∼20–25% ...

  12. Glucose metabolism in diabetic blood vessels

    International Nuclear Information System (INIS)

    Brown, B.J.; Crass, M.F. III

    1986-01-01

    Since glycolysis appears to be coupled to active ion transport in vascular smooth muscle, alterations in glucose metabolism may contribute to cellular dysfunction and angiopathy in diabetes. Uptake and utilization of glucose were studied in perfused blood vessels in which pulsatile flow and perfusion pressure were similar to those measured directly in vivo. Thoracic aortae isolated from 8-wk alloxan diabetic (D) and nondiabetic control rabbits were cannulated, tethered, and perfused with oxygenated buffer containing 7 or 25 mM glucose and tracer amounts of glucose-U -14 C. Norepinephrine (NE) (10 -6 M) and/or insulin (I) (150 μU/ml) and albumin (0.2%) were added. NE-induced tension development increased glucose uptake 39% and 14 CO 2 and lactate production 2.3-fold. With 7 mM glucose, marked decreases in glucose uptake (74%), 14 CO 2 (68%), lactate (30%), total tissue glycogen (75%), and tissue phospholipids (70%) were observed in D. Addition of I or elevation of exogenous glucose to 25 mM normalized glucose uptake, but had differential effects on the pattern of substrate utilization. Thus, in D, there was a marked depression of vascular glucose metabolism that was partially reversed by addition of low concentrations of insulin or D levels of glucose

  13. Electrochemical non-enzymatic glucose sensors

    International Nuclear Information System (INIS)

    Park, Sejin; Boo, Hankil; Chung, Taek Dong

    2006-01-01

    The electrochemical determination of glucose concentration without using enzyme is one of the dreams that many researchers have been trying to make come true. As new materials have been reported and more knowledge on detailed mechanism of glucose oxidation has been unveiled, the non-enzymatic glucose sensor keeps coming closer to practical applications. Recent reports strongly imply that this progress will be accelerated in 'nanoera'. This article reviews the history of unraveling the mechanism of direct electrochemical oxidation of glucose and making attempts to develop successful electrochemical glucose sensors. The electrochemical oxidation of glucose molecules involves complex processes of adsorption, electron transfer, and subsequent chemical rearrangement, which are combined with the surface reactions on the metal surfaces. The information about the direct oxidation of glucose on solid-state surfaces as well as new electrode materials will lead us to possible breakthroughs in designing the enzymeless glucose sensing devices that realize innovative and powerful detection. An example of those is to introduce nanoporous platinum as an electrode, on which glucose is oxidized electrochemically with remarkable sensitivity and selectivity. Better model of such glucose sensors is sought by summarizing and revisiting the previous reports on the electrochemistry of glucose itself and new electrode materials

  14. [Contribution of the kidney to glucose homeostasis].

    Science.gov (United States)

    Segura, Julián; Ruilope, Luis Miguel

    2013-09-01

    The kidney is involved in glucose homeostasis through three major mechanisms: renal gluconeogenesis, renal glucose consumption, and glucose reabsorption in the proximal tubule. Glucose reabsorption is one of the most important physiological functions of the kidney, allowing full recovery of filtered glucose, elimination of glucose from the urine, and prevention of calorie loss. Approximately 90% of the glucose is reabsorbed in the S1 segment of the proximal tubule, where glucose transporter-2 (GLUT2) and sodium-glucose transporter-2 (SGLT2) are located, while the remaining 10% is reabsorbed in the S3 segment by SGLT1 and GLUT1 transporters. In patients with hyperglycemia, the kidney continues to reabsorb glucose, thus maintaining hyperglycemia. Most of the renal glucose reabsorption is mediated by SGLT2. Several experimental and clinical studies suggest that pharmacological blockade of this transporter might be beneficial in the management of hyperglycemia in patients with type 2 diabetes. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  15. Glucose kinetics in infants of diabetic mothers

    International Nuclear Information System (INIS)

    Cowett, R.M.; Susa, J.B.; Giletti, B.; Oh, W.; Schwartz, R.

    1983-01-01

    Glucose kinetic studies were performed to define the glucose turnover rate with 78% enriched D-[U-13C] glucose by the prime constant infusion technique at less than or equal to 6 hours of age in nine infants of diabetic mothers (four insulin-dependent and five chemical diabetic patients) at term. Five normal infants were studied as control subjects. All infants received 0.9% saline intravenously during the study with the tracer. Fasting plasma glucose, insulin, and glucose13/12C ratios were measured during the steady state, and the glucose turnover rate was derived. The average plasma glucose concentration was similar during the steady state in the infants of the diabetic mothers and in the control infants, and the glucose turnover rate was not significantly different among the groups: 2.3 +/- 0.6 mg . kg-1 min-1 in infants of insulin-dependent diabetic patients; 2.4 +/- 0.4 mg . kg-1 min-1 in infants of chemical diabetic patients; and 3.2 +/- 0.3 mg . kg-1 min-1 in the control subjects. Good control of maternal diabetes evidenced by the normal maternal hemoglobin A1c and plasma glucose concentration at delivery and cord plasma glucose concentration resulted in glucose kinetic values in the infants of diabetic mothers that were indistinguishable from those of control subjects. The data further support the importance of good control of the diabetic state in the pregnant woman to minimize or prevent neonatal hypoglycemia

  16. Release of PYY from pig intestinal mucosa; luminal and neural regulation

    DEFF Research Database (Denmark)

    Sheikh, S P; Holst, J J; Orskov, C

    1989-01-01

    in release of PYY into the circulation. Stimulation of the splanchnic nerves did not affect the basal release of PYY. PYY-immunoreactivity extracted from ileal tissue or released to plasma or perfusate from the ileum was indistinguishable from synthetic porcine PYY by gel filtration and reverse phase HPLC...... of PYY was observed in isolated perfused pig ileum in response to luminal stimulation with glucose and vascular administration of the neuropeptide gastrin-releasing peptide (GRP). Electrical stimulation of the vagus nerve supply to the distal small intestine in intact anaesthetized pigs resulted...

  17. Development of new releasing agents for preparation of thin self-supporting target films

    Energy Technology Data Exchange (ETDEWEB)

    Sugai, I; Takaku, S; Hasegawa, T [Tokyo Univ., Tanashi (Japan). Inst. for Nuclear Study

    1978-06-01

    Several kinds of materials were examined for the usefulness as releasing agents in the preparation of various thin self-supporting target films for use in nuclear reaction experiments. NaCl, BaCl/sub 2/, KCl, CsI, Teepol, glucose, KIO/sub 3/, mica, nitrocellulose of Formvar was deposited onto glass plates as the release agent by vacuum evaporation or dipping method. The obtained target film was tested on impurities from the release agent by using nuclear reactions. The relative effectiveness of each release agent was also considered from ease in the stripping of target films.

  18. Development of new releasing agents for preparation of thin self-supporting target films

    International Nuclear Information System (INIS)

    Sugai, Isao; Takaku, Seisaku; Hasegawa, Takeo

    1978-01-01

    Several kinds of materials were examined for the usefulness as releasing agents in the preparation of various thin self-supporting target films for use in nuclear reaction experiments. NaCl, BaCl 2 , KCl, CsI, Teepol, glucose, KIO 3 , mica, nitrocellulose of Formvar was deposited onto glass plates as the release agent by vacuum evaporation or dipping method. The obtained target film was tested on impurities from the release agent by using nuclear reactions. The relative effectiveness of each release agent was also considered from ease in the stripping of target films. (auth.)

  19. Changes in blood glucose and salivary cortisol are not necessary for arousal to enhance memory in young or older adults.

    Science.gov (United States)

    Gore, Jane B; Krebs, Desiree L; Parent, Marise B

    2006-06-01

    Emotional arousal enhances memory, and this memory-enhancing effect may involve neurochemicals released by arousal, such as glucose and cortisol. Physiological consequences of arousal change with age, and these changes may contribute to age-related memory decline. The present study examined whether emotionally arousing pictures would affect glucose and cortisol levels and enhance memory in young and older adults. Blood glucose and salivary cortisol were measured once before and six times after young and old adults viewed either 60 highly arousing or 60 relatively neutral pictures. Recall for the stimuli was measured 75 min later. The results indicated that recall was impaired in older adults. Arousal as measured by self-report enhanced recall in both young and older adults. However, arousal did not affect glucose or cortisol levels in either group. These findings demonstrate that changes in blood glucose or salivary cortisol levels are not necessary for arousal to enhance memory.

  20. Subversion of Schwann Cell Glucose Metabolism by Mycobacterium leprae*

    Science.gov (United States)

    Medeiros, Rychelle Clayde Affonso; Girardi, Karina do Carmo de Vasconcelos; Cardoso, Fernanda Karlla Luz; Mietto, Bruno de Siqueira; Pinto, Thiago Gomes de Toledo; Gomez, Lilian Sales; Rodrigues, Luciana Silva; Gandini, Mariana; Amaral, Julio Jablonski; Antunes, Sérgio Luiz Gomes; Corte-Real, Suzana; Rosa, Patricia Sammarco; Pessolani, Maria Cristina Vidal; Nery, José Augusto da Costa; Sarno, Euzenir Nunes; Batista-Silva, Leonardo Ribeiro; Sola-Penna, Mauro; Oliveira, Marcus Fernandes; Moraes, Milton Ozório; Lara, Flavio Alves

    2016-01-01

    Mycobacterium leprae, the intracellular etiological agent of leprosy, infects Schwann promoting irreversible physical disabilities and deformities. These cells are responsible for myelination and maintenance of axonal energy metabolism through export of metabolites, such as lactate and pyruvate. In the present work, we observed that infected Schwann cells increase glucose uptake with a concomitant increase in glucose-6-phosphate dehydrogenase (G6PDH) activity, the key enzyme of the oxidative pentose pathway. We also observed a mitochondria shutdown in infected cells and mitochondrial swelling in pure neural leprosy nerves. The classic Warburg effect described in macrophages infected by Mycobacterium avium was not observed in our model, which presented a drastic reduction in lactate generation and release by infected Schwann cells. This effect was followed by a decrease in lactate dehydrogenase isoform M (LDH-M) activity and an increase in cellular protection against hydrogen peroxide insult in a pentose phosphate pathway and GSH-dependent manner. M. leprae infection success was also dependent of the glutathione antioxidant system and its main reducing power source, the pentose pathway, as demonstrated by a 50 and 70% drop in intracellular viability after treatment with the GSH synthesis inhibitor buthionine sulfoximine, and aminonicotinamide (6-ANAM), an inhibitor of G6PDH 6-ANAM, respectively. We concluded that M. leprae could modulate host cell glucose metabolism to increase the cellular reducing power generation, facilitating glutathione regeneration and consequently free-radical control. The impact of this regulation in leprosy neuropathy is discussed. PMID:27555322

  1. Hydraulic release oil tool

    International Nuclear Information System (INIS)

    Mims, M.G.; Mueller, M.D.; Ehlinger, J.C.

    1992-01-01

    This patent describes a hydraulic release tool. It comprises a setting assembly; a coupling member for coupling to drill string or petroleum production components, the coupling member being a plurality of sockets for receiving the dogs in the extended position and attaching the coupling member the setting assembly; whereby the setting assembly couples to the coupling member by engagement of the dogs in the sockets of releases from and disengages the coupling member in movement of the piston from its setting to its reposition in response to a pressure in the body in exceeding the predetermined pressure; and a relief port from outside the body into its bore and means to prevent communication between the relief port and the bore of the body axially of the piston when the piston is in the setting position and to establish such communication upon movement of the piston from the setting position to the release position and reduce the pressure in the body bore axially of the piston, whereby the reduction of the pressure signals that the tool has released the coupling member

  2. APASS Data Release 10

    Science.gov (United States)

    Henden, Arne A.; Levine, Stephen; Terrell, Dirk; Welch, Douglas L.; Munari, Ulisse; Kloppenborg, Brian K.

    2018-06-01

    The AAVSO Photometric All-Sky Survey (APASS) has been underway since 2010. This survey covers the entire sky from 7.5 knowledge of the optical train distortions. With these changes, DR10 includes many more stars than prior releases. We describe the survey, its remaining limitations, and prospects for the future, including a very-bright-star extension.

  3. Release the Prisoners Game

    Science.gov (United States)

    Van Hecke, Tanja

    2011-01-01

    This article presents the mathematical approach of the optimal strategy to win the "Release the prisoners" game and the integration of this analysis in a math class. Outline lesson plans at three different levels are given, where simulations are suggested as well as theoretical findings about the probability distribution function and its mean…

  4. Development of a glucose-sensitive drug delivery device: Microencapsulated liposomes and poly(2-ethylacrylic acid)

    Science.gov (United States)

    Kanokpanont, Sorada

    The current study is the development a self-regulated, glucose responsive drug delivery system, using dioleoylphosphatidylcholine (DOPC) liposomes, a pH sensitive polymer, poly (2-ethylacrylic acid)(PEAA), and the feed back reaction of glucose with glucose oxidase enzyme (GO). The thesis investigates the use of PEAR and liposomes to work inside a microcapsule in response to the glucose level of the environment, by following the release of fluorescence probes, 8-aminonapthalene-1,3,6-trisulfonic acid, disodium salt/p-xylene-bis-pyridimuim bromide (ANTS/DPX) and a model protein, myoglobin. The continuing studies of PEAR and liposome interaction indicated an evidence of the previous hypothesis of two-mode release at different pHs. Differential scanning calorimetric studies of DOPC and PEAA complexes revealed the possibility of polymer adsorption to the liposomes in the pH range 5.5--7.0 and insertion in the liposome bilayer at pH pH, PEAR concentration, presence of cholesterol in the liposomes, Ca 2+, and the concentration of sodium alginate. We have also shown possibilities of anchoring PEAR on to liposome by covalent conjugation although this led to inactivation of the polymer. It is also possible to entrap small molecular weight PEAA in liposomes. The evidence of the pH-induced protein release by the interaction of PEAA and liposomes was first demonstrated in this thesis. Kinetic parameters of GO were estimated to use as a basis for determination optimal concentration in the capsules. The pH reduction inside the capsule due to GO reaction showed positive results for the use of GO in a non-buffered system. The procedure of liquid-core alginate capsules was modified to facilitate the pH-responsive release of ANTS/DPX and myoglobin. The capsules responded to high blood glucose concentration by releasing myoglobin within 30 minutes. Although more studies are required to improve the response of the system to the normal blood glucose and to control the total protein

  5. Sustained nonoxidative glucose utilization and depletion of glycogen in reperfused canine myocardium

    International Nuclear Information System (INIS)

    Schwaiger, M.; Neese, R.A.; Araujo, L.

    1989-01-01

    Ischemically injured reperfused myocardium is characterized by increased 18F-fluorodeoxyglucose uptake as demonstrated by positron emission tomography. To elucidate the metabolic fate of exogenous glucose entering reperfused myocardium, D-[6-14C] glucose and L-[U-13C] lactate were used to determine glucose uptake, glucose oxidation and the contribution of exogenous glucose to lactate production. The pathologic model under investigation consisted of a 3 h balloon occlusion of the left anterior descending coronary artery followed by 24 h of reperfusion in canine myocardium. The extent and severity of myocardial injury after the ischemia and reperfusion were assessed by histochemical evaluation (triphenyltetrazolium chloride and periodic acid-Schiff stains). Thirteen intervention and four control dogs were studied. The glucose uptake in the occluded/reperfused area was significantly enhanced compared with that in control dogs (0.40 +/- 0.14 versus 0.15 +/- 0.10 mumol/ml, respectively). In addition, a significantly greater portion of the glucose extracted immediately entered glycolysis in the intervention group (75%) than in the control dogs (33%). The activity of the nonoxidative glycolytic pathway was markedly increased in the ischemically injured reperfused area, as evidenced by the four times greater lactate release in this area compared with the control value. The dual carbon-labeled isotopes showed that 57% of the exogenous glucose entering glycolysis was being converted to lactate. Exogenous glucose contributed to greater than 90% of the observed lactate production. This finding was confirmed by the histochemical finding of sustained glycogen depletion in the occlusion/reperfusion area. The average area of glycogen depletion (37%) significantly exceeded the average area of necrosis

  6. Glucose sensing by GABAergic neurons in the mouse nucleus tractus solitarii

    Science.gov (United States)

    Boychuk, Carie R.; Gyarmati, Peter; Xu, Hong

    2015-01-01

    Changes in blood glucose concentration alter autonomic function in a manner consistent with altered neural activity in brain regions controlling digestive processes, including neurons in the brain stem nucleus tractus solitarii (NTS), which process viscerosensory information. With whole cell or on-cell patch-clamp recordings, responses to elevating glucose concentration from 2.5 to 15 mM were assessed in identified GABAergic NTS neurons in slices from transgenic mice that express EGFP in a subset of GABA neurons. Single-cell real-time RT-PCR was also performed to detect glutamic acid decarboxylase (GAD67) in recorded neurons. In most identified GABA neurons (73%), elevating glucose concentration from 2.5 to 15 mM resulted in either increased (40%) or decreased (33%) neuronal excitability, reflected by altered membrane potential and/or action potential firing. Effects on membrane potential were maintained when action potentials or fast synaptic inputs were blocked, suggesting direct glucose sensing by GABA neurons. Glucose-inhibited GABA neurons were found predominantly in the lateral NTS, whereas glucose-excited cells were mainly in the medial NTS, suggesting regional segregation of responses. Responses were prevented in the presence of glucosamine, a glucokinase (GCK) inhibitor. Depolarizing responses were prevented when KATP channel activity was blocked with tolbutamide. Whereas effects on synaptic input to identified GABAergic neurons were variable in GABA neurons, elevating glucose increased glutamate release subsequent to stimulation of tractus solitarius in unlabeled, unidentified neurons. These results indicate that GABAergic NTS neurons act as GCK-dependent glucose sensors in the vagal complex, providing a means of modulating central autonomic signals when glucose is elevated. PMID:26084907

  7. Modulation of the effect of acetylcholine on insulin release by the membrane potential of B cells

    International Nuclear Information System (INIS)

    Hermans, M.P.; Schmeer, W.; Henquin, J.C.

