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Sample records for insulin-mediated glucose disposal

  1. Insulin-mediated glucose disposal in black south Africans with essential hypertension.

    PubMed

    Wing, J R; van der Merwe, M T; Joffe, B I; Panz, V R; Seftel, H C

    1994-07-01

    We used the hyperinsulinaemic euglycaemic clamp method to assess insulin-mediated glucose disposal in ten black South African patients with newly-diagnosed essential hypertension, compared to ten normotensive controls. The patients were all nonobese with normal glucose tolerance. Comparisons were made before and 12 weeks after treatment with a long-acting ACE inhibitor. The mean glucose disposal (M) and disposal expressed as glucose sensitivity index (M/I) were significantly reduced in the hypertensives vs. controls (M: 6.8 +/- 0.9 vs. 9.7 +/- 0.8 mg/kg/min; MI: 7.1 +/- 1.0 vs. 12.5 +/- 1.7 mg/kg/min/mU/l x 100) (p = 0.03 and 0.01, respectively). Following therapy, M/I increased in the patients to values not significantly different to those of the controls. Insulin resistance is an independent feature of essential hypertension in black South African patients, and is partially corrected by treatment with a long-acting ACE inhibitor.

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

    PubMed Central

    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 or not they elicit an additive response on IMGD. We hypothesized that CAF + ADR would elicit a greater effect than either CAF or ADR alone (i.e. that CAF effects would not be solely attributed to ADR). Subjects (n = 8) completed four trials in a randomized manner. An isoglycaemic–hyperinsulinaemic clamp was performed 30 min after the following treatments were administered: (1) placebo capsules and saline infusion ([ADR]= 0.29 nm) (PL trial), (2) CAF capsules (dose = 5 mg kg−1) and saline infusion ([ADR]= 0.62 nm) (CAF trial), (3) PL capsules and ADR infusion ([ADR]= 1.19 nm) (ADR trial), and (4) CAF capsules (dose = 5 mg kg−1) and ADR infusion ([ADR]= 0.93 nm) (CAF + ADR trial). As expected, CAF, ADR and CAF + ADR decreased (P ≤ 0.05) IMGD compared to PL. CAF + ADR resulted in a more pronounced decrease in IMGD versus PL (42%) compared to CAF (26%) or ADR (24%) alone; however, the effect was not fully additive (P = 0.08). Furthermore, CAF decreased IMGD to a similar magnitude as ADR despite a 50% lower [ADR]. In summary, while ADR contributes to the CAF-induced impairment in IMGD, it is not solely responsible for caffeine's effects. PMID:17656440

  3. Carotid artery intima-media thickness is associated with insulin-mediated glucose disposal in nondiabetic normotensive offspring of type 2 diabetic patients.

    PubMed

    Cardellini, Marina; Marini, Maria Adelaide; Frontoni, Simona; Hribal, Marta Letizia; Andreozzi, Francesco; Perticone, Francesco; Federici, Massimo; Lauro, Davide; Sesti, Giorgio

    2007-01-01

    The aim of this study was to investigate whether insulin resistance is independently associated with early manifestations of atherosclerosis. To this end, 176 normotensive offspring of type 2 diabetic patients were subjected to euglycemic hyperinsulinemic clamp to assess insulin sensitivity. Early atherosclerosis was studied by ultrasonography of the common carotid artery. Of the total 176 subjects, 145 were glucose tolerant, 18 had impaired fasting glucose, and 13 had impaired glucose tolerance. Univariate correlations showed that age, body mass index, waist, blood pressure, 2-h postchallenge glucose, fasting insulin, triglycerides, interleukin-6, fibrinogen, and white blood cell count were significantly correlated with carotid intima-media thickness (IMT), whereas HDL cholesterol and glucose disposal showed a negative correlation. A stepwise multivariate regression analysis including sex, age, waist circumference, smoking status, systolic blood pressure, diastolic blood pressure, triglyceride, HDL cholesterol, 2-h postchallenge glucose, plasma IL-6, fibrinogen, white blood cell count, insulin-stimulated glucose disposal, and fasting insulin showed that the four variables that remained significantly associated with carotid IMT were waist circumference, insulin-stimulated glucose disposal, white blood cell count, and diastolic blood pressure, accounting for 33.7% of its variation. These findings support the concept that insulin sensitivity, rather than plasma insulin levels, is associated with early atherosclerosis in nondiabetic normotensive offspring of type 2 diabetic patients.

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

    PubMed

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

    1992-05-01

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

  5. Insulin-mediated glucose disposal in type 1 (insulin-dependent) diabetic subjects treated by continuous subcutaneous or intraperitoneal insulin fusion.

    PubMed

    Beylot, M; Khalfallah, Y; Laville, M; Sautot, G; Dechaud, H; Serusclat, P; Berthezene, F; Riou, J P; Mornex, R

    1987-01-01

    In order to determine if intraperitoneal insulin infusion could improve the insulin resistance of type 1 diabetic patients we have used the englycaemic insulin clamp technique in order to study the effects of insulin on glucose disposal in four C peptide negative type 1 diabetic patients treated by continuous subcutaneous or intraperitoneal insulin infusion and in five control subjects. Compared to control subjects, the diabetic patients treated by subcutaneous insulin infusion had a decreased maximal capacity of glucose utilization (diabetics: 12.6 +/- 0.3 mg.kg-1.min-1; controls: 15.7 +/- 0.7 mg/kg-1.min-1, p less than 0.01) and a trend towards higher half-maximally effective insulin concentrations (diabetics: 70 +/- 11 mU/l-1, controls: 48 +/- 4 mU/l-1). Treatment of the diabetic patients by intraperitoneal insulin infusion for 2 months decreased their mean peripheral free insulin levels (during subcutaneous infusion: 23.5 +/- 2.2 mU/l-1; during intraperitoneal infusion: 18.4 +/- 1.4 mU/l-1, p less than 0.05). However, mean daily insulin requirements were not decreased (during subcutaneous infusion: 0.59 +/- 0.05 U/kg-1.day-1; during intraperitoneal infusion: 0.57 +/- 0.03 U/kg-1.min-1). Moreover, the diabetic patients had a consistently lower maximal capacity of glucose utilization (12.6 +/- 0.7 mg kg-1.min-1) than control subjects (p less than 0.01) without modification of the half-maximally effective insulin concentration (62 +/- 10 mU.l-1). In conclusion, the only benefit of intraperitoneal insulin infusion was a reduction of peripheral free insulin levels; this decrease of peripheral insulinaemia was not associated with an improvement in the insulin resistance of diabetic patients.

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

    PubMed Central

    Beaton, Nigel; Rudigier, Carla; Moest, Hansjörg; Müller, Sebastian; Mrosek, Nadja; Röder, Eva; Rudofsky, Gottfried; Rülicke, Thomas; Ukropec, Jozef; Ukropcova, Barbara; Augustin, Robert; Neubauer, Heike; Wolfrum, Christian

    2015-01-01

    Objective Failure to properly dispose of glucose in response to insulin is a serious health problem, occurring during obesity and is associated with type 2 diabetes development. Insulin-stimulated glucose uptake is facilitated by the translocation and plasma membrane fusion of vesicles containing glucose transporter 4 (GLUT4), the rate-limiting step of post-prandial glucose disposal. Methods We analyzed the role of Tusc5 in the regulation of insulin-stimulated Glut4-mediated glucose uptake in vitro and in vivo. Furthermore, we measured Tusc5 expression in two patient cohorts. Results Herein, we report that TUSC5 controls insulin-stimulated glucose uptake in adipocytes, in vitro and in vivo. TUSC5 facilitates the proper recycling of GLUT4 and other key trafficking proteins during prolonged insulin stimulation, thereby enabling proper protein localization and complete vesicle formation, processes that ultimately enable insulin-stimulated glucose uptake. Tusc5 knockout mice exhibit impaired glucose disposal and TUSC5 expression is predictive of glucose tolerance in obese individuals, independent of body weight. Furthermore, we show that TUSC5 is a PPARγ target and in its absence the anti-diabetic effects of TZDs are significantly blunted. 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. PMID:26629404

  7. Central insulin-mediated regulation of hepatic glucose production [Review].

    PubMed

    Inoue, Hiroshi

    2016-01-01

    Insulin controls hepatic glucose production (HGP) and maintains glucose homeostasis through the direct action of hepatic insulin receptors, as well as the indirect action of insulin receptors in the central nervous system. Insulin acts on insulin receptors in the hypothalamic arcuate nucleus, activates ATP-sensitive potassium channels in a phosphoinositide 3-kinase (PI3K)-dependent manner, induces hyperpolarization of the hypothalamic neurons, and regulates HGP via the vagus nerve. In the liver, central insulin action augments IL-6 expression in Kupffer cells and activates STAT3 transcription factors in hepatocytes. Activated STAT3 suppresses the gene expression of gluconeogenic enzymes, thereby reducing HGP. It has become evident that nutrients such as glucose, fatty acids, and amino acids act upon the hypothalamus together with insulin, affecting HGP. On the other hand, HGP control by central insulin action is impeded in obesity and impeded by insulin resistance due to disturbance of PI3K signaling and inflammation in the hypothalamus or inhibition of STAT3 signaling in the liver. Although the mechanism of control of hepatic gluconeogenic gene expression by central insulin action is conserved across species, its importance in human glucose metabolism has not been made entirely clear and its elucidation is anticipated in the future.

  8. Use of a two-stage insulin infusion study to assess the relationship between insulin suppression of lipolysis and insulin-mediated glucose uptake in overweight/obese, nondiabetic women.

    PubMed

    McLaughlin, Tracey; Yee, Gail; Glassford, Alec; Lamendola, Cindy; Reaven, Gerald

    2011-12-01

    Differences in insulin regulation of free fatty acids (FFAs) are not readily apparent at the same insulin concentrations used to differentiate relative insulin-mediated glucose disposal. Resistance to insulin-mediated glucose disposal and higher daylong FFA concentrations occur more commonly in obese individuals. However, the relationship between the ability of insulin to suppress FFA release from adipose tissue and stimulate glucose disposal in muscle has not been clearly defined in this population. The current study was initiated to test the hypothesis that these 2 facets of insulin action are related, with greater defects in insulin-mediated glucose disposal associated with less effective insulin inhibition of FFA release from adipose tissue. Subjects included 56 healthy nondiabetic overweight/moderately obese women classified as insulin resistant or insulin sensitive based on whole-body glucose disposal. All underwent a modified 240-minute 2-stage insulin infusion with basal (∼15 µU/mL) and physiologically elevated (∼80 µU/mL) steady-state insulin concentrations. Plasma glucose, insulin, FFA, and glycerol were measured throughout. Whereas plasma glucose differed most during physiological hyperinsulinemia in insulin-resistant vs insulin-sensitive subjects, plasma FFA/glycerol differed most during basal insulin concentrations. The FFA concentrations during the basal insulin steady state correlated highly (r = 0.85, P < .001) with glucose concentrations during the hyperinsulinemic steady state. Overweight/moderately obese women exhibit dramatic differences in the ability of insulin to suppress plasma FFA, which correlate highly with differences in insulin-mediated glucose disposal. Variability in insulin regulation of FFA is most apparent at basal insulin concentrations, whereas differences in glucose disposal are most apparent during physiologic hyperinsulinemia. Both can be quantified using a simple 2-stage insulin infusion study, with first-stage FFA

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

    PubMed

    Wallenius, Kristina; Kjellstedt, Ann; Thalén, Pia; Löfgren, Lars; Oakes, Nicholas D

    2013-01-01

    lean controls, obese controls, and obese rats treated with the dual peroxisome proliferator activated receptor (PPAR) α/γ agonist, tesaglitazar, 3  μ mol/kg/day for 3 weeks. Whole body glucose disposal rate (R d ) and hepatic glucose output (HGO) were assessed under basal fasting and hyperinsulinemic isoglycemic clamp conditions using [3,(3)H]glucose. Indices of tissue specific glucose utilization (R g ') were measured at basal, physiological, and supraphysiological levels of insulinemia using 2-deoxy-D-[2,6-(3)H]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-(13)C]glucose, 2-deoxy-D-[U-(14)C]glucose, [U-(14)C]palmitate, and [9,10-(3)H]-(R)-bromopalmitate. Tesaglitazar improved whole body insulin action by greater suppression of HGO and stimulation of R d compared to obese controls. This involved increased insulin stimulation of R g ' in fat and skeletal muscle as well as increased glycogen synthesis. Tesaglitazar dramatically improved insulin mediated suppression of plasma FFA level, whole body turnover (R fa ), and muscle, liver, and fat utilization. At basal insulin levels, tesaglitazar failed to lower HGO or R fa 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.

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

    PubMed Central

    Wallenius, Kristina; Kjellstedt, Ann; Thalén, Pia; Löfgren, Lars; Oakes, Nicholas D.

    2013-01-01

    Metabolic flexibility was assessed in male Zucker rats: lean controls, obese controls, and obese rats treated with the dual peroxisome proliferator activated receptor (PPAR) α/γ agonist, tesaglitazar, 3 μmol/kg/day for 3 weeks. Whole body glucose disposal rate (R d) 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 (R g′) 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 R d compared to obese controls. This involved increased insulin stimulation of R g′ in fat and skeletal muscle as well as increased glycogen synthesis. Tesaglitazar dramatically improved insulin mediated suppression of plasma FFA level, whole body turnover (R fa), and muscle, liver, and fat utilization. At basal insulin levels, tesaglitazar failed to lower HGO or R fa 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. PMID:24285952

  11. Opposite effects of genistein on the regulation of insulin-mediated glucose homeostasis in adipose tissue.

    PubMed

    Wang, M; Gao, X J; Zhao, W W; Zhao, W J; Jiang, C H; Huang, F; Kou, J P; Liu, B L; Liu, K

    2013-09-01

    Genistein is an isoflavone phytoestrogen found in a number of plants such as soybeans and there is accumulating evidence that it has beneficial effects on the regulation of glucose homeostasis. In this study we evaluated the effect of genistein on glucose homeostasis and its underlying mechanisms in normal and insulin-resistant conditions. To induce insulin resistance, mice or differentiated 3T3-L1 adipocytes were treated with macrophage-derived conditioned medium. A glucose tolerance test was used to investigate the effect of genistein. Insulin signalling activation, glucose transporter-4 (GLUT4) translocation and AMP-activated PK (AMPK) activation were detected by Western blot analysis or elisa. Genistein impaired glucose tolerance and attenuated insulin sensitivity in normal mice by inhibiting the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1) at tyrosine residues, leading to inhibition of insulin-mediated GLUT4 translocation in adipocytes. Mac-CM, an inflammatory stimulus induced glucose intolerance accompanied by impaired insulin sensitivity; genistein reversed these changes by restoring the disturbed IRS1 function, leading to an improvement in GLUT4 translocation. In addition, genistein increased AMPK activity under both normal and inflammatory conditions; this was shown to contribute to the anti-inflammatory effect of genistein, which leads to an improvement in insulin signalling and the amelioration of insulin resistance. Genistein showed opposite effects on insulin sensitivity under normal and inflammatory conditions in adipose tissue and this action was derived from its negative or positive regulation of IRS1 function. Its up-regulation of AMPK activity contributes to the inhibition of inflammation implicated in insulin resistance. © 2013 The British Pharmacological Society.

  12. Opposite effects of genistein on the regulation of insulin-mediated glucose homeostasis in adipose tissue

    PubMed Central

    Wang, M; Gao, X J; Zhao, W W; Zhao, W J; Jiang, C H; Huang, F; Kou, J P; Liu, B L; Liu, K

    2013-01-01

    BACKGROUND AND PURPOSE Genistein is an isoflavone phytoestrogen found in a number of plants such as soybeans and there is accumulating evidence that it has beneficial effects on the regulation of glucose homeostasis. In this study we evaluated the effect of genistein on glucose homeostasis and its underlying mechanisms in normal and insulin-resistant conditions. EXPERIMENTAL APPROACH To induce insulin resistance, mice or differentiated 3T3-L1 adipocytes were treated with macrophage-derived conditioned medium. A glucose tolerance test was used to investigate the effect of genistein. Insulin signalling activation, glucose transporter-4 (GLUT4) translocation and AMP-activated PK (AMPK) activation were detected by Western blot analysis or elisa. KEY RESULTS Genistein impaired glucose tolerance and attenuated insulin sensitivity in normal mice by inhibiting the insulin-induced phosphorylation of insulin receptor substrate-1 (IRS1) at tyrosine residues, leading to inhibition of insulin-mediated GLUT4 translocation in adipocytes. Mac-CM, an inflammatory stimulus induced glucose intolerance accompanied by impaired insulin sensitivity; genistein reversed these changes by restoring the disturbed IRS1 function, leading to an improvement in GLUT4 translocation. In addition, genistein increased AMPK activity under both normal and inflammatory conditions; this was shown to contribute to the anti-inflammatory effect of genistein, which leads to an improvement in insulin signalling and the amelioration of insulin resistance. CONCLUSION AND IMPLICATIONS Genistein showed opposite effects on insulin sensitivity under normal and inflammatory conditions in adipose tissue and this action was derived from its negative or positive regulation of IRS1 function. Its up-regulation of AMPK activity contributes to the inhibition of inflammation implicated in insulin resistance. PMID:23763311

  13. Relative contribution of glycogen synthesis and glycolysis to insulin-mediated glucose uptake. A dose-response euglycemic clamp study in normal and diabetic rats.

    PubMed Central

    Rossetti, L; Giaccari, A

    1990-01-01

    To examine the relationship between plasma insulin concentration and intracellular glucose metabolism in control and diabetic rats, we measured endogenous glucose production, glucose uptake, whole body glycolysis, muscle and liver glycogen synthesis, and rectus muscle glucose-6-phosphate (G-6-P) concentration basally and during the infusion of 2, 3, 4, 12, and 18 mU/kg.min of insulin. The contribution of glycolysis decreased and that of muscle glycogen synthesis increased as the insulin levels rose. Insulin-mediated glucose disposal was decreased by 20-30% throughout the insulin dose-response curve in diabetics compared with controls. While at low insulin infusions (2 and 3 mU/kg.min) reductions in both the glycolytic and glycogenic fluxes contributed to the defective tissue glucose uptake in diabetic rats, at the three higher insulin doses the impairment in muscle glycogen repletion accounted for all of the difference between diabetic and control rats. The muscle G-6-P concentration was decreased (208 +/- 11 vs. 267 +/- 18 nmol/g wet wt; P less than 0.01) compared with saline at the lower insulin infusion, but was gradually increased twofold (530 +/- 16; P less than 0.01 vs. basal) as the insulin concentration rose. The G-6-P concentration in diabetic rats was similar to control despite the reduction in glucose uptake. These data suggest that (a) glucose transport is the major determinant of glucose disposal at low insulin concentration, while the rate-limiting step shifts to an intracellular site at high physiological insulin concentration; and (b) prolonged moderate hyperglycemia and hypoinsulinemia determine two distinct cellular defects in skeletal muscle at the levels of glucose transport/phosphorylation and glycogen synthesis. PMID:2189891

  14. Aldose reductase inhibitor improves insulin-mediated glucose uptake and prevents migration of human coronary artery smooth muscle cells induced by high glucose.

    PubMed

    Yasunari, K; Kohno, M; Kano, H; Minami, M; Yoshikawa, J

    2000-05-01

    We examined involvement of the polyol pathway in high glucose-induced human coronary artery smooth muscle cell (SMC) migration using Boyden's chamber method. Chronic glucose treatment for 72 hours potentiated, in a concentration-dependent manner (5.6 to 22.2 mol/L), platelet-derived growth factor (PDGF) BB-mediated SMC migration. This potentiation was accompanied by an increase in PDGF BB binding, because of an increased number of PDGF-beta receptors, and this potentiation was blocked by the aldose reductase inhibitor epalrestat. Epalrestat at concentrations of 10 and 100 nmol/L inhibited high glucose-potentiated (22.2 mmol/L), PDGF BB-mediated migration. Epalrestat at 100 nmol/L inhibited a high glucose-induced increase in the reduced/oxidized nicotinamide adenine dinucleotide ratio and membrane-bound protein kinase C (PKC) activity in SMCs. PKC inhibitors calphostin C (100 nmol/L) and chelerythrine (1 micromol/L) each inhibited high glucose-induced, PDGF BB-mediated SMC migration. High glucose-induced suppression of insulin-mediated [(3)H]-deoxyglucose uptake, which was blocked by both calphostin C (100 nmol/L) and chelerythrine (1 micromol/L), was decreased by epalrestat (100 nmol/L). Chronic high glucose treatment for 72 hours increased intracellular oxidative stress, which was directly measured by flow cytometry using carboxydichlorofluorescein diacetate bis-acetoxymethyl ester, and this increase was significantly suppressed by epalrestat (100 nmol/L). Antisense oligonucleotide to PKC-beta isoform inhibited high glucose-mediated changes in SMC migration, insulin-mediated [(3)H]-deoxyglucose uptake, and oxidative stress. These findings suggest that high glucose concentrations potentiate SMC migration in coronary artery and that the aldose reductase inhibitor epalrestat inhibits high glucose-potentiated, PDGF BB-induced SMC migration, possibly through suppression of PKC (PKC-beta), impaired insulin-mediated glucose uptake, and oxidative stress.

  15. Effects of endogenous androgens and abdominal fat distribution on the interrelationship between insulin and non-insulin-mediated glucose uptake in females.

    PubMed

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

    2013-04-01

    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. 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. 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. 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. 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. 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.

  16. Comparison of impedance to insulin-mediated glucose uptake in normal subjects and in subjects with latent diabetes

    PubMed Central

    Shen, Shiao-Wei; Reaven, Gerald M.; Farquhar, John W.

    1970-01-01

    A technique was devised for a more accurate measurement than has been heretofore possible of one of the factors responsible for hyperglycemia in the complex syndrome of diabetes. This factor is termed impedance and represents the tissues' insensitivity or resistance to insulin-mediated glucose uptake. It was measured by use of steady-state exogenous insulin and glucose infusions during a period of pharmacological suppression of endogenous insulin secretion. Endogenous new glucose production was also inhibited. Impedance as calculated is a direct function of steady-state glucose concentrations, since exogenous insulin concentrations were similar in all studies. Two groups of normal weight subjects were studied. One had maturity onset latent diabetes, and the other (matched for age, weight, and per cent adiposity) was normal. Impedance was closely reproducible in the same individual and remained relatively constant during prolonged infusions. The diabetics had average infusion glucose concentrations (and thus impedance) 68% higher than the normal group, and it is of note that their previously measured glucose intolerance differed by a similar degree; that is, the diabetic's intolerance (as defined by mean weighted plasma glucose response after oral glucose) was 52% greater than that of the normal individuals. PMID:5480843

  17. Insulin Mediated 14C-Glucose Incorporation Into Adipose Tissue: An Undergraduate Biochemistry Experiment

    ERIC Educational Resources Information Center

    Landman, A. D.; Eskin, N. A. M.

    1975-01-01

    Describes an experiment in which rat adipose tissue samples are exposed to labeled glucose; insulin is added to one sample. Subsequent scintillation counting demonstrates the ability of insulin to facilitate the entry of glucose into the tissue. (MLH)

  18. Insulin Mediated 14C-Glucose Incorporation Into Adipose Tissue: An Undergraduate Biochemistry Experiment

    ERIC Educational Resources Information Center

    Landman, A. D.; Eskin, N. A. M.

    1975-01-01

    Describes an experiment in which rat adipose tissue samples are exposed to labeled glucose; insulin is added to one sample. Subsequent scintillation counting demonstrates the ability of insulin to facilitate the entry of glucose into the tissue. (MLH)

  19. Antioxidants improve impaired insulin-mediated glucose uptake and prevent migration and proliferation of cultured rabbit coronary smooth muscle cells induced by high glucose.

    PubMed

    Yasunari, K; Kohno, M; Kano, H; Yokokawa, K; Minami, M; Yoshikawa, J

    1999-03-16

    To explore the role of intracellular oxidative stress in high glucose-induced atherogenesis, we examined the effect of probucol and/or alpha-tocopherol on the migration and growth characteristics of cultured rabbit coronary vascular smooth muscle cells (VSMCs). Chronic high-glucose-medium (22. 2 mmol/L) treatment increased platelet-derived growth factor (PDGF)-BB-mediated VSMC migration, [3H]thymidine incorporation, and cell number compared with VSMCs treated with normal-glucose medium (5.6 mmol/L+16.6 mmol/L mannose). Probucol and alpha-tocopherol significantly suppressed high glucose-induced increase in VSMC migration, cell number, and [3H]thymidine incorporation. Probucol and alpha-tocopherol suppressed high glucose-induced elevation of the cytosolic ratio of NADH/NAD+, phospholipase D, and membrane-bound protein kinase C activation. Probucol, alpha-tocopherol, and calphostin C improved the high glucose-induced suppression of insulin-mediated [3H]deoxyglucose uptake. Chronic high-glucose treatment increased the oxidative stress, which was significantly suppressed by probucol, alpha-tocopherol, suramin, and calphostin C. These findings suggest that probucol and alpha-tocopherol may suppress high glucose-induced VSMC migration and proliferation via suppression of increases in the cytosolic ratio of free NADH/NAD+, phospholipase D, and protein kinase C activation induced by high glucose, which result in reduction in intracellular oxidative stress.

  20. The reduced insulin-mediated glucose oxidation in skeletal muscle from type 2 diabetic subjects may be of genetic origin--evidence from cultured myotubes.

    PubMed

    Gaster, Michael; Beck-Nielsen, Henning

    2004-09-06

    Several defects in response to insulin have been described in vivo and in vitro in type 2 diabetes: a decreased glucose transport, defective glucose oxidation and altered glycogen synthesis. At present, it is unknown whether glucose oxidation is primarily affected or secondarily affected by, e.g. increased free fatty acids (FFA). The aim of this study was to evaluate whether myotubes established from type 2 diabetic subjects express a primarily or a FFA-induced reduced insulin-mediated glucose oxidation. We have therefore investigated glucose oxidation under basal, physiological conditions and during acute insulin stimulation with/without FFA. We found that myotubes established from type 2 diabetic subjects express a reduced insulin-stimulated increase in glucose oxidation. Moreover, an acute exposure to FFA reduces insulin-mediated glucose oxidation without alterations in glucose uptake and glycogen synthesis. Thus, we conclude that the diminished increase in insulin-stimulated glucose oxidation seen in type 2 diabetic subjects in vivo may be of genetic origin. Moreover, the glucose-fatty acid cycle seems not to be crucial for the pathophysiology of insulin resistance.

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

    PubMed Central

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

    2013-01-01

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

  2. Computational model of cellular metabolic dynamics: effect of insulin on glucose disposal in human skeletal muscle

    PubMed Central

    Li, Yanjun; Solomon, Thomas P. J.; Haus, Jacob M.; Saidel, Gerald M.; Cabrera, Marco E.

    2010-01-01

    Identifying the mechanisms by which insulin regulates glucose metabolism in skeletal muscle is critical to understanding the etiology of insulin resistance and type 2 diabetes. Our knowledge of these mechanisms is limited by the difficulty of obtaining in vivo intracellular data. To quantitatively distinguish significant transport and metabolic mechanisms from limited experimental data, we developed a physiologically based, multiscale mathematical model of cellular metabolic dynamics in skeletal muscle. The model describes mass transport and metabolic processes including distinctive processes of the cytosol and mitochondria. The model simulated skeletal muscle metabolic responses to insulin corresponding to human hyperinsulinemic-euglycemic clamp studies. Insulin-mediated rate of glucose disposal was the primary model input. For model validation, simulations were compared with experimental data: intracellular metabolite concentrations and patterns of glucose disposal. Model variations were simulated to investigate three alternative mechanisms to explain insulin enhancements: Model 1 (M.1), simple mass action; M.2, insulin-mediated activation of key metabolic enzymes (i.e., hexokinase, glycogen synthase, pyruvate dehydrogenase); or M.3, parallel activation by a phenomenological insulin-mediated intracellular signal that modifies reaction rate coefficients. These simulations indicated that models M.1 and M.2 were not sufficient to explain the experimentally measured metabolic responses. However, by application of mechanism M.3, the model predicts metabolite concentration changes and glucose partitioning patterns consistent with experimental data. The reaction rate fluxes quantified by this detailed model of insulin/glucose metabolism provide information that can be used to evaluate the development of type 2 diabetes. PMID:20332360

  3. Effects of adrenaline on whole-body glucose metabolism and insulin-mediated regulation of glycogen synthase and PKB phosphorylation in human skeletal muscle.

    PubMed

    Jensen, Jørgen; Ruge, Toralph; Lai, Yu-Chiang; Svensson, Maria K; Eriksson, Jan W

    2011-02-01

    In the present study, we investigated the effect of adrenaline on insulin-mediated regulation of glucose and fat metabolism with focus on regulation of skeletal muscle PKB, GSK-3, and glycogen synthase (GS) phosphorylation. Ten healthy subjects (5 men and 5 women) received a 240-minute intravenous infusion of adrenaline (0.05 μg/[kg min]) or saline; after 120 minutes, a hyperinsulinemic-euglycemic clamp was added. Adrenaline infusion increased blood glucose concentration by approximately 50%, but the hyperinsulinemic clamp normalized blood glucose within 30 minutes. Glucose infusion rate during the last hour was approximately 60% lower during adrenaline infusion compared with saline (4.3 ± 0.5 vs 11.2 ± 0.6 mg/kg lean body mass per minute). Insulin increased PKB Ser⁴⁷³, PKB Thr³⁰⁸, and GSK-3β Ser⁹ phosphorylation in skeletal muscles; coinfusion of adrenaline did not influence insulin-stimulated PKB and GSK-3 phosphorylation. Adrenaline alone did not influence phosphorylation of PKB and GSK-3β. Insulin increased GS fractional activity and decreased GS Ser⁶⁴¹ and Ser⁶⁴⁵,⁶⁴⁹,⁶⁵³,⁶⁵⁷ phosphorylation. In the presence of adrenaline, insulin did neither activate GS nor dephosphorylate GS Ser⁶⁴¹. Surprisingly, GS Ser⁷ phosphorylation was not influenced by adrenaline. Adrenaline increased plasma lactate concentration; and muscle glycogen content was reduced in skeletal muscle the day after adrenaline infusion, supporting that insulin does not stimulate glycogen synthesis in skeletal muscles when adrenaline is present. In conclusion, adrenaline did not influence basal or insulin-stimulated PKB and GSK-3β phosphorylation in muscles, but completely blocked insulin-mediated GS activation and Ser⁶⁴¹ dephosphorylation. Still, insulin normalized adrenaline-mediated hyperglycemia.

  4. Pinitol Supplementation Does Not Affect Insulin-Mediated Glucose Metabolism and Muscle Insulin Receptor Content and Phosphorylation in Older Humans12

    PubMed Central

    Campbell, Wayne W.; Haub, Mark D.; Fluckey, James D.; Ostlund, Richard E.; Thyfault, John P.; Morse-Carrithers, Hannah; Hulver, Matthew W.; Birge, Zonda K.

    2008-01-01

    This study assessed the effect of oral pinitol supplementation on oral and intravenous glucose tolerances and on skeletal muscle insulin receptor content and phosphorylation in older people. Fifteen people (6 men, 9 women; age 66 ± 8 y; BMI 27.9 ± 3.3 kg/m2; hemoglobin A1c 5.39 ± 0.46%, mean ± SD) completed a 7-wk protocol. Subjects were randomly assigned to groups that during wk 2−7 consumed twice daily either a non-nutritive beverage (Placebo group, n = 8) or the same beverage with 1000 mg pinitol dissolved into it (Pinitol group, n = 7, total dose = 2000 mg pinitol/d). Testing was done at wk 1 and wk 7. In the Pinitol group with supplementation, 24-h urinary pinitol excretion increased 17-fold. The fasting concentrations of glucose, insulin, and C-peptide, and the 180-min area under the curve for these compounds, in response to oral (75 g) and intravenous (300 mg/kg) glucose tolerance challenges, were unchanged from wk 1 to wk 7 and were not influenced by pinitol. Also, pinitol did not affect indices of hepatic and whole-body insulin sensitivity from the oral glucose tolerance test and indices of insulin sensitivity, acute insulin response to glucose, and glucose effectiveness from the intravenous glucose tolerance test, estimated using minimal modeling. Pinitol did not differentially affect total insulin receptor content and insulin receptor phosphotyrosine 1158 and insulin receptor phosphotyrosine 1162/1163 activation in vastus lateralis samples taken during an oral-glucose–induced hyperglycemic and hyperinsulinemic state. These data suggest that pinitol supplementation does not influence whole-body insulin-mediated glucose metabolism and muscle insulin receptor content and phosphorylation in nondiabetic, older people. PMID:15514265

  5. Somatostatin and insulin mediate glucose-inhibited glucagon secretion in the pancreatic α-cell by lowering cAMP.

    PubMed

    Elliott, Amicia D; Ustione, Alessandro; Piston, David W

    2015-01-15

    The dysregulation of glucose-inhibited glucagon secretion from the pancreatic islet α-cell is a critical component of diabetes pathology and metabolic disease. We show a previously uncharacterized [Ca(2+)]i-independent mechanism of glucagon suppression in human and murine pancreatic islets whereby cAMP and PKA signaling are decreased. This decrease is driven by the combination of somatostatin, which inhibits adenylyl cyclase production of cAMP via the Gαi subunit of the SSTR2, and insulin, which acts via its receptor to activate phosphodiesterase 3B and degrade cytosolic cAMP. Our data indicate that both somatostatin and insulin signaling are required to suppress cAMP/PKA and glucagon secretion from both human and murine α-cells, and the combination of these two signaling mechanisms is sufficient to reduce glucagon secretion from isolated α-cells as well as islets. Thus, we conclude that somatostatin and insulin together are critical paracrine mediators of glucose-inhibited glucagon secretion and function by lowering cAMP/PKA signaling with increasing glucose. Copyright © 2015 the American Physiological Society.

  6. Somatostatin and insulin mediate glucose-inhibited glucagon secretion in the pancreatic α-cell by lowering cAMP

    PubMed Central

    Elliott, Amicia D.; Ustione, Alessandro

    2014-01-01

    The dysregulation of glucose-inhibited glucagon secretion from the pancreatic islet α-cell is a critical component of diabetes pathology and metabolic disease. We show a previously uncharacterized [Ca2+]i-independent mechanism of glucagon suppression in human and murine pancreatic islets whereby cAMP and PKA signaling are decreased. This decrease is driven by the combination of somatostatin, which inhibits adenylyl cyclase production of cAMP via the Gαi subunit of the SSTR2, and insulin, which acts via its receptor to activate phosphodiesterase 3B and degrade cytosolic cAMP. Our data indicate that both somatostatin and insulin signaling are required to suppress cAMP/PKA and glucagon secretion from both human and murine α-cells, and the combination of these two signaling mechanisms is sufficient to reduce glucagon secretion from isolated α-cells as well as islets. Thus, we conclude that somatostatin and insulin together are critical paracrine mediators of glucose-inhibited glucagon secretion and function by lowering cAMP/PKA signaling with increasing glucose. PMID:25406263

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

    PubMed

    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.

  8. Ophthalmic Glucose Monitoring Using Disposable Contact Lenses—A Review

    PubMed Central

    Badugu, Ramachandram; Lakowicz, Joseph R.; Geddes, Chris D.