    1987-01-01

    Mouse islets were used to test the hypothesis that the B cell membrane must be depolarized for acetylcholine to increase insulin release. The resting membrane potential of B cells (at 3 mM glucose) was slightly decreased (5 mV) by acetylcholine, but no electrical activity appeared. This depolarization was accompanied by a Ca-independent acceleration of 86 Rb and 45 Ca efflux but no insulin release. When the B cell membrane was depolarized by a stimulatory concentration of glucose (10 mM), acetylcholine potentiated electrical activity, accelerated 86 Rb and 45 Ca efflux, and increased insulin release. This latter effect, but not the acceleration of 45 Ca efflux, was totally dependent on extracellular Ca. If glucose-induced depolarization of the B cell membrane was prevented by diazoxide, acetylcholine lost all effects but those produced at low glucose. In contrast, when the B cell membrane was depolarized by leucine or tolbutamide (at 3 mM glucose), acetylcholine triggered a further depolarization with appearance of electrical activity, accelerated 86 Rb and 45 Ca efflux, and stimulated insulin release. Acetylcholine produced similar effects (except for electrical activity) in the presence of high K or arginine which, unlike the above test agents, depolarize the B cell membrane by a mechanism other than a decrease in K+ permeability. Omission of extracellular Ca abolished the releasing effect of acetylcholine under all conditions but only partially decreased the stimulation of 45 Ca efflux. The results show thus that acetylcholine stimulation of insulin release does not result from mobilization of cellular Ca but requires that the B cell membrane be sufficiently depolarized to reach the threshold potential where Ca channels are activated. This may explain why acetylcholine alone does not initiate release but becomes active in the presence of a variety of agents

  8. A metabolic switch in brain: glucose and lactate metabolism modulation by ascorbic acid.

    Science.gov (United States)

    Castro, Maite A; Beltrán, Felipe A; Brauchi, Sebastián; Concha, Ilona I

    2009-07-01

    In this review, we discuss a novel function of ascorbic acid in brain energetics. It has been proposed that during glutamatergic synaptic activity neurons preferably consume lactate released from glia. The key to this energetic coupling is the metabolic activation that occurs in astrocytes by glutamate and an increase in extracellular [K(+)]. Neurons are cells well equipped to consume glucose because they express glucose transporters and glycolytic and tricarboxylic acid cycle enzymes. Moreover, neuronal cells express monocarboxylate transporters and lactate dehydrogenase isoenzyme 1, which is inhibited by pyruvate. As glycolysis produces an increase in pyruvate concentration and a decrease in NAD(+)/NADH, lactate and glucose consumption are not viable at the same time. In this context, we discuss ascorbic acid participation as a metabolic switch modulating neuronal metabolism between rest and activation periods. Ascorbic acid is highly concentrated in CNS. Glutamate stimulates ascorbic acid release from astrocytes. Ascorbic acid entry into neurons and within the cell can inhibit glucose consumption and stimulate lactate transport. For this switch to occur, an ascorbic acid flow is necessary between astrocytes and neurons, which is driven by neural activity and is part of vitamin C recycling. Here, we review the role of glucose and lactate as metabolic substrates and the modulation of neuronal metabolism by ascorbic acid.

  9. Ratiometric glucose sensing based on fluorescent oxygen films and glucose oxidase

    Directory of Open Access Journals (Sweden)

    Fengyu Su

    2017-06-01

    Full Text Available A new two-layer sensor film was constructed for sensing glucose based on glucose oxidase and oxygen sensing material. The first layer of film containing the oxygen sensor and intra-reference material was polymerized, then the second layer of glucose oxidase and glutaraldehyde was formed on the oxygen sensor layer. The two-layer sensor film has a resolution up to 0.05 mM and a detection range from 0 to 5 mM to glucose. The effects of pH and temperature on the sensing performance were systematically investigated. The selective detection of glucose among other monosaccharides, such as fructose, mannose and galactose indicated that the sensing film has excellent selectivity. The prepared sensor was successfully applied for glucose sample detection of glucose concentration in artificial tears. Keywords: Glucose sensor, Glucose oxidase, Fluorescence, Oxygen film, Diabetes

  10. Heterogeneity in glucose response curves during an oral glucose tolerance test and associated cardiometabolic risk

    DEFF Research Database (Denmark)

    Hulman, Adam; Simmons, Rebecca Kate; Vistisen, Dorte

    2017-01-01

    patterns of plasma glucose change during the oral glucose tolerance test. Cardiometabolic risk factor profiles were compared between the identified groups. Using latent class trajectory analysis, five glucose response curves were identified. Despite similar fasting and 2-h values, glucose peaks and peak......We aimed to examine heterogeneity in glucose response curves during an oral glucose tolerance test with multiple measurements and to compare cardiometabolic risk profiles between identified glucose response curve groups. We analyzed data from 1,267 individuals without diabetes from five studies...... in Denmark, the Netherlands and the USA. Each study included between 5 and 11 measurements at different time points during a 2-h oral glucose tolerance test, resulting in 9,602 plasma glucose measurements. Latent class trajectories with a cubic specification for time were fitted to identify different...

  11. Continuous Glucose Monitoring in Patients with Abnormal Glucose Tolerance during Pregnancy: A Case Series

    Directory of Open Access Journals (Sweden)

    Mie Tonoike

    2016-01-01

    Full Text Available Abnormal glucose tolerance during pregnancy is associated with perinatal complications. We used continuous glucose monitoring (CGM in pregnant women with glucose intolerance to achieve better glycemic control and to evaluate the maternal glucose fluctuations. We also used CGM in women without glucose intolerance (the control cases. Furthermore, the standard deviation (SD and mean amplitude of glycemic excursions (MAGE were calculated for each case. For the control cases, the glucose levels were tightly controlled within a very narrow range; however, the SD and MAGE values in pregnant women with glucose intolerance were relativity high, suggesting postprandial hyperglycemia. Our results demonstrate that pregnant women with glucose intolerance exhibited greater glucose fluctuations compared with the control cases. The use of CGM may help to improve our understanding of glycemic patterns and may have beneficial effects on perinatal glycemic control, such as the detection of postprandial hyperglycemia in pregnant women.

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

    Science.gov (United States)

    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.

  13. Interfacial electron transfer of glucose oxidase on poly(glutamic acid)-modified glassy carbon electrode and glucose sensing.

    Science.gov (United States)

    Zhou, Xuechou; Tan, Bingcan; Zheng, Xinyu; Kong, Dexian; Li, Qinglu

    2015-11-15

    The interfacial electron transfer of glucose oxidase (GOx) on a poly(glutamic acid)-modified glassy carbon electrode (PGA/GCE) was investigated. The redox peaks measured for GOx and flavin adenine dinucleotide (FAD) are similar, and the anodic peak of GOx does not increase in the presence of glucose in a mediator-free solution. These indicate that the electroactivity of GOx is not the direct electron transfer (DET) between GOx and PGA/GCE and that the observed electroactivity of GOx is ascribed to free FAD that is released from GOx. However, efficient electron transfer occurred if an appropriate mediator was placed in solution, suggesting that GOx is active. The PGA/GCE-based biosensor showed wide linear response in the range of 0.5-5.5 mM with a low detection limit of 0.12 mM and high sensitivity and selectivity for measuring glucose. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Glucose, relational memory, and the hippocampus.

    Science.gov (United States)

    Stollery, Brian; Christian, Leonie

    2015-06-01

    Many studies suggest that glucose can temporarily enhance hippocampal-dependent memories. As the hippocampus plays a key role in associative learning, we examined the influence of glucose on verbal paired associate memory. This study examines how glucose modifies performance on a relational memory task by examining its influence on learning, subsequent forgetting and relearning. A selective reminding procedure was used to show high and low imagability paired associates to 80 participants, who were seen twice. On the first session, they received 25 g glucose pre-learning, 25 g glucose post-learning or placebo. On the second session, 1 week later, they received 25 g glucose or placebo. Cued-recall was evaluated after each learning trial, 1 week later to assess forgetting and after an opportunity to relearn the material forgotten. Glucose did not influence paired associate acquisition. Those given glucose pre-learning tended to forget less material the following week, and independently, glucose at retrieval facilitated cued-recall. Both forms of facilitation were equally apparent on low and high imagability pairs. The benefit of glucose pre-learning was eliminated once the paired associates had been seen again, but the benefit of glucose at retrieval extended into the second relearning trial. The discussion considers the cognitive processes and hippocampal basis for paired associate learning and retention and the implications for glucose's mode of action. It is proposed that glucose during encoding serves to make the delayed memories initially more available, whereas its influence during delayed retrieval makes available memories temporarily more accessible.

  15. Coping with an exogenous glucose overload: glucose kinetics of rainbow trout during graded swimming.

    Science.gov (United States)

    Choi, Kevin; Weber, Jean-Michel

    2016-03-15

    This study examines how chronically hyperglycemic rainbow trout modulate glucose kinetics in response to graded exercise up to critical swimming speed (Ucrit), with or without exogenous glucose supply. Our goals were 1) to quantify the rates of hepatic glucose production (Ra glucose) and disposal (Rd glucose) during graded swimming, 2) to determine how exogenous glucose affects the changes in glucose fluxes caused by exercise, and 3) to establish whether exogenous glucose modifies Ucrit or the cost of transport. Results show that graded swimming causes no change in Ra and Rd glucose at speeds below 2.5 body lengths per second (BL/s), but that glucose fluxes may be stimulated at the highest speeds. Excellent glucoregulation is also achieved at all exercise intensities. When exogenous glucose is supplied during exercise, trout suppress hepatic production from 16.4 ± 1.6 to 4.1 ± 1.7 μmol·kg(-1)·min(-1) and boost glucose disposal to 40.1 ± 13 μmol·kg(-1)·min(-1). These responses limit the effects of exogenous glucose to a 2.5-fold increase in glycemia, whereas fish showing no modulation of fluxes would reach dangerous levels of 114 mM of blood glucose. Exogenous glucose reduces metabolic rate by 16% and, therefore, causes total cost of transport to decrease accordingly. High glucose availability does not improve Ucrit because the fish are unable to take advantage of this extra fuel during maximal exercise and rely on tissue glycogen instead. In conclusion, trout have a remarkable ability to adjust glucose fluxes that allows them to cope with the cumulative stresses of a glucose overload and graded exercise. Copyright © 2016 the American Physiological Society.

  16. Blood glucose level reconstruction as a function of transcapillary glucose transport.

    Science.gov (United States)

    Koutny, Tomas

    2014-10-01

    A diabetic patient occasionally undergoes a detailed monitoring of their glucose levels. Over the course of a few days, a monitoring system provides a detailed track of their interstitial fluid glucose levels measured in their subcutaneous tissue. A discrepancy in the blood and interstitial fluid glucose levels is unimportant because the blood glucose levels are not measured continuously. Approximately five blood glucose level samples are taken per day, and the interstitial fluid glucose level is usually measured every 5min. An increased frequency of blood glucose level sampling would cause discomfort for the patient; thus, there is a need for methods to estimate blood glucose levels from the glucose levels measured in subcutaneous tissue. The Steil-Rebrin model is widely used to describe the relationship between blood and interstitial fluid glucose dynamics. However, we measured glucose level patterns for which the Steil-Rebrin model does not hold. Therefore, we based our research on a different model that relates present blood and interstitial fluid glucose levels to future interstitial fluid glucose levels. Using this model, we derived an improved model for calculating blood glucose levels. In the experiments conducted, this model outperformed the Steil-Rebrin model while introducing no additional requirements for glucose sample collection. In subcutaneous tissue, 26.71% of the calculated blood glucose levels had absolute values of relative differences from smoothed measured blood glucose levels less than or equal to 5% using the Steil-Rebrin model. However, the same difference interval was encountered in 63.01% of the calculated blood glucose levels using the proposed model. In addition, 79.45% of the levels calculated with the Steil-Rebrin model compared with 95.21% of the levels calculated with the proposed model had 20% difference intervals. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Multipathway modulation of exercise and glucose stress effects upon GH secretion in healthy men.

    Science.gov (United States)

    Veldhuis, Johannes D; Olson, Thomas P; Takahashi, Paul Y; Miles, John M; Joyner, Michael J; Yang, Rebecca J; Wigham, Jean

    2015-09-01

    Exercise evokes pulsatile GH release followed by autonegative feedback, whereas glucose suppresses GH release followed by rebound-like GH release (feedforward escape). Here we test the hypothesis that age, sex steroids, insulin, body composition and physical power jointly determine these dynamic GH responses. This was a prospectively randomized glucose-blinded study conducted in the Mayo Center for Advancing Translational Sciences in healthy men ages 19-77 years (N=23). Three conditions, fasting/rest/saline, fasting/exercise/saline and fasting/rest/iv glucose infusions, were used to drive GH dynamics during 10-min blood sampling for 6h. Linear correlation analysis was applied to relate peak/nadir GH dynamics to age, sex steroids, insulin, CT-estimated abdominal fat and physical power (work per unit time). Compared with the fasting/rest/saline (control) day, fasting/exercise/saline infusion evoked peak GH within 1h, followed by negative feedback 3-5h later. The dynamic GH excursion was strongly (R(2)=0.634) influenced by (i) insulin negatively (P=0.011), (ii) power positively (P=0.0008), and (iii) E2 positively (P=0.001). Dynamic glucose-modulated GH release was determined by insulin negatively (P=0.0039) and power positively (P=0.0034) (R(2)=0.454). Under rest/saline, power (P=0.031) and total abdominal fat (P=0.012) (R(2)=0.267) were the dominant correlates of GH excursions. In healthy men, dynamic GH perturbations induced by exercise and glucose are strongly related to physical power, insulin, estradiol, and body composition, thus suggesting a network of regulatory pathways. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Use of digitonin permeabilization for characterization of calcium incorporated into. beta. cells in response to glucose

    Energy Technology Data Exchange (ETDEWEB)

    Wesslen, N [Uppsala Univ. (Sweden)

    1985-01-01

    ..beta.. cell-rich pancreatic islets were used to characterize /sup 45/Ca uptake into pools with different sensitivities to permeabilization with digitonin. The plasma and secretory granule membranes were among the membranes most sensitive to digitonin treatment whereas the mitochondria were more resistant. Most of the /sup 45/Ca incorporated in response to glucose was found in a fraction released after exposure to a high concentration of digitonin. The results suggest that glucose promotes active sequestration of calcium in mitochondria and that the uptake of /sup 45/Ca in the secretory granules in secondary to a raised cytosolic Ca/sup 2 +/ activity.

  19. Decrease of glucose-induced insulin secretion of rat pancreatic islets after irradiation in vitro

    Energy Technology Data Exchange (ETDEWEB)

    Heinzmann, D; Nadrowitz, R; Besch, W; Schmidt, W; Hahn, H J [Zentralinstitut fuer Diabetes, Karlsburg (German Democratic Republic); Ernst-Moritz-Arndt-Universitaet, Greifswald (German Democratic Republic). Radiologische Klinik)

    1983-01-01

    In vitro irradiation of rat pancreatic islets up to a dose of 2.5 Gy did neither alter glucose- nor isobutylmethyl xanthine (IBMX)-induced insulin secretion. Insulin as well as glucagon content of irradiated islets corresponded to that of the control tissue. So it was in islets irradiated with 25 Gy which were characterized by a decreased insulin secretion in the presence of glucose and IBMX, respectively. There was no indication of an enhanced hormone output in the radiation medium and it is to be suggested that higher radiation doses affect the insulin release of pancreatic islets in vitro. This must be taken into consideration for radioimmunosuppression experiments.

  20. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

    DEFF Research Database (Denmark)

    Saxena, Richa; Hivert, Marie-France; Langenberg, Claudia

    2010-01-01

    Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6,958-30,620)......Glucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n = 6...

  1. Decontamination for free release

    Energy Technology Data Exchange (ETDEWEB)

    Simpson, K A; Elder, G R [Bradtec Ltd., Bristol (United Kingdom)

    1997-02-01

    Many countries are seeking to treat radioactive waste in ways which meet the local regulatory requirements, but yet are cost effective when all contributing factors are assessed. In some countries there are increasing amounts of waste, arising from nuclear plant decommissioning, which are categorized as low level waste: however with suitable treatment a large part of such wastes might become beyond regulatory control and be able to be released as non-radioactive. The benefits and disadvantages of additional treatment before disposal need to be considered. Several processes falling within the overall description of decontamination for free release have been developed and applied, and these are outlined. In one instance the process seeks to take advantage of techniques and equipment used for decontaminating water reactor circuits intermittently through reactor life. (author). 9 refs, 1 fig., 3 tabs.

  2. Atmospheric Release Advisory Capability

    International Nuclear Information System (INIS)

    Dickerson, M.H.; Gudiksen, P.H.; Sullivan, T.J.

    1983-02-01

    The Atmospheric Release Advisory Capability (ARAC) project is a Department of Energy (DOE) sponsored real-time emergency response service available for use by both federal and state agencies in case of a potential or actual atmospheric release of nuclear material. The project, initiated in 1972, is currently evolving from the research and development phase to full operation. Plans are underway to expand the existing capability to continuous operation by 1984 and to establish a National ARAC Center (NARAC) by 1988. This report describes the ARAC system, its utilization during the past two years, and plans for its expansion during the next five to six years. An integral part of this expansion is due to a very important and crucial effort sponsored by the Defense Nuclear Agency to extend the ARAC service to approximately 45 Department of Defense (DOD) sites throughout the continental US over the next three years

  3. Border cell release

    DEFF Research Database (Denmark)

    Mravec, Jozef

    2017-01-01

    Plant border cells are specialised cells derived from the root cap with roles in the biomechanics of root growth and in forming a barrier against pathogens. The mechanism of highly localised cell separation which is essential for their release to the environment is little understood. Here I present...... in situ analysis of Brachypodium distachyon, a model organism for grasses which possess type II primary cell walls poor in pectin content. Results suggest similarity in spatial dynamics of pectic homogalacturonan during dicot and monocot border cell release. Integration of observations from different...... species leads to the hypothesis that this process most likely does not involve degradation of cell wall material but rather employs unique cell wall structural and compositional means enabling both the rigidity of the root cap as well as detachability of given cells on its surface....

  4. Energy released in fission

    International Nuclear Information System (INIS)

    James, M.F.

    1969-05-01

    The effective energy released in and following the fission of U-235, Pu-239 and Pu-241 by thermal neutrons, and of U-238 by fission spectrum neutrons, is discussed. The recommended values are: U-235 ... 192.9 ± 0.5 MeV/fission; U-238 ... 193.9 ± 0.8 MeV/fission; Pu-239 ... 198.5 ± 0.8 MeV/fission; Pu-241 ... 200.3 ± 0.8 MeV/fission. These values include all contributions except from antineutrinos and very long-lived fission products. The detailed contributions are discussed, and inconsistencies in the experimental data are pointed out. In Appendix A, the contribution to the total useful energy release in a reactor from reactions other than fission are discussed briefly, and in Appendix B there is a discussion of the variations in effective energy from fission with incident neutron energy. (author)

  5. Metformin Ameliorates Dysfunctional Traits of Glibenclamide- and Glucose-Induced Insulin Secretion by Suppression of Imposed Overactivity of the Islet Nitric Oxide Synthase-NO System.

    Directory of Open Access Journals (Sweden)

    Ingmar Lundquist

    Full Text Available Metformin lowers diabetic blood glucose primarily by reducing hepatic gluconeogenesis and increasing peripheral glucose uptake. However, possible effects by metformin on beta-cell function are incompletely understood. We speculated that metformin might positively influence insulin secretion through impacting the beta-cell nitric oxide synthase (NOS-NO system, a negative modulator of glucose-stimulated insulin release. In short-time incubations with isolated murine islets either glibenclamide or high glucose augmented insulin release associated with increased NO production from both neural and inducible NOS. Metformin addition suppressed the augmented NO generation coinciding with amplified insulin release. Islet culturing with glibenclamide or high glucose revealed pronounced fluorescence of inducible NOS in the beta-cells being abolished by metformin co-culturing. These findings were reflected in medium nitrite-nitrate levels. A glucose challenge following islet culturing with glibenclamide or high glucose revealed markedly impaired insulin response. Metformin co-culturing restored this response. Culturing murine islets and human islets from controls and type 2 diabetics with high glucose or high glucose + glibenclamide induced a pronounced decrease of cell viability being remarkably restored by metformin co-culturing. We show here, that imposed overactivity of the beta-cell NOS-NO system by glibenclamide or high glucose leads to insulin secretory dysfunction and reduced cell viability and also, importantly, that these effects are relieved by metformin inhibiting beta-cell NO overproduction from both neural and inducible NOS thus ameliorating a concealed negative influence by NO induced by sulfonylurea treatment and/or high glucose levels. This double-edged effect of glibenclamide on the beta-cellsuggests sulfonylurea monotherapy in type 2 diabetes being avoided.

  6. Slow-release fertilizer

    Science.gov (United States)

    Ming, Douglas W.; Golden, D. C.

    1992-10-01

    A synthetic apatite containing agronutrients and a method for making the apatite are disclosed. The apatite comprises crystalline calcium phosphate having agronutrients dispersed in the crystalline structure. The agronutrients can comprise potassium, magnesium, sulfur, iron, manganese, molybdenum, chlorine, boron, copper and zinc in amounts suited for plant growth. The apatite can optionally comprise a carbonate and/or silicon solubility control agent. The agronutrients are released slowly as the apatite dissolves.

  7. EIA new releases

    International Nuclear Information System (INIS)

    1994-12-01

    This report was prepared by the Energy Information Administration. It contains news releases on items of interest to the petroleum, coal, nuclear, electric and alternate fuels industries ranging from economic outlooks to environmental concerns. There is also a listing of reports by industry and an energy education resource listing containing sources for free or low-cost energy-related educational materials for educators and primary and secondary students

  8. Atmospheric release advisory capability

    International Nuclear Information System (INIS)

    Sullivan, T.J.

    1981-01-01

    The ARAC system (Atmospheric Release Advisory Capability) is described. The system is a collection of people, computers, computer models, topographic data and meteorological input data that together permits a calculation of, in a quasi-predictive sense, where effluent from an accident will migrate through the atmosphere, where it will be deposited on the ground, and what instantaneous and integrated dose an exposed individual would receive

  9. Slow-release fertilizer

    Science.gov (United States)

    Ming, Douglas W. (Inventor); Golden, Dadigamuwage C. (Inventor)

    1995-01-01

    A synthetic apatite containing agronutrients and a method for making the apatite are disclosed. The apatite comprises crystalline calcium phosphate having agronutrients dispersed in the crystalline structure. The agronutrients can comprise potassium, magnesium, sulfur, iron, manganese, molybdenum, chlorine, boron, copper and zinc in amounts suited for plant growth. The apatite can optionally comprise a carbonate and/or silicon solubility control agent. The agronutrients are released slowly as the apatite dissolves.

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

    Science.gov (United States)

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

    1986-01-01

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

  11. BMI modulates calorie-dependent dopamine changes in accumbens from glucose intake.

    Directory of Open Access Journals (Sweden)

    Gene-Jack Wang

    Full Text Available Dopamine mediates the rewarding effects of food that can lead to overeating and obesity, which then trigger metabolic neuroadaptations that further perpetuate excessive food consumption. We tested the hypothesis that the dopamine response to calorie intake (independent of palatability in striatal brain regions is attenuated with increases in weight.We used positron emission tomography with [11C]raclopride to measure dopamine changes triggered by calorie intake by contrasting the effects of an artificial sweetener (sucralose devoid of calories to that of glucose to assess their association with body mass index (BMI in nineteen healthy participants (BMI range 21-35.Neither the measured blood glucose concentrations prior to the sucralose and the glucose challenge days, nor the glucose concentrations following the glucose challenge vary as a function of BMI. In contrast the dopamine changes in ventral striatum (assessed as changes in non-displaceable binding potential of [11C]raclopride triggered by calorie intake (contrast glucose - sucralose were significantly correlated with BMI (r = 0.68 indicating opposite responses in lean than in obese individuals. Specifically whereas in normal weight individuals (BMI <25 consumption of calories was associated with increases in dopamine in the ventral striatum in obese individuals it was associated with decreases in dopamine.These findings show reduced dopamine release in ventral striatum with calorie consumption in obese subjects, which might contribute to their excessive food intake to compensate for the deficit between the expected and the actual response to food consumption.

  12. Optimization of a Liquid Crystal-based Sensory Platform for Monitoring Enzymatic Glucose Oxidation

    Energy Technology Data Exchange (ETDEWEB)

    Wei, Yibin; Jang, Chang-Hyun [Gachon University, Seongnam (Korea, Republic of)

    2016-05-15

    Managing glucose levels in human blood is extremely important for the treatment of diabetes. Here, an innovative sensory strategy has been developed to monitor the enzymatic activities of glucose and glucose oxidase by using confined liquid crystal (LC) birefringent droplet patterns. Acidic products released during the glucose oxidation process lead to a slight decrease in the pH of aqueous systems that can be monitored by pH-sensitive LC materials. Of the existing pH-sensitive LC materials, dodecanoic acid-doped 4-cyano-4'-pentylbiphenyl is inexpensive and easily adjusted to satisfy the 7.4 ± 0.05 pH requirement of human blood. Moreover, the orientational alignment of capillary-confined pH-responsive LCs can be disrupted at the aqueous/LC interface following a slight decrease in the critical pH of aqueous reaction systems, which results in an optical signal that can be observed with the naked eye by using polarizing optical microscopy. Based on the stable LC droplet patterns generated by the cylindrical confinement system, the functionalized LCs can selectively detect glucose at concentrations as low as 0.1 pM. This study further advances the previously reported LC-based glucose monitoring systems by reducing production costs and instituting a smarter LC sensory design. This improved system shows potential for the use in clinical bioassay applications.

  13. Increased muscle glucose uptake during contractions

    DEFF Research Database (Denmark)

    Ploug, Thorkil; Galbo, Henrik; Richter, Erik

    1984-01-01

    We reinvestigated the prevailing concept that muscle contractions only elicit increased muscle glucose uptake in the presence of a so-called "permissive" concentration of insulin (Berger et al., Biochem. J. 146: 231-238, 1975; Vranic and Berger, Diabetes 28: 147-163, 1979). Hindquarters from rats...... in severe ketoacidosis were perfused with a perfusate containing insulin antiserum. After 60 min perfusion, electrical stimulation increased glucose uptake of the contracting muscles fivefold. Also, subsequent contractions increased glucose uptake in hindquarters from nondiabetic rats perfused for 1.5 h......-methylglucose uptake increased during contractions and glucose uptake was negative at rest and zero during contractions. An increase in muscle transport and uptake of glucose during contractions does not require the presence of insulin. Furthermore, glucose transport in contracting muscle may only increase if glycogen...

  14. Glucose production during exercise in humans

    DEFF Research Database (Denmark)

    Bergeron, R; Kjaer, M; Simonsen, L

    1999-01-01

    at 50.4 +/- 1.5(SE)% maximal O(2) consumption, followed by 30 min at 69.0 +/- 2.2% maximal O(2) consumption. The splanchnic blood flow was estimated by continuous infusion of indocyanine green, and net splanchnic glucose output was calculated as the product of splanchnic blood flow and a-hv blood...... glucose concentration differences. Glucose appearance rate was determined by a primed, continuous infusion of [3-(3)H]glucose and was calculated by using formulas for a modified single compartment in non-steady state. Glucose production was similar whether determined by the a-hv balance technique......The present study compared the arteriohepatic venous (a-hv) balance technique and the tracer-dilution method for estimation of hepatic glucose production during both moderate and heavy exercise in humans. Eight healthy young men (aged 25 yr; range, 23-30 yr) performed semisupine cycling for 40 min...

  15. Contact: Releasing the news

    Science.gov (United States)

    Pinotti, Roberto

    The problem of mass behavior after man's future contacts with other intelligences in the universe is not only a challenge for social scientists and political leaders all over the world, but also a cultural time bomb as well. In fact, since the impact of CETI (Contact with Extraterrestrial Intelligence) on human civilization, with its different cultures, might cause a serious socio-anthropological shock, a common and predetermined worldwide strategy is necessary in releasing the news after the contact, in order to keep possible manifestations of fear, panic and hysteria under control. An analysis of past studies in this field and of parallel historical situations as analogs suggests a definite "authority crisis" in the public as a direct consequence of an unexpected release of the news, involving a devastating "chain reaction" process (from both the psychological and sociological viewpoints) of anomie and maybe the collapse of today's society. The only way to prevent all this is to prepare the world's public opinion concerning contact before releasing the news, and to develop a long-term strategy through the combined efforts of scientists, political leaders, intelligence agencies and the mass media, in order to create the cultural conditions in which a confrontation with ETI won't affect mankind in a traumatic way. Definite roles and tasks in this multi-level model are suggested.

  16. Postprandial glucose response to selected tropical fruits in normal glucose-tolerant Nigerians.

    Science.gov (United States)

    Edo, A; Eregie, A; Adediran, O; Ohwovoriole, A; Ebengho, S

    2011-01-01

    The glycemic response to commonly eaten fruits in Nigeria has not been reported. Therefore, this study assessed the plasma glucose response to selected fruits in Nigeria. Ten normal glucose-tolerant subjects randomly consumed 50 g carbohydrate portions of three fruits: banana (Musa paradisiaca), pineapple (Ananus comosus), and pawpaw (Carica papaya), and a 50-g glucose load at 1-week intervals. Blood samples were collected in the fasting state and half-hourly over a 2-h period post-ingestion of the fruits or glucose. The samples were analyzed for plasma glucose concentrations. Plasma glucose responses were assessed by the peak plasma glucose concentration, maximum increase in plasma glucose, 2-h postprandial plasma glucose level, and incremental area under the glucose curve and glycemic index (GI). The results showed that the blood glucose response to these three fruits was similar in terms of their incremental areas under the glucose curve, maximum increase in plasma glucose, and glycemic indices (GIs). The 2-h postprandial plasma glucose level of banana was significantly higher than that of pineapple, P < 0.025. The mean ± SEM GI values were as follows: pawpaw; 86 ± 26.8%; banana, 75.1 ± 21.8%; pineapple, 64.5 ± 11.3%. The GI of glucose is taken as 100. The GI of pineapple was significantly lower than that of glucose (P < 0.05). Banana, pawpaw, and pineapple produced a similar postprandial glucose response. Measured portions of these fruits may be used as fruit exchanges with pineapple having the most favorable glycemic response.

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

    Science.gov (United States)

    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.

  18. Elucidation of the glucose transport pathway in glucose transporter 4 via steered molecular dynamics simulations.

    Directory of Open Access Journals (Sweden)

    Aswathy Sheena

    Full Text Available BACKGROUND: GLUT4 is a predominant insulin regulated glucose transporter expressed in major glucose disposal tissues such as adipocytes and muscles. Under the unstimulated state, GLUT4 resides within intracellular vesicles. Various stimuli such as insulin translocate this protein to the plasma membrane for glucose transport. In the absence of a crystal structure for GLUT4, very little is known about the mechanism of glucose transport by this protein. Earlier we proposed a homology model for GLUT4 and performed a conventional molecular dynamics study revealing the conformational rearrangements during glucose and ATP binding. However, this study could not explain the transport of glucose through the permeation tunnel. METHODOLOGY/PRINCIPAL FINDINGS: To elucidate the molecular mechanism of glucose transport and its energetic, a steered molecular dynamics study (SMD was used. Glucose was pulled from the extracellular end of GLUT4 to the cytoplasm along the pathway using constant velocity pulling method. We identified several key residues within the tunnel that interact directly with either the backbone ring or the hydroxyl groups of glucose. A rotation of glucose molecule was seen near the sugar binding site facilitating the sugar recognition process at the QLS binding site. CONCLUSIONS/SIGNIFICANCE: This study proposes a possible glucose transport pathway and aids the identification of several residues that make direct interactions with glucose during glucose transport. Mutational studies are required to further validate the observation made in this study.

  19. Why control blood glucose levels?

    Science.gov (United States)

    Rossini, A A

    1976-03-01

    The controversy as to the relationship between the degree of control of diabetes and the progression of the complications of the disease has not been solved. However, in this review, various studies suggesting a relationship between the metabolic abnormality and the diabetic complications are examined. The disadvantages of the uncontrolled diabetes mellitus can be divided into two major categories-short-term and long-term. The short-term disadvantages of controlled diabetes mellitus include the following: (1) ketoacidosis and hyperosmolar coma; (2) intracellular dehydration; (3) electrolyte imbalance; (4) decreased phagocytosis; (5) immunologic and lymphocyte activity; (6) impairment of wound healing; and (7) abnormality of lipids. The long-term disadvantages of uncontrolled diabetes melitus include the following: (1) nephropathy; (2) neuropathy; (3) retinopathy; (4) cataract formation; (5) effect on perinatal mortality; (6) complications of vascular disease; and (7) the evaluation of various clinical studies suggesting the relationship of elevated blood glucose levels and complications of diabetes mellitus. It is suggested that until the question of control can absolutely be resolved, the recommendation is that the blood glucose levels should be controlled as close to the normal as possible.

  20. Sex steroids and glucose metabolism

    Directory of Open Access Journals (Sweden)

    Carolyn A Allan

    2014-04-01

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

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

    Science.gov (United States)

    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.

  2. Protecting privacy in data release

    CERN Document Server

    Livraga, Giovanni

    2015-01-01

    This book presents a comprehensive approach to protecting sensitive information when large data collections are released by their owners. It addresses three key requirements of data privacy: the protection of data explicitly released, the protection of information not explicitly released but potentially vulnerable due to a release of other data, and the enforcement of owner-defined access restrictions to the released data. It is also the first book with a complete examination of how to enforce dynamic read and write access authorizations on released data, applicable to the emerging data outsou

  3. Triggered Release from Polymer Capsules

    Energy Technology Data Exchange (ETDEWEB)

    Esser-Kahn, Aaron P. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Odom, Susan A. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry; Sottos, Nancy R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Materials Science and Engineering; White, Scott R. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Aerospace Engineering; Moore, Jeffrey S. [Univ. of Illinois, Urbana, IL (United States). Beckman Inst. for Advanced Science and Technology and Dept. of Chemistry

    2011-07-06

    Stimuli-responsive capsules are of interest in drug delivery, fragrance release, food preservation, and self-healing materials. Many methods are used to trigger the release of encapsulated contents. Here we highlight mechanisms for the controlled release of encapsulated cargo that utilize chemical reactions occurring in solid polymeric shell walls. Triggering mechanisms responsible for covalent bond cleavage that result in the release of capsule contents include chemical, biological, light, thermal, magnetic, and electrical stimuli. We present methods for encapsulation and release, triggering methods, and mechanisms and conclude with our opinions on interesting obstacles for chemically induced activation with relevance for controlled release.

  4. Effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices

    Directory of Open Access Journals (Sweden)

    Torres I.L.S.

    2001-01-01

    Full Text Available It has been suggested that glucocorticoids released during stress might impair neuronal function by decreasing glucose uptake by hippocampal neurons. Previous work has demonstrated that glucose uptake is reduced in hippocampal and cerebral cortex slices 24 h after exposure to acute stress, while no effect was observed after repeated stress. Here, we report the effect of acute and repeated restraint stress on glucose oxidation to CO2 in hippocampal and cerebral cortex slices and on plasma glucose and corticosterone levels. Male adult Wistar rats were exposed to restraint 1 h/day for 50 days in the chronic model. In the acute model there was a single exposure. Immediately or 24 h after stress, the animals were sacrificed and the hippocampus and cerebral cortex were dissected, sliced, and incubated with Krebs buffer, pH 7.4, containing 5 mM glucose and 0.2 µCi D-[U-14C] glucose. CO2 production from glucose was estimated. Trunk blood was also collected, and both corticosterone and glucose were measured. The results showed that corticosterone levels after exposure to acute restraint were increased, but the increase was smaller when the animals were submitted to repeated stress. Blood glucose levels increased after both acute and repeated stress. However, glucose utilization, measured as CO2 production in hippocampal and cerebral cortex slices, was the same in stressed and control groups under conditions of both acute and chronic stress. We conclude that, although stress may induce a decrease in glucose uptake, this effect is not sufficient to affect the energy metabolism of these cells.

  5. Impact of Glucose Tolerance Status, Sex, and Body Size on Glucose Absorption Patterns During OGTTs

    DEFF Research Database (Denmark)

    Faerch, K.; Pacini, G.; Nolan, J. J.

    2013-01-01

    OBJECTIVEWe studied whether patterns of glucose absorption during oral glucose tolerance tests (OGTTs) were abnormal in individuals with impaired glucose regulation and whether they were related to sex and body size (height and fat-free mass). We also examined how well differences in insulin......, reflected the differences for these parameters between those with normal and impaired glucose regulation as measured by gold-standard tests.CONCLUSIONSGlucose absorption patterns during an OGTT are significantly related to plasma glucose levels and body size, which should be taken into account when.......RESULTSMore rapid glucose absorption (P 0.036) and reduced late glucose absorption (P 0.039) were observed in the i-IFG group relative to NGT and i-IGT groups. Women with i-IGT had a lower early glucose absorption than did men with i-IGT (P = 0.041); however, this difference did not persist when differences in body...

  6. Ozone modifies the metabolic and endocrine response to glucose: Reproduction of effects with the stress hormone corticosterone.

    Science.gov (United States)

    Thomson, Errol M; Pilon, Shinjini; Guénette, Josée; Williams, Andrew; Holloway, Alison C

    2018-03-01

    Air pollution is associated with increased incidence of metabolic disease (e.g. metabolic syndrome, obesity, diabetes); however, underlying mechanisms are poorly understood. Air pollutants increase the release of stress hormones (human cortisol, rodent corticosterone), which could contribute to metabolic dysregulation. We assessed acute effects of ozone, and stress axis involvement, on glucose tolerance and on the metabolic (triglyceride), endocrine/energy regulation (insulin, glucagon, GLP-1, leptin, ghrelin, corticosterone), and inflammatory/endothelial (TNF, IL-6, VEGF, PAI-1) response to exogenous glucose. Male Fischer-344 rats were exposed to clean air or 0.8 ppm ozone for 4 h in whole body chambers. Hypothalamic-pituitary-adrenal (HPA) axis involvement in ozone effects was tested through subcutaneous administration of the glucocorticoid synthesis inhibitor metyrapone (50 mg/kg body weight), corticosterone (10 mg/kg body weight), or vehicle (40% propylene glycol) prior to exposure. A glucose tolerance test (2 g/kg body weight glucose) was conducted immediately after exposure, with blood samples collected at 0, 30, 60, 90, and 120 min. Ozone exposure impaired glucose tolerance, an effect accompanied by increased plasma triglycerides but no impairment of insulin release. Ozone diminished glucagon, GLP-1, and ghrelin responses to glucose, but did not significantly impact inflammatory/endothelial analytes. Metyrapone reduced corticosterone but increased glucose and triglycerides, complicating evaluation of the impact of glucocorticoid inhibition. However, administration of corticosterone reproduced the profile of ozone effects, supporting a role for the HPA axis. The results show that ozone-dependent changes in glucose tolerance are accompanied by altered metabolic and endocrine responses to glucose challenge that are reproduced by exogenous stress hormone. Crown Copyright © 2018. Published by Elsevier Inc. All rights reserved.