    2016-01-01

    We have developed a range of disposable and colorless tear glucose sensing contact lenses, using off-the-shelf lenses embedded with new water soluble, highly fluorescent and glucose sensitive boronic acid containing fluorophores. The new lenses are readily able to track tear glucose levels and therefore blood glucose levels, which are ideally suited for potential use by diabetics. The fluorescence responses from the lenses can be monitored using simple excitation and emission detection devices. The novelty of our approach is two fold. Firstly, the notion of sensing extremely low glucose concentrations in tears, which track blood levels, by our contact lens approach, and secondly, the unique compatibility of our new glucose signaling probes with the internal mildly acidic contact lens environment. The new lenses are therefore ideal for the non-invasive and continuous monitoring of tear glucose, with about 15-min response time, and a measured shelf life in excess of 3 months. In this review article, we show that fluorescence based signaling using plastic disposable lenses, which have already been industrially optimized with regard to vision correction and oxygen/analyte permeability etc, may a notable alternative to invasive and random finger pricking, the most widely used glucose monitoring technology by diabetics. PMID:15617269

  9. Ophthalmic glucose monitoring using disposable contact lenses--a review.

    PubMed

    Badugu, Ramachandram; Lakowicz, Joseph R; Geddes, Chris D

    2004-09-01

    We have developed a range of disposable and colorless tear glucose sensing contact lenses, using off-the-shelf lenses embedded with new water soluble, highly fluorescent and glucose sensitive boronic acid containing fluorophores. The new lenses are readily able to track tear glucose levels and therefore blood glucose levels, which are ideally suited for potential use by diabetics. The fluorescence responses from the lenses can be monitored using simple excitation and emission detection devices. The novelty of our approach is two fold. Firstly, the notion of sensing extremely low glucose concentrations in tears, which track blood levels, by our contact lens approach, and secondly, the unique compatibility of our new glucose signaling probes with the internal mildly acidic contact lens environment. The new lenses are therefore ideal for the non-invasive and continuous monitoring of tear glucose, with about 15-min response time, and a measured shelf life in excess of 3 months. In this review article, we show that fluorescence based signaling using plastic disposable lenses, which have already been industrially optimized with regard to vision correction and oxygen/analyte permeability etc, may a notable alternative to invasive and random finger pricking, the most widely used glucose monitoring technology by diabetics.

  10. Natural anti-diabetic compound 1,2,3,4,6-penta-O-galloyl-D-glucopyranose binds to insulin receptor and activates insulin-mediated glucose transport signaling pathway.

    PubMed

    Li, Yunsheng; Kim, Jaekyung; Li, Jing; Liu, Fang; Liu, Xueqing; Himmeldirk, Klaus; Ren, Yulin; Wagner, Thomas E; Chen, Xiaozhuo

    2005-10-21

    Insulin mimetics from natural sources are potential therapeutics that can act alone or supplement insulin and other anti-diabetic drugs in the prevention and treatment of diabetes. We recently reported the insulin-like glucose transport stimulatory activity of tannic acid (TA) in 3T3-L1 adipocytes. In this study, we find that chemically synthesized 1,2,3,4,6-penta-O-galloyl-beta-D-glucopyranose (beta-PGG), one of the components of TA, as well as its natural anomer alpha-PGG possess activity. Mechanistic studies in adipocytes with alpha-PGG, the more potent of the two anomers, reveal that inhibitors that block the insulin-mediated glucose transport, including one that inhibits the insulin receptor (IR), also completely abolish the glucose transport activated by alpha-PGG. In addition, alpha-PGG induces phosphorylation of the IR and Akt, activates PI 3-kinase, and stimulates membrane translocation of GLUT 4. Receptor binding studies indicate that alpha-PGG binds to the IR and affects the binding between insulin and IR by reducing the maximum binding of insulin to IR without significantly altering the binding affinity of insulin to IR. Western blotting analysis of the products of a cross-linking reaction suggests that alpha-PGG may bind to IR at a site located on the alpha-subunit of the receptor. Animal studies demonstrate that PGG reduces blood glucose levels and improves glucose tolerance in diabetic and obese animals. Our results suggest that PGG may serve as a model for the development of new types of anti-diabetic and anti-metabolic syndrome therapeutics.

  11. T-1032, a cyclic GMP phosphodiesterase-5 inhibitor, acutely blocks physiologic insulin-mediated muscle haemodynamic effects and glucose uptake in vivo.

    PubMed

    Mahajan, Hema; Richards, Stephen M; Rattigan, Stephen; Clark, Michael G

    2003-12-01

    1. Cyclic GMP phosphodiesterase-5 inhibitors have been shown to alter blood flow in specific tissues by potentiating local NO-dependent vasodilatory mechanisms. Since the haemodynamic effects of physiologic insulin, particularly capillary recruitment, may be critical for muscle glucose uptake in vivo and are blocked by inhibitors of nitric oxide synthase, we have explored the acute effects of the specific cGMP phosphodiesterase-5 inhibitor T-1032 on physiologic insulin action in anaesthetized healthy rats in vivo. 2. Whole-body glucose infusion (GIR), femoral blood flow (FBF), hind leg vascular resistance (VR), hind leg glucose uptake (HGU), 2-deoxyglucose uptake into muscles of the lower leg (R'g), hind leg metabolism of infused 1-methylxanthine (1-MX), a measure of capillary recruitment, and muscle cGMP were determined. The experimental groups were T-1032 (10 microg min-1 kg-1) infused for 1 h before and during a euglycaemic insulin clamp (3 mU min-1 kg-1 x 2 h), T-1032 infused for 3 h with saline, T-1032 during a 2 h clamp, T-1032 with saline for 2 h, and a 2 h saline control. 3. Insulin increased GIR from zero to 13 mg min-1 kg-1, HGU from 0.1+/-0.01 to 0.43+/-0.05 micromol min-1, R'g and 1-MX, marginally increased FBF, and had no effect on blood pressure or heart rate. T-1032 alone had no effect on blood pressure, heart rate, FBF, VR, HGU, R'g or 1-MX, but increased muscle cGMP. T-1032 1 h before and during insulin completely blocked GIR (1 h), HGU (2 h), R'g (2 h), and 1-MX (2 h). T-1032 commenced with insulin had only partial blocking activity against insulin. 4. We conclude that T-1032 is a potent acutely acting inhibitor of the muscle effects of physiologic insulin on capillary recruitment and glucose uptake in vivo. These, together with inhibition of whole-body glucose infusion during insulin, may caution against the use of isoenzyme-5-specific cyclic GMP phosphodiesterase inhibitors as therapeutic agents.

  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

    SciTech Connect

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

    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. IL-6 induces lipolysis and mitochondrial dysfunction, but does not affect insulin-mediated glucose transport in 3T3-L1 adipocytes.

    PubMed

    Ji, Chenbo; Chen, Xiaohui; Gao, Chunlin; Jiao, Liuhong; Wang, Jianguo; Xu, Guangfeng; Fu, Hailong; Guo, Xirong; Zhao, Yaping

    2011-08-01

    Interleukin-6 (IL-6) has emerged as an important cytokine involved in the regulation of metabolism. However, the role of IL-6 in the etiology of obesity and insulin resistance is not fully understood. Mitochondria are key organelles of energy metabolism, and there is growing evidence that mitochondrial dysfunction plays a crucial role in the pathogenesis of obesity-associated insulin resistance. In this study, we determined the direct effect of IL-6 on lipolysis in adipocytes, and the effects of IL-6 on mitochondrial function were investigated. We found that cells treated with IL-6 displayed fewer lipids and an elevated glycerol release rate. Further, IL-6 treatment led to decreased mitochondrial membrane potential, decreased cellular ATP production, and increased intracellular ROS levels. The mitochondria in IL-6-treated cells became swollen and hollow with reduced or missing cristae. However, insulin-stimulated glucose transport was unaltered. PGC-1α, NRF1, and mtTFA mRNA levels were markedly increased, and the mitochondrial contents were also increased. Our results demonstrate that IL-6 can exert a direct lipolytic effect and induce mitochondrial dysfunction. However, IL-6 did not affect insulin sensitivity in adipocytes in vitro. We deduce that in these cells, enhanced mitochondrial biogenesis might play a compensatory role in glucose transport.

  14. Strength training increases insulin-mediated glucose uptake, GLUT4 content, and insulin signaling in skeletal muscle in patients with type 2 diabetes.

    PubMed

    Holten, Mads K; Zacho, Morten; Gaster, Michael; Juel, Carsten; Wojtaszewski, Jørgen F P; Dela, Flemming

    2004-02-01

    Strength training represents an alternative to endurance training for patients with type 2 diabetes. Little is known about the effect on insulin action and key proteins in skeletal muscle, and the necessary volume of strength training is unknown. A total of 10 type 2 diabetic subjects and 7 healthy men (control subjects) strength-trained one leg three times per week for 6 weeks while the other leg remained untrained. Each session lasted no more than 30 min. After strength training, muscle biopsies were obtained, and an isoglycemic-hyperinsulinemic clamp combined with arterio-femoral venous catheterization of both legs was carried out. In general, qualitatively similar responses were obtained in both groups. During the clamp, leg blood flow was higher (P < 0.05) in trained versus untrained legs, but despite this, arterio-venous extraction glucose did not decrease in trained legs. Thus, leg glucose clearance was increased in trained legs (P < 0.05) and more than explained by increases in muscle mass. Strength training increased protein content of GLUT4, insulin receptor, protein kinase B-alpha/beta, glycogen synthase (GS), and GS total activity. In conclusion, we found that strength training for 30 min three times per week increases insulin action in skeletal muscle in both groups. The adaptation is attributable to local contraction-mediated mechanisms involving key proteins in the insulin signaling cascade.

  15. 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.

    PubMed

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

    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 120mg/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. Copyright © 2011 Elsevier Inc. All rights reserved.

  16. Effects of GLP-1 on Forearm Vasodilator Function and Glucose Disposal During Hyperinsulinemia in the Metabolic Syndrome

    PubMed Central

    Tesauro, Manfredi; Schinzari, Francesca; Adamo, Angelo; Rovella, Valentina; Martini, Francesca; Mores, Nadia; Barini, Angela; Pitocco, Dario; Ghirlanda, Giovanni; Lauro, Davide; Campia, Umberto; Cardillo, Carmine

    2013-01-01

    OBJECTIVE Patients with the metabolic syndrome (MetS) have impaired insulin-induced enhancement of vasodilator responses. The incretin hormone glucagon-like peptide 1 (GLP-1), beyond its effects on blood glucose, has beneficial actions on vascular function. This study, therefore, aimed to assess whether GLP-1 affects insulin-stimulated vasodilator reactivity in patients with the MetS. RESEARCH DESIGN AND METHODS Forearm blood flow responses to acetylcholine (ACh) and sodium nitroprusside (SNP) were assessed in MetS patients before and after the addition of GLP-1 to an intra-arterial infusion of saline (n = 5) or insulin (n = 5). The possible involvement of oxidative stress in the vascular effects of GLP-1 in this setting was investigated by infusion of vitamin C (n = 5). The receptor specificity of GLP-1 effect during hyperinsulinemia was assessed by infusing its metabolite GLP-1(9-36) (n = 5). The metabolic actions of GLP-1 were also tested by analyzing forearm glucose disposal during hyperinsulinemia (n = 5). RESULTS In MetS patients, GLP-1 enhanced endothelium-dependent and -independent responses to ACh and SNP, respectively, during hyperinsulinemia (P < 0.001 for both), but not during saline (P > 0.05 for both). No changes in vasodilator reactivity to ACh and SNP were seen after GLP-1 was added to insulin and vitamin C (P > 0.05 for both) and after GLP-1(9-36) was given during hyperinsulinemia (P > 0.05 for both). Also, GLP-1 did not affect forearm glucose extraction and uptake during hyperinsulinemia (P > 0.05 for both). CONCLUSIONS In patients with the MetS, GLP-1 improves insulin-mediated enhancement of endothelium-dependent and -independent vascular reactivity. This effect may be influenced by vascular oxidative stress and is possibly exerted through a receptor-mediated mechanism. PMID:23069838

  17. Determinants of insulin-stimulated glucose disposal in middle-aged, premenopausal women.

    PubMed

    Toth, M J; Sites, C K; Cefalu, W T; Matthews, D E; Poehlman, E T

    2001-07-01

    Controversy exists regarding the relative importance of adiposity, physical fitness, and physical activity in the regulation of insulin-stimulated glucose disposal. To address this issue, we measured insulin-stimulated glucose disposal [mg. kg fat-free mass (FFM)(-1). min(-1); oxidative and nonoxidative components] in 45 nondiabetic, nonobese, premenopausal women (mean +/- SD; 47 +/- 3 yr) by use of hyperinsulinemic euglycemic clamp (40 mU. m(-2). min(-1)) and [6,6-2H2]glucose dilution techniques. We also measured body composition, abdominal fat distribution, thigh muscle fat content, maximal oxygen consumption (VO2 max), and physical activity energy expenditure ((2)H(2)(18)O kinetics) as possible correlates of glucose disposal. VO2 max was the strongest correlate of glucose disposal (r = 0.63, P < 0.01), whereas whole body and abdominal adiposity showed modest associations (range of r values from -0.32 to -0.46, P < 0.05 to P < 0.01). A similar pattern of correlations was observed for nonoxidative glucose disposal. None of the variables measured correlated with oxidative glucose disposal. The relationship of VO2 max to glucose disposal persisted after statistical control for FFM, percent body fat, and intra-abdominal fat (r = 0.40, P < 0.01). In contrast, correlations of total and regional adiposity measures to insulin sensitivity were no longer significant after statistical adjustment for VO2 max. VO2 max was the only variable to enter stepwise regression models as a significant predictor of total and nonoxidative glucose disposal. Our results highlight the importance of VO2 max as a determinant of glucose disposal and suggest that it may be a stronger determinant of variation in glucose disposal than total and regional adiposity in nonobese, nondiabetic, premenopausal women.

  18. Insulin-mediated hypokalemia and paralysis in familial hypokalemic periodic paralysis.

    PubMed

    Minaker, K L; Meneilly, G S; Flier, J S; Rowe, J W

    1988-06-01

    To elucidate a potential role for insulin-mediated extra-renal potassium disposal in the clinical syndrome of hypokalemic periodic paralysis, an obese affected man was studied using the euglycemic insulin clamp, which, in normal and obese subjects, produces predictable, insulin dose-dependent declines in plasma potassium levels. During a 20 mU/m2/minute euglycemic clamp (insulin level, 88 microU/ml) procedure, while the patient with hypokalemic periodic paralysis demonstrated severe resistance to insulin-mediated glucose uptake (glucose uptake 50 percent of that of normal control subjects, n = 17), his plasma potassium declined to a degree similar to that seen in normal subjects. During a subsequent higher dose, 200 mU/m2/minute insulin infusion (insulin level, 914 microU/ml), plasma potassium declined to 2.5 meq/liter, a value significantly below that seen in normal (n = 19) (3.3 +/- 0.1 meq/liter) and obese (n = 6) (3.2 +/- 0.1 meq/liter) subjects. During this study, paralysis began in the patient's hand and forearm at the potassium nadir and lasted three hours, despite restoration of normokalemia 30 minutes after paralysis began. Glucose disposal rates during this high-dose insulin infusion were one-half that seen in lean control subjects (n = 19) and similar to those in obese control subjects. If these findings are representative of hypokalemic periodic paralysis and can be generalized to larger numbers of patients, they indicate several new features of this syndrome. The ability of insulin to induce hypokalemia is enhanced in this syndrome even in the presence of marked coexistent obesity-related resistance to the action of insulin to promote glucose utilization. Enhanced sensitivity of potassium uptake systems to activation by insulin (and other factors) may be a central feature of this syndrome. Additionally, paralytic hypokalemia can be induced during a euglycemic insulin clamp procedure, which could be utilized as a diagnostic test for this syndrome.

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

    PubMed Central

    Vaitheesvaran, B.; LeRoith, D.

    2014-01-01

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

  20. Dapagliflozin improves muscle insulin sensitivity but enhances endogenous glucose production.

    PubMed

    Merovci, Aurora; Solis-Herrera, Carolina; Daniele, Giuseppe; Eldor, Roy; Fiorentino, Teresa Vanessa; Tripathy, Devjit; Xiong, Juan; Perez, Zandra; Norton, Luke; Abdul-Ghani, Muhammad A; DeFronzo, Ralph A

    2014-02-01

    Chronic hyperglycemia impairs insulin action, resulting in glucotoxicity, which can be ameliorated in animal models by inducing glucosuria with renal glucose transport inhibitors. Here, we examined whether reduction of plasma glucose with a sodium-glucose cotransporter 2 (SGLT2) inhibitor could improve insulin-mediated tissue glucose disposal in patients with type 2 diabetes. Eighteen diabetic men were randomized to receive either dapagliflozin (n = 12) or placebo (n = 6) for 2 weeks. We measured insulin-mediated whole body glucose uptake and endogenous glucose production (EGP) at baseline and 2 weeks after treatment using the euglycemic hyperinsulinemic clamp technique. Dapagliflozin treatment induced glucosuria and markedly lowered fasting plasma glucose. Insulin-mediated tissue glucose disposal increased by approximately 18% after 2 weeks of dapagliflozin treatment, while placebo-treated subjects had no change in insulin sensitivity. Surprisingly, following dapagliflozin treatment, EGP increased substantially and was accompanied by an increase in fasting plasma glucagon concentration. Together, our data indicate that reduction of plasma glucose with an agent that works specifically on the kidney to induce glucosuria improves muscle insulin sensitivity. However, glucosuria induction following SGLT2 inhibition is associated with a paradoxical increase in EGP. These results provide support for the glucotoxicity hypothesis, which suggests that chronic hyperglycemia impairs insulin action in individuals with type 2 diabetes.

  1. Portal 5-hydroxytryptophan infusion enhances glucose disposal in conscious dogs

    PubMed Central

    Moore, Mary Courtney; Kimura, Kazuhiro; Shibata, Haruki; Honjoh, Tsutomu; Saito, Masayuki; Everett, Carrie A.; Smith, Marta S.; Cherrington, Alan D.

    2008-01-01

    Intraportal serotonin infusion enhances net hepatic glucose uptake (NHGU) during glucose infusion but blunts nonhepatic glucose uptake and can cause gastrointestinal discomfort and diarrhea at high doses. Whether the serotonin precursor 5-hydroxytryptophan (5-HTP) could enhance NHGU without gastrointestinal side effects during glucose infusion was examined in conscious 42-h-fasted dogs, using arteriovenous difference and tracer ([3-3H]glucose) techniques. Experiments consisted of equilibration (−120 to −30 min), basal (−30 to 0 min), and experimental (EXP; 0–270 min) periods. During EXP, somatostatin, fourfold basal intraportal insulin, basal intraportal glucagon, and peripheral glucose (to double the hepatic glucose load) were infused. In one group of dogs (HTP, n = 6), saline was infused intraportally from 0 to 90 min (P1), and 5-HTP was infused intraportally at 10, 20, and 40 μg·kg−1·min−1 from 90 to 150 (P2), 150 to 210 (P3), and 210 to 270 (P4) min, respectively. In the other group (SAL, n = 7), saline was infused intraportally from 0 to 270 min. NHGU in SAL was 14.8 ± 1.9, 18.5 ± 2.3, 16.3 ± 1.4, and 19.7 ± 1.6 μmol·kg−1·min−1 in P1–P4, whereas NHGU in 5-HTP averaged 16.4 ± 2.6, 18.5 ± 1.4, 20.8 ± 2.0, and 27.6 ± 2.6 μmol·kg−1·min−1 (P < 0.05 vs. SAL). Nonhepatic glucose uptake (μmol·kg−1·min−1) in SAL was 30.2 ± 4.3, 36.8 ± 5.8, 44.3 ± 5.8, and 54.6 ± 11.8 during P1–P4, respectively, whereas in HTP the corresponding values were 26.3 ± 6.8, 44.9 ± 10.1, 47.5 ± 11.7, and 51.4 ± 13.2 (not significant between groups). Intraportal 5-HTP enhances NHGU without significantly altering nonhepatic glucose uptake or causing gastrointestinal side effects, raising the possibility that a related agent might have a role in reducing postprandial hyperglycemia. PMID:15755767

  2. Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women.

    PubMed

    Ellis, Amy C; Alvarez, Jessica A; Granger, Wesley M; Ovalle, Fernando; Gower, Barbara A

    2012-05-01

    Intravenous glucose tolerance tests have demonstrated lower whole-body insulin sensitivity (S(I)) among African Americans (AA) compared with European Americans (EA). Whole-body S(I) represents both insulin-stimulated glucose disposal, primarily by skeletal muscle, and insulin's suppression of endogenous glucose production (EGP) by liver. A mathematical model was recently introduced that allows for distinction between disposal and hepatic S(I). The purpose of this study was to examine specific indexes of S(I) among AA and EA women to determine whether lower whole-body S(I) in AA may be attributed to insulin action at muscle, liver, or both. Participants were 53 nondiabetic, premenopausal AA and EA women. Profiles of EGP and indexes of Disposal S(I) and Hepatic S(I) were calculated by mathematical modeling and incorporation of a stable isotope tracer ([6,6-(2)H(2)]glucose) into the intravenous glucose tolerance test. Body composition was assessed by dual-energy x-ray absorptiometry. After adjustment for percentage fat, both Disposal S(I) and Hepatic S(I) were lower among AA (P = .009 for both). Time profiles for serum insulin and EGP revealed higher peak insulin response and corresponding lower EGP among AA women compared with EA. Indexes from a recently introduced mathematical model suggest that lower whole-body S(I) among nondiabetic AA women is due to both hepatic and peripheral components. Despite lower Hepatic S(I), AA displayed lower EGP, resulting from higher postchallenge insulin levels. Future research is needed to determine the physiological basis of lower insulin sensitivity among AA and its implications for type 2 diabetes mellitus risk.

  3. Effect of ovarian suppression with gonadotropin-releasing hormone agonist on glucose disposal and insulin secretion.

    PubMed

    Toth, Michael J; Cooper, Brian C; Pratley, Richard E; Mari, Andrea; Matthews, Dwight E; Casson, Peter R

    2008-06-01

    Several lines of evidence suggest that ovarian hormones influence glucose homeostasis, although their exact role in humans has not been clearly defined. In the present study, we sought to test the hypothesis that ovarian hormones regulate glucose homeostasis by examining the effect of pharmacologically induced ovarian hormone deficiency on glucose disposal and insulin secretion. Young, healthy women with regular menstrual patterns were studied during the follicular and luteal phases of their cycle at baseline and after 2 mo of treatment with gonadotropin-releasing hormone agonist (GnRHa; n = 7) or placebo (n = 6). Using hyperglycemic clamps, in combination with stable isotope-labeled (i.e., (13)C and (2)H) glucose tracers, we measured glucose disposal and insulin secretion. Additionally, we assessed body composition and regional fat distribution using radiologic imaging techniques as well as glucoregulatory hormones. Ovarian hormone suppression with GnRHa did not alter body composition, abdominal fat distribution, or thigh tissue composition. There was no effect of ovarian suppression on total, oxidative, or nonoxidative glucose disposal expressed relative to plasma insulin level. Similarly, no effect of ovarian hormone deficiency was observed on first- or second-phase insulin secretion or insulin clearance. Finally, ovarian hormone deficiency was associated with an increase in circulating adiponectin levels but no change in leptin concentration. Our findings suggest that a brief period of ovarian hormone deficiency in young, healthy, eugonadal women does not alter glucose disposal index or insulin secretion, supporting the conclusion that ovarian hormones play a minimal role in regulating glucose homeostasis. Our data do, however, support a role for ovarian hormones in the regulation of plasma adiponectin levels.

  4. Ethnic differences in glucose disposal, hepatic insulin sensitivity, and endogenous glucose production among African American and European American women

    PubMed Central

    Ellis, Amy C.; Alvarez, Jessica A.; Granger, Wesley M.; Ovalle, Fernando; Gower, Barbara A.

    2011-01-01

    Objective Intravenous glucose tolerance tests (IVGTT) have demonstrated lower whole-body insulin sensitivity (SI) among African Americans (AA) compared to European Americans (EA). Whole-body SI represents both insulin-stimulated glucose disposal, primarily by skeletal muscle, and insulin's suppression of endogenous glucose production (EGP) by liver. A mathematical model was recently introduced that allows for distinction between disposal and hepatic insulin sensitivity. The purpose of this study was to examine specific indexes of insulin sensitivity among AA and EA women to determine whether lower whole-body insulin sensitivity in AA may be attributed to insulin action at muscle, liver, or both. Methods Participants were 53 non-diabetic, premenopausal AA and EA women. Profiles of EGP and indexes of Disposal SI and Hepatic SI were calculated by mathematical modeling and incorporation of a stable isotope tracer (6,6-2H2glucose) into the IVGTT. Body composition was assessed by dual energy X-ray absorptiometry. Results After adjustment for percent fat, both Disposal SI and Hepatic SI were lower among AA (p=0.009 for both). Time profiles for serum insulin and EGP revealed higher peak insulin response and corresponding lower EGP among AA women compared to EA. Conclusions Indexes from a recently-introduced mathematical model suggest that lower whole-body insulin sensitivity among non-diabetic AA women is due to both hepatic and peripheral components. Despite lower Hepatic SI, AA displayed lower EGP, resulting from higher post-challenge insulin levels. Future research is needed to determine the physiological basis of lower insulin senstivity among AA and its implications for type 2 diabetes risk. PMID:22071009

  5. Disposable amperometric biosensor based on nanostructured bacteriophages for glucose detection

    NASA Astrophysics Data System (ADS)

    Kang, Yu Ri; Hwang, Kyung Hoon; Kim, Ju Hwan; Nam, Chang Hoon; Kim, Soo Won

    2010-10-01

    The selection of electrode material profoundly influences biosensor science and engineering, as it heavily influences biosensor sensitivity. Here we propose a novel electrochemical detection method using a working electrode consisting of bio-nanowires from genetically modified filamentous phages and nanoparticles. fd-tet p8MMM filamentous phages displaying a three-methionine (MMM) peptide on the major coat protein pVIII (designated p8MMM phages) were immobilized on the active area of an electrochemical sensor through physical adsorption and chemical bonding. Bio-nanowires composed of p8MMM phages and silver nanoparticles facilitated sensitive, rapid and selective detection of particular molecules. We explored whether the composite electrode with bio-nanowires was an effective platform to detect the glucose oxidase. The current response of the bio-nanowire sensor was high at various glucose concentrations (0.1 µm-0.1 mM). This method provides a considerable advantage to demonstrate analyte detection over low concentration ranges. Especially, phage-enabled bio-nanowires can serve as receptors with high affinity and specificity for the detection of particular biomolecules and provide a convenient platform for designing site-directed multifunctional scaffolds based on bacteriophages and may serve as a simple method for label-free detection.

  6. Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module

    PubMed Central

    Lee, Hyunjae; Song, Changyeong; Hong, Yong Seok; Kim, Min Sung; Cho, Hye Rim; Kang, Taegyu; Shin, Kwangsoo; Choi, Seung Hong; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2017-01-01

    Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging. We present a wearable/disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module. Careful multilayer patch design and miniaturization of sensors increase the efficiency of the sweat collection and sensing process. Multimodal glucose sensing, as well as its real-time correction based on pH, temperature, and humidity measurements, maximizes the accuracy of the sensing. The minimal layout design of the same sensors also enables a strip-type disposable device. Drugs for the feedback transdermal therapy are loaded on two different temperature-responsive phase change nanoparticles. These nanoparticles are embedded in hyaluronic acid hydrogel microneedles, which are additionally coated with phase change materials. This enables multistage, spatially patterned, and precisely controlled drug release in response to the patient’s glucose level. The system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus. PMID:28345030

  7. Wearable/disposable sweat-based glucose monitoring device with multistage transdermal drug delivery module.

    PubMed

    Lee, Hyunjae; Song, Changyeong; Hong, Yong Seok; Kim, Min Sung; Cho, Hye Rim; Kang, Taegyu; Shin, Kwangsoo; Choi, Seung Hong; Hyeon, Taeghwan; Kim, Dae-Hyeong

    2017-03-01

    Electrochemical analysis of sweat using soft bioelectronics on human skin provides a new route for noninvasive glucose monitoring without painful blood collection. However, sweat-based glucose sensing still faces many challenges, such as difficulty in sweat collection, activity variation of glucose oxidase due to lactic acid secretion and ambient temperature changes, and delamination of the enzyme when exposed to mechanical friction and skin deformation. Precise point-of-care therapy in response to the measured glucose levels is still very challenging. We present a wearable/disposable sweat-based glucose monitoring device integrated with a feedback transdermal drug delivery module. Careful multilayer patch design and miniaturization of sensors increase the efficiency of the sweat collection and sensing process. Multimodal glucose sensing, as well as its real-time correction based on pH, temperature, and humidity measurements, maximizes the accuracy of the sensing. The minimal layout design of the same sensors also enables a strip-type disposable device. Drugs for the feedback transdermal therapy are loaded on two different temperature-responsive phase change nanoparticles. These nanoparticles are embedded in hyaluronic acid hydrogel microneedles, which are additionally coated with phase change materials. This enables multistage, spatially patterned, and precisely controlled drug release in response to the patient's glucose level. The system provides a novel closed-loop solution for the noninvasive sweat-based management of diabetes mellitus.

  8. Differential regulation of baicalin and scutellarin on AMPK and Akt in promoting adipose cell glucose disposal.

    PubMed

    Yang, Le-Le; Xiao, Na; Liu, Jinfeng; Liu, Kang; Liu, Baolin; Li, Ping; Qi, Lian-Wen

    2017-02-01

    Baicalin and scutellarin, two flavonoid glucuronic acids isolated from Scutellaria baicalensis, exhibit beneficial effects on glucose homeostasis. Baicalin and scutellarin are similar in structure except scutellarin has an additional hydroxyl at composition C-4'. In this work, we observed that baicalin and scutellarin promoted glucose disposal in mice and in adipocytes. Baicalin selectively increased phosphorylation of AMP-activated kinase (AMPK), while scutellarin selectively enhanced Akt phosphorylation. Both of them increased AS160 phosphorylation and glucose uptake in basal condition. AMPK inhibitor or knockdown of AMPK by siRNA blocked baicalin-induced AS160 phosphorylation and glucose uptake, but showed no effects on scutellarin. In contrast, Akt inhibitor and knockdown of Akt with siRNA decreased scutellarin-stimulated glucose uptake but had no effects on baicalin. The molecular dynamic simulations analysis showed that the binding energy of baicalin to AMPK (-34.30kcal/mol) was more favorable than scutellarin (-21.27kcal/mol), while the binding energy of scutellarin (-29.81kcal/mol) to Akt was much more favorable than baicalin (4.04kcal/mol). Interestingly, a combined treatment with baicalin and scutellarin acted synergistically to enhance glucose uptake in adipocytes (combination index: 0.94-0.046). In conclusion, baicalin and scutellarin, though structurally similar, promoted glucose disposal in adipocytes by differential regulation on AMPK and Akt activity. Our data provide insight that multicomponent herbal medicines may act synergistically on multiple targets.

  9. Facile and scalable disposable sensor based on laser engraved graphene for electrochemical detection of glucose

    NASA Astrophysics Data System (ADS)

    Tehrani, Farshad; Bavarian, Behzad

    2016-06-01

    A novel and highly sensitive disposable glucose sensor strip was developed using direct laser engraved graphene (DLEG) decorated with pulse deposited copper nanocubes (CuNCs). The high reproducibility (96.8%), stability (97.4%) and low cost demonstrated by this 3-step fabrication method indicates that it could be used for high volume manufacturing of disposable glucose strips. The fabrication method also allows for a high degree of flexibility, allowing for control of the electrode size, design, and functionalization method. Additionally, the excellent selectivity and sensitivity (4,532.2 μA/mM.cm2), low detection limit (250 nM), and suitable linear range of 25 μM–4 mM, suggests that these sensors may be a great potential platform for glucose detection within the physiological range for tear, saliva, and/or sweat.

  10. Facile and scalable disposable sensor based on laser engraved graphene for electrochemical detection of glucose.

    PubMed

    Tehrani, Farshad; Bavarian, Behzad

    2016-06-16

    A novel and highly sensitive disposable glucose sensor strip was developed using direct laser engraved graphene (DLEG) decorated with pulse deposited copper nanocubes (CuNCs). The high reproducibility (96.8%), stability (97.4%) and low cost demonstrated by this 3-step fabrication method indicates that it could be used for high volume manufacturing of disposable glucose strips. The fabrication method also allows for a high degree of flexibility, allowing for control of the electrode size, design, and functionalization method. Additionally, the excellent selectivity and sensitivity (4,532.2 μA/mM.cm(2)), low detection limit (250 nM), and suitable linear range of 25 μM-4 mM, suggests that these sensors may be a great potential platform for glucose detection within the physiological range for tear, saliva, and/or sweat.

  11. Facile and scalable disposable sensor based on laser engraved graphene for electrochemical detection of glucose

    PubMed Central

    Tehrani, Farshad; Bavarian, Behzad

    2016-01-01

    A novel and highly sensitive disposable glucose sensor strip was developed using direct laser engraved graphene (DLEG) decorated with pulse deposited copper nanocubes (CuNCs). The high reproducibility (96.8%), stability (97.4%) and low cost demonstrated by this 3-step fabrication method indicates that it could be used for high volume manufacturing of disposable glucose strips. The fabrication method also allows for a high degree of flexibility, allowing for control of the electrode size, design, and functionalization method. Additionally, the excellent selectivity and sensitivity (4,532.2 μA/mM.cm2), low detection limit (250 nM), and suitable linear range of 25 μM–4 mM, suggests that these sensors may be a great potential platform for glucose detection within the physiological range for tear, saliva, and/or sweat. PMID:27306706

  12. Visceral adipose tissue is an independent correlate of glucose disposal in older obese postmenopausal women.

    PubMed

    Brochu, M; Starling, R D; Tchernof, A; Matthews, D E; Garcia-Rubi, E; Poehlman, E T

    2000-07-01

    Older obese postmenopausal women have an increased risk for type 2 diabetes and cardiovascular disease. Increased abdominal obesity may contribute to these comorbidities. There is considerable controversy, however, regarding the effects of visceral adipose tissue as a singular predictor of insulin resistance compared to the other constituents of adiposity. To address this issue, we examined the independent association of regional adiposity and total fat mass with glucose disposal in obese older postmenopausal women. A secondary objective examined the association between glucose disposal with markers of skeletal muscle fat content (muscle attenuation) and physical activity levels. We studied 44 healthy obese postmenopausal women between 50 and 71 yr of age (mean +/- SD, 56.5 +/- 5.3 yr). The rate of glucose disposal was measured using the euglycemic/hyperinsulinemic clamp technique. Visceral and sc adipose tissue areas and midthigh muscle attenuation were measured from computed tomography. Fat mass and lean body mass were estimated from dual energy x-ray absorptiometry. Peak VO2 was measured from a treadmill test to volitional fatigue. Physical activity energy expenditure was measured from indirect calorimetry and doubly labeled water. Pearson correlations indicated that glucose disposal was inversely related to visceral adipose tissue area (r = -0.40; P < 0.01), but not to sc adipose tissue area (r = 0.17), total fat mass (r = 0.05), midthigh muscle attenuation (r = 0.01), peak VO2 (r = -0.22), or physical activity energy expenditure (r = -0.01). The significant association persisted after adjusting visceral adipose tissue for fat mass and abdominal sc adipose tissue levels (r = -0.45; P < 0.005; in both cases). Additional analyses matched two groups of women for fat mass, but with different visceral adipose tissue levels. Results showed that obese women with high visceral adipose tissue levels (283 +/- 59 vs. 137 +/- 24 cm2; P < 0.0001) had a lower glucose

  13. Glucose oxidation and nonoxidative glucose disposal during prolonged fasts of the northern elephant seal pup (Mirounga angustirostris).

    PubMed

    Houser, Dorian S; Crocker, Daniel E; Tift, Michael S; Champagne, Cory D

    2012-09-01

    Elephant seal weanlings demonstrate rates of endogenous glucose production (EGP) during protracted fasts that are higher than predicted on the basis of mass and time fasting. To determine the nonoxidative and oxidative fate of endogenously synthesized glucose, substrate oxidation, metabolic rate, glycolysis, and EGP were measured in fasting weanlings. Eight weanlings were sampled at 14 days of fasting, and a separate group of nine weanlings was sampled at 49 days of fasting. Metabolic rate was determined via flow-through respirometry, and substrate-specific oxidation was determined from the respiratory quotient and urinary nitrogen measurements. The rate of glucose disposal (Glu((R)(d))) was determined through a primed, constant infusion of [3-(3)H]glucose, and glycolysis was determined from the rate of appearance of (3)H in the body water pool. Glu((R)(d)) was 1.41 ± 0.27 and 0.95 ± 0.21 mmol/min in the early and late fasting groups, respectively. Nearly all EGP went through glycolysis, but the percentage of Glu((R)(d)) oxidized to meet the daily metabolic demand was only 24.1 ± 4.4% and 16.7 ± 5.9% between the early and late fasting groups. Glucose oxidation was consistently less than 10% of the metabolic rate in both groups. This suggests that high rates of EGP do not support substrate provisions for glucose-demanding tissues. It is hypothesized that rates of EGP may be ancillary to the upregulation of the tricarboxylic acid cycle to meet high rates of lipid oxidation while mitigating ketosis.