  7. CMOS image sensor-based implantable glucose sensor using glucose-responsive fluorescent hydrogel.

    Science.gov (United States)

    Tokuda, Takashi; Takahashi, Masayuki; Uejima, Kazuhiro; Masuda, Keita; Kawamura, Toshikazu; Ohta, Yasumi; Motoyama, Mayumi; Noda, Toshihiko; Sasagawa, Kiyotaka; Okitsu, Teru; Takeuchi, Shoji; Ohta, Jun

    2014-11-01

    A CMOS image sensor-based implantable glucose sensor based on an optical-sensing scheme is proposed and experimentally verified. A glucose-responsive fluorescent hydrogel is used as the mediator in the measurement scheme. The wired implantable glucose sensor was realized by integrating a CMOS image sensor, hydrogel, UV light emitting diodes, and an optical filter on a flexible polyimide substrate. Feasibility of the glucose sensor was verified by both in vitro and in vivo experiments.

  8. Valsartan Improves β-Cell Function and Insulin Sensitivity in Subjects With Impaired Glucose Metabolism

    Science.gov (United States)

    van der Zijl, Nynke J.; Moors, Chantalle C.M.; Goossens, Gijs H.; Hermans, Marc M.H.; Blaak, Ellen E.; Diamant, Michaela

    2011-01-01

    OBJECTIVE Recently, the Nateglinide and Valsartan in Impaired Glucose Tolerance Outcomes Research Trial demonstrated that treatment with the angiotensin receptor blocker (ARB) valsartan for 5 years resulted in a relative reduction of 14% in the incidence of type 2 diabetes in subjects with impaired glucose metabolism (IGM). We investigated whether improvements in β-cell function and/or insulin sensitivity underlie these preventive effects of the ARB valsartan in the onset of type 2 diabetes. RESEARCH DESIGN AND METHODS In this randomized controlled, double-blind, two-center study, the effects of 26 weeks of valsartan (320 mg daily; n = 40) or placebo (n = 39) on β-cell function and insulin sensitivity were assessed in subjects with impaired fasting glucose and/or impaired glucose tolerance, using a combined hyperinsulinemic-euglycemic and hyperglycemic clamp with subsequent arginine stimulation and a 2-h 75-g oral glucose tolerance test (OGTT). Treatment effects were analyzed using ANCOVA, adjusting for center, glucometabolic status, and sex. RESULTS Valsartan increased first-phase (P = 0.028) and second-phase (P = 0.002) glucose-stimulated insulin secretion compared with placebo, whereas the enhanced arginine-stimulated insulin secretion was comparable between groups (P = 0.25). In addition, valsartan increased the OGTT-derived insulinogenic index (representing first-phase insulin secretion after an oral glucose load; P = 0.027). Clamp-derived insulin sensitivity was significantly increased with valsartan compared with placebo (P = 0.049). Valsartan treatment significantly decreased systolic and diastolic blood pressure compared with placebo (P valsartan treatment increased glucose-stimulated insulin release and insulin sensitivity in normotensive subjects with IGM. These findings may partly explain the beneficial effects of valsartan in the reduced incidence of type 2 diabetes. PMID:21330640

  9. Monoaminergic Control of Cellular Glucose Utilization by Glycogenolysis in Neocortex and Hippocampus.

    Science.gov (United States)

    DiNuzzo, Mauro; Giove, Federico; Maraviglia, Bruno; Mangia, Silvia

    2015-12-01

    Brainstem nuclei are the principal sites of monoamine (MA) innervation to major forebrain structures. In the cortical grey matter, increased secretion of MA neuromodulators occurs in response to a wealth of environmental and homeostatic challenges, whose onset is associated with rapid, preparatory changes in neural activity as well as with increases in energy metabolism. Blood-borne glucose is the main substrate for energy production in the brain. Once entered the tissue, interstitial glucose is equally accessible to neurons and astrocytes, the two cell types accounting for most of cellular volume and energy metabolism in neocortex and hippocampus. Astrocytes also store substantial amounts of glycogen, but non-stimulated glycogen turnover is very small. The rate of cellular glucose utilization in the brain is largely determined by hexokinase, which under basal conditions is more than 90 % inhibited by its product glucose-6-phosphate (Glc-6-P). During rapid increases in energy demand, glycogen is a primary candidate in modulating the intracellular level of Glc-6-P, which can occur only in astrocytes. Glycogenolysis can produce Glc-6-P at a rate higher than uptake and phosphorylation of glucose. MA neurotransmitter are released extrasinaptically by brainstem neurons projecting to neocortex and hippocampus, thus activating MA receptors located on both neuronal and astrocytic plasma membrane. Importantly, MAs are glycogenolytic agents and thus they are exquisitely suitable for regulation of astrocytic Glc-6-P concentration, upstream substrate flow through hexokinase and hence cellular glucose uptake. Conforming to such mechanism, Gerald A. Dienel and Nancy F. Cruz recently suggested that activation of noradrenergic locus coeruleus might reversibly block astrocytic glucose uptake by stimulating glycogenolysis in these cells, thereby anticipating the rise in glucose need by active neurons. In this paper, we further develop the idea that the whole monoaminergic system

  10. Effects of Insulin on Brain Glucose Metabolism in Impaired Glucose Tolerance

    Science.gov (United States)

    Hirvonen, Jussi; Virtanen, Kirsi A.; Nummenmaa, Lauri; Hannukainen, Jarna C.; Honka, Miikka-Juhani; Bucci, Marco; Nesterov, Sergey V.; Parkkola, Riitta; Rinne, Juha; Iozzo, Patricia; Nuutila, Pirjo

    2011-01-01

    OBJECTIVE Insulin stimulates brain glucose metabolism, but this effect of insulin is already maximal at fasting concentrations in healthy subjects. It is not known whether insulin is able to stimulate glucose metabolism above fasting concentrations in patients with impaired glucose tolerance. RESEARCH DESIGN AND METHODS We studied the effects of insulin on brain glucose metabolism and cerebral blood flow in 13 patients with impaired glucose tolerance and nine healthy subjects using positron emission tomography (PET). All subjects underwent PET with both [18F]fluorodeoxyglucose (for brain glucose metabolism) and [15O]H2O (for cerebral blood flow) in two separate conditions (in the fasting state and during a euglycemic-hyperinsulinemic clamp). Arterial blood samples were acquired during the PET scans to allow fully quantitative modeling. RESULTS The hyperinsulinemic clamp increased brain glucose metabolism only in patients with impaired glucose tolerance (whole brain: +18%, P = 0.001) but not in healthy subjects (whole brain: +3.9%, P = 0.373). The hyperinsulinemic clamp did not alter cerebral blood flow in either group. CONCLUSIONS We found that insulin stimulates brain glucose metabolism at physiological postprandial levels in patients with impaired glucose tolerance but not in healthy subjects. These results suggest that insulin stimulation of brain glucose metabolism is maximal at fasting concentrations in healthy subjects but not in patients with impaired glucose tolerance. PMID:21270256

  11. Genetic variation in GIPR influences the glucose and insulin responses to an oral glucose challenge

    NARCIS (Netherlands)

    R. Saxena (Richa); M.-F. Hivert (Marie-France); C. Langenberg (Claudia); T. Tanaka (Toshiko); J.S. Pankow (James); P. Vollenweider (Peter); V. Lyssenko (Valeriya); N. Bouatia-Naji (Nabila); J. Dupuis (Josée); A.U. Jackson (Anne); W.H.L. Kao (Wen); M. Li (Man); N.L. Glazer (Nicole); A.K. Manning (Alisa); J. Anluan (Jian); H.M. Stringham (Heather); I. Prokopenko (Inga); T. Johnson (Toby); N. Grarup (Niels); T.W. Boesgaard (Trine); C. Lecoeur (Cécile); P. Shrader (Peter); J.R. O´Connell; E. Ingelsson (Erik); D.J. Couper (David); K. Rice (Kenneth); K. Song (Kijoung); C.H. Andreasen (Camilla); C. Dina (Christian); A. Köttgen (Anna); O.L. Bacquer (Olivier); F. Pattou (François); J. Taneera (Jalal); V. Steinthorsdottir (Valgerdur); D. Rybin (Denis); K.G. Ardlie (Kristin); M.J. Sampson (Michael); L. Qi (Lu); M.V. Hoek; M.N. Weedon (Michael); Y.S. Aulchenko (Yurii); B.F. Voight (Benjamin); H. Grallert (Harald); B. Balkau (Beverley); R.N. Bergman (Richard); S.J. Bielinski (Suzette); A. Bonnefond (Amélie); L.L. Bonnycastle (Lori); K. Borch-Johnsen; Y. Böttcher (Yvonne); E. Brunner (Eric); T.A. Buchanan (Thomas); S. Bumpstead (Suzannah); C. Cavalcanti-Proença (Christine); G. Charpentier (Guillaume); Y.D.I. Chen (Yii-Der Ida); P.S. Chines (Peter); F.S. Collins (Francis); M. Cornelis (Marilyn); G. Crawford (Gabe); J. Delplanque (Jerome); A.S.F. Doney (Alex); J.M. Egan (Josephine); M.R. Erdos (Michael); M. Firmann (Mathieu); N.G. Forouhi (Nita); C.S. Fox (Caroline); M. Goodarzi (Mark); J. Graessler (Jürgen); A. Hingorani (Aroon); B. Isomaa (Bo); T. Jørgensen (Torben); M. Kivimaki (Mika); P. Kovacs (Peter); K. Krohn (Knut); M. Kumari (Meena); T. Lauritzen (Torsten); C. Lévy-Marchal (Claire); V. Mayor (Vladimir); J.B. McAteer (Jarred); D. Meyre (David); B.D. Mitchell (Braxton); K.L. Mohlke (Karen); M.A. Morken (Mario); N. Narisu (Narisu); C.N.A. Palmer (Colin); R. Pakyz (Ruth); L. Pascoe (Laura); F. Payne (Felicity); D. Pearson (Daniel); W. Rathmann (Wolfgang); A. Sandbaek (Annelli); A.A. Sayer; L.J. Scott (Laura); S.J. Sharp (Stephen); E.J.G. Sijbrands (Eric); A. Singleton (Andrew); D.S. Siscovick (David); N.L. Smith (Nicholas); T. Sparsø (Thomas); A.J. Swift (Amy); H. Syddall (Holly); G. Thorleifsson (Gudmar); A. Tönjes (Anke); T. Tuomi (Tiinamaija); J. Tuomilehto (Jaakko); T.T. Valle (Timo); G. Waeber (Gérard); A. Walley (Andrew); D. Waterworth (Dawn); E. Zeggini (Eleftheria); J.H. Zhao (Jing Hua); G. Consortium (Giant); T. Illig (Thomas); H.E. Wichmann (Erich); J.F. Wilson (James); C.M. van Duijn (Cornelia); F.B. Hu (Frank); A.D. Morris (Andrew); T.M. Frayling (Timothy); A.T. Hattersley (Andrew); U. Thorsteinsdottir (Unnur); J-A. Zwart (John-Anker); P. Nilsson (Peter); A.C. Syvänen; A.R. Shuldiner (Alan); M. Walker (Mark); S.R. Bornstein (Stefan); P. Schwarz (Peter); G.H. Williams (Gordon); D.M. Nathan (David); J. Kuusisto (Johanna); M. Laakso (Markku); C. Cooper (Charles); M. Marmot (Michael); L. Ferrucci (Luigi); V. Mooser (Vincent); M. Stumvoll (Michael); R.J.F. Loos (Ruth); D. Altshuler (David); B.M. Psaty (Bruce); J.I. Rotter (Jerome); E.A. Boerwinkle (Eric); T. Hansen (Torben); O. Pedersen (Oluf); J.C. Florez (Jose); M.I. McCarthy (Mark); M. Boehnke (Michael); I.E. Barroso (Inês); R. Sladek (Rob); P. Froguel (Philippe); J.B. Meigs (James); L. Groop (Leif); N.J. Wareham (Nick); R.M. Watanabe (Richard)

    2010-01-01

    textabstractGlucose levels 2 h after an oral glucose challenge are a clinical measure of glucose tolerance used in the diagnosis of type 2 diabetes. We report a meta-analysis of nine genome-wide association studies (n = 15,234 nondiabetic individuals) and a follow-up of 29 independent loci (n =

  12. What goes up must come down: glucose variability and glucose control in diabetes and critical illness

    NARCIS (Netherlands)

    Siegelaar, S.E.

    2011-01-01

    The central question of this thesis is whether it is necessary to curb all glucose peaks. From the studies presented in this thesis we conclude that this is not always the case. In diabetes it is important to lower mean glucose while avoiding hypoglycaemia, but we found that lowering of glucose to

  13. Ex vivo changes in blood glucose levels seldom change blood glucose control algorithm recommendations

    NARCIS (Netherlands)

    de Groene, L.; Harmsen, R. E.; Binnekade, J. M.; Spronk, P. E.; Schultz, M. J.

    2010-01-01

    Background. Hyperglycemia and glycemic variabilities are associated with adverse outcomes in critically ill patients. Blood glucose control with insulin mandates an adequate and precise assessment of blood glucose levels. Blood glucose levels, however, can change ex vivo after sampling. The aim of

  14. Correlation between blood glucose levels and salivary glucose levels with oral ulcer in diabetic patients

    Directory of Open Access Journals (Sweden)

    Fildzah Rahman

    2016-06-01

    Full Text Available Diabetes Mellitus (DM is a syndrome in metabolism of carbohydrates which indicated by the increased level of blood glucose and also may increase salivary glucose levels. Oral ulcer has been frequently recognized in diabetic patients, which can be due to increased glucose in oral fluids and immune dysfunction. This study aimed to determine the correlation of blood glucose levels and salivary glucose levels with oral ulcer in diabetic patients. Analytic observational study was carried out through the determination of blood glucose levels just by way of strip using a glucometer and salivary glucose levels with the method "GOD-PAP test enzymatic colorimetric". Oral ulcer was determined in presenting ulcer on 30 patients with DM. The results showed r = 0.228, which is higher salivary glucose levels followed by high levels of blood glucose, and intraoral examination of oral ulcer found in the whole sample and the most location commonly found in buccal mucosa and lingual. It was concluded that there is a correlation between blood glucose levels and salivary glucose levels, and glucose levels affect the occurrence of oral ulcer in patients with DM

  15. Glucose reactivity with filling materials as a limitation for using the glucose leakage model

    NARCIS (Netherlands)

    Shemesh, H.; Souza, E.M.; Wu, M.K.; Wesselink, P.R.

    2008-01-01

    Aim To evaluate the reactivity of different endodontic materials and sealers with glucose and to asses the reliability of the glucose leakage model in measuring penetration of glucose through these materials. Methodology Ten uniform discs (radius 5 mm, thickness 2 mm) were made of each of the

  16. Intraperitoneal Glucose Sensing is Sometimes Surprisingly Rapid

    Directory of Open Access Journals (Sweden)

    Anders Lyngvi Fougner

    2016-04-01

    Full Text Available Rapid, accurate and robust glucose measurements are needed to make a safe artificial pancreas for the treatment of diabetes mellitus type 1 and 2. The present gold standard of continuous glucose sensing, subcutaneous (SC glucose sensing, has been claimed to have slow response and poor robustness towards local tissue changes such as mechanical pressure, temperature changes, etc. The present study aimed at quantifying glucose dynamics from central circulation to intraperitoneal (IP sensor sites, as an alternative to the SC location. Intraarterial (IA and IP sensors were tested in three anaesthetized non-diabetic pigs during experiments with intravenous infusion of glucose boluses, enforcing rapid glucose level excursions in the range 70--360 mg/dL (approximately 3.8--20 mmol/L. Optical interferometric sensors were used for IA and IP measurements. A first-order dynamic model with time delay was fitted to the data after compensating for sensor dynamics. Additionally, off-the-shelf Medtronic Enlite sensors were used for illustration of SC glucose sensing. The time delay in glucose excursions from central circulation (IA to IP sensor location was found to be in the range 0--26 s (median: 8.5 s, mean: 9.7 s, SD 9.5 s, and the time constant was found to be 0.5--10.2 min (median: 4.8 min, mean: 4.7 min, SD 2.9 min. IP glucose sensing sites have a substantially faster and more distinctive response than SC sites when sensor dynamics is ignored, and the peritoneal fluid reacts even faster to changes in intravascular glucose levels than reported in previous animal studies. This study may provide a benchmark for future, rapid IP glucose sensors.

  17. Hypothalamic glucose sensing: making ends meet

    Directory of Open Access Journals (Sweden)

    Vanessa eRouth

    2014-12-01

    Full Text Available The neuroendocrine system governs essential survival and homeostatic functions. For example, growth is needed for development. Thermoregulation maintains optimal core temperature in a changing environment. Reproduction ensures species survival. Stress and immune responses enable an organism to overcome external and internal threats. The circadian system regulates arousal and sleep such that vegetative and active functions do not overlap. All of these functions require a significant portion of the body’s energy. As the integrator of the neuroendocrine system, the hypothalamus carefully assesses the energy status of the body in order to appropriately partition resources to provide for each system without compromising the others. While doing so the hypothalamus must ensure that adequate glucose levels are preserved for brain function since glucose is the primary fuel of the brain. To this end, the hypothalamus contains specialized glucose sensing neurons which are scattered throughout the nuclei controlling distinct neuroendocrine functions. We hypothesize that these neurons play a key role in enabling the hypothalamus to partition energy to meet these peripheral survival needs without endangering the brain’s glucose supply. The goal of this review is to describe the varied mechanisms underlying glucose sensing in neurons within discrete hypothalamic nuclei. We will then evaluate the way in which peripheral energy status regulates glucose sensitivity. For example, during energy deficit such as fasting specific hypothalamic glucose sensing neurons become sensitized to decreased glucose. This increases the gain of the information relay when glucose availability is a greater concern for the brain. Finally, changes in glucose sensitivity under pathological conditions (e.g., recurrent insulin-hypoglycemia, diabetes will be addressed. The overall goal of this review is to place glucose sensing neurons within the context of hypothalamic control of

  18. Riola release report

    Energy Technology Data Exchange (ETDEWEB)

    Woodward, E.C.

    1983-08-04

    Eleven hours after execution of the Riola Event (at 0826 PDT on 25 September 1980) in hole U2eq of the Nevada Test Site (NTS), a release of radioactivity began. When the seepage stopped at about noon the following day, up to some 3200 Ci of activity had been dispersed by light variable winds. On 26 September, examination of the geophone records showed six hours of low-level, but fairly continuous, activity before the release. Electrical measurements indicated that most cables were still intact to a depth below the stemming platform. A survey of the ground zero area showed that the seepage came through cracks between the surface conductor and the pad, through cracks in the pad, and through a crack adjacent to the pad around the mousehole (a small hole adjacent to the emplacement hole). To preclude undue radiation exposure or injury from a surprise subsidence, safety measures were instituted. Tritium seepage was suffucient to postpone site activities until a box and pipeline were emplaced to contain and remove the gas. Radiation release modeling and calculations were generally consistent with observations. Plug-hole interaction calculations showed that the alluvium near the bottom of the plug may have been overstressed and that improvements in the design of the plug-medium interface can be made. Experimental studies verified that the surface appearance of the plug core was caused by erosion, but, assuming a normal strength for the plug material, that erosion alone could not account for the disappearance of such a large portion of the stemming platform. Samples from downhole plug experiments show that the plug may have been considerably weaker than had been indicted by quality assurance (QA) samples. 19 references, 32 figures, 10 tables.

  19. Riola release report

    International Nuclear Information System (INIS)

    Woodward, E.C.

    1983-01-01

    Eleven hours after execution of the Riola Event (at 0826 PDT on 25 September 1980) in hole U2eq of the Nevada Test Site (NTS), a release of radioactivity began. When the seepage stopped at about noon the following day, up to some 3200 Ci of activity had been dispersed by light variable winds. On 26 September, examination of the geophone records showed six hours of low-level, but fairly continuous, activity before the release. Electrical measurements indicated that most cables were still intact to a depth below the stemming platform. A survey of the ground zero area showed that the seepage came through cracks between the surface conductor and the pad, through cracks in the pad, and through a crack adjacent to the pad around the mousehole (a small hole adjacent to the emplacement hole). To preclude undue radiation exposure or injury from a surprise subsidence, safety measures were instituted. Tritium seepage was suffucient to postpone site activities until a box and pipeline were emplaced to contain and remove the gas. Radiation release modeling and calculations were generally consistent with observations. Plug-hole interaction calculations showed that the alluvium near the bottom of the plug may have been overstressed and that improvements in the design of the plug-medium interface can be made. Experimental studies verified that the surface appearance of the plug core was caused by erosion, but, assuming a normal strength for the plug material, that erosion alone could not account for the disappearance of such a large portion of the stemming platform. Samples from downhole plug experiments show that the plug may have been considerably weaker than had been indicted by quality assurance (QA) samples. 19 references, 32 figures, 10 tables

  20. Pseudo-bi-enzyme glucose sensor: ZnS hollow spheres and glucose oxidase concerted catalysis glucose.

    Science.gov (United States)

    Shuai, Ying; Liu, Changhua; Wang, Jia; Cui, Xiaoyan; Nie, Ling

    2013-06-07

    This work creatively uses peroxidase-like ZnS hollow spheres (ZnS HSs) to cooperate with glucose oxidase (GOx) for glucose determinations. This approach is that the ZnS HSs electrocatalytically oxidate the enzymatically generated H2O2 to O2, and then the O2 circularly participates in the previous glucose oxidation by glucose oxidase. Au nanoparticles (AuNPs) and carbon nanotubes (CNTs) are used as electron transfer and enzyme immobilization matrices, respectively. The biosensor of glucose oxidase-carbon nanotubes-Au nanoparticles-ZnS hollow spheres-gold electrode (GOx-CNT-AuNPs-ZnS HSs-GE) exhibits a rapid response, a low detection limit (10 μM), a wide linear range (20 μM to 7 mM) as well as good anti-interference, long-term longevity and reproducibility.

  1. Minor long-term changes in weight have beneficial effects on insulin sensitivity and beta-cell function in obese subjects

    DEFF Research Database (Denmark)

    Rosenfalck, A M; Hendel, Helle Westergren; Rasmussen, M H

    2002-01-01

    To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function.......To evaluate the long-term effect of changes in body composition induced by weight loss on insulin sensitivity (SI), non-insulin mediated glucose disposal, glucose effectiveness (SG)and beta-cell function....

  2. Allegheny County Toxics Release Inventory

    Data.gov (United States)

    Allegheny County / City of Pittsburgh / Western PA Regional Data Center — The Toxics Release Inventory (TRI) data provides information about toxic substances released into the environment or managed through recycling, energy recovery, and...

  3. Application of reaction type of C-peptide release test in diabetes mellitus

    International Nuclear Information System (INIS)

    Chen Dong; Duan Wenruo; He Juan; Lu Zhenfang

    2001-01-01

    The author is to confirm the effect of C-peptide release test and types of release reaction in appraisal of pancreas function of β-cell and selection of treatment for diabetes mellitus (DM) patients. The serum C-peptide release test of 67 normal controls and 217 DM patients were determined by RIA, and the results were analyzed and compared. C-peptide release test can reflect the pancreas function of β-cell better, the peak of C-peptide ≥ 0.6 nmol/L after lunch can be the limit of whether to reduce the level of blood glucose only by oral drug. The authors should adjust the treatment through analyzing the type of C-peptide release reaction. C-peptide release test is very important in evaluating the pancreas function of β-cell, classifying the type of DM and selecting the treatment

  4. Effect of a new drug releasing system on microencapsulated islet transplantation

    Science.gov (United States)

    Lu, Binjie; Gao, Qingkun; Liu, Rui; Ren, Ming; Wu, Yan; Jiang, Zaixing; Zhou, Yi

    2015-01-01

    Objective: This study aimed to develop a novel release system for grafted islets. Materials and methods: A graphene oxide-FTY720 release system was constructed to test the drug loading and releasing capacity. The recipient rats were divided into four groups as following: Experiment group A (EG A) and B (EG B); Control group A (CG A) and B (CG B). In each group, (2000±100) IEQ microencapsulated islets were implanted into the abdominal cavity of the recipients with oral FTY720, local graphene oxide-FTY720 injection, without immunosuppressants, and with graphene oxide-saturated solution respectively. We detected the immunological data, the blood glucose level, and pericapsular overgrowth to show the transplantation effect. Results: 31% of adsorptive FTY720 was released within 6 h, and 82% of FTY720 was released within 48 h. From day 5 to 8, the amount of PBL in EG B was significantly less than those in EG A (PGraphene oxide-FTY720 complex showed a drug releasing effect. Local application of graphene-FTY720 releasing system could decrease the amount of peripheral blood lymphocytes (PBL) and the percentage of CD3 and CD8 T lymphocytes in blood for longer time than oral drug application. This releasing system could achieve a better blood glucose control. PMID:26722425

  5. Atypical antipsychotics and glucose homeostasis.

    Science.gov (United States)

    Bergman, Richard N; Ader, Marilyn

    2005-04-01

    Persistent reports have linked atypical antipsychotics with diabetes, yet causative mechanisms responsible for this linkage are unclear. Goals of this review are to outline the pathogenesis of nonimmune diabetes and to survey the available literature related to why antipsychotics may lead to this disease. We accessed the literature regarding atypical antipsychotics and glucose homeostasis using PubMed. The search included English-language publications from 1990 through October 2004. Keywords used included atypical antipsychotics plus one of the following: glucose, insulin, glucose tolerance, obesity, or diabetes. In addition, we culled information from published abstracts from several national and international scientific meetings for the years 2001 through 2004, including the American Diabetes Association, the International Congress on Schizophrenia Research, and the American College of Neuropsychopharmacology. The latter search was necessary because of the paucity of well-controlled prospective studies. We examined publications with significant new data or publications that contributed to the overall comprehension of the impact of atypical antipsychotics on glucose metabolism. We favored original peer-reviewed articles and were less likely to cite single case studies and/or anecdotal information. Approximately 75% of the fewer than 150 identified articles were examined and included in this review. Validity of data was evaluated using the existence of peer-review status as well as our own experience with methodology described in the specific articles. The metabolic profile caused by atypical antipsychotic treatment resembles type 2 diabetes. These agents cause weight gain in treated subjects and may induce obesity in both visceral and subcutaneous depots, as occurs in diabetes. Insulin resistance, usually associated with obesity, occurs to varying degrees with different antipsychotics, although more comparative studies with direct assessment of resistance are

  6. Thermoinactivation Mechanism of Glucose Isomerase

    Science.gov (United States)

    Lim, Leng Hong; Saville, Bradley A.

    In this article, the mechanisms of thermoinactivation of glucose isomerase (GI) from Streptomyces rubiginosus (in soluble and immobilized forms) were investigated, particularly the contributions of thiol oxidation of the enzyme's cysteine residue and a "Maillard-like" reaction between the enzyme and sugars in high fructose corn syrup (HFCS). Soluble GI (SGI) was successfully immobilized on silica gel (13.5 μm particle size), with an activity yield between 20 and 40%. The immobilized GI (IGI) has high enzyme retention on the support during the glucose isomerization process. In batch reactors, SGI (half-life =145 h) was more stable than IGI (half-life=27 h) at 60°C in HFCS, whereas at 80°C, IGI (half-life=12 h) was more stable than SGI (half-life=5.2 h). IGI was subject to thiol oxidation at 60°C, which contributed to the enzyme's deactivation. IGI was subject to thiol oxidation at 80°C, but this did not contribute to the deactivation of the enzyme. SGI did not undergo thiol oxidation at 60°C, but at 80°C SGI underwent severe precipitation and thiol oxidation, which caused the enzyme to deactivate. Experimental results show that immobilization suppresses the destablizing effect of thiol oxidation on GI. A "Maillard-like" reaction between SGI and the sugars also caused SGI thermoinactivation at 60, 70, and 80°C, but had minimal effect on IGI. At 60 and 80°C, IGI had higher thermostability in continuous reactors than in batch reactors, possibily because of reduced contact with deleterious compounds in HFCS.

  7. Oral L-Arginine Stimulates GLP-1 Secretion to Improve Glucose Tolerance in Male Mice

    DEFF Research Database (Denmark)

    Clemmensen, Christoffer; Smajilovic, Sanela; Smith, Eric P

    2013-01-01

    Pharmacological and surgical interventions that increase glucagon-like peptide 1 (GLP-1) action are effective to improve glucose homeostasis in type 2 diabetes mellitus. In light of this, nutritional strategies to enhance postprandial GLP-1 secretion, particularly in the context of diet......-induced obesity, may provide an alternative therapeutic approach. Importantly, recent evidence suggests the amino acid l-arginine, a well-known insulin secretagogue, can also stimulate release of GLP-1 from isolated rat intestine. Here we tested the hypothesis that oral l-arginine acts as a GLP-1 secretagogue...... in vivo, to augment postprandial insulin secretion and improve glucose tolerance. To test this, we administered l-arginine or vehicle by oral gavage, immediately prior to an oral glucose tolerance test in lean and diet-induced obese mice. In both lean and obese mice oral l-arginine increased plasma GLP-1...

  8. Blood glucose response to pea fiber

    DEFF Research Database (Denmark)

    Hamberg, O; Rumessen, J J; Gudmand-Høyer, E

    1989-01-01

    Two new fiber types, pea fiber (PF) and sugar beet fiber (BF), were compared with wheat bran (WB) to investigate the effect on postprandial blood glucose and serum insulin responses in normal subjects. The control meal consisted of 150 g ground beef mixed with 50 g glucose and 20 g lactulose. Onl...

  9. Non Invasive Glucose Monitoring System Using Nanosensors

    Directory of Open Access Journals (Sweden)

    Rajasekaran C.

    2016-03-01

    Full Text Available The most existing future technology is an outcome of the fields of computer science, electronics and Biology. Health inequalities have become the focus of a number of descriptive and analytical studies. One of the health related problem is diabetes. Diabetes at its serious stage leads to blindness. Monitoring glucose level in blood is one preventive measure to check diabetes. Increase in Glucose is a common risk factor which leads to hyperglycemia, Hypoglycemia, heart attack, stokes and aneurysms. A glucose monitoring system continuously measures and monitors the glucose level in a patient’s blood. Normal blood glucose level of human is 70-110 milligram/deciliter. The level is maintained by using the secretion of insulin inside the body. When the insulin level gets increased it leads to hyperglycemia, and hypoglycemia when the level gets decreased. Hyperglycemia disease includes cataract,edema, hypertension, polyuria and polydipsia. Hypoglycemaia disease includes confusion, giddiness, unconsciousness, coma and death. The proposed system finds a new way for measuring the glucose level. The work uses Nanopellets which measure’s the glucose level, when the glucose level gets increased or decreased, it will be automatically get monitored and processed using microcontroller (MSP430G2553. The information is then send to the doctor through GSM.

  10. Toward CMOS image sensor based glucose monitoring.

    Science.gov (United States)

    Devadhasan, Jasmine Pramila; Kim, Sanghyo

    2012-09-07

    Complementary metal oxide semiconductor (CMOS) image sensor is a powerful tool for biosensing applications. In this present study, CMOS image sensor has been exploited for detecting glucose levels by simple photon count variation with high sensitivity. Various concentrations of glucose (100 mg dL(-1) to 1000 mg dL(-1)) were added onto a simple poly-dimethylsiloxane (PDMS) chip and the oxidation of glucose was catalyzed with the aid of an enzymatic reaction. Oxidized glucose produces a brown color with the help of chromogen during enzymatic reaction and the color density varies with the glucose concentration. Photons pass through the PDMS chip with varying color density and hit the sensor surface. Photon count was recognized by CMOS image sensor depending on the color density with respect to the glucose concentration and it was converted into digital form. By correlating the obtained digital results with glucose concentration it is possible to measure a wide range of blood glucose levels with great linearity based on CMOS image sensor and therefore this technique will promote a convenient point-of-care diagnosis.

  11. Glucose sensing issues for the artificial pancreas

    NARCIS (Netherlands)

    DeVries, J. Hans

    2008-01-01

    The first retrospective continuous glucose monitor entered the market in 1999. Now that this tool gives online data, the question arises whether it is ready to be incorporated into a closed-loop system. The author discusses the following questions: (1) Is the accuracy of current continuous glucose

  12. 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, ...

  13. Direct effect of gonadal and contraceptive steroids on insulin release from mouse pancreatic islets in organ culture

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    1984-01-01

    Sex steroids are supposed to contribute to the normal glucose homeostasis and to the altered glucose and insulin metabolism in pregnancy and during contraception. In the present study isolated mouse pancreatic islets were maintained in tissue culture medium RPMI 1640 supplemented with 0.5% newborn...... calf serum and 100 ng/ml of one of the following steroids: oestradiol, progesterone, testosterone, megestrol acetate, medroxyprogesterone, chlormadinone acetate, norethynodrel, norethindrone acetate, and ethynyloestradiol. Release of insulin to the culture medium was measured during a 2 week culture...... in the presence of oestradiol, progesterone, or testosterone were subjected to 30 min stimulation with 5.5, 11, 22 mmol/l glucose, only the progesterone-treated islets released more insulin in response to glucose than the control islets. It is concluded that progesterone and its derivatives have a direct effect...

  14. Insulin-releasing action of the novel antidiabetic agent BTS 67 582.

    Science.gov (United States)

    McClenaghan, N H; Flatt, P R; Bailey, C J

    1998-02-01

    1. BTS 67582 (1,1-dimethyl-2-(2-morpholinophenyl)guanidine fumarate) is a novel antidiabetic agent with a short-acting insulin-releasing effect. This study examined its mode of action in the clonal B-cell line BRIN-BD11. 2. BTS 67582 increased insulin release from BRIN-BD11 cells in a concentration-dependent manner (10[-8] to 10[-4] M) at both non-stimulating (1.1 mM) and stimulating (16.7 mM) concentrations of glucose. 3. BTS 67582 (10[-4] M) potentiated the insulin-releasing effect of a depolarizing concentration of K+ (30 mM), whereas the K+ channel openers pinacidil (400 microM) and diazoxide (300 microM) inhibited BTS 67582-induced release. 4. Suppression of Ca+ channel activity with verapamil (20 microM) reduced the insulin-releasing effect of BTS 67582 (10[-4] M). 5. BTS 67582 (10[-4] M) potentiated insulin release induced by amino acids (10 mM), and enhanced the combined stimulant effects of glucose plus either the fatty acid palmitate (10 mM), or agents which raise intracellular cyclic AMP concentrations (25 microM forskolin and 1 mM isobutylmethylxanthine), or the cholinoceptor agonist carbachol (100 microM). 6. Inhibition of glucose-stimulated insulin release by adrenaline or noradrenaline (10 microM) was partially reversed by BTS 67582 (10[-4] M). 7. These data suggest that the insulin-releasing effect of BTS 67582 involves regulation of ATP-sensitive K+ channel activity and Ca2+ influx, and that the drug augments the stimulant effects of nutrient insulin secretagogues and agents which enhance adenylate cyclase and phospholipase C. BTS 67582 may also exert insulin-releasing effects independently of ATP-sensitive K+ channel activity.

  15. TXNIP regulates peripheral glucose metabolism in humans

    DEFF Research Database (Denmark)

    Parikh, Hemang; Carlsson, Emma; Chutkow, William A

    2007-01-01

    combined human insulin/glucose clamp physiological studies with genome-wide expression profiling to identify thioredoxin interacting protein (TXNIP) as a gene whose expression is powerfully suppressed by insulin yet stimulated by glucose. In healthy individuals, its expression was inversely correlated...... expression is consistently elevated in the muscle of prediabetics and diabetics, although in a panel of 4,450 Scandinavian individuals, we found no evidence for association between common genetic variation in the TXNIP gene and T2DM. CONCLUSIONS: TXNIP regulates both insulin-dependent and insulin......-independent pathways of glucose uptake in human skeletal muscle. Combined with recent studies that have implicated TXNIP in pancreatic beta-cell glucose toxicity, our data suggest that TXNIP might play a key role in defective glucose homeostasis preceding overt T2DM....

  16. Glucose absorption in acute peritoneal dialysis.

    Science.gov (United States)

    Podel, J; Hodelin-Wetzel, R; Saha, D C; Burns, G

    2000-04-01

    During acute peritoneal dialysis (APD), it is known that glucose found in the dialysate solution contributes to the provision of significant calories. It has been well documented in continuous ambulatory peritoneal dialysis (CAPD) that glucose absorption occurs. In APD, however, it remains unclear how much glucose absorption actually does occur. Therefore, the purpose of this study was to determine whether it is appropriate to use the formula used to calculate glucose absorption in CAPD (Grodstein et al) among patients undergoing APD. Actual measurements of glucose absorption (Method I) were calculated in 9 patients undergoing APD treatment for >24 hours who were admitted to the intensive care unit. Glucose absorption using the Grodstein et al formula (Method II) was also determined and compared with the results of actual measurements. The data was then further analyzed based on the factors that influence glucose absorption, specifically dwell time and concentration. The mean total amount of glucose absorbed was 43% +/- 15%. However, when dwell time and concentration were further examined, significant differences were noted. Method I showed a cumulative increase over time. Method II showed that absorption was fixed. This suggests that with the variation in dwell time commonly seen in the acute care setting, the use of Method II may not be accurate. In each of the 2 methods, a significant difference in glucose absorption was noted when comparing the use of 1.5% and 4.25% dialysate concentrations. The established formula designed for CAPD should not be used for calculating glucose absorption in patients receiving APD because variation in dwell time and concentration should be taken into account. Because of the time constraints and staffing required to calculate each exchange individually, combined with the results of the study, we recommend the use of the percentage estimate of 40% to 50%.