  14. A modified minimal model analysis of insulin sensitivity and glucose-mediated glucose disposal in insulin-dependent diabetes.

    PubMed

    Ward, G M; Weber, K M; Walters, I M; Aitken, P M; Lee, B; Best, J D; Boston, R C; Alford, F P

    1991-01-01

    Although glucose utilization is impaired in insulin-dependent diabetes mellitus (IDDM), it is unclear whether this is due to reductions in insulin sensitivity (Si) and/or glucose-mediated glucose disposal (SG). The minimal model of Bergman et al can be applied to a frequently sampled intravenous glucose tolerance test (FSIGT) to simultaneously estimate Sl and SG, but cannot accommodate data from diabetics. Exogenous insulin approximating the normal pattern of insulin secretion was infused during FSIGTs in eight young non-obese C-peptide-negative IDDM subjects, but with the total dose modified to achieve sufficient glucose disappearance rates (KG) to allow analysis of data. The minimal model was modified to model the effects of the exogenous insulin on glucose kinetics to estimate SI and SG. Despite deliberately achieving supranormal plasma-free insulin levels during the FSIGT ("first-phase insulin" = 62 +/- 9 SE mU/L; "second phase insulin" = 34 +/- 9 mU/L), the diabetics showed low-normal KG values (1.3 +/- 0.29 min-1 X 10(2). Using the model, good parameter resolution (fractional SD [FSD] less than .5) was achieved (IDDM v controls: SI = 2.5 +/- 0.6 v 8.3 +/- 1.5 min-1.mU-1.L-1 X 10(4); SG = 1.6 +/- 0.5 v 2.6 +/- 0.2 min-1 X 10(2); P less than .05). This reduction in SG was confirmed in the same IDDM subjects by FSIGT during basal insulin infusion only (SG = 1.0 +/- 0.3 min-1 X 10(2)).(ABSTRACT TRUNCATED AT 250 WORDS)

  15. A Disposable Tear Glucose Biosensor—Part 2: System Integration and Model Validation

    PubMed Central

    La Belle, Jeffrey T.; Bishop, Daniel K.; Vossler, Stephen R.; Patel, Dharmendra R.; Cook, Curtiss B.

    2010-01-01

    Background We presented a concept for a tear glucose sensor system in an article by Bishop and colleagues in this issue of Journal of Diabetes Science and Technology. A unique solution to collect tear fluid and measure glucose was developed. Individual components were selected, tested, and optimized, and system error modeling was performed. Further data on prototype testing are now provided. Methods An integrated fluidics portion of the prototype was designed, cast, and tested. A sensor was created using screen-printed sensors integrated with a silicone rubber fluidics system and absorbent polyurethane foam. A simulated eye surface was prepared using fluid-saturated poly(2-hydroxyethyl methacrylate) sheets, and the disposable prototype was tested for both reproducibility at 0, 200, and 400 μM glucose (n = 7) and dynamic range of glucose detection from 0 to 1000 μM glucose. Results From the replicated runs, an established relative standard deviation of 15.8% was calculated at 200 μM and a lower limit of detection was calculated at 43.4 μM. A linear dynamic range was demonstrated from 0 to 1000 μM with an R2 of 99.56%. The previously developed model predicted a 14.9% variation. This compares to the observed variance of 15.8% measured at 200 μM glucose. Conclusion With the newly designed fluidics component, an integrated tear glucose prototype was assembled and tested. Testing of this integrated prototype demonstrated a satisfactory lower limit of detection for measuring glucose concentration in tears and was reproducible across a physiological sampling range. The next step in the device design process will be initial animal studies to evaluate the current prototype for factors such as eye irritation, ease of use, and correlation with blood glucose. PMID:20307390

  16. Effects of Exercise Intensity on Postprandial Improvement in Glucose Disposal and Insulin Sensitivity in Prediabetic Adults

    PubMed Central

    Rynders, Corey A.; Weltman, Judy Y.; Jiang, Boyi; Breton, Marc; Patrie, James; Barrett, Eugene J.

    2014-01-01

    Background: A single bout of exercise improves postprandial glycemia and insulin sensitivity in prediabetic patients; however, the impact of exercise intensity is not well understood. The present study compared the effects of acute isocaloric moderate (MIE) and high-intensity (HIE) exercise on glucose disposal and insulin sensitivity in prediabetic adults. Methods: Subjects (n = 18; age 49 ± 14 y; fasting glucose 105 ± 11 mg/dL; 2 h glucose 170 ± 32 mg/dL) completed a peak O2 consumption/lactate threshold (LT) protocol plus three randomly assigned conditions: 1) control, 1 hour of seated rest, 2) MIE (at LT), and 3) HIE (75% of difference between LT and peak O2 consumption). One hour after exercise, subjects received an oral glucose tolerance test (OGTT). Plasma glucose, insulin, and C-peptide concentrations were sampled at 5- to 10-minute intervals at baseline, during exercise, after exercise, and for 3 hours after glucose ingestion. Total, early-phase, and late-phase area under the glucose and insulin response curves were compared between conditions. Indices of insulin sensitivity (SI) were derived from OGTT data using the oral minimal model. Results: Compared with control, SI improved by 51% (P = .02) and 85% (P < .001) on the MIE and HIE days, respectively. No differences in SI were observed between the exercise conditions (P = .62). Improvements in SI corresponded to significant reductions in the glucose, insulin, and C-peptide area under the curve values during the late phase of the OGTT after HIE (P < .05), with only a trend for reductions after MIE. Conclusion: These results suggest that in prediabetic adults, acute exercise has an immediate and intensity-dependent effect on improving postprandial glycemia and insulin sensitivity. PMID:24243632

  17. Glucagon dose-response curve for hepatic glucose production and glucose disposal in type 2 diabetic patients and normal individuals.

    PubMed

    Matsuda, Masafumi; Defronzo, Ralph A; Glass, Leonard; Consoli, Agostino; Giordano, Mauro; Bressler, Peter; Delprato, Stefano

    2002-09-01

    This study sought to examine whether enhanced hepatic sensitivity to glucagon contributes to impaired glucose homeostasis in subjects with type 2 diabetes mellitus (T2DM). Eight T2DM and 9 age-, weight-, and gender-matched nondiabetic subjects received a 4-hour glucagon infusion at the rates of 0.2, 0.5, 2, 6, and 8 ng. kg(-1). min(-1) while maintaining the plasma insulin concentration constant at the basal level with exogenous infusions of somatostatin and insulin. On the evening prior to study, diabetic subjects received a low-dose insulin infusion at a rate designed to maintain euglycemia and this infusion rate was continued until the end of the glucagon infusion study on the following day. Each glucagon infusion study was performed on a separate day and in random order. 3-(3)H-glucose was infused in all studies to measure endogenous glucose production (EGP) and the rate of whole body glucose disposal. During the first 2 hours (0 to 120 minutes) of glucagon infusion, EGP increased sharply in both groups, and the initial rate of rise in EGP was higher in control versus diabetic subjects. During the last 2 hours (120 to 240 minutes) of glucagon infusion, EGP in the diabetics tended to be higher than controls during the 3 lower glucagon infusion rates and this difference reached statistical significance (P <.05 to.01) during the 6 and 8 ng. kg(-1). min(-1) infusions. During the 2 hours following cessation of glucagon (240- to 360-minute time period), the stimulation of glucose disappearance from plasma was impaired (P <.05) during all 5 glucagon infusion rates in the diabetics compared to controls. We conclude that in T2DM patients, the initial (0 to 120 minutes) stimulation of hepatic glucose output (which primarily reflects glycogenolysis) by glucagon is not enhanced in T2DM patients. The late (120 to 240 minutes) stimulation of hepatic glucose output (which primarily reflects gluconeogenesis) by glucagon tends to be increased, especially at supraphysiologic

  18. Electrocardiogram-Based Sleep Spectrogram Measures of Sleep Stability and Glucose Disposal in Sleep Disordered Breathing

    PubMed Central

    Pogach, Melanie S.; Punjabi, Naresh M.; Thomas, Neil; Thomas, Robert J.

    2012-01-01

    spectrogram measures of sleep stability and glucose disposal in sleep disordered breathing. SLEEP 2012;35(1):139-148. PMID:22215928

  19. Exercise Improves Glucose Disposal and Insulin Signaling in Pregnant Mice Fed a High Fat Diet

    PubMed Central

    Carter, Lindsay G; Ngo Tenlep, Sara Y; Woollett, Laura A; Pearson, Kevin J

    2016-01-01

    Objective Physical activity has been suggested as a non-pharmacological intervention that can be used to improve glucose homeostasis in women with gestational diabetes mellitus. The purpose of this study was to determine the effects of voluntary exercise on glucose tolerance and body composition in pregnant high fat diet fed mice. Methods Female mice were put on a standard diet or high fat diet for two weeks. The mice were then split into 4 groups; control standard diet fed, exercise standard diet fed, control high fat diet fed, and exercise high fat diet fed. Exercise mice had voluntary access to a running wheel in their home cage one week prior to mating, during mating, and throughout pregnancy. Glucose tolerance and body composition were measured during pregnancy. Akt levels were quantified in skeletal muscle and adipose tissue isolated from saline or insulin injected pregnant dams as a marker for insulin signaling. Results Consumption of the high fat diet led to significantly increased body weight, fat mass, and impaired glucose tolerance in control mice. However, voluntary running in the high fat diet fed dams significantly reduced weight gain and fat mass and ultimately improved glucose tolerance compared to control high fat diet fed dams. Further, body weight, fat mass, and glucose disposal in exercise high fat diet dams were indistinguishable from control dams fed the standard diet. High fat diet fed exercise dams also had significantly increased insulin stimulated phosphorylated Akt expression in adipose tissue, but not skeletal muscle, compared to control dams on high fat diet. Conclusion The use of voluntary exercise improves glucose homeostasis and body composition in pregnant female mice. Thus, future studies could investigate potential long-term health benefits in offspring born to obese exercising dams. PMID:26966635

  20. Modelling the effect of insulin on the disposal of meal-attributable glucose in type 1 diabetes.

    PubMed

    García-García, Fernando; Hovorka, Roman; Wilinska, Malgorzata E; Elleri, Daniela; Hernando, M Elena

    2017-02-01

    The management of postprandial glucose excursions in type 1 diabetes has a major impact on overall glycaemic control. In this work, we propose and evaluate various mechanistic models to characterize the disposal of meal-attributable glucose. Sixteen young volunteers with type 1 diabetes were subject to a variable-target clamp which replicated glucose profiles observed after a high-glycaemic-load ([Formula: see text]) or a low-glycaemic-load ([Formula: see text]) evening meal. [6,6-[Formula: see text

  1. Relationship between plasma glucose and insulin concentration, glucose production, and glucose disposal in normal subjects and patients with non-insulin-dependent diabetes.

    PubMed Central

    Chen, Y D; Jeng, C Y; Hollenbeck, C B; Wu, M S; Reaven, G M

    1988-01-01

    The changes in hepatic glucose production (Ra), tissue glucose disposal (Rd), and plasma glucose and insulin concentration that took place over a 16-h period from 10 to 2 p.m. were documented in 14 individuals; 8 with non-insulin-dependent diabetes mellitus (NIDDM) and 6 with normal glucose tolerance. Values for Ra were higher than normal in patients with NIDDM at 10 p.m. (4.73 +/- 0.41 vs. 3.51 +/- 0.36 mg/kg per min, P less than 0.001), but fell at a much faster rate throughout the night than that seen in normal subjects. As a consequence, the difference between Ra in normal individuals and patients with NIDDM progressively narrowed, and by 2 p.m., had ceased to exist (1.75 +/- 0.61 vs. 1.67 +/- 0.47 mg/kg per min, P = NS). Plasma glucose concentration also declined in patients with NIDDM over the same period of time, but they remained quite hyperglycemic, and the value of 245 +/- 27 mg/dl at 2 p.m. was about three times greater than in normal individuals. Plasma insulin concentrations also fell progressively from 10 to 2 p.m., and were similar in both groups throughout most of the 16-h study period. Thus, the progressive decline in Ra in patients with NIDDM occurred despite concomitant falls in both plasma glucose and insulin concentration. Glucose disposal rates also fell progressively in both groups, but the magnitude of the fall was greater in patients with NIDDM. Consequently, Rd in patients with NIDDM was higher at 10 p.m. (3.97 +/- 0.48 vs. 3.25 +/- 0.13 mg/kg per min, P less than 0.001) and lower the following day at 2 p.m. (1.64 +/- 0.21 vs. 1.97 +/- 0.35 mg/kg per min, P less than 0.01). These results indicate that a greatly expanded pool size can exist in patients with NIDDM at a time when values for Ra are identical to those in normal subjects studied under comparable conditions, which suggests that fasting hyperglycemia in NIDDM is not simply a function of an increase in Ra. PMID:3292584

  2. Performance effects and metabolic consequences of caffeine and caffeinated energy drink consumption on glucose disposal.

    PubMed

    Shearer, Jane; Graham, Terry E

    2014-10-01

    This review documents two opposing effects of caffeine and caffeine-containing energy drinks, i.e., their positive effects on athletic performance and their negative impacts on glucose tolerance in the sedentary state. Analysis of studies examining caffeine administration prior to performance-based exercise showed caffeine improved completion time by 3.6%. Similar analyses following consumption of caffeine-containing energy drinks yielded positive, but more varied, benefits, which were likely due to the diverse nature of the studies performed, the highly variable composition of the beverages consumed, and the range of caffeine doses administered. Conversely, analyses of studies administering caffeine prior to either an oral glucose tolerance test or insulin clamp showed a decline in whole-body glucose disposal of ~30%. The consequences of this resistance are unknown, but there may be implications for the development of a number of chronic diseases. Both caffeine-induced performance enhancement and insulin resistance converge with the primary actions of caffeine on skeletal muscle.

  3. Retinoblastoma Protein Knockdown Favors Oxidative Metabolism and Glucose and Fatty Acid Disposal in Muscle Cells.

    PubMed

    Petrov, Petar D; Ribot, Joan; López-Mejía, Isabel C; Fajas, Lluís; Palou, Andreu; Bonet, M Luisa

    2016-03-01

    Deficiency in the retinoblastoma protein (Rb) favors leanness and a healthy metabolic profile in mice largely attributed to activation of oxidative metabolism in white and brown adipose tissues. Less is known about Rb modulation of skeletal muscle metabolism. This was studied here by transiently knocking down Rb expression in differentiated C2C12 myotubes using small interfering RNAs. Compared with control cells transfected with non-targeting RNAs, myotubes silenced for Rb (by 80-90%) had increased expression of genes related to fatty acid uptake and oxidation such as Cd36 and Cpt1b (by 61% and 42%, respectively), increased Mitofusin 2 protein content (∼2.5-fold increase), increased mitochondrial to nuclear DNA ratio (by 48%), increased oxygen consumption (by 65%) and decreased intracellular lipid accumulation. Rb silenced myotubes also displayed up-regulated levels of glucose transporter type 4 expression (∼5-fold increase), increased basal glucose uptake, and enhanced insulin-induced Akt phosphorylation. Interestingly, exercise in mice led to increased Rb phosphorylation (inactivation) in skeletal muscle as evidenced by immunohistochemistry analysis. In conclusion, the silencing of Rb enhances mitochondrial oxidative metabolism and fatty acid and glucose disposal in skeletal myotubes, and changes in Rb status may contribute to muscle physiological adaptation to exercise. © 2015 Wiley Periodicals, Inc.

  4. Hexim1, a Novel Regulator of Leptin Function, Modulates Obesity and Glucose Disposal

    PubMed Central

    Dhar-Mascareno, Manya; Ramirez, Susan N.; Rozenberg, Inna; Rouille, Yves; Kral, John G.

    2016-01-01

    Leptin triggers signaling events with significant transcriptional responses that are essential to metabolic processes affecting obesity and glucose disposal. We asked whether hexamethylene bis-acetamide inducible-1 (Hexim1), an inhibitor of RNA II polymerase-dependent transcription elongation, regulates leptin-Janus kinase 2 signaling axis in the hypothalamus. We subjected C57BL6 Hexim1 heterozygous (HT) mice to high-fat diet and when compared with wild type, HT mice were resistant to high-fat diet-induced weight gain and remain insulin sensitive. HT mice exhibited increased leptin-pY705Stat3 signaling in the hypothalamus, with normal adipocyte size, increased type I oxidative muscle fiber density, and enhanced glucose transporter 4 expression. We also observed that normal Hexim1 protein level is required to facilitate the expression of CCAAT/enhancer-binding proteins (C/EBPs) required for adipogenesis and inducible suppressor of cytokine signaling 3 (SOCS) expression. Further support on the role of Hexim1 regulating C/EBPs during adipocyte differentiation was shown when HT 3T3L1 fibroblasts failed to undergo adipogenesis. Hexim1 selectively modulates leptin-mediated signal transduction pathways in the hypothalamus, the expression of C/EBPs and peroxisome proliferator-activated receptor-γ (PPAR γ) in skeletal muscle and adipose tissue during the adaptation to metabolic stress. We postulate that Hexim1 might be a novel factor involved in maintaining whole-body energy balance. PMID:26859361

  5. Hexim1, a Novel Regulator of Leptin Function, Modulates Obesity and Glucose Disposal.

    PubMed

    Dhar-Mascareno, Manya; Ramirez, Susan N; Rozenberg, Inna; Rouille, Yves; Kral, John G; Mascareno, Eduardo J

    2016-03-01

    Leptin triggers signaling events with significant transcriptional responses that are essential to metabolic processes affecting obesity and glucose disposal. We asked whether hexamethylene bis-acetamide inducible-1 (Hexim1), an inhibitor of RNA II polymerase-dependent transcription elongation, regulates leptin-Janus kinase 2 signaling axis in the hypothalamus. We subjected C57BL6 Hexim1 heterozygous (HT) mice to high-fat diet and when compared with wild type, HT mice were resistant to high-fat diet-induced weight gain and remain insulin sensitive. HT mice exhibited increased leptin-pY(705)Stat3 signaling in the hypothalamus, with normal adipocyte size, increased type I oxidative muscle fiber density, and enhanced glucose transporter 4 expression. We also observed that normal Hexim1 protein level is required to facilitate the expression of CCAAT/enhancer-binding proteins (C/EBPs) required for adipogenesis and inducible suppressor of cytokine signaling 3 (SOCS) expression. Further support on the role of Hexim1 regulating C/EBPs during adipocyte differentiation was shown when HT 3T3L1 fibroblasts failed to undergo adipogenesis. Hexim1 selectively modulates leptin-mediated signal transduction pathways in the hypothalamus, the expression of C/EBPs and peroxisome proliferator-activated receptor-γ (PPAR γ) in skeletal muscle and adipose tissue during the adaptation to metabolic stress. We postulate that Hexim1 might be a novel factor involved in maintaining whole-body energy balance.

  6. Insulin receptor autophosphorylation in cultured myoblasts correlates to glucose disposal in Pima Indians.

    PubMed

    Youngren, J F; Goldfine, I D; Pratley, R E

    1999-05-01

    In a previous study [Youngren, J. F., I. D. Goldfire, and R. E. Pratley. Am. J. Physiol. 273 (Endocrinol. Metab. 36): E276-E283, 1997] of skeletal muscle biopsies from insulin-resistant, nondiabetic Pima Indians, we demonstrated that diminished insulin receptor (IR) autophosphorylation correlated with in vivo insulin resistance. In the present study, to determine whether decreased IR function is a primary trait of muscle, and not secondary to an altered in vivo environment, we cultured myoblasts from 17 nondiabetic Pima Indians in whom insulin-stimulated glucose disposal (M) was measured during hyperinsulinemic-euglycemic glucose clamps. Myoblast IR autophosphorylation was determined by a highly sensitive ELISA. IR autophosphorylation directly correlated with M (r = 0.56, P = 0.02) and inversely correlated with the fasting plasma insulin (r = -0.58, P < 0.05). The relationship between M and IR autophosphorylation remained significant after M was adjusted for the effects of percent body fat (partial r = 0.53, P < 0.04). The relationship between insulin resistance and the capacity for myoblast IR autophosphorylation in nondiabetic Pima Indians suggests that variations in IR-signaling capacity may be intrinsic characteristics of muscle that contribute to the genetic component determining insulin action in this population.

  7. Laforin and malin knockout mice have normal glucose disposal and insulin sensitivity.

    PubMed

    DePaoli-Roach, Anna A; Segvich, Dyann M; Meyer, Catalina M; Rahimi, Yasmeen; Worby, Carolyn A; Gentry, Matthew S; Roach, Peter J

    2012-04-01

    Lafora disease is a fatal, progressive myoclonus epilepsy caused in ~90% of cases by mutations in the EPM2A or EPM2B genes. Characteristic of the disease is the formation of Lafora bodies, insoluble deposits containing abnormal glycogen-like material in many tissues, including neurons, muscle, heart and liver. Because glycogen is important for glucose homeostasis, the aberrant glycogen metabolism in Lafora disease might disturb whole-body glucose handling. Indeed, Vernia et al. [Vernia, S., Heredia, M., Criado, O., Rodriguez de Cordoba, S., Garcia-Roves, P.M., Cansell, C., Denis, R., Luquet, S., Foufelle, F., Ferre, P. et al. (2011) Laforin, a dual-specificity phosphatase involved in Lafora disease, regulates insulin response and whole-body energy balance in mice. Hum. Mol. Genet., 20, 2571-2584] reported that Epm2a-/- mice had enhanced glucose disposal and insulin sensitivity, leading them to suggest that laforin, the Epm2a gene product, is involved in insulin signaling. We analyzed 3-month- and 6-7-month-old Epm2a-/- mice and observed no differences in glucose tolerance tests (GTTs) or insulin tolerance tests (ITTs) compared with wild-type mice of matched genetic background. At 3 months, Epm2b-/- mice also showed no differences in GTTs and ITTs. In the 6-7-month-old Epm2a-/- mice, there was no evidence for increased insulin stimulation of the phosphorylation of Akt, GSK-3 or S6 in skeletal muscle, liver and heart. From metabolic analyses, these animals were normal with regard to food intake, oxygen consumption, energy expenditure and respiratory exchange ratio. By dual-energy X-ray absorptiometry scan, body composition was unaltered at 3 or 6-7 months of age. Echocardiography showed no defects of cardiac function in Epm2a-/- or Epm2b-/- mice. We conclude that laforin and malin have no effect on whole-body glucose metabolism and insulin sensitivity, and that laforin is not involved in insulin signaling.

  8. Cultured 3T3L1 adipocytes dispose of excess medium glucose as lactate under abundant oxygen availability

    PubMed Central

    Sabater, David; Arriarán, Sofía; Romero, María del Mar; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2014-01-01

    White adipose tissue (WAT) produces lactate in significant amount from circulating glucose, especially in obesity;Under normoxia, 3T3L1 cells secrete large quantities of lactate to the medium, again at the expense of glucose and proportionally to its levels. Most of the glucose was converted to lactate with only part of it being used to synthesize fat. Cultured adipocytes were largely anaerobic, but this was not a Warburg-like process. It is speculated that the massive production of lactate, is a process of defense of the adipocyte, used to dispose of excess glucose. This way, the adipocyte exports glucose carbon (and reduces the problem of excess substrate availability) to the liver, but the process may be also a mechanism of short-term control of hyperglycemia. The in vivo data obtained from adipose tissue of male rats agree with this interpretation. PMID:24413028

  9. Cultured 3T3L1 adipocytes dispose of excess medium glucose as lactate under abundant oxygen availability

    NASA Astrophysics Data System (ADS)

    Sabater, David; Arriarán, Sofía; Romero, María Del Mar; Agnelli, Silvia; Remesar, Xavier; Fernández-López, José Antonio; Alemany, Marià

    2014-01-01

    White adipose tissue (WAT) produces lactate in significant amount from circulating glucose, especially in obesity;Under normoxia, 3T3L1 cells secrete large quantities of lactate to the medium, again at the expense of glucose and proportionally to its levels. Most of the glucose was converted to lactate with only part of it being used to synthesize fat. Cultured adipocytes were largely anaerobic, but this was not a Warburg-like process. It is speculated that the massive production of lactate, is a process of defense of the adipocyte, used to dispose of excess glucose. This way, the adipocyte exports glucose carbon (and reduces the problem of excess substrate availability) to the liver, but the process may be also a mechanism of short-term control of hyperglycemia. The in vivo data obtained from adipose tissue of male rats agree with this interpretation.

  10. Sex differences in the control of glucose homeostasis.

    PubMed

    Blaak, Ellen

    2008-07-01

    A markedly higher prevalence of impaired glucose tolerance has been reported in women than in men, whereas the opposite was seen for impaired fasting glucose. The present review focuses on the underlying mechanisms. An increased meal glucose appearance and disturbances in postprandial glucose disposal may contribute to higher glucose concentrations in women. An increased, similar or reduced insulin sensitivity has been reported in women than in men, which makes it unclear to what extent a disturbed insulin-mediated glucose disposal may contribute to increased postprandial glucose concentrations in women. This discrepancy may be explained by differences in the phase of menstrual cycle during the study, the use of oral contraceptives and different degrees of physical fitness. Nevertheless, there are consistent data indicating that women are protected against fatty acid-induced insulin resistance. Furthermore, both disturbances in endogenous glucose output and metabolic clearance of glucose may contribute to the reduced fasting glucose concentrations in women. There is an urgent need for studies that test whether sex-related disturbances in glucose metabolism may be involved in the pathogenesis of type 2 diabetes and the metabolic syndrome, taking age, menstrual cycle, the use of oral contraceptives and physical activity into account.

  11. Design and synthesis of inositolphosphoglycan putative insulin mediators.

    PubMed

    López-Prados, Javier; Cuevas, Félix; Reichardt, Niels-Christian; de Paz, José-Luis; Morales, Ezequiel Q; Martín-Lomas, Manuel

    2005-03-07

    The binding modes of a series of molecules, containing the glucosamine (1-->6) myo-inositol structural motif, into the ATP binding site of the catalytic subunit of cAMP-dependent protein kinase (PKA) have been analysed using molecular docking. These calculations predict that the presence of a phosphate group at the non-reducing end in pseudodisaccharide and pseudotrisaccharide structures properly orientate the molecule into the binding site and that pseudotrisaccharide structures present the best shape complementarity. Therefore, pseudodisaccharides and pseudotrisaccharides have been synthesised from common intermediates using effective synthetic strategies. On the basis of this synthetic chemistry, the feasibility of constructing small pseudotrisaccharide libraries on solid-phase using the same intermediates has been explored. The results from the biological evaluation of these molecules provide additional support to an insulin-mediated signalling system which involves the intermediacy of inositolphosphoglycans as putative insulin mediators.

  12. Bed Rest Worsens Impairments in Fat and Glucose Metabolism in Older, Overweight Adults

    PubMed Central

    2014-01-01

    Background. The effects of bed rest on the dysregulation of fatty acid and glucose metabolism have not been addressed in the older population. Objective. We examined the effect of 10 days of bed rest on fatty acid kinetics and hepatic and peripheral insulin resistance in aging. Methods. We utilized an octreotide, basal glucagon replacement, multistage insulin infusion, and the concomitant infusion of [6,6 2H2]glucose to derive insulin-mediated suppression of glucose production and insulin-stimulated glucose disposal in nine older, overweight individuals (body mass index 28.1 ± 1.7 kg m−2; 39.9% ± 1.9% fat). During the multistage insulin infusion, we also infused [1-13C]palmitate to examine free fatty acid rate of appearance (R a). Results. Body weight, % body fat, and energy metabolism did not change with bed rest. There was a significant decrease (−2291 ± 316cm3) in visceral fat, and no change in abdominal subcutaneous fat with bed rest. Insulin-mediated suppression of glucose production was modest prior to bed rest and was further reduced (>15% ± 2%) by bed rest. There was also a minor decrease in the insulin-mediated suppression of free fatty acid R a after bed rest and, as a consequence, a small variation in plasma free fatty acid from pre- to post-bed rest in the first stage of the multistage insulin infusion. There was also a significant bed rest–induced decline (>2.0 ± 0.6 mg kg FFM−1 min− 1) in insulin-stimulated glucose disposal. Conclusions. Preexisting impairments in insulin sensitivity are worsened by bed rest and seem linked to alterations in the regulation of free fatty acid in older, overweight individuals. PMID:23902932

  13. Epoxyeicosatrienoic acids mediate insulin-mediated augmentation in skeletal muscle perfusion and blood volume

    PubMed Central

    Shim, Chi Young; Kim, Sajeevani; Chadderdon, Scott; Wu, Melinda; Qi, Yue; Xie, Aris; Alkayed, Nabil J.; Davidson, Brian P.

    2014-01-01

    Skeletal muscle microvascular blood flow (MBF) increases in response to physiological hyperinsulinemia. This vascular action of insulin may facilitate glucose uptake. We hypothesized that epoxyeicosatrienoic acids (EETs), a family of arachadonic, acid-derived, endothelium-derived hyperpolarizing factors, are mediators of insulin's microvascular effects. Contrast-enhanced ultrasound (CEU) was performed to quantify skeletal muscle capillary blood volume (CBV) and MBF in wild-type and obese insulin-resistant (db/db) mice after administration of vehicle or trans-4-[4-(3-adamantan-1-ylureido)cyclohexyloxy]benzoic acid (t-AUCB), an inhibitor of soluble epoxide hydrolase that converts EETs to less active dihydroxyeicosatrienoic acids. Similar studies were performed in rats pretreated with l-NAME. CEU was also performed in rats undergoing a euglycemic hyperinsulinemic clamp, half of which were pretreated with the epoxygenase inhibitor MS-PPOH to inhibit EET synthesis. In both wild-type and db/db mice, intravenous t-AUCB produced an increase in CBV (65–100% increase at 30 min, P < 0.05) and in MBF. In db/db mice, t-AUCB also reduced plasma glucose by ∼15%. In rats pretreated with l-NAME, t-AUCB after produced a significant ≈20% increase in CBV, indicating a component of vascular response independent of nitric oxide (NO) production. Hyperinsulinemic clamp produced a time-dependent increase in MBF (19 ± 36 and 76 ± 49% at 90 min, P = 0.026) that was mediated in part by an increase in CBV. Insulin-mediated changes in both CBV and MBF during the clamp were blocked entirely by MS-PPOH. We conclude that EETs are a mediator of insulin-mediated augmentation in skeletal muscle perfusion and are involved in regulating changes in CBV during hyperinsulinemia. PMID:25336524

  14. Abscisic acid enhances glucose disposal and induces brown fat activity in adipocytes in vitro and in vivo.

    PubMed

    Sturla, Laura; Mannino, Elena; Scarfì, Sonia; Bruzzone, Santina; Magnone, Mirko; Sociali, Giovanna; Booz, Valeria; Guida, Lucrezia; Vigliarolo, Tiziana; Fresia, Chiara; Emionite, Laura; Buschiazzo, Ambra; Marini, Cecilia; Sambuceti, Gianmario; De Flora, Antonio; Zocchi, Elena

    2017-02-01

    Abscisic acid (ABA) is a plant hormone also present in animals, where it is involved in the regulation of innate immune cell function and of glucose disposal, through its receptor LANCL2. ABA stimulates glucose uptake by myocytes and pre-adipocytes in vitro and oral ABA improves glycemic control in rats and in healthy subjects. Here we investigated the role of the ABA/LANCL2 system in the regulation of glucose uptake and metabolism in adipocytes. Silencing of LANCL2 abrogated both the ABA- and insulin-induced increase of glucose transporter-4 expression and of glucose uptake in differentiated 3T3-L1 murine adipocytes; conversely, overexpression of LANCL2 enhanced basal, ABA- and insulin-stimulated glucose uptake. As compared with insulin, ABA treatment of adipocytes induced lower triglyceride accumulation, CO2 production and glucose-derived fatty acid synthesis. ABA per se did not induce pre-adipocyte differentiation in vitro, but stimulated adipocyte remodeling in terminally differentiated cells, with a reduction in cell size, increased mitochondrial content, enhanced O2 consumption, increased transcription of adiponectin and of brown adipose tissue (BAT) genes. A single dose of oral ABA (1μg/kg body weight) increased BAT glucose uptake 2-fold in treated rats compared with untreated controls. One-month-long ABA treatment at the same daily dose significantly upregulated expression of BAT markers in the WAT and in WAT-derived preadipocytes from treated mice compared with untreated controls. These results indicate a hitherto unknown role of LANCL2 in adipocyte sensitivity to insulin-stimulated glucose uptake and suggest a role for ABA in the induction and maintenance of BAT activity. Copyright © 2016 Elsevier B.V. All rights reserved.

  15. Disposable Non-Enzymatic Glucose Sensors Using Screen-Printed Nickel/Carbon Composites on Indium Tin Oxide Electrodes.

    PubMed

    Jeon, Won-Yong; Choi, Young-Bong; Kim, Hyug-Han

    2015-12-10

    Disposable screen-printed nickel/carbon composites on indium tin oxide (ITO) electrodes (DSPNCE) were developed for the detection of glucose without enzymes. The DSPNCE were prepared by screen-printing the ITO substrate with a 50 wt% nickel/carbon composite, followed by curing at 400 °C for 30 min. The redox couple of Ni(OH)₂/NiOOH was deposited on the surface of the electrodes via cyclic voltammetry (CV), scanning from 0-1.5 V for 30 cycles in 0.1 M NaOH solution. The DSPNCE were characterized by field-emission scanning electron microscopy (FE-SEM), X-ray photoelectron spectroscopy (XPS), and electrochemical methods. The resulting electrical currents, measured by CV and chronoamperometry at 0.65 V vs. Ag/AgCl, showed a good linear response with glucose concentrations from 1.0-10 mM. Also, the prepared electrodes showed no interference from common physiologic interferents such as uric acid (UA) or ascorbic acid (AA). Therefore, this approach allowed the development of a simple, disposable glucose biosensor.

  16. Genetic disruption of the cardiomyocyte circadian clock differentially influences insulin-mediated processes in the heart.

    PubMed

    McGinnis, Graham R; Tang, Yawen; Brewer, Rachel A; Brahma, Manoja K; Stanley, Haley L; Shanmugam, Gobinath; Rajasekaran, Namakkal Soorappan; Rowe, Glenn C; Frank, Stuart J; Wende, Adam R; Abel, E Dale; Taegtmeyer, Heinrich; Litovsky, Silvio; Darley-Usmar, Victor; Zhang, Jianhua; Chatham, John C; Young, Martin E

    2017-09-01

    Cardiovascular physiology exhibits time-of-day-dependent oscillations, which are mediated by both extrinsic (e.g., environment/behavior) and intrinsic (e.g., circadian clock) factors. Disruption of circadian rhythms negatively affects multiple cardiometabolic parameters. Recent studies suggest that the cardiomyocyte circadian clock directly modulates responsiveness of the heart to metabolic stimuli (e.g., fatty acids) and stresses (e.g., ischemia/reperfusion). The aim of this study was to determine whether genetic disruption of the cardiomyocyte circadian clock impacts insulin-regulated pathways in the heart. Genetic disruption of the circadian clock in cardiomyocyte-specific Bmal1 knockout (CBK) and cardiomyocyte-specific Clock mutant (CCM) mice altered expression (gene and protein) of multiple insulin signaling components in the heart, including p85α and Akt. Both baseline and insulin-mediated Akt activation was augmented in CBK and CCM hearts (relative to littermate controls). However, insulin-mediated glucose utilization (both oxidative and non-oxidative) and AS160 phosphorylation were attenuated in CBK hearts, potentially secondary to decreased Inhibitor-1. Consistent with increased Akt activation in CBK hearts, mTOR signaling was persistently increased, which was associated with attenuation of autophagy, augmented rates of protein synthesis, and hypertrophy. Importantly, pharmacological inhibition of mTOR (rapamycin; 10days) normalized cardiac size in CBK mice. These data suggest that disruption of cardiomyocyte circadian clock differentially influences insulin-regulated processes, and provide new insights into potential pathologic mediators following circadian disruption. Copyright © 2017 Elsevier Ltd. All rights reserved.

  17. A ~60-min brisk walk increases insulin-stimulated glucose disposal but has no effect on hepatic and adipose tissue insulin sensitivity in older women.

    PubMed

    Wang, Xuewen; Patterson, Bruce W; Smith, Gordon I; Kampelman, Janine; Reeds, Dominic N; Sullivan, Shelby A; Mittendorfer, Bettina

    2013-06-01

    The purpose of this study was to determine whether brisk walking improves multiorgan (liver, muscle, adipose tissue) insulin sensitivity in older women. Ten nonobese older women (age: 66.7 ± 1.5 yr, mean ± SE) completed two 2-stage hyperinsulinemic-euglycemic clamp procedures [insulin infusion rate stage 1: 10 mU/m(2) body surface area (BSA) per min; stage 2: 50 mU/m(2) BSA per min] in conjunction with stable isotope-labeled glucose and palmitate tracer infusions: one in the morning after a single, ∼1-h bout of brisk treadmill walking, the other after an equivalent period of rest in the late afternoon of the preceding day. We found that basal glucose rate of appearance (Ra) into plasma was not different after rest and after exercise (17.3 ± 0.8 and 17.1 ± 0.4 μmol/kg fat-free mass per min, respectively). The insulin-mediated decrease in glucose Ra during stage 1 of the clamp was also not different after rest and exercise (82.2% ± 3.4% and 77.7% ± 2.1%, respectively), but glucose rate of disappearance (Rd) during stage 2 of the clamp was significantly greater (P < 0.05) after exercise than rest (88.0 ± 5.9 and 78.4 ± 6.5 μmol/kg fat-free mass per min, respectively). There were no differences in palmitate Ra during basal conditions or insulin infusion after exercise and after rest. Therefore, we conclude that a single bout of brisk walking for ∼1 h improves muscle insulin sensitivity but has no effect on liver and adipose tissue insulin sensitivity in older women.

  18. Bariatric Surgery in Morbidly Obese Insulin Resistant Humans Normalises Insulin Signalling but Not Insulin-Stimulated Glucose Disposal

    PubMed Central

    de Berker, David A. R.; May, Margaret T.; Hers, Ingeborg; Dayan, Colin M.; Andrews, Robert C.; Tavaré, Jeremy M.

    2015-01-01

    Aims Weight-loss after bariatric surgery improves insulin sensitivity, but the underlying molecular mechanism is not clear. To ascertain the effect of bariatric surgery on insulin signalling, we examined glucose disposal and Akt activation in morbidly obese volunteers before and after Roux-en-Y gastric bypass surgery (RYGB), and compared this to lean volunteers. Materials and Methods The hyperinsulinaemic euglycaemic clamp, at five infusion rates, was used to determine glucose disposal rates (GDR) in eight morbidly obese (body mass index, BMI=47.3±2.2 kg/m2) patients, before and after RYGB, and in eight lean volunteers (BMI=20.7±0.7 kg/m2). Biopsies of brachioradialis muscle, taken at fasting and insulin concentrations that induced half-maximal (GDR50) and maximal (GDR100) GDR in each subject, were used to examine the phosphorylation of Akt-Thr308, Akt-473, and pras40, in vivo biomarkers for Akt activity. Results Pre-operatively, insulin-stimulated GDR was lower in the obese compared to the lean individuals (P<0.001). Weight-loss of 29.9±4 kg after surgery significantly improved GDR50 (P=0.004) but not GDR100 (P=0.3). These subjects still remained significantly more insulin resistant than the lean individuals (p<0.001). Weight loss increased insulin-stimulated skeletal muscle Akt-Thr308 and Akt-Ser473 phosphorylation, P=0.02 and P=0.03 respectively (MANCOVA), and Akt activity towards the substrate PRAS40 (P=0.003, MANCOVA), and in contrast to GDR, were fully normalised after the surgery (obese vs lean, P=0.6, P=0.35, P=0.46, respectively). Conclusions Our data show that although Akt activity substantially improved after surgery, it did not lead to a full restoration of insulin-stimulated glucose disposal. This suggests that a major defect downstream of, or parallel to, Akt signalling remains after significant weight-loss. PMID:25876175

  19. Defective liver disposal of free fatty acids in patients with impaired glucose tolerance.

    PubMed

    Iozzo, Patricia; Turpeinen, Anu K; Takala, Teemu; Oikonen, Vesa; Bergman, Jörgen; Grönroos, Tove; Ferrannini, Ele; Nuutila, Pirjo; Knuuti, Juhani

    2004-07-01

    The liver exchanges high fluxes of glucose and free fatty acids (FFA) and is one main site of their reciprocal regulation. Acute exposure to hyperglycemia and hyperinsulinemia has been shown to reduce splanchnic beta-oxidation in healthy humans. We investigated whether a spontaneous condition of chronic mild hyperglycemia and hyperinsulinemia affects liver FFA uptake. Hepatic FFA influx rate constant (LKi) was measured after a 12-15-h fast in 10 patients with impaired glucose tolerance (IGT) and eight control subjects using positron emission tomography in combination with the long-chain FFA analog 14(R,S)-[18F]fluoro-6-thia-heptadecanoic acid. Compared with controls, IGT patients had higher serum insulin, glucose, and triglyceride levels (1.71 +/- 0.24 vs. 0.59 +/- 0.06 mmol/liter, P < 0.001), lower high-density lipoprotein (1.04 +/- 0.11 vs. 1.42 +/- 0.13 mmol/liter, P < 0.05), and similar FFA levels (0.59 +/- 0.06 vs. 0.56 +/- 0.05 mmol/liter(-1), P = not significant). LKi was significantly reduced in IGT (0.288 +/- 0.014 min(-1)) compared with control subjects (0.341 +/- 0.014 min(-1), P < 0.02). LKi was negatively correlated with plasma glucose (r = 0.51, P < 0.03), glycosylated hemoglobin (r = 0.55, P < 0.02), and blood lactate levels (r = 0.52, P < 0.03). We conclude that, in IGT patients, the ability of the liver to extract FFA from the circulation appears to be impaired. The reciprocal relationship between hepatic FFA extraction and glucose/lactate flux may derive from intrahepatic substrate competition.

  20. Effects of aerobic and resistive exercise training on glucose disposal and skeletal muscle metabolism in older men.

    PubMed

    Ferrara, Cynthia M; Goldberg, Andrew P; Ortmeyer, Heidi K; Ryan, Alice S

    2006-05-01

    Aging is associated with insulin resistance, primarily as a result of physical inactivity and increased abdominal obesity. We hypothesized that aerobic (AEX) or resistive (RT) exercise training would result in comparable improvements in glucose disposal in older men, but that there would be different metabolic adaptations in skeletal muscle. Thirty-nine older (63+/-1 years, mean+/-standard error of the mean), overweight and obese (body mass index=30.3+/-0.4 kg/m2) men were assigned to AEX (treadmill walking and/or jogging, n=19) or RT (upper and lower body, n=20) programs 3 d/wk for 6 months, with 9 completing AEX and 13 completing RT. Testing before and after the exercise programs included body composition, euglycemic-hyperinsulinemic clamps, and vastus lateralis muscle biopsies. Maximal oxygen consumption (VO2max) increased by 16% after AEX (p<.01), while leg and arm muscle strength increased by 45+/-5% and 27+/-5% after RT (p<.0001). Although participants were monitored to maintain their body weight during the exercise program, body weight decreased by 2% after AEX (p<.05), and increased by 2% after RT (p<.05). Whole-body glucose disposal, determined during the last 30 minutes of a 2-hour 480 pmol/m2/min euglycemic-hyperinsulinemic clamp, increased comparably by 20%-25% after AEX (51+/-5 to 61+/-5 microM/kgfat-free mass/min, p<.05) and RT (49+/-3 to 58+/-3 microM/kgfat-free mass/min, p<.05). The increase in vastus lateralis muscle glycogen synthase fractional activity in response to insulin stimulation was significantly higher after AEX compared to after RT (279+/-59% compared to 100+/-28% change, p<.05). Neither AEX nor RT altered muscle glycogen synthase total activity, glycogen content, or levels of phosphotidylinositol 3-kinase. These results suggest that AEX and RT result in comparable improvements in glucose metabolism in older men, whereas an increase in insulin activation of glycogen synthase occurred only with AEX. These improvements in insulin

  1. Quercetin, luteolin, and epigallocatechin gallate promote glucose disposal in adipocytes with regulation of AMP-activated kinase and/or sirtuin 1 activity.

    PubMed

    Xiao, Na; Mei, Fan; Sun, Yan; Pan, Guojun; Liu, Baolin; Liu, Kang

    2014-08-01

    Quercetin, luteolin, and epigallocatechin gallate are flavonoids abundant in edible and medicinal plants with beneficial effects on glucose homeostasis. This study explored the action of these flavonoids on glucose disposal in adipocytes. Quercetin, luteolin, and epigallocatechin gallate enhanced glucose consumption with the positive regulation of AMP-activated kinase phosphorylation, and the AMP-activated kinase inhibitor compound C abolished their effects on glucose consumption. Luteolin and epigallocatechin gallate, but not quercetin, increased sirtuin 1 abundance, and their regulation of glucose consumption was also attenuated by co-treatment with sirtuin 1 inhibitor nicotinamide. Quercetin, luteolin, and epigallocatechin gallate suppressed nuclear factor-κB activation by inhibition of p65 phosphorylation with beneficial regulation of adipokine expression, whereas these actions were diminished by coincubation with compound C. The sirtuin 1 inhibitor nicotinamide attenuated the effects of luteolin and EGCG on p65 phosphorylation and adipokine expression without any influence on the activity of quercetin. Results of Western blot and fluorescence microscopy also showed that quercetin, luteolin, and epigallocatechin gallate increased Akt substrate of 160 kDa phosphorylation and promoted 2-deoxy-D-glucose uptake by adipocytes under basal and inflammatory conditions. These findings suggested that quercetin, luteolin, and epigallocatechin gallate inhibited inflammation and promoted glucose disposal in adipocytes with the regulation of AMP-activated kinase and/or sirtuin 1.

  2. Effects of a nucleoside reverse transcriptase inhibitor, stavudine, on glucose disposal and mitochondrial function in muscle of healthy adults

    PubMed Central

    Fleischman, Amy; Johnsen, Stine; Systrom, David M.; Hrovat, Mirko; Farrar, Christian T.; Frontera, Walter; Fitch, Kathleen; Thomas, Bijoy J.; Torriani, Martin; Côté, Hélène C. F.; Grinspoon, Steven K.

    2011-01-01

    Mitochondrial dysfunction may contribute to the development of insulin resistance and type 2 diabetes. Nucleoside reverse transcriptase inhibitors (NRTIs), specifically stavudine, are known to alter mitochondrial function in human immunodeficiency virus (HIV)-infected individuals, but the effects of stavudine on glucose disposal and mitochondrial function in muscle have not been prospectively evaluated. In this study, we investigated short-term stavudine administration among healthy control subjects to determine effects on insulin sensitivity. A secondary aim was to determine the effects of stavudine on mitochondrial DNA (mtDNA) and function. Sixteen participants without personal or family history of diabetes were enrolled. Subjects were randomized to receive stavudine, 30 – 40 mg, twice a day, or placebo for 1 mo. Insulin sensitivity determined by glucose infusion rate during the hyperinsulinemic euglycemic clamp was significantly reduced after 1-mo exposure in the stavudine-treated subjects compared with placebo (−0.8 ± 0.5 vs. +0.7 ± 0.3 mg· kg−1 · min−1, P = 0.04, stavudine vs. placebo). In addition, muscle biopsy specimens in the stavudine-treated group showed significant reduction in mtDNA/nuclear DNA (−52%, P = 0.005), with no change in placebo-treated subjects (+8%, P = 0.9). 31P magnetic resonance spectroscopy (MRS) studies of mitochondrial function correlated with insulin sensitivity measures (r2 = 0.5, P = 0.008). These findings demonstrate that stavudine administration has potent effects on insulin sensitivity among healthy subjects. Further studies are necessary to determine whether changes in mtDNA resulting from stavudine contribute to effects on insulin sensitivity. PMID:17284576

  3. Disposable, enzymatically modified printed film carbon electrodes for use in the high-performance liquid chromatographic-electrochemical detection of glucose or hydrogen peroxide from immobilized enzyme reactors.

    PubMed

    Osborne, P G; Yamamoto, K

    1998-04-10

    Disposable screen-printed, film carbon electrodes (PFCE) were modified with cast-coated Osmium-polyvinylpyrridine-wired horse radish peroxidase gel polymer (Os-gel-HRP) to enable the detection of the reduction at 0 mV of hydrogen peroxide (H2O2) derived from a post-column immobilized enzyme reactor (IMER) containing acetylcholinesterase and choline oxidase. In another series of experiments PFCE were initially modified with cast-coated Os-gel-HRP and then treated with glucose oxidase in bovine serum albumin (BSA) and cross-linked with glutaraldehyde to form a bi-layer glucose-Os-gel-HRP PFCE. This bi-layer glucose-Os-gel-HRP PFCE generated a reduction current at 0 mV to H2O2 derived from the reaction of glucose oxidase and glucose in solution. These enzyme-modified PFCE were housed in a radial flow cell and coupled with cation-exchange liquid chromatographic methods to temporally separate substrates in solution for the determination of acetylcholine (ACh) and choline (Ch) in the first experimental series, or glucose in the second experimental series. These two disposable enzyme-modified PFCE exhibited linear current vs. substrate relations, were durable, being usable for approximately 40 determinations, and were sufficiently sensitive to be employed in biological sampling. Both assays utilized the same HPLC equipment. The limit of detection for ACh was 16 fmol/10 microl and that for glucose was 12 micromol/7.5 microl. ACh and Ch were measured from a microdialysate from the frontal cortex of a rat. Glucose in human urine was determined using the bi-layer glucose oxidase-Os-gel-HRP PFCE.

  4. Disposable all-solid-state pH and glucose sensors based on conductive polymer covered hierarchical AuZn oxide.

    PubMed

    Kim, Dong-Min; Cho, Seong Je; Cho, Chul-Ho; Kim, Kwang Bok; Kim, Min-Yeong; Shim, Yoon-Bo

    2016-05-15

    Poly(terthiophene benzoic acid) (pTBA) layered-AuZn alloy oxide (AuZnOx) deposited on the screen printed carbon electrode (pTBA/AuZnOx/SPCE) was prepared to create a disposable all-solid-state pH sensor at first. Further, FAD-glucose oxidase (GOx) was immobilized onto the pTBA/AuZnOx/SPCE to fabricate a glucose sensor. The characterizations of the sensor probe reveal that AuZnOx forms a homogeneous hierarchical structure, and that the polymerized pTBA layer on the alloy oxide surface captures GOx covalently. The benzoic acid group of pTBA coated on the probe layer synergetically improved the pH response of the alloy oxide and provide chemical binding sites to enzyme, which resulted in a Nernstian behavior (59.2 ± 0.5 mV/pH) in the pH range of 2-13. The experimental parameters affecting the glucose analysis were studied in terms of pH, temperature, humidity, and interferences. The sensor exhibited a fast response time <1s and a dynamic range between 30 and 500 mg/dL glucose with a detection limit of 17.23 ± 0.32 mg/dL. The reliabilities of the disposable pH and glucose sensors were examined for biological samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  5. Changes in glucose disposal after a caloric restriction-induced weight loss program in obese postmenopausal women: characteristics of positive and negative responders in a Montreal-Ottawa New Emerging Team study.

    PubMed

    Myette-Côté, Étienne; Doucet, Éric; Prud'homme, Denis; Rabasa-Lhoret, Rémi; Lavoie, Jean-Marc; Brochu, Martin

    2015-01-01

    This study aims to investigate individual characteristics that explain interindividual variations in glucose disposal in response to a 6-month weight loss program in obese postmenopausal women. The cohort was divided into tertiles based on changes in glucose disposal after weight loss. Only women in the upper tertile (positive responders: Δ glucose disposal ≥ 0.92 mg/kg/min; n = 19) and lower tertile (negative responders: Δ glucose disposal ≤ -0.23 mg/kg/min; n = 19) were considered for analyses. Outcome measures included body weight, lean body mass (LBM), LBM index (= LBM / height [m]), fat mass (FM), FM index (= FM / height [m]), visceral fat, subcutaneous abdominal fat, high-sensitivity C-reactive protein (hsCRP) levels, interleukin-6, lipid profile, physical activity levels, fasting blood glucose and insulin levels, glucose disposal by hyperinsulinemic-euglycemic clamp technique, and resting blood pressure. At baseline, positive responders had higher triglycerides and hsCRP levels and lower glucose disposal (0.01 < P < 0.05) than negative responders. Except for visceral fat, the entire cohort showed significant decreases in all measures of body composition (P < 0.005) after weight loss, with greater decreases in body weight, body mass index, and FM index in positive responders (P < 0.005). Finally, data revealed that only positive responders showed decreases in LBM, LBM index, and hsCRP levels after weight loss (P between 0.01 and 0.001). An important interindividual variability in changes in glucose disposal after weight loss is observed. Interestingly, participants who display improvements in glucose disposal also show significant decreases in LBM, LBM index, and hsCRP after weight loss.

  6. [Estimated glucose disposal rate in patients under 18 years of age with type 1 diabetes mellitus and overweight or obesity].

    PubMed

    Palomo Atance, Enrique; Ballester Herrera, M José; Giralt Muiña, Patricio; Ruiz Cano, Rafael; León Martín, Alberto; Giralt Muiña, Juan

    2013-01-01

    To assess the estimated glucose disposal rate (eGDR), insulin dose, and lipoprotein profile in children with type 1 diabetes mellitus (T1DM) and overweight or obesity as compared to children with T1DM and normal weight. A total of 115 patients (aged 5-16 years) with T1DM on intensive insulin therapy were recruited. The following parameters were measured: weight, height, body mass index, waist and hip circumference, insulin dose, eGDR, glycosylated hemoglobin, blood pressure, and lipoprotein profile. Results were stratified by sex and age. No significant differences were found in eGDR between children with normal weight, overweight, and obesity. However, obese children older than 11 years had lower eGDR values (9.3±1.3 vs 10.1±0.8 mg kg(-1)min(-1); p<0.01). Insulin dose was higher in overweight and obese children, especially in IU/m2/day (37.7 vs 36.1 vs. 29.4 respectively; p<0.01). Obese children had higher low-density lipoprotein cholesterol levels than children with overweight and normal weight (106.5 vs 91.7 vs 91.5mg/dL respectively; p<0.01). No correlation was found between waist circumference and the different markers of insulin resistance. Values of eGDR values were lower in obese children with T1DM older than 11 years, and this may therefore be considered a marker of insulin resistance. Insulin dose was higher in diabetic patients with overweight or obesity, specially in IU/m2/day. Obese children with T1DM had a lipoprotein profile of cardiovascular risk. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  7. A novel method for simulating insulin mediated GLUT4 translocation.

    PubMed

    Jezewski, Andrew J; Larson, Joshua J; Wysocki, Beata; Davis, Paul H; Wysocki, Tadeusz

    2014-12-01

    Glucose transport in humans is a vital process which is tightly regulated by the endocrine system. Specifically, the insulin hormone triggers a cascade of intracellular signals in target cells mediating the uptake of glucose. Insulin signaling triggers cellular relocalization of the glucose transporter protein GLUT4 to the cell surface, which is primarily responsible for regulated glucose import. Pathology associated with the disruption of this pathway can lead to metabolic disorders, such as type II diabetes mellitus, characterized by the failure of cells to appropriately uptake glucose from the blood. We describe a novel simulation tool of the insulin intracellular response, incorporating the latest findings regarding As160 and GEF interactions. The simulation tool differs from previous computational approaches which employ algebraic or differential equations; instead, the tool incorporates statistical variations of kinetic constants and initial molecular concentrations which more accurately mimic the intracellular environment. Using this approach, we successfully recapitulate observed in vitro insulin responses, plus the effects of Wortmannin-like inhibition of the pathway. The developed tool provides insight into transient changes in molecule concentrations throughout the insulin signaling pathway, and may be employed to identify or evaluate potentially critical components of this pathway, including those associated with insulin resistance. In the future, this highly tractable platform may be useful for simulating other complex cell signaling pathways. Biotechnol. Bioeng. 2014;111: 2454-2465. © 2014 Wiley Periodicals, Inc.

  8. FDP-E induces adipocyte inflammation and suppresses insulin-stimulated glucose disposal: effect of inflammation and obesity on fibrinogen Bβ mRNA.

    PubMed

    Kang, Minsung; Vaughan, Roger A; Paton, Chad M

    2015-12-01

    Obesity is associated with increased fibrinogen production and fibrin formation, which produces fibrin degradation products (FDP-E and FDP-D). Fibrin and FDPs both contribute to inflammation, which would be expected to suppress glucose uptake and insulin signaling in adipose tissue, yet the effect of FDP-E and FDP-D on adipocyte function and glucose disposal is completely unknown. We tested the effects of FDPs on inflammation in 3T3-L1 adipocytes and primary macrophages and adipocyte glucose uptake in vitro. High-fat-fed mice increased hepatic fibrinogen mRNA expression ninefold over chow-fed mice, with concomitant increases in plasma fibrinogen protein levels. Obese mice also displayed increased fibrinogen content of epididymal fat pads. We treated cultured 3T3-L1 adipocytes and primary macrophages with FDP-E, FDP-D, or fibrinogen degradation products (FgnDP-E). FDP-D and FgnDP-E had no effect on inflammation or glucose uptake. Cytokine mRNA expression in RAW264.7 macrophage-like cells and 3T3-L1 adipocytes treated with FDP-E induced inflammation with maximal effects at 100 nM and 6 h. Insulin-stimulated 2-deoxy-d-[(3)H]glucose uptake was reduced by 71% in adipocytes treated with FDP-E. FDP-E, but not FDP-D or FgnDP-E, induces inflammation in macrophages and adipocytes and decreases glucose uptake in vitro. FDP-E may contribute toward obesity-associated acute inflammation and glucose intolerance, although its chronic role in obesity remains to be elucidated. Copyright © 2015 the American Physiological Society.

  9. Inositols in the Treatment of Insulin-Mediated Diseases

    PubMed Central

    Muscogiuri, Giovanna; Palomba, Stefano

    2016-01-01

    A growing body of research is currently focused on the role of inositol isomers and in particular myo-inositol (MYO-INS) and D-chiroinositol (DCI) in the treatment of insulin resistance states. Both isomers have been shown to exert insulin-mimetic action and to lower postprandial glucose. Further, insulin resistance-related diseases were associated to derangements in inositol metabolism. Thus, the aim of this review is to provide current evidence on the potential benefits of inositol isomers (MYO-INS and DCI) in the treatment of disease associated to insulin resistance such as polycystic ovary syndrome (PCOS), gestational diabetes, and metabolic syndrome. Finally, molecular insights into inositol insulin-sensitizing effects will be covered focusing on the possible role of inositol glycans as insulin second messengers. PMID:27688754

  10. Opuntia ficus-indica ingestion stimulates peripheral disposal of oral glucose before and after exercise in healthy men.

    PubMed

    Van Proeyen, Karen; Ramaekers, Monique; Pischel, Ivo; Hespel, Peter

    2012-08-01

    The purpose of this study was to investigate the effect of Opuntia ficus-indica (OFI) cladode and fruit-skin extract on blood glucose and plasma insulin increments due to high-dose carbohydrate ingestion, before and after exercise. Healthy, physically active men (n = 6; 21.0 ± 1.6 years, 78.1 ± 6.0 kg) participated in a double-blind placebo-controlled crossover study involving 2 experimental sessions. In each session, the subjects successively underwent an oral glucose tolerance test at rest (OGTT(R)), a 30-min cycling bout at ~75% VO(2max), and another OGTT after exercise (OGTT(EX)). They received capsules containing either 1,000 mg OFI or placebo (PL) 30 min before and immediately after the OGTT(R). Blood samples were collected before (t₀) and at 30-min intervals after ingestion of 75 g glucose for determination of blood glucose and serum insulin. In OGTT(EX) an additional 75-g oral glucose bolus was administered at t₆₀. In OGTT(R), OFI administration reduced the area under the glucose curve (AUC(GLUC)) by 26%, mainly due to lower blood glucose levels at t₃₀ and t₆₀ (p < .05). Furthermore, a higher serum insulin concentration was noted after OFI intake at baseline and at t₃₀ (p < .05). In OGTT(EX), blood glucose at t₆₀ was ~10% lower in OFI than in PL, which resulted in a decreased AUC(GLUC) (-37%, p < .05). However, insulin values and AUC(INS) were not different between OFI and PL. In conclusion, the current study shows that OFI extract can increase plasma insulin and thereby facilitate the clearance of an oral glucose load from the circulation at rest and after endurance exercise in healthy men.

  11. Rat liver insulin mediator which stimulates pyruvate dehydrogenase phosphate contains galactosamine and D-chiroinositol.

    PubMed

    Larner, J; Huang, L C; Schwartz, C F; Oswald, A S; Shen, T Y; Kinter, M; Tang, G Z; Zeller, K

    1988-03-30

    It has been established that insulin treatment of cells, isolated plasma membranes, or whole animals leads to the generation of low molecular weight mediators which serve as intermediates in the signalling pathway. At least two distinct classes of mediator have been described, based on differences in apparent molecular weight, isoelectric point and biological activity (Cheng, K., and Larner, J. (1985) Ann. Rev. Physiol. 45, 407-424). Recently, Saltiel's (Saltiel, A.R., and Cuatrecasas, P. (1986) Proc. Natl. Acad. Sci. U.S.A. 83, 5793-5797) and Mato's (Mato, J.M., Kelly, K.L., Abler, A., and Jarett, L. (1987) J. Biol. Chem. 262, 2131-2137) laboratories have described an insulin "modulator" which was apparently derived from glycosylphosphoinositol linker, similar to those known to anchor proteins to the external surface of the cell membrane (Low, M.G. (1987) Bioch. J. 244, 1-13). In this paper, we report that highly purified preparations of the insulin mediator which stimulates pyruvate dehydrogenase phosphatase contain mannose, galactosamine, and D-chiroinositol. These determinations are based upon analyses using paper chromatography and gas chromatography/mass spectroscopy. Nitrous acid deamination of the mediator resulted in release of inositol phosphate, indicating that the galactosamine and D-chiroinositol are linked. Although the presence of chiroinositol in modulator from H35 hepatoma cells has been recently reported (Mato, J.M., Kelly, K.L., Abler, A., Jarett, L., Corkey, B.E., Cashel, J.A., and Zopf, D. (1987) Bioch. Biophys. Res. Comm. 146, 764-770), the optical identity of the inositol remained unknown until the present report. Likewise, the presence of galactosamine rather than glucosamine in insulin mediator is a novel finding. These findings, coupled with those of Saltiel and Mato's groups, provide clear evidence for the existence of multiple forms of insulin mediators. Additionally, the results presented here afford further confirmation for the

  12. Development of a disposable glucose biosensor using electroless-plated Au/Ni/copper low electrical resistance electrodes.

    PubMed

    Lee, Seung-Ro; Lee, Young-Tae; Sawada, Kazuaki; Takao, Hidekuni; Ishida, Makoto

    2008-11-15

    This paper presents a glucose biosensor, which was developed using a Au/Ni/copper electrode. Until now, research regarding the low electrical resistance and uniformity of this biosensor electrode has not been conducted. Glucose oxidase (GOD) immobilized on the electrode effectively plays the role of an electron shuttle, and allows glucose to be detected at 0.055 V with a dramatically reduced resistance to easily oxidizable constituents. The Au/Ni/copper electrode has a low electrical resistance, which is less than 0.01 Omega, and it may be possible to mass produce the biosensor electrode with a uniform electrical resistance. The low electrical resistance has the advantage in that the redox peak occurs at a low applied potential. Using a low operating potential (0.055 V), the GOD/Au/Ni/copper structure creates a good sensitivity to detect glucose, and efficiently excludes interferences from common coexisting substances. The GOD/Au/Ni/copper sensor exhibits a relatively short response time (about 3s), and a sensitivity of 0.85 microA mM(-1) with a linear range of buffer to 33 mM of glucose. The sensor has excellent reproducibility with a correlation coefficient of 0.9989 (n=100 times) and a total non-linearity error of 3.17%.

  13. A Disposable Tear Glucose Biosensor-Part 4: Preliminary Animal Model Study Assessing Efficacy, Safety, and Feasibility.

    PubMed

    La Belle, Jeffrey T; Engelschall, Erica; Lan, Kenneth; Shah, Pankti; Saez, Neil; Maxwell, Stephanie; Adamson, Teagan; Abou-Eid, Michelle; McAferty, Kenyon; Patel, Dharmendra R; Cook, Curtiss B

    2014-01-01

    A prototype tear glucose (TG) sensor was tested in New Zealand white rabbits to assess eye irritation, blood glucose (BG) and TG lag time, and correlation with BG. A total of 4 animals were used. Eye irritation was monitored by Lissamine green dye and analyzed using image analysis software. Lag time was correlated with an oral glucose load while recording TG and BG readings. Correlation between TG and BG were plotted against one another to form a correlation diagram, using a Yellow Springs Instrument (YSI) and self-monitoring of blood glucose as the reference measurements. Finally, TG levels were calculated using analytically derived expressions. From repeated testing carried over the course of 12 months, little to no eye irritation was detected. TG fluctuations over time visually appeared to trace the same pattern as BG with an average lag times of 13 minutes. TG levels calculated from the device current measurements ranged from 4 to 20 mg/dL and correlated linearly with BG levels of 75-160 mg/dL (TG = 0.1723 BG = 7.9448 mg/dL; R(2) = .7544). The first steps were taken toward preliminary development of a sensor for self-monitoring of tear glucose (SMTG). No conjunctival irritation in any of the animals was noted. Lag time between TG and BG was found to be noticeable, but a quantitative modeling to correlate lag time in this study is unnecessary. Measured currents from the sensors and the calculated TG showed promising correlation to BG levels. Previous analytical bench marking showed BG and TG levels consistent with other literature. © 2014 Diabetes Technology Society.

  14. Dual Actions of Apolipoprotein A-I on Glucose-Stimulated Insulin Secretion and Insulin-Independent Peripheral Tissue Glucose Uptake Lead to Increased Heart and Skeletal Muscle Glucose Disposal.

    PubMed

    Domingo-Espín, Joan; Lindahl, Maria; Nilsson-Wolanin, Oktawia; Cushman, Samuel W; Stenkula, Karin G; Lagerstedt, Jens O

    2016-07-01

    Apolipoprotein A-I (apoA-I) of HDL is central to the transport of cholesterol in circulation. ApoA-I also provides glucose control with described in vitro effects of apoA-I on β-cell insulin secretion and muscle glucose uptake. In addition, apoA-I injections in insulin-resistant diet-induced obese (DIO) mice lead to increased glucose-stimulated insulin secretion (GSIS) and peripheral tissue glucose uptake. However, the relative contribution of apoA-I as an enhancer of GSIS in vivo and as a direct stimulator of insulin-independent glucose uptake is not known. Here, DIO mice with instant and transient blockade of insulin secretion were used in glucose tolerance tests and in positron emission tomography analyses. Data demonstrate that apoA-I to an equal extent enhances GSIS and acts as peripheral tissue activator of insulin-independent glucose uptake and verify skeletal muscle as an apoA-I target tissue. Intriguingly, our analyses also identify the heart as an important target tissue for the apoA-I-stimulated glucose uptake, with potential implications in diabetic cardiomyopathy. Explorations of apoA-I as a novel antidiabetic drug should extend to treatments of diabetic cardiomyopathy and other cardiovascular diseases in patients with diabetes. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  15. Chronic dietary exposure to branched chain amino acids impairs glucose disposal in vegans but not in omnivores.

    PubMed

    Gojda, J; Rossmeislová, L; Straková, R; Tůmová, J; Elkalaf, M; Jaček, M; Tůma, P; Potočková, J; Krauzová, E; Waldauf, P; Trnka, J; Štich, V; Anděl, M

    2017-05-01

    Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores. Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months. Anthropometry, blood analyses, glucose clamp, arginine test, subcutaneous abdominal adipose tissue (AT) and skeletal muscle (SM) biopsies (mRNA levels of selected metabolic markers, respiratory chain (RC) activity) were performed at baseline, after the intervention and after a 6 month wash-out period. Compared with omnivores, vegans had higher IS at baseline (GIR, glucose infusion rate: 9.6±2.4 vs 7.1±2.4 mg/kg/min, 95% CI for difference: 0.55 to 5.82) that declined after the intervention and returned to baseline values after the wash-out period (changes in GIR with 95% CI, 3-0 months: -1.64 [-2.5; -0.75] and 9-3 months: 1.65 [0.75; 2.54] mg/kg/min). No such change was observed in omnivores. In omnivores the intervention led to an increased expression of lipogenic genes (DGAT2, FASN, PPARγ, SCD1) in AT. SM RC activity increased in both groups. Negative impact of increased BCAA intake on IS was only detected in vegans, that is, subjects with low basal amino acids/BCAA intake, which appear to be unable to induce sufficient compensatory changes within AT and SM on a BCAA challenge.

  16. The effect of caffeine on glucose kinetics in humans – influence of adrenaline

    PubMed Central

    Battram, Danielle S; Graham, Terry E; Richter, Erik A; Dela, Flemming

    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 caffeine and HAdr decreased GIR by 13 (P < 0.05) and 34% (P < 0.05) versus the placebo, respectively, LAdr did not result in a significant reduction (5%) in GIR versus the placebo. Due to the fact that both caffeine and LAdr resulted in similar adrenaline concentrations, but resulted in different decreases in GIR, it is concluded that adrenaline alone does not account for the effects of caffeine and additional mechanisms must be involved. PMID:16150793

  17. Altered glucose and lipid homeostasis in liver and adipose tissue pre-dispose inducible NOS knockout mice to insulin resistance

    PubMed Central

    Kanuri, Babu Nageswararao; Kanshana, Jitendra S.; Rebello, Sanjay C.; Pathak, Priya; Gupta, Anand P.; Gayen, Jiaur R.; Jagavelu, Kumaravelu; Dikshit, Madhu

    2017-01-01

    On the basis of diet induced obesity and KO mice models, nitric oxide is implied to play an important role in the initiation of dyslipidemia induced insulin resistance. However, outcomes using iNOS KO mice have so far remained inconclusive. The present study aimed to assess IR in iNOS KO mice after 5 weeks of LFD feeding by monitoring body composition, energy homeostasis, insulin sensitivity/signaling, nitrite content and gene expressions changes in the tissues. We found that body weight and fat content in KO mice were significantly higher while the respiratory exchange ratio (RER), volume of carbon dioxide (VCO2), and heat production were lower as compared to WT mice. Furthermore, altered systemic glucose tolerance, tissue insulin signaling, hepatic gluconeogenesis, augmented hepatic lipids, adiposity, as well as gene expression regulating lipid synthesis, catabolism and efflux were evident in iNOS KO mice. Significant reduction in eNOS and nNOS gene expression, hepatic and adipose tissue nitrite content, circulatory nitrite was also observed. Oxygen consumption rate of mitochondrial respiration has remained unaltered in KO mice as measured using extracellular flux analyzer. Our findings establish a link between the NO status with systemic and tissue specific IR in iNOS KO mice at 5 weeks. PMID:28106120

  18. Activation of cAMP signaling attenuates impaired hepatic glucose disposal in aged male p21-activated protein kinase-1 knockout mice.

    PubMed

    Chiang, Yu-Ting Alex; Ip, Wilfred; Shao, Weijuan; Song, Zhuolun Eric; Chernoff, Jonathan; Jin, Tianru

    2014-06-01

    p21-activated protein kinase-1 (Pak1) plays a role in insulin secretion and glucagon-like peptide-1 (GLP-1) production. Pak1(-/-) mice were found to carry a defect in ip pyruvate tolerance test (IPPTT), leading us to speculate whether Pak1 represses hepatic gluconeogenesis. We show here that the defect in IPPTT became more severe in aged Pak1(-/-) mice. In primary hepatocytes, 2,2'-dihydroxy-1,1'-dinaphthyldisulfide, a potent inhibitor of group I Paks, reduced basal glucose production (GP), attenuated forskolin- or glucagon-stimulated GP, and attenuated the stimulation of forskolin on the expression of Pck1 and G6pc. In addition, the capacity of primary hepatocytes isolated from Pak1(-/-) mice in GP at the basal level is significantly lower than that of the control littermates. These in vitro observations imply that the direct effect of Paks in hepatocytes is the stimulation of gluconeogenesis and that the impairment in IPPTT in Pak1(-/-) mice is due to the lack of Pak1 elsewhere. Consecutive ip injection of forskolin for 2 weeks increased gut proglucagon expression, associated with improved IPPTT in aged Pak1(-/-) mice and wild-type controls. In addition, administration of the DPP-IV (dipeptidyl peptidase-4) inhibitor sitagliptin for 1 week reversed the defect in IPPTT in aged Pak1(-/-) mice, associated with increased plasma GLP-1 levels. Our observations indicate a potential role of Pak1 in the gut/pancreas/liver axis in controlling glucose disposal and affirmed the therapeutic application of GLP-1 and DPP-IV inhibitors in attenuating hepatic gluconeogenesis.