  17. Challenges and perspectives in continuous glucose monitoring.

    Science.gov (United States)

    van Enter, Benjamin Jasha; von Hauff, Elizabeth

    2018-04-24

    Diabetes is a global epidemic that threatens the health and well-being of hundreds of millions of people. The first step in patient treatment is to monitor glucose levels. Currently this is most commonly done using enzymatic strips. This approach suffers from several limitations, namely it requires a blood sample and is therefore invasive, the quality and the stability of the enzymatic strips vary widely, and the patient is burdened by performing the measurement themselves. This results in dangerous fluctuations in glucose levels often going undetected. There is currently intense research towards new approaches in glucose detection that would enable non-invasive continuous glucose monitoring (CGM). In this review, we explore the state-of-the-art in glucose detection technologies. In particular, we focus on the physical mechanisms behind different approaches, and how these influence and determine the accuracy and reliability of glucose detection. We begin by reviewing the basic physical and chemical properties of the glucose molecule. Although these play a central role in detection, especially the anomeric ratio, they are surprisingly often overlooked in the literature. We then review state-of-the art and emerging detection methods. Finally, we survey the current market for glucometers. Recent results show that past challenges in glucose detection are now being overcome, thereby enabling the development of smart wearable devices for non-invasive continuous glucose monitoring. These new directions in glucose detection have enormous potential to improve the quality of life of millions of diabetics, as well as offer insight into the development, treatment and even prevention of the disease.

  18. Radiometric assays for glycerol, glucose, and glycogen

    International Nuclear Information System (INIS)

    Bradley, D.C.; Kaslow, H.R.

    1989-01-01

    We have developed radiometric assays for small quantities of glycerol, glucose and glycogen, based on a technique described by Thorner and Paulus for the measurement of glycerokinase activity. In the glycerol assay, glycerol is phosphorylated with [32P]ATP and glycerokinase, residual [32P]ATP is hydrolyzed by heating in acid, and free [32P]phosphate is removed by precipitation with ammonium molybdate and triethylamine. Standard dose-response curves were linear from 50 to 3000 pmol glycerol with less than 3% SD in triplicate measurements. Of the substances tested for interference, only dihydroxyacetone gave a slight false positive signal at high concentration. When used to measure glycerol concentrations in serum and in media from incubated adipose tissue, the radiometric glycerol assay correlated well with a commonly used spectrophotometric assay. The radiometric glucose assay is similar to the glycerol assay, except that glucokinase is used instead of glycerokinase. Dose response was linear from 5 to 3000 pmol glucose with less than 3% SD in triplicate measurements. Glucosamine and N-acetylglucosamine gave false positive signals when equimolar to glucose. When glucose concentrations in serum were measured, the radiometric glucose assay agreed well with hexokinase/glucose-6-phosphate dehydrogenase (H/GDH)-based and glucose oxidase/H2O2-based glucose assays. The radiometric method for glycogen measurement incorporates previously described isolation and digestion techniques, followed by the radiometric assay of free glucose. When used to measure glycogen in mouse epididymal fat pads, the radiometric glycogen assay correlated well with the H/GDH-based glycogen assay. All three radiometric assays offer several practical advantages over spectral assays

  19. Cobalt release from inexpensive jewellery

    DEFF Research Database (Denmark)

    Thyssen, Jacob Pontoppidan; Jellesen, Morten Stendahl; Menné, Torkil

    2010-01-01

    . Conclusions: This study showed that only a minority of inexpensive jewellery purchased in Denmark released cobalt when analysed with the cobalt spot test. As fashion trends fluctuate and we found cobalt release from dark appearing jewellery, cobalt release from consumer items should be monitored in the future......Objectives: The aim was to study 354 consumer items using the cobalt spot test. Cobalt release was assessed to obtain a risk estimate of cobalt allergy and dermatitis in consumers who would wear the jewellery. Methods: The cobalt spot test was used to assess cobalt release from all items...

  20. Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons.

    Science.gov (United States)

    Lund, Trine M; Risa, Oystein; Sonnewald, Ursula; Schousboe, Arne; Waagepetersen, Helle S

    2009-07-01

    Ketone bodies serve as alternative energy substrates for the brain in cases of low glucose availability such as during starvation or in patients treated with a ketogenic diet. The ketone bodies are metabolized via a distinct pathway confined to the mitochondria. We have compared metabolism of [2,4-(13)C]beta-hydroxybutyrate to that of [1,6-(13)C]glucose in cultured glutamatergic neurons and investigated the effect of neuronal activity focusing on the aspartate-glutamate homeostasis, an essential component of the excitatory activity in the brain. The amount of (13)C incorporation and cellular content was lower for glutamate and higher for aspartate in the presence of [2,4-(13)C]beta-hydroxybutyrate as opposed to [1,6-(13)C]glucose. Our results suggest that the change in aspartate-glutamate homeostasis is due to a decreased availability of NADH for cytosolic malate dehydrogenase and thus reduced malate-aspartate shuttle activity in neurons using beta-hydroxybutyrate. In the presence of glucose, the glutamate content decreased significantly upon activation of neurotransmitter release, whereas in the presence of only beta-hydroxybutyrate, no decrease in the glutamate content was observed. Thus, the fraction of the glutamate pool available for transmitter release was diminished when metabolizing beta-hydroxybutyrate, which is in line with the hypothesis of formation of transmitter glutamate via an obligatory involvement of the malate-aspartate shuttle.

  1. Astrocyte-derived adenosine is central to the hypnogenic effect of glucose

    Science.gov (United States)

    Scharbarg, Emeric; Daenens, Marion; Lemaître, Frédéric; Geoffroy, Hélène; Guille-Collignon, Manon; Gallopin, Thierry; Rancillac, Armelle

    2016-01-01

    Sleep has been hypothesised to maintain a close relationship with metabolism. Here we focus on the brain structure that triggers slow-wave sleep, the ventrolateral preoptic nucleus (VLPO), to explore the cellular and molecular signalling pathways recruited by an increase in glucose concentration. We used infrared videomicroscopy on ex vivo brain slices to establish that glucose induces vasodilations specifically in the VLPO via the astrocytic release of adenosine. Real-time detection by in situ purine biosensors further revealed that the adenosine level doubles in response to glucose, and triples during the wakefulness period. Finally, patch-clamp recordings uncovered the depolarizing effect of adenosine and its A2A receptor agonist, CGS-21680, on sleep-promoting VLPO neurons. Altogether, our results provide new insights into the metabolically driven release of adenosine. We hypothesise that adenosine adjusts the local energy supply to local neuronal activity in response to glucose. This pathway could contribute to sleep-wake transition and sleep intensity. PMID:26755200

  2. Glucose-induced insulin resistance of skeletal-muscle glucose transport and uptake

    DEFF Research Database (Denmark)

    Richter, Erik; Hansen, B F; Hansen, S A

    1988-01-01

    in the presence of glucose and insulin. The data indicate that exposure to a moderately increased glucose concentration (12 mM) leads to rapidly developing resistance of skeletal-muscle glucose transport and uptake to maximal insulin stimulation. The effect of glucose is enhanced by simultaneous insulin exposure......, whereas exposure for 5 h to insulin itself does not cause measurable resistance to maximal insulin stimulation.......The ability of glucose and insulin to modify insulin-stimulated glucose transport and uptake was investigated in perfused skeletal muscle. Here we report that perfusion of isolated rat hindlimbs for 5 h with 12 mM-glucose and 20,000 microunits of insulin/ml leads to marked, rapidly developing...

  3. 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

  4. 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

  5. A glucose oxidase-coupled DNAzyme sensor for glucose detection in tears and saliva.

    Science.gov (United States)

    Liu, Chengcheng; Sheng, Yongjie; Sun, Yanhong; Feng, Junkui; Wang, Shijin; Zhang, Jin; Xu, Jiacui; Jiang, Dazhi

    2015-08-15

    Biosensors have been widely investigated and utilized in a variety of fields ranging from environmental monitoring to clinical diagnostics. Glucose biosensors have triggered great interest and have been widely exploited since glucose determination is essential for diabetes diagnosis. In here, we designed a novel dual-enzyme biosensor composed of glucose oxidase (GOx) and pistol-like DNAzyme (PLDz) to detect glucose levels in tears and saliva. First, GOx, as a molecular recognition element, catalyzes the oxidation of glucose forming H2O2; then PLDz recognizes the produced H2O2 as a secondary signal and performs a self-cleavage reaction promoted by Mn(2+), Co(2+) and Cu(2+). Thus, detection of glucose could be realized by monitoring the cleavage rate of PLDz. The slope of the cleavage rate of PLDz versus glucose concentration curve was fitted with a Double Boltzmann equation, with a range of glucose from 100 nM to 10mM and a detection limit of 5 μM. We further applied the GOx-PLDz 1.0 biosensor for glucose detection in tears and saliva, glucose levels in which are 720±81 μM and 405±56 μM respectively. Therefore, the GOx-PLDz 1.0 biosensor is able to determine glucose levels in tears and saliva as a noninvasive glucose biosensor, which is important for diabetic patients with frequent/continuous glucose monitoring requirements. In addition, induction of DNAzyme provides a new approach in the development of glucose biosensors. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Glucose turnover, gluconeogenesis from glycerol, and estimation of net glucose cycling in cancer patients

    International Nuclear Information System (INIS)

    Lundholm, K.; Edstroem, S.; Karlberg, I.; Ekman, L.; Schersten, T.

    1982-01-01

    A double isotope method was used in patients with progressive malignancy and in control patients to measure: glucose turnover, conversion rate of carbon skeleton of glycerol into glucose, and the interorgan cycling of glucose carbons (Cori-cycle plus alanine-glucose cycle). [U- 14 C]glycerol and [6- 3 H]glucose were given intravenously as a single dose injection. The time course of the specific radioactivities of [6- 3 H] and [U- 14 C]glucose was followed in blood. The pool size and the turnover rate of glucose were increased in the cancer group as compared with the control patients. The net recycling of glucose carbons was not increased in the cancer group, despite the increased turnover of glucose. The alterations in the metabolism of glucose did not correlate with the plasma levels of insulin or thyroid hormones (T4, T3, rT3) neither in the entire cancer group nor in those cancer patients who were repeatedly investigated at different intervals of time. The turnover rate of glucose in the cancer patients correlated inversely to their body weight index. The gluconeogenesis rate, given as the fractional conversion rate of the injected radioactive dose of [ 14 C]glycerol, or as mol glucose . kg body weight-1 . day-1, was increased in the cancer group, but still contributed only 3% of the glucose turnover rate in both cancer and control patients. We conclude that an increased gluconeogenesis from glycerol is not significant in terms of energy expenditure in patients with progressive malignancy, as has previously been concluded for the gluconeogenesis from alanine. It seems that increased turnover of glucose may contribute to inappropriately high energy expenditure in cancer patients

  7. 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

    2016-12-01

    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

  8. 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

  9. Blockade of store-operated calcium entry alleviates high glucose-induced neurotoxicity via inhibiting apoptosis in rat neurons.

    Science.gov (United States)

    Xu, Zhenkuan; Xu, Wenzhe; Song, Yan; Zhang, Bin; Li, Feng; Liu, Yuguang

    2016-07-25

    Altered store-operated calcium entry (SOCE) has been suggested to be involved in many diabetic complications. However, the association of altered SOCE and diabetic neuronal damage remains unclear. This study aimed to investigate the effects of altered SOCE on primary cultured rat neuron injury induced by high glucose. Our data demonstrated that high glucose increased rat neuron injury and upregulated the expression of store-operated calcium channel (SOC). Inhibition of SOCE by a pharmacological inhibitor and siRNA knockdown of stromal interaction molecule 1 weakened the intracellular calcium overload, restored mitochondrial membrane potential, downregulated cytochrome C release and inhibited cell apoptosis. As well, treatment with the calcium chelator BAPTA-AM prevented cell apoptosis by ameliorating the high glucose-increased intracellular calcium level. These findings suggest that SOCE blockade may alleviate high glucose-induced neuronal damage by inhibiting apoptosis. SOCE might be a promising therapeutic target in diabetic neurotoxicity. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  10. Direct evidence for insulin-induced capillary recruitment in skin of healthy subjects during physiological hyperinsulinemia

    NARCIS (Netherlands)

    Serne, EH; IJzerman, RG; Gans, ROB; Nijveldt, R; de Vries, G; Evertz, R; Donker, AJM; Stehouwer, CDA

    It has been proposed that insulin-mediated changes in muscle perfusion modulate insulin-mediated glucose uptake. However, the putative effects of insulin on the microcirculation that permit such modulation have not been studied in humans. We examined the effects of systemic hyperinsulinemia on skin

  11. 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.

  12. Exercising Tactically for Taming Postmeal Glucose Surges

    Directory of Open Access Journals (Sweden)

    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.

  13. Standardization versus customization of glucose reporting.

    Science.gov (United States)

    Rodbard, David

    2013-05-01

    Bergenstal et al. (Diabetes Technol Ther 2013;15:198-211) described an important approach toward standardization of reporting and analysis of continuous glucose monitoring and self-monitoring of blood glucose (SMBG) data. The ambulatory glucose profile (AGP), a composite display of glucose by time of day that superimposes data from multiple days, is perhaps the most informative and useful of the many graphical approaches to display glucose data. However, the AGP has limitations; some variations are desirable and useful. Synchronization with respect to meals, traditionally used in glucose profiles for SMBG data, can improve characterization of postprandial glucose excursions. Several other types of graphical display are available, and recently developed ones can augment the information provided by the AGP. There is a need to standardize the parameters describing glycemic variability and cross-validate the available computer programs that calculate glycemic variability. Clinical decision support software can identify and prioritize clinical problems, make recommendations for modifications of therapy, and explain its justification for those recommendations. The goal of standardization is challenging in view of the diversity of clinical situations and of computing and display platforms and software. Standardization is desirable but must be done in a manner that permits flexibility and fosters innovation.

  14. Effects of pentylenetetrazole and glutamate on metabolism of [U-(13)C]glucose in cultured cerebellar granule neurons.

    Science.gov (United States)

    Eloqayli, Haytham; Qu, Hong; Unsgård, Geirmund; Sletvold, Olav; Hadidi, Hakam; Sonnewald, Ursula

    2002-02-01

    This study was performed to analyze the effects of glutamate and the epileptogenic agent pentylenetetrazole (PTZ) on neuronal glucose metabolism. Cerebellar granule neurons were incubated for 2 h in medium containing 3 mM [U-(13)C]glucose, with and without 0.25 mM glutamate and/or 10 mM PTZ. In the presence of PTZ, decreased glucose consumption with unchanged lactate release was observed, indicating decreased glucose oxidation. PTZ also slowed down tricarboxylic acid (TCA) cycle activity as evidenced by the decreased amounts of labeled aspartate and [1,2-(13)C]glutamate. When glutamate was present, glucose consumption was also decreased. However, the amount of glutamate, derived from [U-(13)C]glucose via the first turn of the TCA cycle, was increased. The decreased amount of [1,2-(13)C]glutamate, derived from the second turn in the TCA cycle, and increased amount of aspartate indicated the dilution of label due to the entrance of unlabeled glutamate into TCA cycle. In the presence of glutamate plus PTZ, the effect of PTZ was enhanced by glutamate. Labeled alanine was detected only in the presence of glutamate plus PTZ, which indicated that oxaloacetate was a better amino acid acceptor than pyruvate. Furthermore, there was also evidence for intracellular compartmentation of oxaloacetate metabolism. Glutamate and PTZ caused similar metabolic changes, however, via different mechanisms. Glutamate substituted for glucose as energy substrate in the TCA cycle, whereas, PTZ appeared to decrease mitochondrial activity.

  15. Biotin enhances ATP synthesis in pancreatic islets of the rat, resulting in reinforcement of glucose-induced insulin secretion.

    Science.gov (United States)

    Sone, Hideyuki; Sasaki, Yuka; Komai, Michio; Toyomizu, Masaaki; Kagawa, Yasuo; Furukawa, Yuji

    2004-02-13

    Previous studies showed that biotin enhanced glucose-induced insulin secretion. Changes in the cytosolic ATP/ADP ratio in the pancreatic islets participate in the regulation of insulin secretion by glucose. In the present study we investigated whether biotin regulates the cytosolic ATP/ADP ratio in glucose-stimulated islets. When islets were stimulated with glucose plus biotin, the ATP/ADP ratio increased to approximately 160% of the ATP/ADP ratio in islets stimulated with glucose alone. The rate of glucose oxidation, assessed by CO(2) production, was also about 2-fold higher in islets treated with biotin. These increasing effects of biotin were proportional to the effects seen in insulin secretion. There are no previous reports of vitamins, such as biotin, directly affecting ATP synthesis. Our data indicate that biotin enhances ATP synthesis in islets following the increased rate of substrate oxidation in mitochondria and that, as a consequence of these events, glucose-induced insulin release is reinforced by biotin.

  16. Distribution and kinetics of glucose in rats analyzed by noncompartmental and compartmental analysis

    International Nuclear Information System (INIS)

    Raman, M.; Radziuk, J.; Hetenyi, G. Jr.

    1990-01-01

    The steady-state kinetics and distribution of glucose were assessed using noncompartmental and various two-compartment models in rats that were infused with insulin (+/- euglycemic clamping), methylprednisolone (MP), or phlorizin (PHL) as well as rats injected with protamine-zinc-insulin (PZI) or rendered diabetic. Decreases in clearance of glucose (PCR) were greatest with insulin infusion, followed by PHL, MP, and PZI treatments. PCR decreased in diabetes to 25% of normal. With hyperinsulinemia and euglycemia, turnover rates were 1.18 times the rate of glucose infusion. In normal rats the ratio of the contents of the two compartments was 0.6-0.8 (depending on the model). Significant increases, of between 2.8 and 5.2, were observed with insulin infusion and between 0.8 and 1.8 with PHL, again depending on the model. Because PHL-induced changes in PCR are renal, these data suggest that variations in glucose distribution depend on changes in PCR as well as insulin. The intercompartmental rate constant decreased, and the noncompartmental volume of distribution increased to reflect the above changes. In non-steady-state studies, glucose release increased in response to insulin but not to PHL in contrast to other species

  17. Effect of somatostatin on nonesterified fatty acid levels modifies glucose homeostasis during fasting

    International Nuclear Information System (INIS)

    Hendrick, G.K.; Frizzell, R.T.; Cherrington, A.D.