  19. Immediate enhancement of first-phase insulin secretion and unchanged glucose effectiveness in patients with type 2 diabetes after Roux-en-Y gastric bypass.

    PubMed

    Martinussen, Christoffer; Bojsen-Møller, Kirstine N; Dirksen, Carsten; Jacobsen, Siv H; Jørgensen, Nils B; Kristiansen, Viggo B; Holst, Jens J; Madsbad, Sten

    2015-03-15

    Roux-en-Y gastric bypass surgery (RYGB) in patients with type 2 diabetes often leads to early disease remission, and it is unknown to what extent this involves improved pancreatic β-cell function per se and/or enhanced insulin- and non-insulin-mediated glucose disposal (glucose effectiveness). We studied 30 obese patients, including 10 with type 2 diabetes, 8 with impaired glucose tolerance, and 12 with normal glucose tolerance before, 1 wk, and 3 mo after RYGB, using an intravenous glucose tolerance test (IVGTT) to estimate first-phase insulin response, insulin sensitivity (Si), and glucose effectiveness with Bergman's minimal model. In the fasting state, insulin sensitivity was estimated by HOMA-S and β-cell function by HOMA-β. Moreover, mixed-meal tests and oral GTTs were performed. In patients with type 2 diabetes, glucose levels normalized after RYGB, first-phase insulin secretion in response to iv glucose increased twofold, and HOMA-β already improved 1 wk postoperatively, with further enhancements at 3 mo. Insulin sensitivity increased in the liver (HOMA-S) at 1 wk and at 3 mo in peripheral tissues (Si), whereas glucose effectiveness did not improve significantly. During oral testing, GLP-1 responses and insulin secretion increased regardless of glucose tolerance. Therefore, in addition to increased insulin sensitivity and exaggerated postprandial GLP-1 levels, diabetes remission after RYGB involves early improvement of pancreatic β-cell function per se, reflected in enhanced first-phase insulin secretion to iv glucose and increased HOMA-β. A major role for improved glucose effectiveness after RYGB was not supported by this study. Copyright © 2015 the American Physiological Society.

  20. Basal and Insulin Mediated VLDL-Triglyceride Kinetics in Type 2 Diabetic Men

    PubMed Central

    Sørensen, Lars P.; Andersen, Iben R.; Søndergaard, Esben; Gormsen, Lars C.; Schmitz, Ole; Christiansen, Jens S.; Nielsen, Søren

    2011-01-01

    OBJECTIVE Increased very-low-density lipoprotein triglycerides (VLDL-TG) concentration is a central feature of diabetic dyslipidemia. The objective was to compare basal and insulin mediated VLDL-TG kinetics, oxidation, and adipose tissue storage in type 2 diabetic and healthy (nondiabetic) men. RESEARCH DESIGN AND METHODS Eleven type 2 diabetic and 11 healthy men, matched for BMI and age, were included. Ex vivo-labeled VLDL-TG tracers, blood and breath samples, fat biopsies, indirect calorimetry, and body composition measures were applied to determine VLDL-TG kinetics, VLDL-TG fatty acids (FA) oxidation, and storage in regional adipose tissue before and during a hyperinsulinemic euglycaemic clamp. RESULTS VLDL-TG secretion was significantly greater in diabetic compared with healthy men (basal: 86.9 [31.0] vs. 61.9 [30.0] μmol/min, P = 0.03; clamp: 60.0 [26.2] vs. 34.2 [17.9] μmol · min−1, P = 0.01). The insulin mediated suppression of VLDL-TG secretion was significant in both groups. VLDL-TG clearance was lower in diabetic men (basal: 84.6 [32.7] vs. 115.4 [44.3] ml · min−1, P = 0.08; clamp: 76.3 [30.6] vs. 119.0 [50.2] ml · min−1, P = 0.03). During hyperinsulinemia fractional VLDL-TG FA oxidation was comparable, but in percentage of energy expenditure (EE), significantly higher in diabetic men. Basal VLDL-TG storage was similar, but significantly greater in abdominal compared with leg fat. CONCLUSIONS Increased VLDL-TG in type 2 diabetic men is caused by greater VLDL-TG secretion and less so by lower VLDL-TG clearance. The ability of hyperinsulinemia to suppress VLDL-TG secretion appears preserved. During hyperinsulinemia VLDL-TG FA oxidation is significantly increased in proportion of EE in type 2 diabetic men. Greater basal abdominal VLDL-TG storage may help explain the accumulation of upper-body fat in insulin-resistant individuals. PMID:20858686

  1. Effect of Oral Sebacic Acid on Postprandial Glycemia, Insulinemia, and Glucose Rate of Appearance in Type 2 Diabetes

    PubMed Central

    Iaconelli, Amerigo; Gastaldelli, Amalia; Chiellini, Chiara; Gniuli, Donatella; Favuzzi, Angela; Binnert, Christophe; Macé, Katherine; Mingrone, Geltrude

    2010-01-01

    OBJECTIVE Dicarboxylic acids are natural products with the potential of being an alternate dietary source of energy. We aimed to evaluate the effect of sebacic acid (a 10-carbon dicarboxylic acid; C10) ingestion on postprandial glycemia and glucose rate of appearance (Ra) in healthy and type 2 diabetic subjects. Furthermore, the effect of C10 on insulin-mediated glucose uptake and on GLUT4 expression was assessed in L6 muscle cells in vitro. RESEARCH DESIGN AND METHODS Subjects ingested a mixed meal (50% carbohydrates, 15% proteins, and 35% lipids) containing 0 g (control) or 10 g C10 in addition to the meal or 23 g C10 as a substitute of fats. RESULTS In type 2 diabetic subjects, the incremental glucose area under the curve (AUC) decreased by 42% (P < 0.05) and 70% (P < 0.05) in the 10 g C10 and 23 g C10 groups, respectively. At the largest amounts used, C10 reduced the glucose AUC in healthy volunteers also. When fats were substituted with 23 g C10, AUC of Ra was significantly reduced on the order of 18% (P < 0.05) in both healthy and diabetic subjects. The insulin-dependent glucose uptake by L6 cells was increased in the presence of C10 (38.7 ± 10.3 vs. 11.4 ± 5.4%; P = 0.026). This increase was associated with a 1.7-fold raise of GLUT4. CONCLUSIONS Sebacic acid significantly reduced hyperglycemia after a meal in type 2 diabetic subjects. This beneficial effect was associated with a reduction in glucose Ra, probably due to lowered hepatic glucose output and increased peripheral glucose disposal. PMID:20724647

  2. Angiotensin 1-7 improves insulin sensitivity by increasing skeletal muscle glucose uptake in vivo.

    PubMed

    Echeverría-Rodríguez, Omar; Del Valle-Mondragón, Leonardo; Hong, Enrique

    2014-01-01

    The renin-angiotensin system (RAS) regulates skeletal muscle insulin sensitivity through different mechanisms. The overactivation of the ACE (angiotensin-converting enzyme)/Ang (angiotensin) II/AT1R (Ang II type 1 receptor) axis has been associated with the development of insulin resistance, whereas the stimulation of the ACE2/Ang 1-7/MasR (Mas receptor) axis improves insulin sensitivity. The in vivo mechanisms by which this axis enhances skeletal muscle insulin sensitivity are scarcely known. In this work, we investigated whether rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis and determined the effect of Ang 1-7 on rat skeletal muscle glucose uptake in vivo. Western blot analysis revealed the expression of ACE2 and MasR, while Ang 1-7 levels were detected in rat soleus muscle by capillary zone electrophoresis. The euglycemic clamp exhibited that Ang 1-7 by itself did not promote glucose transport, but it increased insulin-stimulated glucose disposal in the rat. In a similar manner, captopril (an ACE inhibitor) enhanced insulin-induced glucose uptake and this effect was blocked by the MasR antagonist A-779. Our results show for the first time that rat soleus muscle expresses the ACE2/Ang 1-7/MasR axis of the RAS, and Ang 1-7 improves insulin sensitivity by enhancing insulin-stimulated glucose uptake in rat skeletal muscle in vivo. Thus, endogenous (systemic and/or local) Ang 1-7 could regulate insulin-mediated glucose transport in vivo.

  3. Doxycycline-Regulated 3T3-L1 Preadipocyte Cell Line with Inducible, Stable Expression of Adenoviral E4orf1 Gene: A Cell Model to Study Insulin-Independent Glucose Disposal

    PubMed Central

    Krishnapuram, Rashmi; Dhurandhar, Emily J.; Dubuisson, Olga; Hegde, Vijay; Dhurandhar, Nikhil V.

    2013-01-01

    Impaired glycemic control and excessive adiposity are major risk factors for Type 2 Diabetes mellitus. In rodent models, Ad36, a human adenovirus, improves glycemic control, independent of dietary fat intake or adiposity. It is impractical to use Ad36 for therapeutic action. Instead, we identified that E4orf1 protein of Ad36, mediates its anti-hyperglycemic action independent of insulin signaling. To further evaluate the therapeutic potential of E4orf1 to improve glycemic control, we established a stable 3T3-L1 cell system in which E4orf1 expression can be regulated. The development and characterization of this cell line is described here. Full-length adenoviral-36 E4orf1 cDNA obtained by PCR was cloned into a tetracycline responsive element containing vector (pTRE-Tight-E4orf1). Upon screening dozens of pTRE-Tight-E4orf1 clones, we identified the one with the highest expression of E4orf1 in response to doxycycline treatment. Furthermore, using this inducible system we characterized the ability of E4orf1 to improve glucose disposal in a time dependent manner. This stable cell line offers a valuable resource to carefully study the novel signaling pathways E4orf1 uses to enhance cellular glucose disposal independent of insulin. PMID:23544159

  4. A Molecular and Whole Body Insight of the Mechanisms Surrounding Glucose Disposal and Insulin Resistance with Hypoxic Treatment in Skeletal Muscle

    PubMed Central

    Mackenzie, R. W. A.; Watt, P.

    2016-01-01

    Although the mechanisms are largely unidentified, the chronic or intermittent hypoxic patterns occurring with respiratory diseases, such as chronic pulmonary disease or obstructive sleep apnea (OSA) and obesity, are commonly associated with glucose intolerance. Indeed, hypoxia has been widely implicated in the development of insulin resistance either via the direct action on insulin receptor substrate (IRS) and protein kinase B (PKB/Akt) or indirectly through adipose tissue expansion and systemic inflammation. Yet hypoxia is also known to encourage glucose transport using insulin-dependent mechanisms, largely reliant on the metabolic master switch, 5′ AMP-activated protein kinase (AMPK). In addition, hypoxic exposure has been shown to improve glucose control in type 2 diabetics. The literature surrounding hypoxia-induced changes to glycemic control appears to be confusing and conflicting. How is it that the same stress can seemingly cause insulin resistance while increasing glucose uptake? There is little doubt that acute hypoxia increases glucose metabolism in skeletal muscle and does so using the same pathway as muscle contraction. The purpose of this review paper is to provide an insight into the mechanisms underpinning the observed effects and to open up discussions around the conflicting data surrounding hypoxia and glucose control. PMID:27274997

  5. Insulin-mediated oxidative stress and DNA damage in LLC-PK1 pig kidney cell line, female rat primary kidney cells, and male ZDF rat kidneys in vivo.

    PubMed

    Othman, Eman Maher; Kreissl, Michael C; Kaiser, Franz R; Arias-Loza, Paula-Anahi; Stopper, Helga

    2013-04-01

    Hyperinsulinemia, a condition with excessively high insulin blood levels, is related to an increased cancer incidence. Diabetes mellitus is the most common of several diseases accompanied by hyperinsulinemia. Because an elevated kidney cancer risk was reported for diabetic patients, we investigated the induction of genomic damage by insulin in LLC-PK1 pig kidney cells, rat primary kidney cells, and ZDF rat kidneys. Insulin at a concentration of 5nM caused a significant increase in DNA damage in vitro. This was associated with the formation of reactive oxygen species (ROS). In the presence of antioxidants, blockers of the insulin, and IGF-I receptors, and a phosphatidylinositol 3-kinase inhibitor, the insulin-mediated DNA damage was reduced. Phosphorylation of protein kinase B (PKB or AKT) was increased and p53 accumulated. Inhibition of the mitochondrial and nicotinamide adenine dinucleotide phosphatase oxidase-related ROS production reduced the insulin-mediated damage. In primary rat cells, insulin also induced genomic damage. In kidneys from healthy, lean ZDF rats, which were infused with insulin to yield normal or high blood insulin levels, while keeping blood glucose levels constant, the amounts of ROS and the tumor protein (p53) were elevated in the high-insulin group compared with the control level group. ROS and p53 were also elevated in diabetic obese ZDF rats. Overall, insulin-induced oxidative stress resulted in genomic damage. If the same mechanisms are active in patients, hyperinsulinemia might cause genomic damage through the induction of ROS contributing to the increased cancer risk, against which the use of antioxidants and/or ROS production inhibitors might exert protective effects.

  6. Increased Slc12a1 expression in β-cells and improved glucose disposal in Slc12a2 heterozygous mice

    PubMed Central

    Alshahrani, Saeed; Almutairi, Mohammed Mashari; Kursan, Shams; Dias-Junior, Eduardo; Almiahuob, Mohamed Mahmoud; Aguilar-Bryan, Lydia; Di Fulvio, Mauricio

    2015-01-01

    The products of the Slc12a1 and Slc12a2 genes, commonly known as Na+-dependent K+2Cl− co-transporters NKCC2 and NKCC1, respectively, are the targets for the diuretic bumetanide. NKCCs are implicated in the regulation of intracellular chloride concentration ([Cl−]i) in pancreatic β-cells, and as such, they may play a role in glucose-stimulated plasma membrane depolarization and insulin secretion. Unexpectedly, permanent elimination of NKCC1 does not preclude insulin secretion, an event potentially linked to the homeostatic regulation of additional Cl− transporters expressed in β-cells. In this report we provide evidence for such a mechanism. Mice lacking a single allele of Slc12a2 exhibit lower fasting glycemia, increased acute insulin response (AIR) and lower blood glucose levels 15–30 min after a glucose load when compared to mice harboring both alleles of the gene. Furthermore, heterozygous expression or complete absence of Slc12a2 associates with increased NKCC2 protein expression in rodent pancreatic β-cells. This has been confirmed by using chronic pharmacological down-regulation of NKCC1 with bumetanide in the mouse MIN6 β-cell line or permanent molecular silencing of NKCC1 in COS7 cells, which results in increased NKCC2 expression. Furthermore, MIN6 cells chronically pretreated with bumetanide exhibit increased initial rates of Cl− uptake while preserving glucose-stimulated insulin secretion. Together, our results suggest that NKCCs are involved in insulin secretion and that a single Slc12a2 allele may protect β-cells from failure due to increased homeostatic expression of Slc12a1. PMID:26400961

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

    SciTech Connect

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

    2008-04-01

    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 3{beta} (GSK-3{beta}) 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-{alpha} (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.

  8. Metformin Protects Kidney Cells From Insulin-Mediated Genotoxicity In Vitro and in Male Zucker Diabetic Fatty Rats.

    PubMed

    Othman, Eman Maher; Oli, R G; Arias-Loza, Paula-Anahi; Kreissl, Michael C; Stopper, Helga

    2016-02-01

    Hyperinsulinemia is thought to enhance cancer risk. A possible mechanism is induction of oxidative stress and DNA damage by insulin, Here, the effect of a combination of metformin with insulin was investigated in vitro and in vivo. The rationales for this were the reported antioxidative properties of metformin and the aim to gain further insights into the mechanisms responsible for protecting the genome from insulin-mediated oxidative stress and damage. The comet assay, a micronucleus frequency test, and a mammalian gene mutation assay were used to evaluate the DNA damage produced by insulin alone or in combination with metformin. For analysis of antioxidant activity, oxidative stress, and mitochondrial disturbances, the cell-free ferric reducing antioxidant power assay, the superoxide-sensitive dye dihydroethidium, and the mitochondrial membrane potential-sensitive dye 5,5',6,6'tetrachloro-1,1',3,3'-tetraethylbenzimidazol-carbocyanine iodide were applied. Accumulation of p53 and pAKT were analyzed. As an in vivo model, hyperinsulinemic Zucker diabetic fatty rats, additionally exposed to insulin during a hyperinsulinemic-euglycemic clamp, were treated with metformin. In the rat kidney samples, dihydroethidium staining, p53 and pAKT analysis, and quantification of the oxidized DNA base 8-oxo-7,8-dihydro-2'-deoxyguanosine were performed. Metformin did not show intrinsic antioxidant activity in the cell-free assay, but protected cultured cells from insulin-mediated oxidative stress, DNA damage, and mutation. Treatment of the rats with metformin protected their kidneys from oxidative stress and genomic damage induced by hyperinsulinemia. Metformin may protect patients from genomic damage induced by elevated insulin levels. This may support efforts to reduce the elevated cancer risk that is associated with hyperinsulinemia.

  9. Peroxisome proliferator-activated receptor-γ activation enhances insulin-stimulated glucose disposal by reducing ped/pea-15 gene expression in skeletal muscle cells: evidence for involvement of activator protein-1.

    PubMed

    Ungaro, Paola; Mirra, Paola; Oriente, Francesco; Nigro, Cecilia; Ciccarelli, Marco; Vastolo, Viviana; Longo, Michele; Perruolo, Giuseppe; Spinelli, Rosa; Formisano, Pietro; Miele, Claudia; Beguinot, Francesco

    2012-12-14

    The gene network responsible for inflammation-induced insulin resistance remains enigmatic. In this study, we show that, in L6 cells, rosiglitazone- as well as pioglitazone-dependent activation of peroxisome proliferator-activated receptor-γ (PPARγ) represses transcription of the ped/pea-15 gene, whose increased activity impairs glucose tolerance in mice and humans. Rosiglitazone enhanced insulin-induced glucose uptake in L6 cells expressing the endogenous ped/pea-15 gene but not in cells expressing ped/pea-15 under the control of an exogenous promoter. The ability of PPARγ to affect ped/pea-15 expression was also lost in cells and in C57BL/6J transgenic mice expressing ped/pea-15 under the control of an exogenous promoter, suggesting that ped/pea-15 repression may contribute to rosiglitazone action on glucose disposal. Indeed, high fat diet mice showed insulin resistance and increased ped/pea-15 levels, although these effects were reduced by rosiglitazone treatment. Both supershift and ChIP assays revealed the presence of the AP-1 component c-JUN at the PED/PEA-15 promoter upon 12-O-tetradecanoylphorbol-13-acetate stimulation of the cells. In these experiments, rosiglitazone treatment reduced c-JUN presence at the PED/PEA-15 promoter. This effect was not associated with a decrease in c-JUN expression. In addition, c-jun silencing in L6 cells lowered ped/pea-15 expression and caused nonresponsiveness to rosiglitazone, although c-jun overexpression enhanced the binding to the ped/pea-15 promoter and blocked the rosiglitazone effect. These results indicate that PPARγ regulates ped/pea-15 transcription by inhibiting c-JUN binding at the ped/pea-15 promoter. Thus, ped/pea-15 is downstream of a major PPARγ-regulated inflammatory network. Repression of ped/pea-15 transcription might contribute to the PPARγ regulation of muscle sensitivity to insulin.

  10. Insulin-Mediated FFA Suppression Is Associated with Triglyceridemia and Insulin Sensitivity Independent of Adiposity

    PubMed Central

    Bush, Nikki C.; Basu, Rita; Rizza, Robert A.; Nair, K. Sreekumaran; Khosla, Sundeep

    2012-01-01

    Context: A central/visceral fat distribution and excess free fatty acid (FFA) availability are associated with dyslipidemia and insulin resistance. However, these two characteristics often coexist, making it difficult to detect the independent contributions of each. Whether FFA suppression is more closely linked to metabolic abnormalities is not clear. Objective: The aim of the study was to examine the relationship between FFA suppression, body fat distribution, and fitness as contributors toward insulin resistance and hypertriglyceridemia. Design: We measured systemic palmitate turnover using an iv infusion of [9,10-3H]palmitate; upper body sc adipose tissue (UBSQ) and visceral adipose tissue (VAT) with dual-energy x-ray absorptiometry and a single-slice abdominal computed tomography scan; fitness with a graded exercise treadmill test; and insulin sensitivity with both the iv glucose tolerance test (IVGTT) (SIIVGTT) and mixed meal tolerance test (SIMeal). Setting: The study was conducted at a General Clinical Research Center. Participants: Baseline data were obtained from 140 elderly adults (age, 60–88 yr; 83 males) and 60 young adults (age, 18–31 yr; 31 males) who participated in a previously published trial assessing the effects of 2-yr supplementation of dehydroepiandrosterone or testosterone on body composition, glucose metabolism, and bone density. Interventions: There were no interventions. Main Outcome Measures: We measured fasting plasma triglyceride (TG) concentrations, SIIVGTT, and SIMeal. Results: Using multivariate regression analysis, the strongest combined predictors of TG concentrations were VAT, postmeal nadir FFA concentrations, sex, and age. The best predictors of SIIVGTT were IVGTT nadir palmitate concentration, VAT, UBSQ fat, fitness, and age, whereas the best predictors of SIMeal were meal nadir palmitate concentration, UBSQ fat, fitness, and sex. Conclusions: FFA suppression is associated with both fasting TG concentrations and insulin

  11. Disposable rabbit

    DOEpatents

    Lewis, Leroy C.; Trammell, David R.

    1986-01-01

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  12. Disposal rabbit

    DOEpatents

    Lewis, L.C.; Trammell, D.R.

    1983-10-12

    A disposable rabbit for transferring radioactive samples in a pneumatic transfer system comprises aerated plastic shaped in such a manner as to hold a radioactive sample and aerated such that dissolution of the rabbit in a solvent followed by evaporation of the solid yields solid waste material having a volume significantly smaller than the original volume of the rabbit.

  13. Disposable Scholarship?

    ERIC Educational Resources Information Center

    Miller, Fredrick

    2004-01-01

    The digital materials that faculty produce for their classrooms often are saved only to storage devices that might become obsolete in a few years. Without an institutional effort to provide access systems, storage, and services for their digital media, are campuses in danger of creating "Disposable Scholarship"? In this article, the author…

  14. Insulin-mediated regulation of decidual protein induced by progesterone (DEPP) in adipose tissue and liver.

    PubMed

    Kuroda, Y; Kuriyama, H; Kihara, S; Kishida, K; Maeda, N; Hibuse, T; Nishizawa, H; Matsuda, M; Funahashi, T; Shimomura, I

    2010-03-01

    We analyzed the profile of the genes expressed in human adipose tissue and identified the fat-derived molecules, adiponectin and aquaporin 7, which modulate glucose and lipid metabolism. The same Bodymap analysis revealed abundant expression of the decidual protein induced by progesterone (DEPP) in the white adipose tissue. Northern blot analysis confirmed that human DEPP mRNA was highly expressed in white adipose tissue. Mouse DEPP mRNA was detected in heart, lung, skeletal muscle, and white adipose tissue under feeding state. In contrast, under fasting state, mouse DEPP mRNA was enhanced in lung, skeletal muscle, and white adipose tissue and it appeared also in the liver and kidney, suggesting up regulation of DEPP by fasting. Because fasting-induced DEPP expression was observed in insulin-sensitive organs, we investigated the regulation of DEPP in white adipose tissue and liver. During adipogenesis of mouse 3T3-L1 cells, DEPP mRNA increased in a differentiation-dependent manner similar to adiponectin and aquaporin 7. Treatment of cultured 3T3-L1 mature adipocytes, rat H4IIE, and human HepG2 hepatoma cells with insulin significantly decreased DEPP mRNA levels in dose- and time-dependent manners. IN VIVO experiments showed significant decrease of hepatic and adipose DEPP mRNA levels in refed mice, compared to fasted animals, and also showed significant increase in DEPP mRNA in streptozotocin-induced insulin-deficient diabetic mice. These results indicate that DEPP is a novel insulin-regulatory molecule expressed abundantly in insulin-sensitive tissues including white adipose tissue and liver.

  15. A model of ovulatory regulation examining the effects of insulin-mediated testosterone production on ovulatory function.

    PubMed

    Graham, Erica J; Selgrade, James F

    2017-03-07

    Polycystic ovary syndrome (PCOS), a common cause of infertility in women, is often accompanied by abnormal reproductive and metabolic hormone levels. Specifically, androgens such as testosterone are elevated in many PCOS women, and the syndrome itself is frequently associated with insulin resistance, which leads to hyperinsulinemia, i.e., elevated insulin. Although the precise role of insulin in ovulatory function is unclear, its role in ovulatory dysfunction is often linked to the effects of increased ovarian androgen production. We present a mathematical model of the menstrual cycle that incorporates regulation by the pituitary-ovarian axis and mechanisms of ovarian testosterone production. We determine a physiological role for testosterone in the normal ovulatory cycle and study the role of hyperinsulinemia in pathological regulation of the cycle. Model results indicate increased ovulatory disruption with elevated insulin-mediated testosterone production and suggest that variations in the response of ovarian follicles to essential signals can alter the degree to which hyperinsulinemia disrupts the ovulatory cycle. The model also provides insight into the various PCOS phenotypes and the severity of ovulatory dysfunction.

  16. Synergic effects of sugar and caffeine on insulin-mediated metabolomic alterations after an acute consumption of soft drinks.

    PubMed

    González-Domínguez, Raúl; Mateos, Rosa María; Lechuga-Sancho, Alfonso María; González-Cortés, José Joaquín; Corrales-Cuevas, Manuel; Rojas-Cots, Juan Alberto; Segundo, Carmen; Schwarz, Mónica

    2017-09-01

    High sugar consumption elicits numerous deleterious effects on health by inducing insulin resistance, which is closely associated with the development of metabolic disorders such as obesity or type-2 diabetes. Furthermore, there is also growing evidence that caffeine may play an important role in the regulation of insulin release and the appearance of related metabolic impairments. Thus, the aim of this work was to investigate the impact of acute sugar and caffeine intake on the metabolic health status by using a metabolomic multi-platform based on the combination of flow injection mass spectrometry and ultra-high performance liquid chromatography mass spectrometry. To this end, we performed a randomized, crossover and double-blind intervention study with different soft drinks from the same brand. Numerous metabolomic changes were detected in serum samples over time after the intake of sugar-sweetened beverages, including energy-related metabolites, amino acids and lipids, thus demonstrating the intense effects provoked by acute sugar consumption on the organism during 3 h of follow-up. However, the most significant findings were observed after the co-ingestion of caffeine, which could be indicative of a synergic effect of this psychostimulant on insulin-mediated perturbations. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. GLP-1(28-36) improves β-cell mass and glucose disposal in streptozotocin-induced diabetic mice and activates cAMP/PKA/β-catenin signaling in β-cells in vitro.

    PubMed

    Shao, Weijuan; Wang, Zhaoxia; Ip, Wilfred; Chiang, Yu-Ting; Xiong, Xiaoquan; Chai, Tuanyao; Xu, Catherine; Wang, Qinghua; Jin, Tianru

    2013-06-15

    Recent studies have demonstrated that the COOH-terminal fragment of the incretin hormone glucagon-like peptide-1 (GLP-1), a nonapeptide GLP-1(28-36)amide, attenuates diabetes and hepatic steatosis in diet-induced obese mice. However, the effect of this nonapeptide in pancreatic β-cells remains largely unknown. Here, we show that in a streptozotocin-induced mouse diabetes model, GLP-1(28-36)amide improved glucose disposal and increased pancreatic β-cell mass and β-cell proliferation. An in vitro investigation revealed that GLP-1(28-36)amide stimulates β-catenin (β-cat) Ser(675) phosphorylation in both the clonal INS-1 cell line and rat primary pancreatic islet cells. In INS-1 cells, the stimulation was accompanied by increased nuclear β-cat content. GLP-1(28-36)amide was also shown to increase cellular cAMP levels, PKA enzymatic activity, and cAMP response element-binding protein (CREB) and cyclic AMP-dependent transcription factor-1 (ATF-1) phosphorylation. Furthermore, GLP-1(28-36)amide treatment enhanced islet insulin secretion and increased the growth of INS-1 cells, which was associated with increased cyclin D1 expression. Finally, PKA inhibition attenuated the effect of GLP-1(28-36)amide on β-cat Ser(675) phosphorylation and cyclin D1 expression in the INS-1 cell line. We have thus revealed the beneficial effect of GLP-1(28-36)amide in pancreatic β-cells in vitro and in vivo. Our observations suggest that GLP-1(28-36)amide may exert its effect through the PKA/β-catenin signaling pathway.

  18. In vivo PET imaging with [(18)F]FDG to explain improved glucose uptake in an apolipoprotein A-I treated mouse model of diabetes.

    PubMed

    Cochran, Blake J; Ryder, William J; Parmar, Arvind; Tang, Shudi; Reilhac, Anthonin; Arthur, Andrew; Charil, Arnaud; Hamze, Hasar; Barter, Philip J; Kritharides, Leonard; Meikle, Steven R; Gregoire, Marie-Claude; Rye, Kerry-Anne

    2016-09-01

    Type 2 diabetes is characterised by decreased HDL levels, as well as the level of apolipoprotein A-I (apoA-I), the main apolipoprotein of HDLs. Pharmacological elevation of HDL and apoA-I levels is associated with improved glycaemic control in patients with type 2 diabetes. This is partly due to improved glucose uptake in skeletal muscle. This study used kinetic modelling to investigate the impact of increasing plasma apoA-I levels on the metabolism of glucose in the db/db mouse model. Treatment of db/db mice with apoA-I for 2 h significantly improved both glucose tolerance (AUC 2574 ± 70 mmol/l × min vs 2927 ± 137 mmol/l × min, for apoA-I and PBS, respectively; p < 0.05) and insulin sensitivity (AUC 388.8 ± 23.8 mmol/l × min vs 194.1 ± 19.6 mmol/l × min, for apoA-I and PBS, respectively; p < 0.001). ApoA-I treatment also increased glucose uptake by skeletal muscle in both an insulin-dependent and insulin-independent manner as evidenced by increased uptake of fludeoxyglucose ([(18)F]FDG) from plasma into gastrocnemius muscle in apoA-I treated mice, both in the absence and presence of insulin. Kinetic modelling revealed an enhanced rate of insulin-mediated glucose phosphorylation (k 3) in apoA-I treated mice (3.5 ± 1.1 × 10(-2) min(-1) vs 2.3 ± 0.7 × 10(-2) min(-1), for apoA-I and PBS, respectively; p < 0.05) and an increased influx constant (3.7 ± 0.6 × 10(-3) ml min(-1) g(-1) vs 2.0 ± 0.3 × 10(-3) ml min(-1) g(-1), for apoA-I and PBS, respectively; p < 0.05). Treatment of L6 rat skeletal muscle cells with apoA-I for 2 h indicated that increased hexokinase activity mediated the increased rate of glucose phosphorylation. These findings indicate that apoA-I improves glucose disposal in db/db mice by improving insulin sensitivity and enhancing glucose phosphorylation.

  19. Impaired insulin-mediated antilipolysis and lactate release in adipose tissue of upper-body obese women.

    PubMed

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

    2012-01-01

    Upper-body/visceral obesity is associated with abnormalities of free fatty acid (FFA) metabolism and greater risk of developing type 2 diabetes compared with lower-body obesity. In lean subjects lipolysis is readily suppressed by insulin; however, metabolic inflexibility with respect to antilipolysis is a frequent finding in obesity, partly determined by body composition. This study investigates effects of insulin on regional adipose tissue lipolysis and lactate levels in upper-body overweight/obese (UBO), lower-body overweight/obese (LBO), and lean women. The microdialysis technique was used to assess adipose tissue glycerol and lactate concentrations in abdominal and femoral fat during a 5-h basal period and a 2-h hyperinsulinemic euglycemic clamp. The main findings were that the antilipolytic effect of insulin was attenuated in abdominal fat of UBO (glycerol reduction, abd (%): UBO 40.4 (-14 to 66), LBO 46.0 (-8 to 66), lean 66.2 (2-78), ANOVA, P < 0.05), and in femoral fat in both obese groups (glycerol reduction, fem (%): UBO 44.4 (35-67), LBO 44.4 (0-63), lean 65.0 (43-79), ANOVA, P < 0.05). Further, abdominal fat insulin-mediated increase in lactate concentration was greater in lean women compared with UBO women (lactate increase, abd (%): UBO -6.1 (-37.1 to 57.4), LBO 16.5 (-32.2 to 112.5), lean 51.4 (-45.7 to 162.9), P < 0.05), whereas no differences were found between groups in femoral fat (lactate increase, fem (%), UBO -12.9 (-43 to 24), LBO 12.7 (-30.7 to 92), lean 27.6 (-9.5 to 123.8), not significant). Respiratory exchange ratio (RER) increased significantly and similarly in all groups. So, UBO women were metabolically inflexible with respect to insulins antilipolytic and lactate increasing effects in abdominal adipose tissue. These phenomena are probably both consequences of insulin resistance of adipose tissue.

  20. Membrane receptor cross talk in gonadotropin-, IGF-I-, and insulin-mediated steroidogenesis in fish ovary: An overview.

    PubMed

    Mukherjee, Dilip; Majumder, Suravi; Roy Moulik, Sujata; Pal, Puja; Gupta, Shreyasi; Guha, Payel; Kumar, Dhynendra

    2017-01-01

    Gonadal steroidogenesis is critical for survival and reproduction of all animals. The pathways that regulate gonadal steroidogenesis are therefore conserved among animals from the steroidogenic enzymes to the intracellular signaling molecules and G protein-coupled receptors (GPCRs) that mediate the activity of these enzymes. Regulation of fish ovarian steroidogenesis in vitro by gonadotropin (GtH) and GPCRs revealed interaction between adenylate cyclase and calcium/calmodulin-dependent protein kinases (CaMKs) and also MAP kinase pathway. Recent studies revealed another important pathway in GtH-induced fish ovarian steroidogenesis: cross talk between GPCRs and membrane receptor tyrosine kinases. Gonadotropin binding to Gαs-coupled membrane receptor in fish ovary leads to production of cAMP which in turn trans-activate the membrane-bound epidermal growth factor receptor (EGFR). This is followed by activation of ERK1/2 signaling that promotes steroid production. Interestingly, GtH-induced trans-activation of EGFR in the fish ovary uniquely requires matrix-metalloproteinase-mediated release of EGF. Inhibition of these proteases blocks GtH-induced steroidogenesis. Increased cAMP production in fish ovarian follicle upregulate follicular cyp19a1a mRNA expression and aromatase activity leading to increased biosynthesis of 17β-estradiol (E2). Evidence for involvement of SF-1 protein in inducing cyp19a1a mRNA and aromatase activity has also been demonstrated. In addition to GtH, insulin-like growth factor (IGF-I) and bovine insulin can alone induced steroidogenesis in fish ovary. In intact follicles and isolated theca cells, IGF-I and insulin had no effect on GtH-induced testosterone and 17a,hydroxysprogeaterone production. GtH-stimulated E2 and 17,20bdihydroxy-4-pregnane 3-one production in granulosa cells however, was significantly increased by IGF-I and insulin. Both IGF-I and insulin mediates their signaling via receptor tyrosine kinases leading to activation of PI3

  1. Ocean Disposal Site Monitoring

    EPA Pesticide Factsheets

    EPA is responsible for managing all designated ocean disposal sites. Surveys are conducted to identify appropriate locations for ocean disposal sites and to monitor the impacts of regulated dumping at the disposal sites.

  2. Insulin-Mediated Downregulation of Apolipoprotein A-I Gene in Human Hepatoma Cell Line HepG2: The Role of Interaction Between FOXO1 and LXRβ Transcription Factors.