    1987-01-01

    In the 7-days fasted conscious dog, unlike the postabsorptive conscious dog, somatostatin infusion results in decreased levels of nonesterified fatty acids (NEFA) and increased glucose utilization (R d ) even when insulin and glucagon levels are held constant. The aim of this study was to determine whether NEFA replacement in such animals would prevent the increase in R d . In each of three protocols there was an 80-min tracer equilibration period, a 40-min basal period, and a 3-h test period. During the test period in the first protocol saline was infused, in the second protocol somatostatin was infused along with intraportal replacement amounts of insulin and glucagon (hormone replacement), while in the third protocol somatostatin plus the pancreatic hormones were infused with concurrent heparin plus Intralipid infusion. Glucose turnover was assessed using [3- 3 H]glucose. The peripheral levels of insulin, glucagon, and glucose were similar and constant in all three protocols; however, during somatostatin infusion, exogenous glucose infusion was necessary to maintain euglycemia. The NEFA level was constant during saline infusion and decreased in the hormone replacement protocol. In the hormone replacement plus NEFA protocol, the NEFA level did not change during the first 90-min period and then increased during the second 90-min period. After a prolonged fast in the dog, (1) somatostatin directly or indirectly inhibits adipose tissue NEFA release and causes a decrease in the plasma NEFA level, and (2) this decrease in the NEFA level causes an increase in R d

  18. Enhancing human islet transplantation by localized release of trophic factors from PLG scaffolds.

    Science.gov (United States)

    Hlavaty, K A; Gibly, R F; Zhang, X; Rives, C B; Graham, J G; Lowe, W L; Luo, X; Shea, L D

    2014-07-01

    Islet transplantation represents a potential cure for type 1 diabetes, yet the clinical approach of intrahepatic delivery is limited by the microenvironment. Microporous scaffolds enable extrahepatic transplantation, and the microenvironment can be designed to enhance islet engraftment and function. We investigated localized trophic factor delivery in a xenogeneic human islet to mouse model of islet transplantation. Double emulsion microspheres containing exendin-4 (Ex4) or insulin-like growth factor-1 (IGF-1) were incorporated into a layered scaffold design consisting of porous outer layers for islet transplantation and a center layer for sustained factor release. Protein encapsulation and release were dependent on both the polymer concentration and the identity of the protein. Proteins retained bioactivity upon release from scaffolds in vitro. A minimal human islet mass transplanted on Ex4-releasing scaffolds demonstrated significant improvement and prolongation of graft function relative to blank scaffolds carrying no protein, and the release profile significantly impacted the duration over which the graft functioned. Ex4-releasing scaffolds enabled better glycemic control in animals subjected to an intraperitoneal glucose tolerance test. Scaffolds releasing IGF-1 lowered blood glucose levels, yet the reduction was insufficient to achieve euglycemia. Ex4-delivering scaffolds provide an extrahepatic transplantation site for modulating the islet microenvironment to enhance islet function posttransplant. © Copyright 2014 The American Society of Transplantation and the American Society of Transplant Surgeons.

  19. Interaction between exogenous insulin, endogenous insulin, and glucose in type 2 diabetes patients.

    Science.gov (United States)

    Janukonyté, Jurgita; Parkner, Tina; Bruun, Niels Henrik; Lauritzen, Torsten; Christiansen, Jens Sandahl; Laursen, Torben

    2015-05-01

    Little is known about the influence of exogenous insulin and actual glucose levels on the release of endogenous insulin in insulin-treated type 2 diabetes mellitus (T2DM) patients. This study investigated the interaction among serum endogenous insulin (s-EI), serum exogenous insulin aspart (s-IAsp), and blood glucose levels in an experimental short-term crossover design. Eight T2DM patients (63.52 years old; range, 49-69 years; mean body mass index, 28.8±3.8 kg/m(2)) were randomized to treatment with individual fixed doses of insulin aspart (0.5-1.5 IU/h) as a continuous subcutaneous insulin infusion (CSII) during a 10-h period on two occasions with different duration of hyperglycemia: (1) transient hyperglycemia for 2 h (visit TH) and (2) continuous hyperglycemia for 12 h (visit CH). During steady state the variances of plasma glucose (p-glucose), s-IAsp, and s-EI were equal within visit TH and within visit CH, but variances were significantly higher during visit CH compared with visit TH. The s-IAsp reached lower levels at visit CH compared with visit TH (test for slope=1, P=0.005). The s-EI depended on p-glucose in a nonlinear fashion during the first 100 min of both visits when s-IAsp was undetectable (adjusted R(2)=0.9). A complex but statistically significant interaction among s-IAsp, s-EI, p-glucose, and patients was observed during measurable s-IAsp levels (adjusted R(2)=0.70). Endogenous and exogenous insulin showed higher variation during continuous hyperglycemia. Significantly lower levels of exogenous insulin were observed following CSII during continuous hyperglycemia compared with transient hyperglycemia. Endogenous insulin levels could in a complex way be explained by an individual interaction among p-glucose and serum exogenous insulin, if present.

  20. Orexins control intestinal glucose transport by distinct neuronal, endocrine, and direct epithelial pathways.

    Science.gov (United States)

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

    2007-10-01

    Orexins are neuropeptides involved in energy homeostasis. We investigated the effect of orexin A (OxA) and orexin B (OxB) on intestinal glucose transport in the rat. Injection of orexins led to a decrease in the blood glucose level in oral glucose tolerance tests (OGTTs). Effects of orexins on glucose entry were analyzed in Ussing chambers using the Na(+)-dependent increase in short-circuit current (Isc) to quantify jejunal glucose transport. The rapid and marked increase in Isc induced by luminal glucose was inhibited by 10 nmol/l OxA or OxB (53 and 59%, respectively). Response curves to OxA and OxB were not significantly different with half-maximal inhibitory concentrations at 0.9 and 0.4 nmol/l, respectively. On the one hand, OxA-induced inhibition of Isc was reduced by the neuronal blocker tetrodotoxin (TTX) and by a cholecystokinin (CCK) 2R antagonist, indicating involvement of neuronal and endocrine CCK-releasing cells. The OX(1)R antagonist SB334867 had no effect on OxA-induced inhibition, which is likely to occur via a neuronal and/or endocrine OX(2)R. On the other hand, SB334867 induced a significant right shift of the concentration-effect curve for OxB. This OxB-preferring OX(1)R pathway was not sensitive to TTX or to CCKR antagonists, suggesting that OxB may act directly on enterocytic OX(1)R. These distinct effects of OxA and OxB are consistent with the expression of OX(1)R and OX(2)R mRNA in the epithelial and nonepithelial tissues, respectively. Our data delineate a new function for orexins as inhibitors of intestinal glucose absorption and provide a new basis for orexin-induced short-term control of energy homeostasis.

  1. Glucose in Urine Test: MedlinePlus Lab Test Information

    Science.gov (United States)

    ... glucose test to help make a diagnosis. References American Diabetes Association [Internet]. Arlington (VA): American Diabetes Association; c1995–2017. Checking Your Blood Glucose [cited 2017 ...

  2. Blood-Brain Glucose Transfer: Repression in Chronic Hyperglycemia

    Science.gov (United States)

    Gjedde, Albert; Crone, Christian

    1981-10-01

    Diabetic patients with increased plasma glucose concentrations may develop cerebral symptoms of hypoglycemia when their plasma glucose is rapidly lowered to normal concentrations. The symptoms may indicate insufficient transport of glucose from blood to brain. In rats with chronic hyperglycemia the maximum glucose transport capacity of the blood-brain barrier decreased from 400 to 290 micromoles per 100 grams per minute. When plasma glucose was lowered to normal values, the glucose transport rate into brain was 20 percent below normal. This suggests that repressive changes of the glucose transport mechanism occur in brain endothelial cells in response to increased plasma glucose.

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

    Science.gov (United States)

    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.

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

    Directory of Open Access Journals (Sweden)

    Jianhui Liu

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

  5. Glucose metabolism disorder in obese children assessed by continuous glucose monitoring system.

    Science.gov (United States)

    Zou, Chao-Chun; Liang, Li; Hong, Fang; Zhao, Zheng-Yan

    2008-02-01

    Continuous glucose monitoring system (CGMS) can measure glucose levels at 5-minute intervals over a few days, and may be used to detect hypoglycemia, guide insulin therapy, and control glucose levels. This study was undertaken to assess the glucose metabolism disorder by CGMS in obese children. Eighty-four obese children were studied. Interstitial fluid (ISF) glucose levels were measured by CGMS for 24 hours covering the time for oral glucose tolerance test (OGTT). Impaired glucose tolerance (IGT), impaired fasting glucose (IFG), type 2 diabetic mellitus (T2DM) and hypoglycemia were assessed by CGMS. Five children failed to complete CGMS test. The glucose levels in ISF measured by CGMS were highly correlated with those in capillary samples (r=0.775, Pobese children who finished the CGMS, 2 children had IFG, 2 had IGT, 3 had IFG + IGT, and 2 had T2DM. Nocturnal hypoglycemia was noted during the overnight fasting in 11 children (13.92%). Our data suggest that glucose metabolism disorder including hyperglycemia and hypoglycemia is very common in obese children. Further studies are required to improve the precision of the CGMS in children.

  6. Effects of taurine on plasma glucose concentration and active glucose transport in the small intestine.

    Science.gov (United States)

    Tsuchiya, Yo; Kawamata, Koichi

    2017-11-01

    Taurine lowers blood glucose levels and improves hyperglycemia. However, its effects on glucose transport in the small intestine have not been investigated. Here, we elucidated the effect of taurine on glucose absorption in the small intestine. In the oral glucose tolerance test, addition of 10 mmol/L taurine suppressed the increase in hepatic portal glucose concentrations. To investigate whether the suppressive effect of taurine occurs via down-regulation of active glucose transport in the small intestine, we performed an assay using the everted sac of the rat jejunum. Addition of taurine to the mucosal side of the jejunum suppressed active glucose transport via sodium-glucose cotransporter 1 (SGLT1). After elimination of chloride ions from the mucosal solution, taurine did not show suppressive effects on active glucose transport. These results suggest that taurine suppressed the increase in hepatic portal glucose concentrations via suppression of SGLT1 activity in the rat jejunum, depending on chloride ions. © 2017 Japanese Society of Animal Science.

  7. Correlation of Salivary Glucose Level with Blood Glucose Level in Diabetes Mellitus

    Directory of Open Access Journals (Sweden)

    Arati S. Panchbhai

    2012-07-01

    Full Text Available Objectives: There is alarming rise in number of people with diabetes mellitus over these years. If glucose in saliva is linked to glucose in blood it can be used to detect diabetes mellitus at an early stage. The present study is undertaken with the aim to assess the correlation of salivary glucose level with blood glucose level in people with diabetes mellitus. Material and Methods: For investigations, 2 sets of samples of people with diabetes and the age and sex matched non-diabetic subjects were recruited. The salivary glucose was analyzed in unstimulated whole saliva samples using glucose oxidase method. Pearson’s correlation coefficient test was applied to assess the correlation between salivary glucose level and blood glucose level. Results: The significant (P < 0.05 positive correlation of salivary glucose level and fasting blood glucose level was observed in people with uncontrolled diabetes in both the sets of samples.Conclusions: Although study suggests some potential for saliva as a marker in monitoring of diabetes mellitus, there are many aspects that need clarification before we reach to a conclusion.

  8. Microbial production of glucose/fructose syrups

    Energy Technology Data Exchange (ETDEWEB)

    Matur, A.; Saglam, N.

    1982-04-01

    With the ever-increasing demand for sugar and the trend in rising price, rapid progress in research on new and/or alternative sweeteners has been inevitable during the past decade or so. Pure glucose, glucose/fructose, glucose/maltose syrups are often called isosyrups. Isosyrups have been recognized as a good alternative sources of sugar. These are used today in the manufacture of soft drinks, jams and jellies, confectionary, baking fermentation, dietetic and infant food, ice-cream, pharmaceutical processes, etc. Isosyrups are produced by hydrolysis of starch and cellulocis raw materials have been utilized for the production of isosyrups.

  9. Plasma glucagon and glucose recovery after hypoglycemia

    DEFF Research Database (Denmark)

    Hilsted, J; Frandsen, Henrik Lund; Holst, Janett

    1991-01-01

    ) and of isolated alpha-adrenergic blockade on hormonal responses to hypoglycemia and on blood glucose recovery after hypoglycemia in healthy subjects. Neither of the pharmacological blockades had any significant effects on plasma glucagon responses to hypoglycemia nor had they any effect on the rate of blood...... glucose recovery after hypoglycemia. We conclude that the autonomic nervous system has no major influence on the glucagon response to hypoglycemia in healthy man. Changes in autonomic nervous activity are not essential for blood glucose recovery after hypoglycemia in healthy man....

  10. Optimal glucose management in the perioperative period.

    Science.gov (United States)

    Evans, Charity H; Lee, Jane; Ruhlman, Melissa K

    2015-04-01

    Hyperglycemia is a common finding in surgical patients during the perioperative period. Factors contributing to poor glycemic control include counterregulatory hormones, hepatic insulin resistance, decreased insulin-stimulated glucose uptake, use of dextrose-containing intravenous fluids, and enteral and parenteral nutrition. Hyperglycemia in the perioperative period is associated with increased morbidity, decreased survival, and increased resource utilization. Optimal glucose management in the perioperative period contributes to reduced morbidity and mortality. To readily identify hyperglycemia, blood glucose monitoring should be instituted for all hospitalized patients. Published by Elsevier Inc.

  11. Lifestyle, glucose regulation and the cognitive effects of glucose load in middle-aged adults.

    Science.gov (United States)

    Riby, Leigh M; McLaughlin, Jennifer; Riby, Deborah M; Graham, Cheryl

    2008-11-01

    Interventions aimed at improving glucose regulatory mechanisms have been suggested as a possible source of cognitive enhancement in the elderly. In particular, previous research has identified episodic memory as a target for facilitation after either moderate increases in glycaemia (after a glucose drink) or after improvements in glucose regulation. The present study aimed to extend this research by examining the joint effects of glucose ingestion and glucose regulation on cognition. In addition, risk factors associated with the development of poor glucose regulation in middle-aged adults were considered. In a repeated measures design, thirty-three middle-aged adults (aged 35-55 years) performed a battery of memory and non-memory tasks after either 25 g or 50 g glucose or a sweetness matched placebo drink. To assess the impact of individual differences in glucose regulation, blood glucose measurements were taken on four occasions during testing. A lifestyle and diet questionnaire was also administered. Consistent with previous research, episodic memory ability benefited from glucose ingestion when task demands were high. Blood glucose concentration was also found to predict performance across a number of cognitive domains. Interestingly, the risk factors associated with poor glucose regulation were linked to dietary impacts traditionally associated with poor health, e.g. the consumption of high-sugar sweets and drinks. The research replicates earlier work suggesting that task demands are critical to the glucose facilitation effect. Importantly, the data demonstrate clear associations between elevated glycaemia and relatively poor cognitive performance, which may be partly due to the effect of dietary and lifestyle factors.

  12. Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

    Science.gov (United States)

    Chukwuma, Chika Ifeanyi; Ibrahim, Mohammed Auwal; Islam, Md Shahidul

    2016-12-01

    The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

  13. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    Energy Technology Data Exchange (ETDEWEB)

    Hsu, Ya-Yun [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Tseng, Yu-Ting [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Lo, Yi-Ching, E-mail: yichlo@kmu.edu.tw [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

    2013-11-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

  14. Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

    International Nuclear Information System (INIS)

    Hsu, Ya-Yun; Tseng, Yu-Ting; Lo, Yi-Ching

    2013-01-01

    Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H 2 O 2 neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS production and

  15. Released radioactivity reducing facility

    International Nuclear Information System (INIS)

    Tanaka, Takeaki.

    1992-01-01

    Upon occurrence of a reactor accident, penetration portions of a reactor container, as a main leakage source from a reactor container, are surrounded by a plurality of gas-tight chambers, the outside of which is surrounded by highly gas-tightly buildings. Branched pipelines of an emergency gas processing system are introduced to each of the gas-tight chambers and they are joined and in communication with an emergency gas processing device. With such a constitution, radioactive materials are prevented from leaking directly from the buildings. Further, pipeline openings of the emergency gas processing facility are disposed in the plurality highly gas-tight penetration chambers. If the radioactive materials are leaked from the reactor to elevate the pressure in the penetration chambers, the radioactive materials are introduced to a filter device in the emergency gas processing facility by way of the branched pipelines, filtered and then released to the atmosphere. Accordingly, the reliability and safety of the system can be improved. (T.M.)

  16. Containment and release management

    International Nuclear Information System (INIS)

    Lehner, J.R.; Pratt, W.T.

    1988-01-01

    Reducing the risk from potentially severe accidents by appropriate accident management strategies is receiving increased attention from the international reactor safety community. Considerable uncertainty still surrounds some of the physical phenomena likely to occur during a severe accident. The USNRC, in developing its research plan for accident management, wants to ensure that both the developers and implementers of accident management strategies are aware of the uncertainty associated with the plant operators' ability to correctly diagnose an accident, as well as the uncertainties associated with various preventive and mitigative strategies. The use of a particular accident management strategy can have both positive and negative effects on the status of a plant and these effects must be carefully weighed before a particular course of action is chosen and implemented. By using examples of severe accident scenarios, initial insights are presented here regarding the indications plant operators may have to alert them to particular accident states. Insights are also offered on the various management actions operators and plant technical staff might pursue for particular accident situations and the pros and cons associated with such actions. The examples given are taken for the most part from the containment and release phase of accident management, since this is the current focus of the effort in the accident management area at Brookhaven National Laboratory. 2 refs

  17. Released radioactivity reducing device

    International Nuclear Information System (INIS)

    Miyamoto, Yumi.

    1995-01-01

    A water scrubber is disposed in a scrubber tank and a stainless steel fiber filter is disposed above the water scrubber. The upper end of the scrubber tank is connected by way of a second bent tube to a capturing vessel incorporating a moisture removing layer and an activated carbon filter. The exit of the capturing vessel is connected to a stack. Upon occurrence of an accident of a BWR-type power plant, gases containing radioactive materials released from a reactor container are discharged into the water scrubber from a first bent tube through a venturi tube nozzle, and water soluble and aerosol-like radioactive materials are captured in the water. Aerosol and splashes of water droplets which can not be captured thoroughly by the water scrubber are captured by the stainless steel fiber filter. Gases passing through the scrubber tank are introduced to a capturing vessel through a second bent tube, and organic iodine is captured by the activated carbon filter. (I.N.)

  18. COMMERCIAL SNF ACCIDENT RELEASE FRACTIONS

    Energy Technology Data Exchange (ETDEWEB)

    S.O. Bader

    1999-10-18

    The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

  19. COMMERCIAL SNF ACCIDENT RELEASE FRACTIONS

    International Nuclear Information System (INIS)

    S.O. Bader

    1999-01-01

    The purpose of this design analysis is to specify and document the total and respirable fractions for radioactive materials that are released from an accident event at the Monitored Geologic Repository (MGR) involving commercial spent nuclear fuel (CSNF) in a dry environment. The total and respirable release fractions will be used to support the preclosure licensing basis for the MGR. The total release fraction is defined as the fraction of total CSNF assembly inventory, typically expressed as an activity inventory (e.g., curies), of a given radionuclide that is released to the environment from a waste form. The radionuclides are released from the inside of breached fuel rods (or pins) and from the detachment of radioactive material (crud) from the outside surfaces of fuel rods and other components of fuel assemblies. The total release fraction accounts for several mechanisms that tend to retain, retard, or diminish the amount of radionuclides that are available for transport to dose receptors or otherwise can be shown to reduce exposure of receptors to radiological releases. The total release fraction includes a fraction of airborne material that is respirable and could result in inhalation doses. This subset of the total release fraction is referred to as the respirable release fraction. Potential accidents may involve waste forms that are characterized as either bare (unconfined) fuel assemblies or confined fuel assemblies. The confined CSNF assemblies at the MGR are contained in shipping casks, canisters, or disposal containers (waste packages). In contrast to the bare fuel assemblies, the container that confines the fuel assemblies has the potential of providing an additional barrier for diminishing the total release fraction should the fuel rod cladding breach during an accident. However, this analysis will not take credit for this additional bamer and will establish only the total release fractions for bare unconfined CSNF assemblies, which may however be

  20. The diabetic phenotype is conserved in myotubes established from diabetic subjects: evidence for primary defects in glucose transport and glycogen synthase activity

    DEFF Research Database (Denmark)

    Gaster, Michael; Petersen, Ingrid; Højlund, Kurt

    2002-01-01

    The most well-described defect in the pathophysiology of type 2 diabetes is reduced insulin-mediated glycogen synthesis in skeletal muscles. It is unclear whether this defect is primary or acquired secondary to dyslipidemia, hyperinsulinemia, or hyperglycemia. We determined the glycogen synthase...