    PubMed

    Shavva, Vladimir S; Bogomolova, Alexandra M; Nikitin, Artemy A; Dizhe, Ella B; Tanyanskiy, Dmitry A; Efremov, Alexander M; Oleinikova, Galina N; Perevozchikov, Andrej P; Orlov, Sergey V

    2017-02-01

    Apolipoprotein A-I (ApoA-I) is a key component of high density lipoproteins which possess anti-atherosclerotic and anti-inflammatory properties. Insulin is a crucial mediator of the glucose and lipid metabolism that has been implicated in atherosclerotic and inflammatory processes. Important mediators of insulin signaling such as Liver X Receptors (LXRs) and Forkhead Box A2 (FOXA2) are known to regulate apoA-I expression in liver. Forkhead Box O1 (FOXO1) is a well-known target of insulin signaling and a key mediator of oxidative stress response. Low doses of insulin were shown to activate apoA-I expression in human hepatoma HepG2 cells. However, the detailed mechanisms for these processes are still unknown. We studied the possible involvement of FOXO1, FOXA2, LXRα, and LXRβ transcription factors in the insulin-mediated regulation of apoA-I expression. Treatment of HepG2 cells with high doses of insulin (48 h, 100 nM) suppresses apoA-I gene expression. siRNAs against FOXO1, FOXA2, LXRβ, or LXRα abrogated this effect. FOXO1 forms a complex with LXRβ and insulin treatment impairs FOXO1/LXRβ complex binding to hepatic enhancer and triggers its nuclear export. Insulin as well as LXR ligand TO901317 enhance the interaction between FOXA2, LXRα, and hepatic enhancer. These data suggest that high doses of insulin downregulate apoA-I gene expression in HepG2 cells through redistribution of FOXO1/LXRβ complex, FOXA2, and LXRα on hepatic enhancer of apoA-I gene. J. Cell. Biochem. 118: 382-396, 2017. © 2016 Wiley Periodicals, Inc.

  3. Identification of DCAP, a drosophila homolog of a glucose transport regulatory complex.

    PubMed

    Yamazaki, Hiroto; Nusse, Roel

    2002-11-01

    In a yeast two-hybrid screen using the Drosophila Axin protein as a bait, we have identified a Drosophila homolog of CAP, a component of the glucose transport regulatory complex. Through alternative splicing, the DCAP gene generates a set of five different proteins with unique N-terminal sequences and a common C-terminal SH3 domain. DCAP is predominantly expressed in the midgut and fat bodies of late-stage embryos, suggesting a role in insulin-mediated glucose transport in these organs. Copyright 2002 Elsevier Science Ireland Ltd.

  4. A chronic physical activity treatment in obese rats normalizes the contributions of ET-1 and NO to insulin-mediated posterior cerebral artery vasodilation.

    PubMed

    Olver, T Dylan; McDonald, Matthew W; Klakotskaia, Diana; Richardson, Rachel A; Jasperse, Jeffrey L; Melling, C W James; Schachtman, Todd R; Yang, Hsiao T; Emter, Craig A; Laughlin, M Harold

    2017-04-01

    rodents, obesity-related deficits in insulin-mediated vasodilation are associated with increased influence of insulin-stimulated ET-1 and depressed influence of insulin-stimulated NOS and 2) a physical activity intervention, initiated after the onset of disease, restores insulin-mediated vasodilation, likely by normalizing insulin-stimulated ET-1 and NOS balance. These data demonstrate that the treatment effects of chronic exercise on insulin-mediated vasodilation extend beyond active skeletal muscle vasculature and include the cerebrovasculature. Copyright © 2017 the American Physiological Society.

  5. The citrus fruit flavonoid naringenin suppresses hepatic glucose production from Fao hepatoma cells.

    PubMed

    Purushotham, Aparna; Tian, Min; Belury, Martha A

    2009-02-01

    Hepatic gluconeogenesis is the major source of fasting hyperglycemia. Here, we investigated the role of the citrus fruit flavonoid naringenin, in the attenuation of hepatic glucose production from hepatoma (Fao) cells. We show that naringenin, but not its glucoside naringin, suppresses hepatic glucose production. Furthermore, unlike insulin-mediated suppression of hepatic glucose production, incubation of hepatocytes with the phosphatidylinositol 3-kinase (PI3-kinase) inhibitor Ly294002 had no effect on the ability of naringenin to suppress hepatic glucose production. Further, naringenin did not increase phosphorylation of Akt at Ser473 or, Thr308, indicating this down-stream target of PI3-kinase is also not a player in naringenin-mediated suppression of hepatic glucose production. Importantly, like the dimethylbiguanide, metformin, naringenin significantly decreased cellular ATP levels without increasing cell cytotoxicity. Together, these results suggest that the aglycone, naringenin, has a role in the attenuation of hyperglycemia and may exert this effect in a manner similar to the drug, metformin.

  6. Drilling fluid disposal

    SciTech Connect

    Nesbitt, L.E.; Sanders, J.A.

    1981-12-01

    A maze of U.S. regulations and regulatory agencies coupled with uncertainty in interpretation of environmental data and an evolving system of disposal engineering will require industry action to monitor the area and derive a solid engineering basis for disposal of spent drilling fluid. A set of disposal methods with approximate costs is presented to serve as an initial guide for disposal. 16 refs.

  7. Glucose Tests

    MedlinePlus

    ... AACC products and services. Advertising & Sponsorship: Policy | Opportunities Glucose Tests Share this page: Was this page helpful? ... the meaning of other test results. Fasting Blood Glucose Glucose Level Indication From 70 to 99 mg/ ...

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

    SciTech Connect

    Vissing, J.; Ohkuwa, Tetsuo; Ploug, T.; Galbo, H. Nagoya Institute of Technology )

    1988-10-01

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

    PubMed

    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)H2]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.

  10. The gut microbiota suppresses insulin-mediated fat accumulation via the short-chain fatty acid receptor GPR43.

    PubMed

    Kimura, Ikuo; Ozawa, Kentaro; Inoue, Daisuke; Imamura, Takeshi; Kimura, Kumi; Maeda, Takeshi; Terasawa, Kazuya; Kashihara, Daiji; Hirano, Kanako; Tani, Taeko; Takahashi, Tomoyuki; Miyauchi, Satoshi; Shioi, Go; Inoue, Hiroshi; Tsujimoto, Gozoh

    2013-01-01

    The gut microbiota affects nutrient acquisition and energy regulation of the host, and can influence the development of obesity, insulin resistance, and diabetes. During feeding, gut microbes produce short-chain fatty acids, which are important energy sources for the host. Here we show that the short-chain fatty acid receptor GPR43 links the metabolic activity of the gut microbiota with host body energy homoeostasis. We demonstrate that GPR43-deficient mice are obese on a normal diet, whereas mice overexpressing GPR43 specifically in adipose tissue remain lean even when fed a high-fat diet. Raised under germ-free conditions or after treatment with antibiotics, both types of mice have a normal phenotype. We further show that short-chain fatty acid-mediated activation of GPR43 suppresses insulin signalling in adipocytes, which inhibits fat accumulation in adipose tissue and promotes the metabolism of unincorporated lipids and glucose in other tissues. These findings establish GPR43 as a sensor for excessive dietary energy, thereby controlling body energy utilization while maintaining metabolic homoeostasis.

  11. Drilling fluid disposal

    SciTech Connect

    Nesbitt, L.E.; Sander, J.A.

    1981-01-01

    This paper attempts to review the effect of the regulatory process on the selection and handling of drilling fluids for proper disposal. It is shown that a maze of regulations and regulatory agencies coupled with uncertainty in interpretation of environmental data and an evolving system of disposal engineering will require industry action to monitor the area and derive a solid engineering basis for disposal of spent drilling fluid. 16 refs.

  12. Disposables in downstream processing.

    PubMed

    Gottschalk, Uwe

    2009-01-01

    Disposable equipment has been used for many years in the downstream processing industry, but mainly for filtration and buffer/media storage. Over the last decade, there has been increasing interest in the use of disposable concepts for chromatography, replacing steel and glass fixed systems with disposable plastic modules that can be discarded once exhausted, fouled or contaminated. These modules save on cleaning and validation costs, and their reduce footprints reduce buffer consumption, water for injection, labor and facility space, contributing to an overall reduction in expenditure that lowers the cost of goods. This chapter examines the practical and economic benefits of disposable modules in downstream processing.

  13. Metabolic and vascular actions of endothelin-1 are inhibited by insulin-mediated vasodilation in perfused rat hindlimb muscle.

    PubMed

    Kolka, Cathryn M; Rattigan, Stephen; Richards, Stephen; Clark, Michael G

    2005-08-01

    Endothelin-1 (ET-1) is a potent endothelium-derived vasoactive peptide and may be involved in the microvascular actions of insulin for the normal delivery of nutrients to muscle, although higher levels may be antagonistic. Our aim was to observe the interaction between ET-1 and insulin. Initially, we attempted to distinguish the vascular from the metabolic effects of ET-1 in the constant-flow pump-perfused rat hindlimb by using various doses of ET-1 and measuring changes in perfusion pressure (PP), oxygen consumption (VO(2)), glucose uptake (GU) and lactate release (LR). Sodium nitroprusside (SNP) was used to block vasoconstriction and to thus assess the relationship between vascular and metabolic effects. Insulin was included in later experiments to determine the interaction between insulin and ET-1 on the above parameters. ET-1 caused a dose-dependent increase in PP. Effects on VO(2) were biphasic, with low doses increasing VO(2), and higher doses leading to a net inhibition. GU and LR were increased at lower doses (ET-1 < or =1 nM), but this effect was lost at higher doses (> or =10 nM ET-1). SNP (50 microM) fully blocked the increase in pressure and metabolism due to low-dose ET-1 and partly blocked both pressure and metabolic responses by the high dose. ET-1 vasodilatory activity was minimal at high or low dose. Insulin (15 nM) alone caused GU, which was not affected by ET-1. Of the other parameters measured, insulin behaved essentially the same as SNP, inhibiting the pressure and oxygen effects. Overall, these results show that ET-1 has a biphasic dose-dependent vasoconstrictor effect on hindlimb blood vessels, able to modulate flow to cause both the stimulation and inhibition of metabolism, although these effects are blocked by insulin, which is able to vasodilate against both low and high doses of ET-1.

  14. Chloroquine stimulates glucose uptake and glycogen synthase in muscle cells through activation of Akt.

    PubMed

    Halaby, Marie-Jo; Kastein, Brandon K; Yang, Da-Qing

    2013-06-14

    Chloroquine is a pharmaceutical agent that has been widely used to treat patients with malaria. Chloroquine has also been reported to have hypoglycemic effects on humans and animal models of diabetes. Despite many previous studies, the mechanism responsible for its hypoglycemic effect is still unclear. Chloroquine was recently reported to be an activator of ATM, the protein deficient in the Ataxia-telagiectasia (A-T) disease. Since ATM is also known as an insulin responsive protein that mediates Akt activation, we tested the effect of chloroquine on the activity of Akt and its downstream targets. In L6 muscle cells treated with insulin and chloroquine, the phosphorylation of Akt and glucose uptake were dramatically increased compared to cells treated with insulin alone, suggesting that chloroquine is a potent activator of Akt and glucose uptake in these cells. We also found that the reduction of insulin-mediated Akt activity in muscle tissues of insulin resistant rats was partially reversed by chloroquine treatment. Moreover, insulin-mediated phosphorylation of glycogen synthase kinase-3β in L6 cells was greatly enhanced by chloroquine. A substantial decrease in phosphorylation of glycogen synthase was also observed in chloroquine-treated L6 cells, indicating enhanced activity of glycogen synthase. Taken together, our results not only show that chloroquine is a novel activator of Akt that stimulates glucose uptake and glycogen synthase, but also validate chloroquine as a potential therapeutic agent for patients with type 2 diabetes mellitus. Copyright © 2013 Elsevier Inc. All rights reserved.

  15. Deep sea waste disposal

    SciTech Connect

    Kester, D.R.; Burt, W.V.; Capuzzo, J.M.; Park, P.K.; Ketchum, B.W.; Duedall, I.W.

    1985-01-01

    The book presents papers on the marine disposal of wastes. Topics considered include incineration at sea, the modelling and biological effects of industrial wastes, microbial studies of ocean dumping, deep-sea mining wastes, the chemical analysis of ferromanganese nodules, and economic aspects of deep-sea disposal.

  16. Disposable Diapers Are OK.

    ERIC Educational Resources Information Center

    Poore, Patricia

    1992-01-01

    A personal account of measuring the pros and cons of disposable diaper usage leads the author to differentiate between a garbage problem and environmental problem. Concludes the disposable diaper issue is a political and economic issue with a local environmental impact and well within our abilities to manage. (MCO)

  17. Disposable Diapers Are OK.

    ERIC Educational Resources Information Center

    Poore, Patricia

    1992-01-01

    A personal account of measuring the pros and cons of disposable diaper usage leads the author to differentiate between a garbage problem and environmental problem. Concludes the disposable diaper issue is a political and economic issue with a local environmental impact and well within our abilities to manage. (MCO)

  18. Disposal of drilling fluids

    SciTech Connect

    Bryson, W.R.

    1983-06-01

    Prior to 1974 the disposal of drilling fluids was not considered to be much of an environmental problem. In the past, disposal of drilling fluids was accomplished in various ways such as spreading on oil field lease roads to stabilize the road surface and control dust, spreading in the base of depressions of sandy land areas to increase water retention, and leaving the fluid in the reserve pit to be covered on closure of the pit. In recent years, some states have become concerned over the indescriminate dumping of drilling fluids into pits or unauthorized locations and have developed specific regulations to alleviate the perceived deterioration of environmental and groundwater quality from uncontrolled disposal practices. The disposal of drilling fluids in Kansas is discussed along with a newer method or treatment in drilling fluid disposal.

  19. Disposal of Vessels at Sea

    EPA Pesticide Factsheets

    Vessel disposal general permits are issued by the EPA under the Marine Protection, Research and Sanctuaries Act. Information is provided for vessel disposal permit applicants and where to dispose a vessel.

  20. Glucose Variability

    PubMed Central

    Le Floch, Jean-Pierre; Kessler, Laurence

    2016-01-01

    Background: Glucose variability has been suspected to be a major factor of diabetic complications. Several indices have been proposed for measuring glucose variability, but their interest remains discussed. Our aim was to compare different indices. Methods: Glucose variability was studied in 150 insulin-treated diabetic patients (46% men, 42% type 1 diabetes, age 52 ± 11 years) using a continuous glucose monitoring system (668 ± 564 glucose values; mean glucose value 173 ± 38 mg/dL). Results from the mean, the median, different indices (SD, MAGE, MAG, glucose fluctuation index (GFI), and percentages of low [<60 mg/dL] and high [>180 mg/dL] glucose values), and ratios (CV = SD/m, MAGE/m, MAG/m, and GCF = GFI/m) were compared using Pearson linear correlations and a multivariate principal component analysis (PCA). Results: CV, MAGE/m (ns), GCF and GFI (P < .05), MAG and MAG/m (P < .01) were not strongly correlated with the mean. The percentage of high glucose values was mainly correlated with indices. The percentage of low glucose values was mainly correlated with ratios. PCA showed 3 main axes; the first was associated with descriptive data (mean, SD, CV, MAGE, MAGE/m, and percentage of high glucose values); the second with ratios MAG/m and GCF and with the percentage of low glucose values; and the third with MAG, GFI, and the percentage of high glucose values. Conclusions: Indices and ratios provide complementary pieces of information associated with high and low glucose values, respectively. The pairs MAG+MAG/m and GFI+GCF appear to be the most reliable markers of glucose variability in diabetic patients. PMID:26880391

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

    PubMed

    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.

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

    PubMed Central

    Choi, Kevin

    2015-01-01

    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. PMID:26719305

  3. Glucose effectiveness is the major determinant of intravenous glucose tolerance in the rat.

    PubMed

    McArthur, M D; You, D; Klapstein, K; Finegood, D T

    1999-04-01

    To determine the importance of insulin for glucose disposal during an intravenous glucose tolerance test in rats, experiments were performed in four cohorts of conscious unrestrained rats fasted overnight. In cohorts 1-3, a bolus of tracer ([3-3H]glucose, 50 microCi) was given alone, with glucose (0.3 g/kg) to induce an endogenous insulin response (approximately 1,100 pmol/l), or with exogenous insulin to give physiological (1,700 pmol/l) or supraphysiological (12,000 pmol/l) plasma levels. Raising plasma insulin within the physiological range had no effect (P > 0.05), but supraphysiological levels induced hypoglycemia (7.3 +/- 0.2 to 3.6 +/- 0.2 mmol/l) and increased [3H]glucose disappearance rate (P < 0.001). In cohort 4, a primed, continuous tracer infusion was started 120 min before saline or glucose bolus injection. [3H]glucose levels fell 15-20%, and the disappearance rate rose 36% (P < 0.05) after glucose injection. These results indicate that in fasted rats a tracer bolus injection protocol is not sufficiently sensitive to measure the physiological effect of insulin released in response to a bolus of glucose because this effect of insulin is small. Glucose itself is the predominant mediator of glucose disposal after a bolus of glucose in the fasted rat.

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

    PubMed

    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 (T4) 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 + T4 (8.0 µg/100 g BM/day × 5 weeks). T4 attenuated glucose intolerance by 15% and decreased IR index (IRI) by 34% in T4-treated OLETF compared to untreated OLETF despite a 31% decrease in muscle Glut4 mRNA expression. T4 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 T4 treatment increased the influx of T4 in skeletal muscle and, with an increase of DI2, increased the availability of the biologically active T3 to upregulate key factors such SIRT1 and UCP2 involved in cellular metabolism and glucose homeostasis.

  5. Mechanisms of action of troglitazone in the prevention of high glucose-induced migration and proliferation of cultured coronary smooth muscle cells.

    PubMed

    Yasunari, K; Kohno, M; Kano, H; Yokokawa, K; Minami, M; Yoshikawa, J

    1997-12-01

    Recent findings suggest that high glucose levels may promote atherosclerosis in coronary vascular smooth muscle cells (VSMCs). To explore the intracellular mechanisms of action by which troglitazone affects this process, we examined the effect of troglitazone on the migration and growth characteristics of cultured rabbit coronary VSMCs. Treatment with chronic high glucose medium (22.2 mmol/L) for 5 days increased VSMC migration by 92%, [3H]thymidine incorporation by 135%, and cell number by 32% compared with VSMCs treated with normal glucose (5.5 mmol/L glucose + 16.6 mmol/L mannose) medium. Trolitazone at 100 nmol/L and 1 mumol/L significantly suppressed high glucose-induced VSMC migration by 34% and 42%, respectively, the proliferative effect (as measured by cell number) by 17% and 27%, and [3H]thymidine incorporation by 45% and 60% (n = 6, P < .05). The high glucose-induced impairment of insulin-mediated [3H]deoxyglucose uptake was blocked by a protein kinase C (PKC) inhibitor (calphostin C, 1 mumol/L) and was also improved by troglitazone without any change in insulin receptor number and affinity. The high glucose-induced insulin-mediated increase in cell number and in [3H]thymidine incorporation was suppressed by troglitazone. Troglitazone (1 mumol/L) also suppressed high glucose-induced phospholipase D activation, elevation of the cytosolic NADH/NAD+ ratio (as measured by the cytosolic ratio of lactate/pyruvate), and membrane-bound PKC activation. Flow cytometric DNA histogram analysis of cell cycle stage showed that high glucose-induced increase in the percentage of cells in the S phase was suppressed by 1 mumol/L troglitazone. These findings suggest that PKC may be a link between impairment of insulin-mediated glucose uptake and the increase in migration and proliferation induced by high glucose levels and that troglitazone may be clinically useful for the treatment of high glucose-induced coronary atherosclerosis.

  6. Disposal of radioactive waste

    NASA Astrophysics Data System (ADS)

    Van Dorp, Frits; Grogan, Helen; McCombie, Charles

    The aim of radioactive and non-radioactive waste management is to protect man and the environment from unacceptable risks. Protection criteria for both should therefore be based on similar considerations. From overall protection criteria, performance criteria for subsystems in waste management can be derived, for example for waste disposal. International developments in this field are summarized. A brief overview of radioactive waste sorts and disposal concepts is given. Currently being implemented are trench disposal and engineered near-surface facilities for low-level wastes. For low-and intermediate-level waste underground facilities are under construction. For high-level waste site selection and investigation is being carried out in several countries. In all countries with nuclear programmes, the predicted performance of waste disposal systems is being assessed in scenario and consequence analyses. The influences of variability and uncertainty of parameter values are increasingly being treated by probabilistic methods. Results of selected performance assessments show that radioactive waste disposal sites can be found and suitable repositories can be designed so that defined radioprotection limits are not exceeded.

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

    PubMed Central

    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. PMID:26785133

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

    PubMed

    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.

  9. Insulin/glucose induces natriuretic peptide clearance receptor in human adipocytes: a metabolic link with the cardiac natriuretic pathway.

    PubMed

    Bordicchia, M; Ceresiani, M; Pavani, M; Minardi, D; Polito, M; Wabitsch, M; Cannone, V; Burnett, J C; Dessì-Fulgheri, P; Sarzani, R

    2016-07-01

    Cardiac natriuretic peptides (NP) are involved in cardiorenal regulation and in lipolysis. The NP activity is largely dependent on the ratio between the signaling receptor NPRA and the clearance receptor NPRC. Lipolysis increases when NPRC is reduced by starving or very-low-calorie diet. On the contrary, insulin is an antilipolytic hormone that increases sodium retention, suggesting a possible functional link with NP. We examined the insulin-mediated regulation of NP receptors in differentiated human adipocytes and tested the association of NP receptor expression in visceral adipose tissue (VAT) with metabolic profiles of patients undergoing renal surgery. Differentiated human adipocytes from VAT and Simpson-Golabi-Behmel Syndrome (SGBS) adipocyte cell line were treated with insulin in the presence of high-glucose or low-glucose media to study NP receptors and insulin/glucose-regulated pathways. Fasting blood samples and VAT samples were taken from patients on the day of renal surgery. We observed a potent insulin-mediated and glucose-dependent upregulation of NPRC, through the phosphatidylinositol 3-kinase pathway, associated with lower lipolysis in differentiated adipocytes. No effect was observed on NPRA. Low-glucose medium, used to simulate in vivo starving conditions, hampered the insulin effect on NPRC through modulation of insulin/glucose-regulated pathways, allowing atrial natriuretic peptide to induce lipolysis and thermogenic genes. An expression ratio in favor of NPRC in adipose tissue was associated with higher fasting insulinemia, HOMA-IR, and atherogenic lipid levels. Insulin/glucose-dependent NPRC induction in adipocytes might be a key factor linking hyperinsulinemia, metabolic syndrome, and higher blood pressure by reducing NP effects on adipocytes. Copyright © 2016 the American Physiological Society.

  10. Magnesium battery disposal characteristics

    NASA Astrophysics Data System (ADS)

    Soffer, Louis; Atwater, Terrill

    1994-12-01

    This study assesses the disposal characteristics of U.S. Army procured military magnesium batteries under current Resource Conservation and Recovery Act (RCRA) hazardous waste identification regulations administered by the U.S. Environmental Protection Agency. Magnesium batteries were tested at 100, 50, 10 and 0 percent remaining state of charge. Present findings indicate that magnesium batteries with less than 50 percent remaining charge do not exceed the federal regulatory limit of 5.0 mg/L for chromium. All other RCRA contaminates were below regulatory limits at all levels of remaining charge. Assay methods, findings, disposal requirements and design implications are discussed.

  11. Nuclear Waste Disposal

    SciTech Connect

    Gee, Glendon W.; Meyer, Philip D.; Ward, Andy L.

    2005-01-12

    Nuclear wastes are by-products of nuclear weapons production and nuclear power generation, plus residuals of radioactive materials used by industry, medicine, agriculture, and academia. Their distinctive nature and potential hazard make nuclear wastes not only the most dangerous waste ever created by mankind, but also one of the most controversial and regulated with respect to disposal. Nuclear waste issues, related to uncertainties in geologic disposal and long-term protection, combined with potential misuse by terrorist groups, have created uneasiness and fear in the general public and remain stumbling blocks for further development of a nuclear industry in a world that may soon be facing a global energy crisis.

  12. The prevalence and risk factors for glucose intolerance in young Korean women with polycystic ovary syndrome.

    PubMed

    Lee, Hyejin; Oh, Jee-Young; Sung, Yeon-Ah; Chung, Hyewon; Cho, Wha Young

    2009-10-01

    Insulin resistance and hyperinsulinemia play important roles in the pathogenesis of polycystic ovary syndrome (PCOS). In addition, some women with PCOS have been shown to have insulin secretory defects and can be predicted to be at an increased risk for glucose intolerance. We performed the present study to determine the prevalence and risk factors for glucose intolerance in Korean women with PCOS. We consecutively recruited 194 women with PCOS diagnosed by American Society for Reproductive Medicine/European Society of Human Reproduction and Embryology (ASRM/ESHRE) criteria. Anthropometric measures, 75 g oral glucose tolerance test (OGTT), and measurement of insulin sensitivity (insulin mediated glucose uptake; IMGU) using euglycemic hyperinsulinemic clamp technique were performed. In women with PCOS, the prevalence of impaired glucose tolerance (IGT) and/or impaired fasting glucose (IFG) was 17.0% and type 2 diabetes 1.0%, and in lean women with PCOS, the prevalence of IGT and/or IFG was 5.9%. The prevalence of glucose intolerance was 28-fold higher in women with PCOS, and 9.8-fold higher in lean women with PCOS compared to age-matched Korean women. Women with glucose intolerance had higher BMI, waist circumference, free testosterone, fasting insulin, 2-h post-load insulin, total cholesterol, LDL cholesterol, triglyceride and lower sex hormone binding globulin and IMGU than women with normal glucose tolerance (NGT) (P < 0.05). IMGU was the most powerful predictor for glucose intolerance after adjustment for age, BMI, waist circumference, and hyperandrogenemia. The 2-h OGTT was the best screening measure for glucose intolerance and diagnosis of diabetes in women with PCOS. Young Korean women with PCOS have high prevalence for glucose intolerance and type 2 diabetes, and insulin resistance is the most important factor associated with glucose intolerance.

  13. Radioactive waste disposal package

    DOEpatents

    Lampe, Robert F.

    1986-01-01

    A radioactive waste disposal package comprising a canister for containing vitrified radioactive waste material and a sealed outer shell encapsulating the canister. A solid block of filler material is supported in said shell and convertible into a liquid state for flow into the space between the canister and outer shell and subsequently hardened to form a solid, impervious layer occupying such space.

  14. Nanomaterial disposal by incineration

    EPA Science Inventory

    As nanotechnology-based products enter into widespread use, nanomaterials will end up in disposal waste streams that are ultimately discharged to the environment. One possible end-of-life scenario is incineration. This review attempts to ascertain the potential pathways by which ...

  15. Nanomaterial disposal by incineration

    EPA Science Inventory

    As nanotechnology-based products enter into widespread use, nanomaterials will end up in disposal waste streams that are ultimately discharged to the environment. One possible end-of-life scenario is incineration. This review attempts to ascertain the potential pathways by which ...

  16. Chemical Stockpile Disposal Program

    SciTech Connect

    Krummel, J.R.; Policastro, A.J.; Olshansky, S.J.; McGinnis, L.D.

    1990-10-01

    As part of the Chemical Stockpile Disposal Program mandated by Public Law 99--145 (Department of Defense Authorization Act), an independent review is presented of the US Army Phase I environmental report for the disposal program at the Pine Bluff Arsenal (PBA) in Arkansas. The Phase I report addressed new and additional concerns not incorporated in the final programmatic environmental impact statement (FPEIS). Those concerns were addressed by examining site-specific data for the PBA and by recommending the scope and content of a more detailed site- specific study. This dependent review evaluates whether the new site-specific data presented in the Phase I report would alter the decision in favor of on-site disposal that was reached in the FPEIS, and whether the recommendations for the scope and content of the site-specific study are adequate. Based on the methods and assumptions presented in the FPEIS, the inclusion of more detailed site-specific data in the Phase I report does not change the decision reached in the FPEIS (which favored on-site disposal at PBA). It is recommended that alternative assumptions about meteorological conditions be considered and that site-specific data on water, ecological, socioeconomic, and cultural resources, and emergency planning and preparedness be considered explicitly in the site-specific EIS decision-making process. 13 refs., 1 fig.

  17. Chemical Stockpile Disposal Program

    SciTech Connect

    Krummel, J.R.; Policastro, A.J.; Olshansky, S.J.; McGinnis, L.D.

    1990-10-01

    As part of the Chemical Stockpile Disposal Program mandated by Public Law 99--145 (Department of Defense Authorization Act), an independent review is presented of the US Army Phase I environmental report for the disposal program at the Umatilla Depot Activity (UMDA) in Hermiston, Oregon. The Phase I report addressed new and additional concerns not incorporated in the final programmatic environmental impact statement (FPEIS). Those concerns were addressed by examining site-specific data for the Umatilla Depot Activity and by recommending the scope and content of a more detailed site-specific study. This independent review evaluates whether the new site-specific data presented in the Phase I report would alter the decision in favor of on-site disposal that was reached in the FPEIS, and whether the recommendations for the scope and content of the site-specific study are adequate. Based on the methods and assumptions presented in the FPEIS, the inclusion of more detailed site-specific data in the Phase I report does not change the decision reached in the FPEIS (which favored on-site disposal at UMDA). It is recommended that alternative assumptions about meteorological conditions be considered and that site-specific data on water, ecological, socioeconomic, and cultural resources; seismicity; and emergency planning and preparedness be considered explicitly in the site-specific EIS decision-making process. 7 refs., 1 fig.

  18. Radioactive waste disposal package

    DOEpatents

    Lampe, Robert F.

    1986-11-04

    A radioactive waste disposal package comprising a canister for containing vitrified radioactive waste material and a sealed outer shell encapsulating the canister. A solid block of filler material is supported in said shell and convertible into a liquid state for flow into the space between the canister and outer shell and subsequently hardened to form a solid, impervious layer occupying such space.

  19. Plumbing and Sewage Disposal.

    ERIC Educational Resources Information Center

    Sutliff, Ronald D.; And Others

    This self-study course is designed to familiarize Marine enlisted personnel with the principles of plumbing and sewage disposal used by Marine Hygiene Equipment Operators to perform their mission. The course contains three study units. Each study unit begins with a general objective, which is a statement of what the student should learn from the…

  20. Waste disposal package

    DOEpatents

    Smith, M.J.

    1985-06-19

    This is a claim for a waste disposal package including an inner or primary canister for containing hazardous and/or radioactive wastes. The primary canister is encapsulated by an outer or secondary barrier formed of a porous ceramic material to control ingress of water to the canister and the release rate of wastes upon breach on the canister. 4 figs.

  1. Disposal of Liquid Propellants

    DTIC Science & Technology

    1990-03-13

    concentrate (formaldehydestrongly catalyzes the formation of nitrosamines from nitrite and secondary amines ). I ° Minimize concentrations of catalytically ...components, as interest in these compounds is relatively new. Therefore, methods for disposing of similar compounds such as triethanol- amine ...appears to have the greatest potential for accomplishing degradation of HAN- based liquid propellant residues in an economical, environmentally safe manner

  2. Alternative Trench Disposal Concepts

    SciTech Connect

    Wilhite, E.

    2001-09-05

    During Fiscal Year 2000, a number of activities were conducted to expand the use of trenches for disposal of low-level waste in the E-Area Low-Level Waste Facility (LLWF). This document presents a summary and interpretation of these activities in the context of future work.

  3. Oil field waste disposal costs at commercial disposal facilities

    SciTech Connect

    Veil, J.A.

    1997-10-01

    The exploration and production segment of the U.S. oil and gas industry generates millions of barrels of nonhazardous oil field wastes annually. In most cases, operators can dispose of their oil fields wastes at a lower cost on-site than off site and, thus, will choose on-site disposal. However, a significant quantity of oil field wastes are still sent to off-site commercial facilities for disposal. This paper provides information on the availability of commercial disposal companies in different states, the treatment and disposal methods they employ, and how much they charge. There appear to be two major off-site disposal trends. Numerous commercial disposal companies that handle oil field wastes exclusively are located in nine oil-and gas-producing states. They use the same disposal methods as those used for on-site disposal. In addition, the Railroad Commission of Texas has issued permits to allow several salt caverns to be used for disposal of oil field wastes. Twenty-two other oil- and gas-producing states contain few or no disposal companies dedicated to oil and gas industry waste. The only off-site commercial disposal companies available handle general industrial wastes or are sanitary landfills. In those states, operators needing to dispose of oil field wastes off-site must send them to a local landfill or out of state. The cost of off-site commercial disposal varies substantially, depending on the disposal method used, the state in which the disposal company is located, and the degree of competition in the area.

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

    PubMed

    Sheena, Aswathy; Mohan, Suma S; Haridas, Nidhina Pachakkil A; Anilkumar, Gopalakrishnapillai

    2011-01-01

    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. 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. 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.

  5. Insulin signalling and glucose transport in the ovary and ovarian function during the ovarian cycle

    PubMed Central

    Dupont, Joëlle; Scaramuzzi, Rex J.

    2016-01-01

    Data derived principally from peripheral tissues (fat, muscle and liver) show that insulin signals via diverse interconnecting intracellular pathways and that some of the major intersecting points (known as critical nodes) are the IRSs (insulin receptor substrates), PI3K (phosphoinositide kinase)/Akt and MAPK (mitogen-activated protein kinase). Most of these insulin pathways are probably also active in the ovary and their ability to interact with each other and also with follicle-stimulating hormone (FSH) and luteinizing hormone (LH) signalling pathways enables insulin to exert direct modulating influences on ovarian function. The present paper reviews the intracellular actions of insulin and the uptake of glucose by ovarian tissues (granulosa, theca and oocyte) during the oestrous/menstrual cycle of some rodent, primate and ruminant species. Insulin signals through diverse pathways and these are discussed with specific reference to follicular cell types (granulosa, theca and oocyte). The signalling pathways for FSH in granulosa cells and LH in granulosa and theca cells are summarized. The roles of glucose and of insulin-mediated uptake of glucose in folliculogenesis are discussed. It is suggested that glucose in addition to its well-established role of providing energy for cellular function may also have insulin-mediated signalling functions in ovarian cells, involving AMPK (AMP-dependent protein kinase) and/or hexosamine. Potential interactions of insulin signalling with FSH or LH signalling at critical nodes are identified and the available evidence for such interactions in ovarian cells is discussed. Finally the action of the insulin-sensitizing drugs metformin and the thiazolidinedione rosiglitazone on follicular cells is reviewed. PMID:27234585

  6. 48 CFR 2845.603 - Disposal methods.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... GOVERNMENT PROPERTY Reporting, Redistribution, and Disposal of Contractor Inventory 2845.603 Disposal methods. Policies pertaining to reutilization and disposal of DOJ property, including requirements for internal...

  7. Disposal of Some Problem Chemicals.

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 1978

    1978-01-01

    Describes procedures for the disposal of chemicals commonly used in secondary school chemistry laboratories. Special reference is given to inorganic salts. It is suggested that cyanides and other highly toxic salts should be disposed of by experts. (MA)

  8. Disposal of Some Problem Chemicals.

    ERIC Educational Resources Information Center

    Journal of Chemical Education, 1978

    1978-01-01

    Describes procedures for the disposal of chemicals commonly used in secondary school chemistry laboratories. Special reference is given to inorganic salts. It is suggested that cyanides and other highly toxic salts should be disposed of by experts. (MA)

  9. Diaper area and disposable diapers.

    PubMed

    Erasala, G N; Romain, C; Merlay, I

    2011-01-01

    Since the 1960s, cloth diapers have been replaced by disposable diapers. The evolution of healthier skin in the diaper area has been demonstrated in parallel to that of disposable diapers. The improvements of disposable diapers--fit, dryness, comfort--have been based on the understanding of factors playing a role in the development of diaper dermatitis.

  10. An Alternative Procedure for the Glucose Oxidase Assay of Glucose as Applied to the Lactase Activity Assay

    NASA Astrophysics Data System (ADS)

    Corbin Mullis, T.; Winge, Jeffery T.; Deal, S. Todd

    1999-12-01

    The glucose oxidase assay of glucose has been modified to eliminate the use of micropipets. The modification involves the use of disposable Pasteur pipets and a specified number of drops of each reagent. This simplified technique gives accurate and reproducible results.

  11. Glucose transporters and in vivo glucose uptake in skeletal and cardiac muscle: fasting, insulin stimulation and immunoisolation studies of GLUT1 and GLUT4.

    PubMed Central

    Kraegen, E W; Sowden, J A; Halstead, M B; Clark, P W; Rodnick, K J; Chisholm, D J; James, D E

    1993-01-01

    Our aim was to study glucose transporters GLUT1 and GLUT4 in relation to in vivo glucose uptake in rat cardiac and skeletal muscle. The levels of both transporters were of a similar order of magnitude in whole muscle tissue (GLUT1/GLUT4 ratio varied from 0.1 to 0.6), suggesting that both may have an important physiological role in regulating muscle glucose metabolism. GLUT4 correlated very strongly (r2 = 0.97) with maximal insulin-stimulated glucose uptake (Rg' max., estimated using the glucose clamp plus 2-deoxy[3H]glucose bolus technique) in six skeletal muscles and heart. A distinct difference in regulation of the two transporters was evident in heart: in 5 h-fasted rats, basal glucose uptake and GLUT1 levels in heart were very high and both were reduced, by 90 and 60% respectively, by 48 h fasting. However, in heart (and in red skeletal muscle), neither GLUT4 levels nor Rg' max. were reduced by 48 h fasting. GLUT1 was shown to be specifically expressed in cardiac myocytes, because intracellular vesicles enriched in GLUT4 contained significant levels of GLUT1. In conclusion, the high association of muscle GLUT4 content with insulin responsiveness in different muscles, and the preservation of both with fasting, supports a predominant role of GLUT4 in insulin-mediated glucose uptake. GLUT1 may play an important role in mediating cardiac muscle glucose uptake in the basal metabolic state. Marked changes in GLUT1 expression with alterations in the metabolic state, such as prolonged fasting, may play an important role in cardiac glucose metabolism. Images Figure 1 Figure 2 PMID:8216230

  12. Insulin Resistance, Defective Insulin-Mediated Fatty Acid Suppression, and Coronary Artery Calcification in Subjects With and Without Type 1 Diabetes

    PubMed Central

    Schauer, Irene E.; Snell-Bergeon, Janet K.; Bergman, Bryan C.; Maahs, David M.; Kretowski, Adam; Eckel, Robert H.; Rewers, Marian

    2011-01-01

    OBJECTIVE To assess insulin action on peripheral glucose utilization and nonesterified fatty acid (NEFA) suppression as a predictor of coronary artery calcification (CAC) in patients with type 1 diabetes and nondiabetic controls. RESEARCH DESIGN AND METHODS Insulin action was measured by a three-stage hyperinsulinemic-euglycemic clamp (4, 8, and 40 mU/m2/min) in 87 subjects from the Coronary Artery Calcification in Type 1 Diabetes cohort (40 diabetic, 47 nondiabetic; mean age 45 ± 8 years; 55% female). RESULTS Peripheral glucose utilization was lower in subjects with type 1 diabetes compared with nondiabetic controls: glucose infusion rate (mg/kg FFM/min) = 6.19 ± 0.72 vs. 12.71 ± 0.66, mean ± SE, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and final clamp glucose and insulin. Insulin-induced NEFA suppression was also lower in type 1 diabetic compared with nondiabetic subjects: NEFA levels (μM) during 8 mU/m2/min insulin infusion = 370 ± 27 vs. 185 ± 25, P < 0.0001, after adjustment for age, sex, BMI, fasting glucose, and time point insulin. Lower glucose utilization and higher NEFA levels, correlated with CAC volume (r = −0.42, P < 0.0001 and r = 0.41, P < 0.0001, respectively) and predicted the presence of CAC (odds ratio [OR] = 0.45, 95% CI = 0.22–0.93, P = 0.03; OR = 2.4, 95% CI = 1.08–5.32, P = 0.032, respectively). Insulin resistance did not correlate with GHb or continuous glucose monitoring parameters. CONCLUSIONS Type 1 diabetic patients are insulin resistant compared with nondiabetic subjects, and the degree of resistance is not related to current glycemic control. Insulin resistance predicts the extent of coronary artery calcification and may contribute to the increased risk of cardiovascular disease in patients with type 1 diabetes as well as subjects without diabetes. PMID:20978091

  13. Space disposal of nuclear wastes

    NASA Technical Reports Server (NTRS)

    Priest, C. C.; Nixon, R. F.; Rice, E. E.

    1980-01-01

    The DOE has been studying several options for nuclear waste disposal, among them space disposal, which NASA has been assessing. Attention is given to space disposal destinations noting that a circular heliocentric orbit about halfway between Earth and Venus is the reference option in space disposal studies. Discussion also covers the waste form, showing that parameters to be considered include high waste loading, high thermal conductivity, thermochemical stability, resistance to leaching, fabrication, resistance to oxidation and to thermal shock. Finally, the Space Shuttle nuclear waste disposal mission profile is presented.

  14. Space disposal of nuclear wastes

    NASA Technical Reports Server (NTRS)

    Priest, C. C.; Nixon, R. F.; Rice, E. E.

    1980-01-01

    The DOE has been studying several options for nuclear waste disposal, among them space disposal, which NASA has been assessing. Attention is given to space disposal destinations noting that a circular heliocentric orbit about halfway between Earth and Venus is the reference option in space disposal studies. Discussion also covers the waste form, showing that parameters to be considered include high waste loading, high thermal conductivity, thermochemical stability, resistance to leaching, fabrication, resistance to oxidation and to thermal shock. Finally, the Space Shuttle nuclear waste disposal mission profile is presented.

  15. Economics of the hydrolysis of cellulosic sludge to glucose.

    PubMed

    Mora, Sandeep; Banerjee, Sujit

    2013-08-01

    Cellulosic sludge from paper mills making bleached products can be enzymatically converted to glucose. A kinetic model that accounts for product inhibition was used to estimate the cost:benefits of the process. In the proposed scheme, the sludge is enzymatically hydrolyzed in a sequence of CSTRs, the ash separated, and the product glucose concentrated through reverse osmosis. The water recovered is mostly recycled. By far, the most important economic variable is the value of the glucose. However, even if the glucose is assumed to be of no value the avoided cost of sludge disposal approximately offsets the process costs. The approach should generate significant revenue if the glucose is valued at market.

  16. Landfill disposal systems

    PubMed Central

    Slimak, Karen M.

    1978-01-01

    The current status of landfill disposal of hazardous wastes in the United States is indicated by presenting descriptions of six operating landfills. These landfills illustrate the variety of techniques that exist in landfill disposal of hazardous wastes. Although some landfills more effectively isolate hazardous waste than others, all landfills must deal with the following problems. Leachate from hazardous waste landfills is generally highly polluted. Most landfills attempt to contain leachate at the site and prevent its discharge to surface or groundwaters. To retain leachate within a disposal area, subsurface barriers of materials such as concrete, asphalt, butyl rubber, vinyl, and clay are used. It is difficult to assure that these materials can seal a landfill indefinitely. When a subsurface barrier fails, the leachate enters the groundwater in a concentrated, narrow band which may bypass monitoring wells. Once a subsurface barrier has failed, repairs are time-consuming and costly, since the waste above the repair site may have to be removed. The central problem in landfill disposal is leachate control. Recent emphasis has been on developing subsurface barriers to contain the wastes and any leachate. Future emphasis should also be on techniques for removing water from hazardous wastes before they are placed in landfills, and on methods for preventing contact of the wastes with water during and after disposal operations. When leachate is eliminated, the problems of monitoring, and subsurface barrier failure and repair can be addressed, and a waste can be effectively isolated. A surface seal landfill design is recommended for maintaining the dry state of solid hazardous wastes and for controlling leachate. Any impervious liner is utilized over the top of the landfill to prevent surface water from seeping into the waste. The surface barrier is also the site where monitoring and maintenance activities are focused. Barrier failure can be detected by visual

  17. Glucose phosphorylation is required for insulin-dependent mTOR signalling in the heart

    PubMed Central

    Sharma, Saumya; Guthrie, Patrick; Chan, Suzanne; Haq, Syed; Taegtmeyer, Heinrich

    2008-01-01

    Objective: Insulin regulates both glucose uptake and postnatal cardiac growth. The anabolic effects of insulin are mediated by the mammalian target of rapamycin (mTOR), an evolutionarily conserved kinase which is also a convergence point between nutrient sensing and cell growth. We postulated that mTOR signalling in the heart requires the metabolism of glucose. Methods: We interrogated the insulin-mediated mTOR signalling pathway in response to different metabolic interventions regulating substrate metabolism in the isolated working rat heart and in isolated cardiomyocytes. Results: Although insulin enhanced Akt activity, phosphorylation of mTOR and its downstream targets (p70S6K and 4EBP1) required the addition of glucose. Glucose-dependent p70S6K phosphorylation was independent of the hexosamine biosynthetic pathway, the AMP kinase pathway, and the pentose phosphate pathway. However, inhibition of glycolysis downstream of hexokinase markedly enhanced p70S6K phosphorylation. Furthermore, 2-deoxyglucose activated p70S6K suggesting that phosphorylation of glucose is required for carbohydrate-mediated mTOR signalling in the heart. Lastly, we also found enhanced p70S6K phosphorylation in the hearts of diabetic rats. Conclusion: Phosphorylation of glucose is necessary for insulin-dependent mTOR activity in the heart, suggesting a link between intermediary metabolism and cardiac growth. PMID:17553476

  18. Water extracts from Momordica charantia increase glucose uptake and adiponectin secretion in 3T3-L1 adipose cells.

    PubMed

    Roffey, Ben W C; Atwal, Avtar S; Johns, Timothy; Kubow, Stan

    2007-05-30

    To examine the effects of Momordica charantia on glucose uptake and adiponectin secretion in adipose cells, 3T3-L1 adipocytes were treated with three concentrations (0.2, 0.3 and 0.4mg/ml) of water and ethanol extracts of Momordica charantia fruit and seeds alone and in combination with either 0.5nM or 50nM insulin. The treatment combination of 0.2mg/ml water extract and 0.5nM insulin was associated with significant (p<0.05) increases in glucose uptake (61%) and adiponectin secretion (75%) over control levels. The ethanol extract was not associated with an increase in glucose uptake; however, a dose-dependent decrease in basal glucose uptake and insulin-mediated glucose uptake was observed with the ethanol extract in combination with 50nM insulin. In the absence of insulin, no effects on glucose uptake were observed in adipocytes exposed to the water extracts whereas the highest concentration (0.4mg/ml) of the ethanol extract was associated with a significant (p<0.05) decrease in glucose uptake relative to controls. The present results indicate that water-soluble component(s) in Momordica charantia enhance the glucose uptake at sub-optimal concentrations of insulin in 3T3-L1 adipocytes, which is accompanied by and may be a result of increased adiponectin secretion from the 3T3-L1 adipocytes.

  19. Adenosine receptors mediate synergistic stimulation of glucose uptake and transport by insulin and by contractions in rat skeletal muscle.

    PubMed Central

    Vergauwen, L; Hespel, P; Richter, E A

    1994-01-01

    The role of adenosine receptors in the regulation of muscle glucose uptake by insulin and contractions was studied in isolated rat hindquarters that were perfused with a standard medium containing no insulin or a submaximal concentration of 100 microU/ml. Adenosine receptor antagonism was induced by caffeine or 8-cyclopentyl-1,3-dipropylxantine (CPDPX). Glucose uptake and transport were measured before and during 30 min of electrically induced muscle contractions. Caffeine nor CPDPX affected glucose uptake in resting hindquarters. In contrast, the contraction-induced increase in muscle glucose uptake was inhibited by 30-50% by caffeine, as well as by CPDPX, resulting in a 20-25% decrease in the absolute rate of glucose uptake during contractions, compared with control values. This inhibition was independent of the rate of perfusate flow and only occurred in hindquarters perfused with insulin added to the medium. Thus, adenosine receptor antagonism inhibited glucose uptake during simultaneous exposure to insulin and contractions only. Accordingly, caffeine inhibited 3-O-methylglucose uptake during contractions only in oxidative muscle fibers that are characterized by a high sensitivity to insulin. In conclusion, the present data demonstrate A1 receptors to regulate insulin-mediated glucose transport in contracting skeletal muscle. The findings provide evidence that stimulation of sarcolemmic adenosine receptors during contractions is involved in the synergistic stimulation of muscle glucose transport by insulin and by contractions. PMID:8132783

  20. NRC disposed to site

    NASA Astrophysics Data System (ADS)

    Carlowicz, Michael

    A committee of the National Research Council (NRC) has found the risk of human exposure to radiation from nuclear waste to be minimal at a proposed underground disposal site. In a report on the U.S. Department of Energy's (DOE) Waste Isolation Pilot Plant (WIPP) in southeastern New Mexico, the NRC committee asserted that the danger of radioactive exposure at the site is unlikely to exceed U.S. and international standards for protection from radiation. Unless the site is breached by humans—most likely those drilling for gas or oil—there is no credible or probable chance of the release of the radioactive waste, the committee said.

  1. Radioactive waste material disposal

    DOEpatents

    Forsberg, C.W.; Beahm, E.C.; Parker, G.W.

    1995-10-24

    The invention is a process for direct conversion of solid radioactive waste, particularly spent nuclear fuel and its cladding, if any, into a solidified waste glass. A sacrificial metal oxide, dissolved in a glass bath, is used to oxidize elemental metal and any carbon values present in the waste as they are fed to the bath. Two different modes of operation are possible, depending on the sacrificial metal oxide employed. In the first mode, a regenerable sacrificial oxide, e.g., PbO, is employed, while the second mode features use of disposable oxides such as ferric oxide. 3 figs.

  2. Radioactive waste material disposal

    DOEpatents

    Forsberg, Charles W.; Beahm, Edward C.; Parker, George W.

    1995-01-01

    The invention is a process for direct conversion of solid radioactive waste, particularly spent nuclear fuel and its cladding, if any, into a solidified waste glass. A sacrificial metal oxide, dissolved in a glass bath, is used to oxidize elemental metal and any carbon values present in the waste as they are fed to the bath. Two different modes of operation are possible, depending on the sacrificial metal oxide employed. In the first mode, a regenerable sacrificial oxide, e.g., PbO, is employed, while the second mode features use of disposable oxides such as ferric oxide.

  3. Glucose kinetics during prolonged exercise in highly trained human subjects: effect of glucose ingestion

    PubMed Central

    Jeukendrup, Asker E; Raben, Anne; Gijsen, Annemie; Stegen, Jos H C H; Brouns, Fred; Saris, Wim H M; Wagenmakers, Anton J M

    1999-01-01

    The objectives of this study were (1) to investigate whether glucose ingestion during prolonged exercise reduces whole body muscle glycogen oxidation, (2) to determine the extent to which glucose disappearing from the plasma is oxidized during exercise with and without carbohydrate ingestion and (3) to obtain an estimate of gluconeogenesis. After an overnight fast, six well-trained cyclists exercised on three occasions for 120 min on a bicycle ergometer at 50% maximum velocity of O2 uptake and ingested either water (Fast), or a 4% glucose solution (Lo-Glu) or a 22% glucose solution (Hi-Glu) during exercise. Dual tracer infusion of [U-13C]-glucose and [6,6-2H2]-glucose was given to measure the rate of appearance (Ra) of glucose, muscle glycogen oxidation, glucose carbon recycling, metabolic clearance rate (MCR) and non-oxidative disposal of glucose. Glucose ingestion markedly increased total Ra especially with Hi-Glu. After 120 min Ra and rate of disappearance (Rd) of glucose were 51-52 μmol kg−1 min−1 during Fast, 73-74 μmol kg−1 min−1 during Lo-Glu and 117–119 μmol kg−1 min−1 during Hi-Glu. The percentage of Rd oxidized was between 96 and 100% in all trials. Glycogen oxidation during exercise was not reduced by glucose ingestion. The vast majority of glucose disappearing from the plasma is oxidized and MCR increased markedly with glucose ingestion. Glucose carbon recycling was minimal suggesting that gluconeogenesis in these conditions is negligible. PMID:10050023

  4. Lakeview, Oregon, Disposal Site

    SciTech Connect

    Linard, Joshua; Hall, Steve

    2016-03-01

    9.1 Compliance Summary The Lakeview, Oregon, Uranium Mill Tailings Radiation Control Act (UMTRCA) Title I Disposal Site was inspected September 16 and 17, 2015. Other than some ongoing concern with erosion-control rock riprap degradation, the disposal cell was in good condition. Some minor fence repairs and vegetation removal, and minor erosion repair work along the west site fence is planned. Inspectors identified no other maintenance needs or cause for a follow-up or contingency inspection. Disposal cell riprap is evaluated annually to ensure continued long-term protection of the cell from erosion during a severe precipitation event. Degradation of the rock riprap was first observed at the site in the mid-1990s. Rock gradation monitoring of the riprap on the west side slope has been performed as part of the annual inspection since 1997 to determine the mean diameter (D50) value. As prescribed by the monitoring procedure, the rock monitoring is routinely conducted at random locations. However, at the U.S. Nuclear Regulatory Commission’s (NRC’s) request, the 2015 rock monitoring approach deviated from the normal procedure by using a pre-established monitoring grid in a subset area of the west side slope. This changed the monitoring approach from random sampling to biased sampling. The D50 value measured during the 2015 gradation monitoring is 2.39 inches, which falls below the original D50 design size range of 2.7–3.9 inches for the Type B size side slope riprap. At NRC’s request, rock durability monitoring was added to the gradation monitoring in 2009 to monitor durability by rock type. Results of the 2015 durability monitoring showed that74 percent of the total rock sampled is durability class code A rock with an assigned durability class of “highly durable” or durability class code B “durable” rock, and that over 90 percent of the 3-inch or larger rock is durability class code A or B. The rock durability

  5. Free Fatty Acid-Induced PP2A Hyperactivity Selectively Impairs Hepatic Insulin Action on Glucose Metabolism

    PubMed Central

    Galbo, Thomas; Olsen, Grith Skytte; Quistorff, Bjørn; Nishimura, Erica

    2011-01-01

    In type 2 Diabetes (T2D) free fatty acids (FFAs) in plasma are increased and hepatic insulin resistance is “selective”, in the sense that the insulin-mediated decrease of glucose production is blunted while insulin's effect on stimulating lipogenesis is maintained. We investigated the molecular mechanisms underlying this pathogenic paradox. Primary rat hepatocytes were exposed to palmitate for twenty hours. To establish the physiological relevance of the in vitro findings, we also studied insulin-resistant Zucker Diabetic Fatty (ZDF) rats. While insulin-receptor phosphorylation was unaffected, activation of Akt and inactivation of the downstream targets Glycogen synthase kinase 3α (Gsk3α and Forkhead box O1 (FoxO1) was inhibited in palmitate-exposed cells. Accordingly, dose-response curves for insulin-mediated suppression of the FoxO1-induced gluconeogenic genes and for de novo glucose production were right shifted, and insulin-stimulated glucose oxidation and glycogen synthesis were impaired. In contrast, similar to findings in human T2D, the ability of insulin to induce triglyceride (TG) accumulation and transcription of the enzymes that catalyze de novo lipogenesis and TG assembly was unaffected. Insulin-induction of these genes could, however, be blocked by inhibition of the atypical PKCs (aPKCs). The activity of the Akt-inactivating Protein Phosphatase 2A (PP2A) was increased in the insulin-resistant cells. Furthermore, inhibition of PP2A by specific inhibitors increased insulin-stimulated activation of Akt and phosphorylation of FoxO1 and Gsk3α. Finally, PP2A mRNA levels were increased in liver, muscle and adipose tissue, while PP2A activity was increased in liver and muscle tissue in insulin-resistant ZDF rats. In conclusion, our findings indicate that FFAs may cause a selective impairment of insulin action upon hepatic glucose metabolism by increasing PP2A activity. PMID:22087313

  6. Radioactive mixed waste disposal

    SciTech Connect

    Jasen, W.G.; Erpenbeck, E.G.

    1993-02-01

    Various types of waste have been generated during the 50-year history of the Hanford Site. Regulatory changes in the last 20 years have provided the emphasis for better management of these wastes. Interpretations of the Atomic Energy Act of 1954 (AEA), the Resource Conservation and Recovery Act of 1976 (RCRA), and the Hazardous and Solid Waste Amendments (HSWA) have led to the definition of radioactive mixed wastes (RMW). The radioactive and hazardous properties of these wastes have resulted in the initiation of special projects for the management of these wastes. Other solid wastes at the Hanford Site include low-level wastes, transuranic (TRU), and nonradioactive hazardous wastes. This paper describes a system for the treatment, storage, and disposal (TSD) of solid radioactive waste.

  7. Military nuclear waste disposal

    NASA Astrophysics Data System (ADS)

    Robb, David W.

    1984-04-01

    A National Research Council (NRC) panel has endorsed a plan for a proposed underground military nuclear waste disposal facility located on a site near Carlsbad, N.M. The Department of Energy (DOE) asked NRC to evaluate the geologic suitability of the site.The NRC panel, chaired by Frank L. Parker of Vanderbilt University, concluded in its final report that “the important issues about the geology of the site have been resolved…” Those issues include the purity and volume of salt, the absence of brine pockets at the repository horizon in the areas excavated, the absence of breccia pipes and of toxic gases, and the nearly horizontal bedding of the salt. Thick underground salt beds have long been considered prime candidates for nuclear waste repositories. The existence of salt beds is believed to indicate long-term stability. In addition, the salt is flexible and will seal cracks and discontinuities over time.

  8. Which Disposable Chest Electrode?

    PubMed Central

    Hubner, P. J. B.

    1969-01-01

    Chest electrodes are preferred to limb electrodes for cardiac monitoring, as limb movements are not restricted and produce less interference of the E.C.G. trace. Eight types of disposable chest electrodes were investigated to compare their performance, skin reactions, cost, ease of application, size, and skin–electrode impedance. Elema-Schonander electrodes were found to be the most efficient and the most expensive. In their application care was required to avoid severe skin reactions. Dracard electrodes were simple to attach, worked well without severe skin reactions, and were cheap. They are recommended for routine use. Smith and Nephew electrodes, a type of “multipoint electrodes” which do not require electrode jelly, frequently produced severe skin reactions, making them unsuitable for monitoring for periods exceeding 12 hours. PMID:5801347

  9. [6]-Gingerol Affects Glucose Metabolism by Dual Regulation via the AMPKα2-Mediated AS160-Rab5 Pathway and AMPK-Mediated Insulin Sensitizing Effects.

    PubMed

    Lee, Jung Ok; Kim, Nami; Lee, Hye Jeong; Moon, Ji Wook; Lee, Soo Kyung; Kim, Su Jin; Kim, Joong Kwan; Park, Sun Hwa; Kim, Hyeon Soo

    2015-07-01

    [6]-Gingerol has been used to control diabetes and dyslipidemia; however, its metabolic role is poorly understood. In this study, [6]-gingerol increased adenosine monophosphate (AMP)-activated protein kinase (AMPK) phosphorylation in mouse skeletal muscle C2C12 cells. Stimulation of glucose uptake by [6]-gingerol was dependent on AMPKα2. Moreover, both Inhibition and knockdown of AMPKα2 blocked [6]-gingerol-induced glucose uptake. [6]-Gingerol significantly decreased the activity of protein phosphatase 2A (PP2A). Inhibition of PP2A activity with okadaic acid enhanced the phosphorylation of AMPKα2. Moreover, the interaction between AMPKα2 and PP2A was increased by [6]-gingerol, suggesting that PP2A mediates the effect of [6]-gingerol on AMPK phosphorylation. In addition, [6]-gingerol increased the phosphorylation of Akt-substrate 160 (AS160), which is a Rab GTPase-activating protein. Inhibition of AMPKα2 blocked [6]-gingerol-induced AS160 phosphorylation. [6]-gingerol increased the Rab5, and AMPKα2 knockdown blocked [6]-gingerol-induced expression of Rab5, indicating AMPK play as an upstream of Rab5. It also increased glucose transporter 4 (GLUT4) mRNA and protein expression and stimulated GLUT4 translocation. Furthermore, insulin-mediated glucose uptake and Akt phosphorylation were further potentiated by [6]-gingerol treatment. This potentiation was not observed in the presence of AMPK inhibitor compound C. In summary, our results suggest that [6]-gingerol plays an important role in glucose metabolism via the AMPKα2-mediated AS160-Rab5 pathway and through potentiation of insulin-mediated glucose regulation. © 2015 Wiley Periodicals, Inc.

  10. A novel fiber composite ingredient incorporated into a beverage and bar blunts postprandial serum glucose and insulin responses: a randomized controlled trial.

    PubMed

    O'Connor, Lauren E; Campbell, Wayne W

    2016-03-01

    Previous research supports that consumption of resistant starch and guar gum independently influences insulin-mediated glucose responses to meals. This research assessed a novel co-processed fiber composite (FC) ingredient comprising whole-grain high-amylose maize flour and viscous guar gum on glucose and insulin responses to co-consumed and subsequent meals in humans. It was hypothesized that a smoothie-type beverage or a cold-pressed snack bar containing the FC would blunt and sustain serum glucose and insulin postprandial responses compared with maltodextrin (MD). The beverage and bar were assessed in 2 separate studies using identical protocols. Young, nondiabetic, nonobese adults participated in 2 testing days (randomized crossover design) separated by at least 1 week for both food forms. On each testing day, the FC or MD product was consumed with a low-fiber standardized breakfast followed by a low-fiber standardized lunch (with no FC or MD) 4 hours later. Blood samples were collected at baseline and incrementally throughout the 8-hour testing day. One-tailed paired t tests were performed to compare treatment areas under the curve, and a doubly repeated-measures analysis of variance was performed to compare treatment responses at individual time points (P< .05, Bonferroni corrected). The FC blunted the postprandial glucose and insulin responses compared with MD, including a robust glucose and insulin response reduction after breakfast and a continued modest glycemic second-meal reduction after lunch in both the beverage and the bar. These findings support the use of this novel whole-grain FC ingredient in a beverage or bar for insulin-mediated glucose control in young healthy adults.

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

    PubMed

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

    2003-06-01

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

  12. Chemical Waste Management and Disposal.

    ERIC Educational Resources Information Center

    Armour, Margaret-Ann

    1988-01-01

    Describes simple, efficient techniques for treating hazardous chemicals so that nontoxic and nonhazardous residues are formed. Discusses general rules for management of waste chemicals from school laboratories and general techniques for the disposal of waste or surplus chemicals. Lists specific disposal reactions. (CW)

  13. Melter Disposal Strategic Planning Document

    SciTech Connect

    BURBANK, D.A.

    2000-09-25

    This document describes the proposed strategy for disposal of spent and failed melters from the tank waste treatment plant to be built by the Office of River Protection at the Hanford site in Washington. It describes program management activities, disposal and transportation systems, leachate management, permitting, and safety authorization basis approvals needed to execute the strategy.

  14. Chemical Waste Management and Disposal.

    ERIC Educational Resources Information Center

    Armour, Margaret-Ann

    1988-01-01

    Describes simple, efficient techniques for treating hazardous chemicals so that nontoxic and nonhazardous residues are formed. Discusses general rules for management of waste chemicals from school laboratories and general techniques for the disposal of waste or surplus chemicals. Lists specific disposal reactions. (CW)

  15. Nuclear waste disposal in space

    NASA Technical Reports Server (NTRS)

    Burns, R. E.; Causey, W. E.; Galloway, W. E.; Nelson, R. W.

    1978-01-01

    Work on nuclear waste disposal in space conducted by the George C. Marshall Space Flight Center, National Aeronautics and Space Administration, and contractors are reported. From the aggregate studies, it is concluded that space disposal of nuclear waste is technically feasible.

  16. NASA Personal Property Disposal Manual

    NASA Technical Reports Server (NTRS)

    1988-01-01

    The NASA Personal Property Disposal Manual is issued pursuant to Subchapters E and H of the Federal Property Management Regulations and the Space Act of 1958, as amended. It sets forth policy and procedural guidance for NASA personnel for the reporting, utilization, redistribution, and disposal of installation and contractor-held NASA excess and surplus personal property.

  17. Disposable diapers: safe and effective.

    PubMed

    Singh, Namita; Purthi, P K; Sachdev, Anupam; Gupta, Suresh

    2003-09-01

    Nappy rash is a common problem in infants due to their thinner skin, wetness, heat and friction under cloth nappy, fecal enzymes and alkaline urine. The disposable diapers containing Super Absorbent Material (SAM) reduce the incidence of nappy rash. SAM quickly absorbs urine and keeps the skin dry. Also disposable diapers prevent fecal contamination by absorbing the urine and containing stools.

  18. Integrated Disposal Facility Risk Assessment

    SciTech Connect

    MANN, F. M.

    2003-06-03

    An environmental risk assessment associated with the disposal of projected Immobilized Low-Activity Waste, solid wastes and failed or decommissioned melters in an Integrated Disposal Facility was performed. Based on the analyses all performance objectives associated with the groundwater, air, and intruder pathways were met.

  19. Canagliflozin Lowers Postprandial Glucose and Insulin by Delaying Intestinal Glucose Absorption in Addition to Increasing Urinary Glucose Excretion

    PubMed Central

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P.; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R.

    2013-01-01

    OBJECTIVE Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. RESEARCH DESIGN AND METHODS This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, 3H-glucose, 14C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. RESULTS Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0–2h] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0–6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups. CONCLUSIONS Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition. PMID:23412078

  20. Rapamycin negatively impacts insulin signaling, glucose uptake and uncoupling protein-1 in brown adipocytes.

    PubMed

    García-Casarrubios, Ester; de Moura, Carlos; Arroba, Ana I; Pescador, Nuria; Calderon-Dominguez, María; Garcia, Laura; Herrero, Laura; Serra, Dolors; Cadenas, Susana; Reis, Flavio; Carvalho, Eugenia; Obregon, Maria Jesus; Valverde, Ángela M

    2016-12-01

    New onset diabetes after transplantation (NODAT) is a metabolic disorder that affects 40% of patients on immunosuppressive agent (IA) treatment, such as rapamycin (also known as sirolimus). IAs negatively modulate insulin action in peripheral tissues including skeletal muscle, liver and white fat. However, the effects of IAs on insulin sensitivity and thermogenesis in brown adipose tissue (BAT) have not been investigated. We have analyzed the impact of rapamycin on insulin signaling, thermogenic gene-expression and mitochondrial respiration in BAT. Treatment of brown adipocytes with rapamycin for 16h significantly decreased insulin receptor substrate 1 (IRS1) protein expression and insulin-mediated protein kinase B (Akt) phosphorylation. Consequently, both insulin-induced glucose transporter 4 (GLUT4) translocation to the plasma membrane and glucose uptake were decreased. Early activation of the N-terminal Janus activated kinase (JNK) was also observed, thereby increasing IRS1 Ser 307 phosphorylation. These effects of rapamycin on insulin signaling in brown adipocytes were partly prevented by a JNK inhibitor. In vivo treatment of rats with rapamycin for three weeks abolished insulin-mediated Akt phosphorylation in BAT. Rapamycin also inhibited norepinephrine (NE)-induced lipolysis, the expression of peroxisome proliferator-activated receptor γ coactivator 1α (PGC-1α) and uncoupling protein (UCP)-1 in brown adipocytes. Importantly, basal mitochondrial respiration, proton leak and maximal respiratory capacity were significantly decreased in brown adipocytes treated with rapamycin. In conclusion, we demonstrate, for the first time the important role of brown adipocytes as target cells of rapamycin, suggesting that insulin resistance in BAT might play a major role in NODAT development.

  1. Amelioration of insulin resistance by scopoletin in high-glucose-induced, insulin-resistant HepG2 cells.

    PubMed

    Zhang, W Y; Lee, J-J; Kim, Y; Kim, I-S; Park, J-S; Myung, C-S

    2010-12-01

    Insulin resistance plays an important role in the development of type 2 diabetes mellitus. Scopoletin, a phenolic coumarin, is reported to regulate hyperglycemia and diabetes. To examine its effect on insulin resistance, we treated high-glucose-induced, insulin-resistant HepG2 cells with scopoletin and measured phosphatidylinositol 3-kinase (PI3 K)-linked protein kinase B (Akt/PKB) phosphorylation. Scopoletin significantly stimulated the reactivation of insulin-mediated Akt/PKB phosphorylation. This effect was blocked by LY294002, a specific PI3 K inhibitor. The ability of scopoletin to activate insulin-mediated Akt/PKB was greater than that of rosiglitazone, a thiazolidinedione, and scopoletin was less adipogenic than rosiglitazone, as shown by the extent of lipid accumulation in differentiated adipocytes. Scopoletin increased the gene expression of both peroxisome proliferator-activated receptor γ2 (PPARγ2), a target receptor for rosiglitazone, and adipocyte-specific fatty acid binding protein, but not to the level induced by rosiglitazone. However, the PPARγ2 protein level was increased equally by rosiglitazone and scopoletin in differentiated adipocytes. Our results suggest that scopoletin can ameliorate insulin resistance in part by upregulating PPARγ2 expression. With its lower adipogenic property, scopoletin may be a useful candidate for managing metabolic disorders, including type 2 diabetes mellitus. © Georg Thieme Verlag KG Stuttgart · New York.

  2. Insulin Signaling in the Control of Glucose and Lipid Homeostasis.

    PubMed

    Saltiel, Alan R

    2016-01-01

    A continuous supply of glucose is necessary to ensure proper function and survival of all organs. Plasma glucose levels are thus maintained in a narrow range around 5 mM, which is considered the physiological set point. Glucose homeostasis is controlled primarily by the liver, fat, and skeletal muscle. Following a meal, most glucose disposals occur in the skeletal muscle, whereas fasting plasma glucose levels are determined primarily by glucose output from the liver. The balance between the utilization and production of glucose is primarily maintained at equilibrium by two opposing hormones, insulin and glucagon. In response to an elevation in plasma glucose and amino acids (after consumption of a meal), insulin is released from the beta cells of the islets of Langerhans in the pancreas. When plasma glucose falls (during fasting or exercise), glucagon is secreted by α cells, which surround the beta cells in the pancreas. Both cell types are extremely sensitive to glucose concentrations, can regulate hormone synthesis, and are released in response to small changes in plasma glucose levels. At the same time, insulin serves as the major physiological anabolic agent, promoting the synthesis and storage of glucose, lipids, and proteins and inhibiting their degradation and release back into the circulation. This chapter will focus mainly on signal transduction mechanisms by which insulin exerts its plethora of effects in liver, muscle, and fat cells, focusing on those pathways that are crucial in the control of glucose and lipid homeostasis.

  3. Unreviewed Disposal Question Evaluation: Waste Disposal In Engineered Trench #3

    SciTech Connect

    Hamm, L. L.; Smith, F. G. III; Flach, G. P.; Hiergesell, R. A.; Butcher, B. T.

    2013-07-29

    Because Engineered Trench #3 (ET#3) will be placed in the location previously designated for Slit Trench #12 (ST#12), Solid Waste Management (SWM) requested that the Savannah River National Laboratory (SRNL) determine if the ST#12 limits could be employed as surrogate disposal limits for ET#3 operations. SRNL documented in this Unreviewed Disposal Question Evaluation (UDQE) that the use of ST#12 limits as surrogates for the new ET#3 disposal unit will provide reasonable assurance that Department of Energy (DOE) 435.1 performance objectives and measures (USDOE, 1999) will be protected. Therefore new ET#3 inventory limits as determined by a Special Analysis (SA) are not required.

  4. Obesity-Associated Inflammatory Cytokines and Prostaglandin E2 Stimulate Glucose Transporter mRNA Expression and Glucose Uptake in Primary Human Adipose Stromal Cells.

    PubMed

    Docanto, Maria M; Ham, Seungmin; Corbould, Anne; Brown, Kristy A

    2015-08-01

    Obesity is associated with chronic low-grade inflammation. This occurs largely as a result of the infiltration of immune cells within the obese adipose, which produce a number of inflammatory factors, including interleukin-6 (IL-6), IL-1β, tumor necrosis factor-α (TNFα), and prostaglandin E(2) (PGE(2)). These factors have previously been shown to affect insulin-mediated glucose uptake in differentiated adipocytes. However, the insulin-independent effect of inflammation on adipocyte precursors, the adipose stromal cells, has not been explored. This study therefore aimed to examine the effect of obesity-associated inflammatory factors on the expression of insulin-independent glucose transporters (GLUT1 and GLUT3) and on the uptake of glucose within adipose stromal cells. Primary human subcutaneous adipose stromal cells were isolated from abdominoplasty, and the effect of inflammatory cytokines (IL-6, IL-1β, and TNFα) and PGE(2) on GLUT mRNA expression and glucose transport was assessed using real-time polymerase chain reaction and radiolabeled deoxyglucose uptake assays, respectively. Results demonstrate that all four inflammatory mediators caused a dose-dependent increase in GLUT1 mRNA expression and glucose uptake. GLUT3 mRNA expression was also upregulated by IL-6 (0.5 ng/mL), TNFα (0.1 and 10 ng/mL), and PGE(2) (0.1 μM). Overall, these results demonstrate that obesity-associated inflammation increases insulin-independent glucose transporter expression and glucose uptake in undifferentiated adipose stromal cells.