  1. Evidence for brain glucose dysregulation in Alzheimer's disease.

    Science.gov (United States)

    An, Yang; Varma, Vijay R; Varma, Sudhir; Casanova, Ramon; Dammer, Eric; Pletnikova, Olga; Chia, Chee W; Egan, Josephine M; Ferrucci, Luigi; Troncoso, Juan; Levey, Allan I; Lah, James; Seyfried, Nicholas T; Legido-Quigley, Cristina; O'Brien, Richard; Thambisetty, Madhav

    2018-03-01

    It is unclear whether abnormalities in brain glucose homeostasis are associated with Alzheimer's disease (AD) pathogenesis. Within the autopsy cohort of the Baltimore Longitudinal Study of Aging, we measured brain glucose concentration and assessed the ratios of the glycolytic amino acids, serine, glycine, and alanine to glucose. We also quantified protein levels of the neuronal (GLUT3) and astrocytic (GLUT1) glucose transporters. Finally, we assessed the relationships between plasma glucose measured before death and brain tissue glucose. Higher brain tissue glucose concentration, reduced glycolytic flux, and lower GLUT3 are related to severity of AD pathology and the expression of AD symptoms. Longitudinal increases in fasting plasma glucose levels are associated with higher brain tissue glucose concentrations. Impaired glucose metabolism due to reduced glycolytic flux may be intrinsic to AD pathogenesis. Abnormalities in brain glucose homeostasis may begin several years before the onset of clinical symptoms. Copyright © 2017 the Alzheimer's Association. All rights reserved.

  2. Underground water stress release models

    Science.gov (United States)

    Li, Yong; Dang, Shenjun; Lü, Shaochuan

    2011-08-01

    The accumulation of tectonic stress may cause earthquakes at some epochs. However, in most cases, it leads to crustal deformations. Underground water level is a sensitive indication of the crustal deformations. We incorporate the information of the underground water level into the stress release models (SRM), and obtain the underground water stress release model (USRM). We apply USRM to the earthquakes occurred at Tangshan region. The analysis shows that the underground water stress release model outperforms both Poisson model and stress release model. Monte Carlo simulation shows that the simulated seismicity by USRM is very close to the real seismicity.

  3. Glucose enhancement of human memory: a comprehensive research review of the glucose memory facilitation effect.

    Science.gov (United States)

    Smith, Michael A; Riby, Leigh M; Eekelen, J Anke M van; Foster, Jonathan K

    2011-01-01

    The brain relies upon glucose as its primary fuel. In recent years, a rich literature has developed from both human and animal studies indicating that increases in circulating blood glucose can facilitate cognitive functioning. This phenomenon has been termed the 'glucose memory facilitation effect'. The purpose of this review is to discuss a number of salient studies which have investigated the influence of glucose ingestion on neurocognitive performance in individuals with (a) compromised neurocognitive capacity, as well as (b) normally functioning individuals (with a focus on research conducted with human participants). The proposed neurocognitive mechanisms purported to underlie the modulatory effect of glucose on neurocognitive performance will also be considered. Many theories have focussed upon the hippocampus, given that this brain region is heavily implicated in learning and memory. Further, it will be suggested that glucose is a possible mechanism underlying the phenomenon that enhanced memory performance is typically observed for emotionally laden stimuli. Copyright © 2010 Elsevier Ltd. All rights reserved.

  4. Fluorometric determination of free glucose and glucose 6-phosphate in cows' milk and other opaque matrices

    DEFF Research Database (Denmark)

    Larsen, Torben

    2015-01-01

    Analyses of free glucose and glucose 6-phosphate in milk have until now been dependent upon several time consuming and troublesome procedures. This has limited investigations in the area. The present article presents a new, reliable, analytical procedure, based on enzymatic degradation and fluoro......Analyses of free glucose and glucose 6-phosphate in milk have until now been dependent upon several time consuming and troublesome procedures. This has limited investigations in the area. The present article presents a new, reliable, analytical procedure, based on enzymatic degradation...... and fluorometric detection. Standards and control materials were based on milk that was stripped of intrinsic glucose and glucose 6-phosphate in order to obtain standards and samples based on the same matrix. The analysis works without pre-treatment of the samples, e.g. without centrifugation and precipitation...

  5. Conditions With High Intracellular Glucose Inhibit Sensing Through Glucose Sensor Snf3 in Saccharomyces cerevisiae

    DEFF Research Database (Denmark)

    Karhumaa, Kaisa; Wu, B.Q.; Kielland-Brandt, Morten

    2010-01-01

    as for amino acids. An alternating-access model of the function of transporter-like sensors has been previously suggested based on amino acid sensing, where intracellular ligand inhibits binding of extracellular ligand. Here we studied the effect of intracellular glucose on sensing of extracellular glucose...... through the transporter-like sensor Snf3 in yeast. Sensing through Snf3 was determined by measuring degradation of Mth1 protein. High intracellular glucose concentrations were achieved by using yeast strains lacking monohexose transporters which were grown on maltose. The apparent affinity...... of extracellular glucose to Snf3 was measured for cells grown in non-fermentative medium or on maltose. The apparent affinity for glucose was lowest when the intracellular glucose concentration was high. The results conform to an alternating-access model for transporter-like sensors. J. Cell. Biochem. 110: 920...

  6. 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.

  7. 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.

  8. Glucose: the worst of all evils?

    African Journals Online (AJOL)

    occurs secondary to elevated levels of cortisol, epinephrine, norepinephrine ... recovery and higher mortality in stroke patients,14,15,16,17 and an increased morbidity and .... TGC come into play.1,24 Avoiding variable blood glucose and exact.

  9. Coffee Consumption Attenuates Insulin Resistance and Glucose ...

    African Journals Online (AJOL)

    olayemitoyin

    Alzheimer's disease (CBS 2012), dementia (Health news 2012) and ... the effects of coffee on insulin resistance and glucose tolerance as ..... mortality among patients with type 2 diabetes. ... transporter family: Structure, function and tissue-.

  10. Glucose (xylose) isomerase production from thermotolerant and ...

    African Journals Online (AJOL)

    Owner

    2012-11-13

    Nov 13, 2012 ... in the production of the high fructose corn syrup (HFCS) from corn starch. ... Key words: Glucose isomerase, xylose isomerase, enzyme activity, Klebsiella, ... Soil, water, and manure (five samples each) were collected from.

  11. Coffee Consumption Attenuates Insulin Resistance and Glucose ...

    African Journals Online (AJOL)

    olayemitoyin

    Intolerance in Rats fed on High-Sucrose Diet. Morakinyo AO*, Adekunbi DA, ... In addition, lipid indices such as TG and LDL as well as the .... blood glucose monitoring system (Accu-Chek. Glucometer ..... parasympathetic nerves. Diabetologia.

  12. Pathophysiological Characteristics Underlying Different Glucose Response Curves

    DEFF Research Database (Denmark)

    Hulman, Adam; Witte, Daniel R; Vistisen, Dorte

    2018-01-01

    different glucose curve patterns and studied their stability and reproducibility over 3 years of follow-up. RESEARCH DESIGN AND METHODS: We analyzed data from participants without diabetes from the observational cohort from the European Group for the Study of Insulin Resistance: Relationship between Insulin...... and secretion. The glucose patterns identified at follow-up were similar to those at baseline, suggesting that the latent class method is robust. We integrated our classification model into an easy-to-use online application that facilitates the assessment of glucose curve patterns for other studies. CONCLUSIONS...... Sensitivity and Cardiovascular Disease study; participants had a five-time point OGTT at baseline (n = 1,443) and after 3 years (n = 1,045). Measures of insulin sensitivity and secretion were assessed at baseline with a euglycemic-hyperinsulinemic clamp and intravenous glucose tolerance test. Heterogeneous...

  13. Glucose isomerization in simulated moving bed reactor by Glucose isomerase

    Directory of Open Access Journals (Sweden)

    Eduardo Alberto Borges da Silva

    2006-05-01

    Full Text Available Studies were carried out on the production of high-fructose syrup by Simulated Moving Bed (SMB technology. A mathematical model and numerical methodology were used to predict the behavior and performance of the simulated moving bed reactors and to verify some important aspects for application of this technology in the isomerization process. The developed algorithm used the strategy that considered equivalences between simulated moving bed reactors and true moving bed reactors. The kinetic parameters of the enzymatic reaction were obtained experimentally using discontinuous reactors by the Lineweaver-Burk technique. Mass transfer effects in the reaction conversion using the immobilized enzyme glucose isomerase were investigated. In the SMB reactive system, the operational variable flow rate of feed stream was evaluated to determine its influence on system performance. Results showed that there were some flow rate values at which greater purities could be obtained.Neste trabalho a tecnologia de Leito Móvel Simulado (LMS reativo é aplicada no processo de isomerização da glicose visando à produção de xarope concentrado de frutose. É apresentada a modelagem matemática e uma metodologia numérica para predizer o comportamento e o desempenho de unidades reativas de leito móvel simulado para verificar alguns aspectos importantes para o emprego desta tecnologia no processo de isomerização. O algoritmo desenvolvido utiliza a abordagem que considera as equivalências entre as unidades reativas de leito móvel simulado e leito móvel verdadeiro. Parâmetros cinéticos da reação enzimática são obtidos experimentalmente usando reatores em batelada pela técnica Lineweaver-Burk. Efeitos da transferência de massa na conversão de reação usando a enzima imobilizada glicose isomerase são verificados. No sistema reativo de LMS, a variável operacional vazão da corrente de alimentação é avaliada para conhecer o efeito de sua influência no

  14. Flash release an alternative for releasing complex MEMS devices

    NARCIS (Netherlands)

    Deladi, S.; Krijnen, Gijsbertus J.M.; Elwenspoek, Michael Curt

    2004-01-01

    A novel time-saving and cost-effective release technique has been developed and is described. The physical nature of the process is explained in combination with experimental observations. The results of the flash release process are compared with those of freeze-drying and supercritical CO2

  15. Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

    Directory of Open Access Journals (Sweden)

    Natalia Gustavsson

    Full Text Available BACKGROUND: Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. METHODOLOGY/PRINCIPAL FINDINGS: In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. CONCLUSIONS: Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

  16. Neuronal calcium sensor synaptotagmin-9 is not involved in the regulation of glucose homeostasis or insulin secretion.

    Science.gov (United States)

    Gustavsson, Natalia; Wang, Xiaorui; Wang, Yue; Seah, Tingting; Xu, Jun; Radda, George K; Südhof, Thomas C; Han, Weiping

    2010-11-09

    Insulin secretion is a complex and highly regulated process. It is well established that cytoplasmic calcium is a key regulator of insulin secretion, but how elevated intracellular calcium triggers insulin granule exocytosis remains unclear, and we have only begun to define the identities of proteins that are responsible for sensing calcium changes and for transmitting the calcium signal to release machineries. Synaptotagmins are primarily expressed in brain and endocrine cells and exhibit diverse calcium binding properties. Synaptotagmin-1, -2 and -9 are calcium sensors for fast neurotransmitter release in respective brain regions, while synaptotagmin-7 is a positive regulator of calcium-dependent insulin release. Unlike the three neuronal calcium sensors, whose deletion abolished fast neurotransmitter release, synaptotagmin-7 deletion resulted in only partial loss of calcium-dependent insulin secretion, thus suggesting that other calcium-sensors must participate in the regulation of insulin secretion. Of the other synaptotagmin isoforms that are present in pancreatic islets, the neuronal calcium sensor synaptotagmin-9 is expressed at the highest level after synaptotagmin-7. In this study we tested whether synaptotagmin-9 participates in the regulation of glucose-stimulated insulin release by using pancreas-specific synaptotagmin-9 knockout (p-S9X) mice. Deletion of synaptotagmin-9 in the pancreas resulted in no changes in glucose homeostasis or body weight. Glucose tolerance, and insulin secretion in vivo and from isolated islets were not affected in the p-S9X mice. Single-cell capacitance measurements showed no difference in insulin granule exocytosis between p-S9X and control mice. Thus, synaptotagmin-9, although a major calcium sensor in the brain, is not involved in the regulation of glucose-stimulated insulin release from pancreatic β-cells.

  17. Pyrolysis of D-Glucose to Acrolein

    Science.gov (United States)

    Shen, Chong; Zhang, Igor Ying; Fu, Gang; Xu, Xin

    2011-06-01

    Despite of its great importance, the detailed molecular mechanism for carbohydrate pyrolysis remains poorly understood. We perform a density functional study with a newly developed XYG3 functional on the processes for D-glucose pyrolysis to acrolein. The most feasible reaction pathway starts from an isomerization from D-glucose to D-fructose, which then undergoes a cyclic Grob fragmentation, followed by a concerted electrocyclic dehydration to yield acrolein. This mechanism can account for the known experimental results.

  18. Oral glucose tolerance test and continuous glucose monitoring to assess diabetes development in cystic fibrosis patients.

    Science.gov (United States)

    Clemente León, María; Bilbao Gassó, Laura; Moreno-Galdó, Antonio; Campos Martorrell, Ariadna; Gartner Tizzano, Silvia; Yeste Fernández, Diego; Carrascosa Lezcano, Antonio

    2018-01-01

    Patients with cystic fibrosis (CF) undergo a slow and progressive process toward diabetes. Oral glucose tolerance test (OGTT) is recommended to diagnose impaired glucose levels in these patients. Continuous glucose monitoring (CGM) measures glucose profiles under real-life conditions. To compare OGTT and CGM results in CF patients. Paired OGTT and 6-day CGM profiles (146.2±9.1h/patient) were performed in 30 CF patients aged 10-18 years. According to OGTT, 14 patients had normal glucose tolerance (NGT), 14 abnormal glucose tolerance (AGT), and two cystic fibrosis-related diabetes (CFRD). In 27 patients (13 NGT, 13 AGT, 1 CFRD), CGM showed glucose values ranging from 140 to 200mg/dL during similar monitoring times (2%-14% with NGT, 1%-16.9% with AGT, and 3% with CFRD). Glucose peak levels ≥200mg/dL were seen in seven patients (3 NGT, 3 AGT, 1 CFRD). According to CGM, two patients had all glucose values under 140mg/dL (1 NGT, 1 AGT). Seventeen patients had glucose levels ranging from 140 to 200mg/dL (10 NGT, 6 AGT, 1 CFRD). Ten patients (3 NGT, 7 AGT) had glucose values ≥200mg/dL for ≤1% of the monitoring time and one (CFRD) for >1% of the monitoring time. OGTT results did not agree with those of the CGM. CGM allows for diagnosis of glucose changes not detected by OGTT. Such changes may contribute to optimize pre-diabetes management in CF patients. Copyright © 2017 SEEN y SED. Publicado por Elsevier España, S.L.U. All rights reserved.

  19. The association between estimated average glucose levels and fasting plasma glucose levels

    Directory of Open Access Journals (Sweden)

    Giray Bozkaya

    2010-01-01

    Full Text Available OBJECTIVE: The level of hemoglobin A1c (HbA1c, also known as glycated hemoglobin, determines how well a patient's blood glucose level has been controlled over the previous 8-12 weeks. HbA1c levels help patients and doctors understand whether a particular diabetes treatment is working and whether adjustments need to be made to the treatment. Because the HbA1c level is a marker of blood glucose for the previous 120 days, average blood glucose levels can be estimated using HbA1c levels. Our aim in the present study was to investigate the relationship between estimated average glucose levels, as calculated by HbA1c levels, and fasting plasma glucose levels. METHODS: The fasting plasma glucose levels of 3891 diabetic patient samples (1497 male, 2394 female were obtained from the laboratory information system used for HbA1c testing by the Department of Internal Medicine at the Izmir Bozyaka Training and Research Hospital in Turkey. These samples were selected from patient samples that had hemoglobin levels between 12 and 16 g/dL. The estimated glucose levels were calculated using the following formula: 28.7 x HbA1c - 46.7. Glucose and HbA1c levels were determined using hexokinase and high performance liquid chromatography (HPLC methods, respectively. RESULTS: A strong positive correlation between fasting plasma glucose levels and estimated average blood glucose levels (r=0.757, p<0.05 was observed. The difference was statistically significant. CONCLUSION: Reporting the estimated average glucose level together with the HbA1c level is believed to assist patients and doctors determine the effectiveness of blood glucose control measures.

  20. In situ green synthesis of antimicrobial carboxymethyl chitosan-nanosilver hybrids with controlled silver release.

    Science.gov (United States)

    Huang, Siqi; Yu, Zhiming; Zhang, Yang; Qi, Chusheng; Zhang, Shifeng

    2017-01-01

    In order to fabricate antimicrobial carboxymethyl chitosan-nanosilver (CMC-Ag) hybrids with controlled silver release, this study demonstrated comparable formation via three synthetic protocols: 1) carboxymethyl chitosan (CMC) and glucose (adding glucose after AgNO 3 ), 2) CMC and glucose (adding glucose before AgNO 3 ), and 3) CMC only. Under principles of green chemistry, the synthesis was conducted in an aqueous medium exposed to microwave irradiation for 10 minutes with nontoxic chemicals. The structure and formation mechanisms of the three CMC-Ag hybrids were explored using X-ray diffraction, ultraviolet-visible spectroscopy, transmission electron microscopy, and Fourier-transform infrared analyses. Additionally, antimicrobial activity and in vitro silver release of the three synthesized hybrids were investigated in detail. The results revealed that a large number of stable, uniform, and small silver nanoparticles (AgNPs) were synthesized in situ on CMC chains via protocol 1. AgNPs were well dispersed with narrow size distribution in the range of 6-20 nm, with mean diameter only 12.22±2.57 nm. The addition of glucose resulted in greater AgNP synthesis. The order of addition of glucose and AgNO 3 significantly affected particle size and size distribution of AgNPs. Compared to CMC alone and commercially available AgNPs, the antimicrobial activities of three hybrids were significantly improved. Of the three hybrids, CMC-Ag1 synthesized via protocol 1 exhibited better antimicrobial activity than CMC-Ag2 and CMC-Ag3, and showed more effective inhibition of Staphylococcus aureus than Escherichia coli . Due to strong coordination and electrostatic interactions between CMC and silver and good steric protection provided by CMC, CMC-Ag1 displayed stable and continuous silver release and better performance in retaining silver for prolonged periods than CMC-Ag2 and CMC-Ag3.