  5. Land Disposal Restrictions for Hazardous Waste

    EPA Pesticide Factsheets

    The land disposal restrictions prohibits the land disposal of untreated hazardous wastes. EPA has specified either concentration levels or methods of treatment for hazardous constituents to meet before land disposal.

  6. Ceramide mediates inhibition of the Akt/eNOS pathway by high levels of glucose in human vascular endothelial cells.

    PubMed

    Wang, Aimin; Li, Chun; Liao, Jie; Dong, Min; Xiao, Zhiming; Lei, Minxiang

    2013-01-01

    To investigate how ceramide mediates the effects of high-glucose-induced inhibition of the Akt/endothelial nitric oxide synthase (eNOS) signalling pathway in human vascular endothelial cells (HUVECs). NO levels were determined by ELISA. Endogenous ceramide levels were determined using a liquid chromatography-mass spectrometry assay. Akt and eNOS protein expressions were determined by Western blotting. High-glucose levels induce ceramide accumulation in a dose- and time-dependent manner (p<0.05). We also show that exposure of HUVECs to high-glucose conditions inhibits the insulin-mediated activation of Akt/eNOS signalling and the subsequent NO generation in a dose-dependent manner (p<0.05). Preventing de novo ceramide synthesis attenuated the antagonistic effects of high-glucose levels on the Akt/eNOS signalling pathway (p<0.05); conversely, inducing ceramide build-up augmented the inhibitory effects of high-glucose levels on the Akt/eNOS signalling pathway (p<0.05). Ceramide is both necessary and sufficient for mediating the inhibition of the Akt/eNOS signalling pathway by high-glucose levels in endothelial cells.

  7. Islet transplantation under the kidney capsule fully corrects the impaired skeletal muscle glucose transport system of streptozocin diabetic rats.

    PubMed Central

    Napoli, R; Davalli, A M; Hirshman, M F; Weitgasser, R; Weir, G C; Horton, E S

    1996-01-01

    Chronic insulin therapy improves but does not restore impaired insulin-mediated muscle glucose uptake in human diabetes or muscle glucose uptake, transport, and transporter translocation in streptozocin diabetic rats. To determine whether this inability is due to inadequate insulin replacement, we studied fasted streptozocin-induced diabetic Lewis rats either untreated or after islet transplantation under the kidney capsule. Plasma glucose was increased in untreated diabetics and normalized by the islet transplantation (110 +/- 5, 452 +/- 9, and 102 +/- 3 mg/dl in controls, untreated diabetics, and transplanted diabetics, respectively). Plasma membrane and intracellular microsomal membrane vesicles were prepared from hindlimb skeletal muscle of basal and maximally insulin-stimulated rats. Islet transplantation normalized plasma membrane carrier-mediated glucose transport Vmax, plasma membrane glucose transporter content, and insulin-induced transporter translocation. There were no differences in transporter intrinsic activity (Vmax/Ro) among the three groups. Microsomal membrane GLUT4 content was reduced by 30% in untreated diabetic rats and normal in transplanted diabetics, whereas the insulin-induced changes in microsomal membrane GLUT4 content were quantitatively similar in the three groups. There were no differences in plasma membrane GLUT1 among the groups and between basal and insulin stimulated states. Microsomal membrane GLUT1 content was increased 60% in untreated diabetics and normalized by the transplantation. In conclusion, an adequate insulin delivery in the peripheral circulation, obtained by islet transplantation, fully restores the muscle glucose transport system to normal in streptozocin diabetic rats. PMID:8617870

  8. Nanomaterial disposal by incineration.

    PubMed

    Holder, Amara L; Vejerano, Eric P; Zhou, Xinzhe; Marr, Linsey C

    2013-09-01

    As nanotechnology-based products enter into widespread use, nanomaterials will end up in disposal waste streams that are ultimately discharged to the environment. One possible end-of-life scenario is incineration. This review attempts to ascertain the potential pathways by which nanomaterials may enter incinerator waste streams and the fate of these nanomaterials during the incineration process. Although the literature on incineration of nanomaterials is scarce, results from studies of their behavior at high temperature or in combustion environments for other applications can help predict their fate within an incinerator. Preliminary evidence suggests nanomaterials may catalyze the formation or destruction of combustion by-products. Depending on their composition, nanomaterials may undergo physical and chemical transformations within the incinerator, impacting their partitioning within the incineration system (e.g., bottom ash, fly ash) and the effectiveness of control technology for removing them. These transformations may also drastically affect nanomaterial transport and impacts in the environment. Current regulations on incinerator emissions do not specifically address nanomaterials, but limits on particle and metal emissions may prove somewhat effective at reducing the release of nanomaterials in incinerator effluent. Control technology used to meet these regulations, such as fabric filters, electrostatic precipitators, and wet electrostatic scrubbers, are expected to be at least partially effective at removing nanomaterials from incinerator flue gas.

  9. Novel role of insulin in the regulation of glucose excretion by mourning doves (Zenaida macroura).

    PubMed

    Sweazea, Karen L; Braun, Eldon J; Sparr, Richard

    2017-06-01

    In mammals, insulin primarily lowers plasma glucose (PGlu) by increasing its uptake into tissues. Studies have also shown that insulin lowers PGlu in mammals by modulating glomerular filtration rate (GFR). Birds have naturally high PGlu and, although insulin administration significantly decreases glucose concentrations, birds are resistant to insulin-mediated glucose uptake into tissues. Since prior work has not examined the effects of insulin on GFR in birds, the purpose of the present study was to assess whether insulin can augment renal glucose excretion and thereby lower PGlu. Therefore, the hypothesis of the present study was that insulin lowers PGlu in birds by augmenting GFR, as estimated by inulin clearance (CIn). Adult mourning doves (Zenaida macroura) were used as experimental animals. Doves were anesthetized and the brachial vein was cannulated for administration of [(14)C]-inulin and insulin and the brachial artery was cannulated for blood collections. Ureteral urine was collected via a catheter inserted into the cloaca. Ten minutes following administration of exogenous insulin (400μg/kg body mass, i.v.) plasma glucose was significantly decreased (p=0.0003). Twenty minutes following insulin administration, increases in GFR (p=0.016) were observed along with decreases in urine glucose concentrations (p=0.008), glucose excretion (p=0.028), and the fractional excretion of glucose (p=0.003). Urine flow rate (p=0.051) also tended to increase after administration of insulin. These data demonstrate a significant role for insulin in modulating GFR in mourning doves, which may in part explain the lower PGlu measured following insulin administration. Copyright © 2017 Elsevier GmbH. All rights reserved.

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

    PubMed

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

    2015-10-01

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

  11. Improper sharp disposal practices among diabetes patients in home care settings: Need for concern?

    PubMed

    Majumdar, Anindo; Sahoo, Jayaprakash; Roy, Gautam; Kamalanathan, Sadishkumar

    2015-01-01

    In the recent years, outbreaks of blood-borne infections have been reported from assisted living facilities, which were traced back to improper blood glucose monitoring practices. Needle-stick injuries have been implicated in many such cases. This directly raises concerns over sharp disposal practices of diabetic patients self-managing their condition in home care settings. With India being home to a huge diabetic population, this issue, if neglected, can cause substantial damage to the health of the population and a marked economic loss. This article discusses the sharp disposal practices prevalent among diabetes patients, the importance of proper sharp disposal, barriers to safe disposal of sharps, and the options available for doing the same. For adopting an environmentally safe wholesome approach, disposal of plastics generated as a result of diabetes self-care at home is important as well. The article also looks at the possible long-term solutions to these issues that are sustainable in an Indian context.

  12. FFTF disposable solid waste cask

    SciTech Connect

    Thomson, J. D.; Goetsch, S. D.

    1983-01-01

    Disposal of radioactive waste from the Fast Flux Test Facility (FFTF) will utilize a Disposable Solid Waste Cask (DSWC) for the transport and burial of irradiated stainless steel and inconel materials. Retrievability coupled with the desire for minimal facilities and labor costs at the disposal site identified the need for the DSWC. Design requirements for this system were patterned after Type B packages as outlined in 10 CFR 71 with a few exceptions based on site and payload requirements. A summary of the design basis, supporting analytical methods and fabrication practices developed to deploy the DSWC is provided in this paper.

  13. Disposable diapers: a hygienic alternative.

    PubMed

    Kamat, Maithili; Malkani, Ram

    2003-11-01

    The use of disposable diapers has offered improved health care benefits. Urine and fecal matter leakage from the cloth nappies and the hand-to-mouth behavior in infants leads to many illnesses with a feco-oral mode of transmission. Also, the tender skin of the infant is more prone to nappy rash. The modern age disposable diapers, when compared to cloth nappy, have displayed a superior ability in containment of urine and feces, thereby reducing contamination and transmission of infection. Also disposable diapers contain Super Absorbent Material (SAM) that successfully reduces the incidence of nappy rash.

  14. Neuroscience of glucose homeostasis.

    PubMed

    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 uptake to prevent hyperglycemia. Although the term homeostasis mostly refers to stable levels, the blood glucose concentrations fluctuate over the day/night cycle, with the highest concentrations occurring just prior to the activity period in anticipation of increased caloric need. In this chapter we describe how the brain, particularly the hypothalamus, is involved in both the daily rhythm of plasma glucose concentrations and acute glucose challenges.

  15. The measurement of alkaline phosphatase at nanomolar concentration within 70 s using a disposable microelectrochemical transistor.

    PubMed

    Astier, Y; Bartlett, P N

    2004-08-01

    We report a new approach to the measurement of alkaline phosphatase concentration based on the use of a disposable poly(aniline) microelectrochemical transistor. The measurement is carried out in a two cell configuration in which the poly(aniline) microelectrochemical transistor operates in acid solution and is connected to the alkaline buffer solution containing the analyte by a salt bridge. Disposable microelectrochemical transistors were reproducibly fabricated by electrochemical deposition of poly(aniline) onto photolithographically fabricated gold microband arrays. Using these devices alkaline phosphatase was detected by employing p-aminophenyl phosphate as the substrate for the enzyme and using glucose and glucose oxidase to recycle the p-aminophenol generated upon enzyme catalysed hydrolysis of the phosphate. Recycling the p-aminophenol with glucose and glucose oxidase amplified the detection of alkaline phosphatase approximately tenfold. Using this approach we obtain linear calibration curves for alkaline phosphatase up to 5 nM within 70 s on single use devices.

  16. Glyceollins, soy isoflavone phytoalexins, improve oral glucose disposal by stimulating glucose uptake

    USDA-ARS?s Scientific Manuscript database

    Glyceollins (glyceollin I, II, and III), isoflavone phytoalexins synthesized by soy in response to environmental stresses such as microbial infections. Glyceollins exhibited anti-cancer and anti-diabetes effects: previously we showed that glyceollins inhibited cancer cell growth in vitro and in viv...

  17. Ultimate disposal of scrubber wastes

    NASA Technical Reports Server (NTRS)

    Cohenour, B. C.

    1978-01-01

    Part of the initial concern with using the wet scrubbers on the hypergolic propellants was the subsequential disposal of the liquid wastes. To do this, consideration was given to all possible methods to reduce the volume of the wastes and stay within the guidelines established by the state and federal environmental protection agencies. One method that was proposed was the use of water hyacinths in disposal ponds to reduce the waste concentration in the effluent to less than EPA tolerable levels. This method was under consideration and even in use by private industry, municipal governments, and NASA for upgrading existing wastewater treatment facilities to a tertiary system. The use of water hyacinths in disposal ponds appears to be a very cost-effective method for reduction and disposal of hypergolic propellants.

  18. Optimization of Waste Disposal - 13338

    SciTech Connect

    Shephard, E.; Walter, N.; Downey, H.; Collopy, P.; Conant, J.

    2013-07-01

    From 2009 through 2011, remediation of areas of a former fuel cycle facility used for government contract work was conducted. Remediation efforts were focused on building demolition, underground pipeline removal, contaminated soil removal and removal of contaminated sediments from portions of an on-site stream. Prior to conducting the remediation field effort, planning and preparation for remediation (including strategic planning for waste characterization and disposal) was conducted during the design phase. During the remediation field effort, waste characterization and disposal practices were continuously reviewed and refined to optimize waste disposal practices. This paper discusses strategic planning for waste characterization and disposal that was employed in the design phase, and continuously reviewed and refined to optimize efficiency. (authors)

  19. Recycling and Disposal of CFLs

    EPA Pesticide Factsheets

    Consumers can help prevent the release of mercury into the environment by taking advantage of available local options for recycling CFLs and other household hazardous wastes, rather than disposing of them in regular household trash.

  20. Disposal phase experimental program plan

    SciTech Connect

    1997-01-31

    The Waste Isolation Pilot Plant (WIPP) facility comprises surface and subsurface facilities, including a repository mined in a bedded salt formation at a depth of 2,150 feet. It has been developed to safely and permanently isolate transuranic (TRU) radioactive wastes in a deep geological disposal site. On April 12, 1996, the DOE submitted a revised Resource Conservation and Recovery Act (RCRA) Part B permit application to the New Mexico Environment Department (NMED). The DOE anticipates receiving an operating permit from the NMED; this permit is required prior to the start of disposal operations. On October 29, 1996, the DOE submitted a Compliance Certification Application (CCA) to the US Environmental Protection Agency (EPA) in accordance with the WIPP land Withdrawal Act (LWA) of 1992 (Public Law 102-579) as amended, and the requirements of Title 40 of the Code of Federal Regulations (40 CFR) Parts 191 and 194. The DOE plans to begin disposal operations at the WIPP in November 1997 following receipt of certification by the EPA. The disposal phase is expected to last for 35 years, and will include recertification activities no less than once every five years. This Disposal Phase Experimental Program (DPEP) Plan outlines the experimental program to be conducted during the first 5-year recertification period. It also forms the basis for longer-term activities to be carried out throughout the 35-year disposal phase. Once the WIPP has been shown to be in compliance with regulatory requirements, the disposal phase gives an opportunity to affirm the compliance status of the WIPP, enhance the operations of the WIPP and the national TRU system, and contribute to the resolution of national and international nuclear waste management technical needs. The WIPP is the first facility of its kind in the world. As such, it provides a unique opportunity to advance the technical state of the art for permanent disposal of long-lived radioactive wastes.

  1. Effects of maternal undernutrition and exercise on glucose kinetics in fetal sheep.

    PubMed

    Leury, B J; Chandler, K D; Bird, A R; Bell, A W

    1990-09-01

    Fetal glucose kinetics were measured using a combination of isotope-dilution and Fick-principle methodology in single-pregnant ewes which were either well-fed throughout, or fed at 0.3-0.4 predicted energy requirement for 7-21 d during late pregnancy. All ewes were studied while standing at rest and then while walking on a treadmill at 0.7 m/s on a 10 degree slope for 60 min. Underfed ewes suffered major decreases in fetal total disposal rate, fetal-placental transfer and umbilical net uptake of glucose, each of which were significantly related to declines in maternal and fetal blood glucose concentrations respectively. In well-fed ewes, fetal endogenous glucose production was negligible, as indicated by the similarity between fetal utilization rate (total glucose disposal rate minus placental uptake of fetal glucose) and umbilical net uptake of glucose, and by nearly identical fetal and maternal arterial blood specific radioactivities of maternally infused D-[2-3H]glucose. By contrast, in underfed ewes, fetal utilization rate greatly exceeded umbilical net uptake of glucose, and the fetal:maternal [3H]glucose specific activity ratio declined significantly, suggesting induction of a substantial rate of fetal endogenous glucogenesis. Exercise caused increases in fetal total glucose disposal rate and glycaemia in fed and underfed ewes. In underfed ewes only, this was accompanied by increased placental uptake of fetal glucose and umbilical net glucose uptake, unchanged fetal glucose utilization and decreased fetal endogenous glucose production. It is concluded that fetal gluconeogenesis makes a major contribution to fetal glucose requirements in undernourished ewes. Increased maternal supply of fetal glucose during exercise substitutes for rather than adds to fetal endogenous glucogenesis.

  2. Low Blood Glucose (Hypoglycemia)

    MedlinePlus

    ... Dental Problems Diabetes & Sexual & Urologic Problems Low Blood Glucose (Hypoglycemia) What is hypoglycemia? Hypoglycemia, also called low ... actions can also help prevent hypoglycemia: Check blood glucose levels Knowing your blood glucose level can help ...

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

    PubMed

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

    2017-09-21

    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. Published by Elsevier B.V.

  4. 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.

    PubMed

    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.

  5. The evolution of commercialized glucose sensors in China.

    PubMed

    Hu, Jamie

    2009-01-01

    The glucose monitor with a screen-printed carbon sensor has been in commercial production since 1994. In last 15 years, around 10 companies have been involved in manufacturing and marketing the meters and glucose test strips and are being strong competitors of the companies which import these products. Comparison of early stage glucose meters and glucose test strips with latest fabrications showed a large increase in production volume and improved functional features. It also showed technological development of glucose monitors including circuit improvement, as more integrated computer processor units (CPU) are now being used. The technology of mass-production of disposable screen-printed test strips has been widely used in local industries mainly for the production of blood glucose test strips. The opportunities and challenges in local diabetes market are discussed in this paper.

  6. 40 CFR 191.24 - Disposal standards.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... PROGRAMS ENVIRONMENTAL RADIATION PROTECTION STANDARDS FOR MANAGEMENT AND DISPOSAL OF SPENT NUCLEAR FUEL, HIGH-LEVEL AND TRANSURANIC RADIOACTIVE WASTES Environmental Standards for Ground-Water Protection § 191.24 Disposal standards. (a) Disposal systems. (1) General. Disposal systems for waste and...

  7. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 2 2011-01-01 2011-01-01 false Disposal site design for land disposal. 61.51 Section 61.51 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Technical Requirements for Land Disposal Facilities § 61.51 Disposal site design for...

  8. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 2 2010-01-01 2010-01-01 false Disposal site design for land disposal. 61.51 Section 61.51 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Technical Requirements for Land Disposal Facilities § 61.51 Disposal site design for...

  9. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 2 2014-01-01 2014-01-01 false Disposal site design for land disposal. 61.51 Section 61.51 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Technical Requirements for Land Disposal Facilities § 61.51 Disposal site design for...

  10. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 2 2013-01-01 2013-01-01 false Disposal site design for land disposal. 61.51 Section 61.51 Energy NUCLEAR REGULATORY COMMISSION (CONTINUED) LICENSING REQUIREMENTS FOR LAND DISPOSAL OF RADIOACTIVE WASTE Technical Requirements for Land Disposal Facilities § 61.51 Disposal site design for...

  11. Tank Waste Disposal Program redefinition

    SciTech Connect

    Grygiel, M.L.; Augustine, C.A.; Cahill, M.A.; Garfield, J.S.; Johnson, M.E.; Kupfer, M.J.; Meyer, G.A.; Roecker, J.H.; Holton, L.K.; Hunter, V.L.; Triplett, M.B.

    1991-10-01

    The record of decision (ROD) (DOE 1988) on the Final Environmental Impact Statement, Hanford Defense High-Level, Transuranic and Tank Wastes, Hanford Site, Richland Washington identifies the method for disposal of double-shell tank waste and cesium and strontium capsules at the Hanford Site. The ROD also identifies the need for additional evaluations before a final decision is made on the disposal of single-shell tank waste. This document presents the results of systematic evaluation of the present technical circumstances, alternatives, and regulatory requirements in light of the values of the leaders and constitutents of the program. It recommends a three-phased approach for disposing of tank wastes. This approach allows mature technologies to be applied to the treatment of well-understood waste forms in the near term, while providing time for the development and deployment of successively more advanced pretreatment technologies. The advanced technologies will accelerate disposal by reducing the volume of waste to be vitrified. This document also recommends integration of the double-and single-shell tank waste disposal programs, provides a target schedule for implementation of the selected approach, and describes the essential elements of a program to be baselined in 1992.

  12. Bioelectroanalysis in a Drop: Construction of a Glucose Biosensor

    ERIC Educational Resources Information Center

    Amor-Gutierrez, O.; Rama, E. C.; Fernandez-Abedul, M. T.; Costa-García, A.

    2017-01-01

    This lab experiment describes a complete method to fabricate an enzymatic glucose electroanalytical biosensor by students. Using miniaturized and disposable screen-printed electrodes (SPEs), students learn how to use them as transducers and understand the importance SPEs have acquired in sensor development during the last years. Students can also…

  13. Indirect Regulation of Endogenous Glucose Production by Insulin: The Single Gateway Hypothesis Revisited.

    PubMed

    Bergman, Richard N; Iyer, Malini S

    2017-07-01

    On the basis of studies that investigated the intraportal versus systemic insulin infusion and transendothelial transport of insulin, we proposed the "single gateway hypothesis," which supposes an indirect regulation of hepatic glucose production by insulin; the rate-limiting transport of insulin across the adipose tissue capillaries is responsible for the slow suppression of free fatty acids (FFAs), which in turn is responsible for delayed suppression of hepatic endogenous glucose production (EGP) during insulin infusion. Preventing the fall in plasma FFAs during insulin infusion either by administering intralipids or by inhibiting adipose tissue lipolysis led to failure in EGP suppression, thus supporting our hypothesis. More recently, mice lacking hepatic Foxo1 in addition to Akt1 and Akt2 (L-AktFoxo1TKO), all required for insulin signaling, surprisingly showed normal glycemia. Inhibiting the fall of plasma FFAs in these mice prevented the suppression of EGP during a clamp, reaffirming that the site of insulin action to control EGP is extrahepatic. Measuring whole-body turnover rates of glucose and FFAs in L-AktFoxo1TKO mice also confirmed that hepatic EGP was regulated by insulin-mediated control of FFAs. The knockout mouse model in combination with sophisticated molecular techniques confirmed our physiological findings and the single gateway hypothesis. © 2017 by the American Diabetes Association.

  14. Depleted uranium disposal options evaluation

    SciTech Connect

    Hertzler, T.J.; Nishimoto, D.D.; Otis, M.D.

    1994-05-01

    The Department of Energy (DOE), Office of Environmental Restoration and Waste Management, has chartered a study to evaluate alternative management strategies for depleted uranium (DU) currently stored throughout the DOE complex. Historically, DU has been maintained as a strategic resource because of uses for DU metal and potential uses for further enrichment or for uranium oxide as breeder reactor blanket fuel. This study has focused on evaluating the disposal options for DU if it were considered a waste. This report is in no way declaring these DU reserves a ``waste,`` but is intended to provide baseline data for comparison with other management options for use of DU. To PICS considered in this report include: Retrievable disposal; permanent disposal; health hazards; radiation toxicity and chemical toxicity.

  15. Blood Test: Glucose

    MedlinePlus

    ... Your 1- to 2-Year-Old Blood Test: Glucose KidsHealth > For Parents > Blood Test: Glucose A A A What's in this article? What ... de sangre: glucosa What It Is A blood glucose test measures the amount of glucose (the main ...

  16. Blood Test: Glucose

    MedlinePlus

    ... TV, Video Games, and the Internet Blood Test: Glucose KidsHealth > For Parents > Blood Test: Glucose Print A A A What's in this article? ... de sangre: glucosa What It Is A blood glucose test measures the amount of glucose (the main ...

  17. CSF glucose test

    MedlinePlus

    Glucose test - CSF; Cerebrospinal fluid glucose test ... The glucose level in the CSF should be 50 to 80 mg/100 mL (or greater than 2/3 ... Abnormal results include higher and lower glucose levels. Abnormal ... or fungus) Inflammation of the central nervous system Tumor

  18. Final disposal of radioactive waste

    NASA Astrophysics Data System (ADS)

    Freiesleben, H.

    2013-06-01

    In this paper the origin and properties of radioactive waste as well as its classification scheme (low-level waste - LLW, intermediate-level waste - ILW, high-level waste - HLW) are presented. The various options for conditioning of waste of different levels of radioactivity are reviewed. The composition, radiotoxicity and reprocessing of spent fuel and their effect on storage and options for final disposal are discussed. The current situation of final waste disposal in a selected number of countries is mentioned. Also, the role of the International Atomic Energy Agency with regard to the development and monitoring of international safety standards for both spent nuclear fuel and radioactive waste management is described.

  19. Disposable telemetry cable deployment system

    DOEpatents

    Holcomb, David Joseph

    2000-01-01

    A disposable telemetry cable deployment system for facilitating information retrieval while drilling a well includes a cable spool adapted for insertion into a drill string and an unarmored fiber optic cable spooled onto the spool cable and having a downhole end and a stinger end. Connected to the cable spool is a rigid stinger which extends through a kelly of the drilling apparatus. A data transmission device for transmitting data to a data acquisition system is disposed either within or on the upper end of the rigid stinger.

  20. DOSE ASSESSMENTS FROM THE DISPOSAL OF LOW ...

    EPA Pesticide Factsheets

    Modeling the long-term performance of the RCRA-C disposal cell and potential doses to off-site receptors is used to derive maximum radionuclide specific concentrations in the wastes that would enable these wastes to be disposed of safely using the RCRA-C disposal cell technology. Modeling potential exposures to derive these waste acceptance concentrations involves modeling exposures to workers during storage, treatment and disposal of the wastes, as well as exposures to individuals after disposal operations have ceased. Post facility closure exposures can result from the slow expected degradation of the disposal cell over long time periods (one thousand years after disposal) and in advertent human intrusion. Provide a means of determining waste acceptance radionuclide concentrations for disposal of debris from radiological dispersal device incidents as well as low-activity wastes generated in commercial, medical and research activities, potentially serve as the technical basis for guidance on disposal of these materials.

  1. The effect of endurance training and subsequent physical inactivity on glycaemic control after oral glucose load and physical exercise in healthy men

    NASA Astrophysics Data System (ADS)

    Radikova, Zofia; Ksinantova, Lucia; Kaciuba-Uscilko, Hanna; Nazar, Krystyna; Vigas, Milan; Koska, Juraj

    2007-02-01

    Physical inactivity during space flight has a profound effect on glucose metabolism. The aim of this study was to test whether endurance training (ET) may improve a negative effect of subsequent -6∘ head-down bed rest (HDBR) on glucose metabolism. Fourteen healthy males completed the study consisting of 6 weeks lasting ET followed by 6 days HDBR. Treadmill exercise at 80% of pre-training VO2max and 75 g oral glucose tolerance test (OGTT) were performed before and after ET as well as after HDBR. ET increased VO2max by 11%. ET significantly lowered while HDBR had no effect on fasting and OGTT plasma glucose levels. ET had no effect while HDBR was followed by an augmentation of insulin and C-peptide response to OGTT. Insulin sensitivity tended to increase after ET and to decrease during HDBR, however, mostly without statistical significance. Plasma glucose, insulin and C-peptide response to exercise were elevated after HDBR only. Our study shows that antecedent physical training could ameliorate a negative effect of simulated microgravity on insulin-mediated glucose metabolism.

  2. Frequent interruptions of sedentary time modulates contraction- and insulin-stimulated glucose uptake pathways in muscle: Ancillary analysis from randomized clinical trials

    PubMed Central

    Bergouignan, Audrey; Latouche, Celine; Heywood, Sarah; Grace, Megan S.; Reddy-Luthmoodoo, Medini; Natoli, Alaina K.; Owen, Neville; Dunstan, David W.; Kingwell, Bronwyn A.

    2016-01-01

    Epidemiological studies have observed associations between frequent interruptions of sitting time with physical activity bouts and beneficial metabolic outcomes, even in individuals who regularly exercise. Frequent interruptions to prolonged sitting reduce postprandial plasma glucose. Here we studied potential skeletal muscle mechanisms accounting for this improved control of glycemia in overweight adults under conditions of one day uninterrupted sitting and sitting interrupted with light-intensity or moderate-intensity walking every 20-min (n = 8); and, after three days of either uninterrupted sitting or light-intensity walking interruptions (n = 5). Contraction- and insulin-mediated glucose uptake signaling pathways as well as changes in oxidative phosphorylation proteins were examined. We showed that 1) both interventions reduce postprandial glucose concentration, 2) acute interruptions to sitting over one day stimulate the contraction-mediated glucose uptake pathway, 3) both acute interruptions to sitting with moderate-intensity activity over one day and light-intensity activity over three days induce a transition to modulation of the insulin-signaling pathway, in association with increased capacity for glucose transport. Only the moderate-intensity interruptions resulted in greater capacity for glycogen synthesis and likely for ATP production. These observations contribute to a mechanistic explanation of improved postprandial glucose metabolism with regular interruptions to sitting time, a promising preventive strategy for metabolic diseases. PMID:27554943

  3. Geological considerations in hazardouswaste disposal

    USGS Publications Warehouse

    Cartwright, K.; Gilkeson, R.H.; Johnson, T.M.

    1981-01-01

    Present regulations assume that long-term isolation of hazardous wastes - including toxic chemical, biological, radioactive, flammable and explosive wastes - may be effected by disposal in landfills that have liners of very low hydraulic conductivity. In reality, total isolation of wastes in humid areas is not possible; some migration of leachate from wastes buried in the gound will always occur. Regulations should provide performance standards applicable on a site-by-site basis rather than rigid criteria for site selection and design. The performance standards should take into account several factors: (1) the categories, segregation, degradation and toxicity of the wastes; (2) the site hydrogeology, which governs the direction and rate of contaminant transport; (3) the attenuation of contaminants by geochemical interactions with geologic materials; and (4) the release rate of unattenuated pollutants to surface or groundwater. An adequate monitoring system is essential. The system should both test the extent to which the operation of the site meets performance standards and provide sufficient warning of pollution problems to allow implementation of remedial measures. In recent years there has been a trend away from numerous, small disposal sites toward fewer and larger sites. The size of a disposal site should be based on the attenuation capacity of the geologic material, which has a finite, though generally not well-defined, limit. For slowly degradable wastes, engineered sites with leachate-collection systems appear to be only a temporary solution since the leachate collected will also require final disposal. ?? 1981.

  4. Ocean Disposal of Dredged Material

    EPA Pesticide Factsheets

    Permits and authorizations for the ocean dumping of dredged material is issued by U.S. Army Corps of Engineers. Information is provided about where to dispose dredged material and the process for obtaining an ocean dumping permit for dredged material.

  5. HANDBOOK: SEPTAGE TREATMENT AND DISPOSAL

    EPA Science Inventory

    The principal purpose of the handbook is to present an up-to-date review of available design, performance, operation and maintenance, cost, and energy information pertaining to the receiving, treatment, and disposal of septage. Septage is the liquid and solid material pumped from...

  6. Disposables: saving by throwing away.

    PubMed

    Wilton, G

    1980-07-18

    The demand for health care facilities and services will remain insatiable, concludes a report by Frost and Sullivan due to be published shortly. The report on trends in the European clinical soft goods market says growth is guaranteed but that the market penetration of disposables is not.

  7. Disposing of Canada's used fuel

    SciTech Connect

    Torgerson, D.F.

    1990-01-01

    The Canadian Nuclear Fuel Waste Management Program is assessing the permanent disposal of used nuclear fuel in a waste vault located 500 to 1,000 m deep in the Precambrian granitic rock of the Canadian Shield. The specific objectives of the program are to develop and demonstrate the technology to site, design, build, and operate a disposal facility in a way that creates no, or negligible, burden on future generations. In addition, the program must develop a methodology to evaluate the performance of the disposal system against safety criteria and demonstrate that sites are likely to exist in the Canadian Shield that satisfy regulatory criteria. These criteria are very stringent. As in other national high-level waste management programs, the Canadian concept for the permanent disposal of nuclear fuel wastes employs a multiple barrier system for isolating contaminants from the environment. The current phase of the work is generic in nature and is not site specific. Research and development (R and D) has advanced to the point where the generic concept will be evaluated under the Canadian environmental assessment review process, which involves public hearings and independent scientific review.

  8. Sludge Treatment, Utilization, and Disposal.

    ERIC Educational Resources Information Center

    Dick, Richard I.

    1978-01-01

    Presents the 1978 literature review of wastewater treatment. This review covers such areas: (1) industrial and hazardous sludges; (2) chemical sludges; (3) stabilization and combustion; (4) ocean disposal; and (5) land application. A list of 411 references is also presented. (HM)

  9. HANDBOOK: SEPTAGE TREATMENT AND DISPOSAL

    EPA Science Inventory

    The principal purpose of the handbook is to present an up-to-date review of available design, performance, operation and maintenance, cost, and energy information pertaining to the receiving, treatment, and disposal of septage. Septage is the liquid and solid material pumped from...

  10. Disposal requirements for PCB waste

    SciTech Connect

    1994-12-01

    Polychlorinated biphenyls (PCBs) are a class of organic chemicals that had become widely used in industrial applications due to their practical physical and chemical properties. Historical uses of PCBs include dielectric fluids (used in utility transformers, capacitors, etc.), hydraulic fluids, and other applications requiring stable, fire-retardant materials. Due to findings that PCBs may cause adverse health effects and due to their persistence and accumulation in the environment, the Toxic Substances Control Act (TSCA), enacted on october 11, 1976, banned the manufacture of PCBs after 1978 [Section 6(e)]. The first PCB regulations, promulgated at 40 CFR Part 761, were finalized on February 17, 1978. These PCB regulations include requirements specifying disposal methods and marking (labeling) procedures, and controlling PCB use. To assist the Department of Energy (DOE) in its efforts to comply with the TSCA statute and implementing regulations, the Office of Environmental Guidance has prepared the document ``Guidance on the Management of Polychlorinated Biphenyls (PCBs).`` That document explains the requirements specified in the statute and regulations for managing PCBs including PCB use, storage, transport, and disposal. PCB materials that are no longer in use and have been declared a waste must be disposed of according to the requirements found at 40 CFR 761.60. These requirements establish disposal options for a multitude of PCB materials including soil and debris, liquid PCBs, sludges and slurries, containers, transformers, capacitors, hydraulic machines, and other electrical equipment. This Information Brief supplements the PCB guidance document by responding to common questions concerning disposal requirements for PCBs. It is one of a series of Information Briefs pertinent to PCB management issues.

  11. Optimizing High Level Waste Disposal

    SciTech Connect

    Dirk Gombert

    2005-09-01

    If society is ever to reap the potential benefits of nuclear energy, technologists must close the fuel-cycle completely. A closed cycle equates to a continued supply of fuel and safe reactors, but also reliable and comprehensive closure of waste issues. High level waste (HLW) disposal in borosilicate glass (BSG) is based on 1970s era evaluations. This host matrix is very adaptable to sequestering a wide variety of radionuclides found in raffinates from spent fuel reprocessing. However, it is now known that the current system is far from optimal for disposal of the diverse HLW streams, and proven alternatives are available to reduce costs by billions of dollars. The basis for HLW disposal should be reassessed to consider extensive waste form and process technology research and development efforts, which have been conducted by the United States Department of Energy (USDOE), international agencies and the private sector. Matching the waste form to the waste chemistry and using currently available technology could increase the waste content in waste forms to 50% or more and double processing rates. Optimization of the HLW disposal system would accelerate HLW disposition and increase repository capacity. This does not necessarily require developing new waste forms, the emphasis should be on qualifying existing matrices to demonstrate protection equal to or better than the baseline glass performance. Also, this proposed effort does not necessarily require developing new technology concepts. The emphasis is on demonstrating existing technology that is clearly better (reliability, productivity, cost) than current technology, and justifying its use in future facilities or retrofitted facilities. Higher waste processing and disposal efficiency can be realized by performing the engineering analyses and trade-studies necessary to select the most efficient methods for processing the full spectrum of wastes across the nuclear complex. This paper will describe technologies being

  12. Glucose uptake stimulatory potential and antidiabetic activity of the Arnebin-1 from Arnabia nobelis.

    PubMed

    Pandeti, Sukanya; Arha, Deepti; Mishra, Akansha; Reddy, Sabbu Sathish; Srivastava, Arvind K; Narender, Tadigoppula; Tamrakar, Akhilesh K

    2016-10-15

    The enhanced disposal of glucose by the peripheral tissue is an important mechanism to regulate hyperglycemia. Here, we investigated the effect of Arnebin-1 from Arnebia nobilis, on glucose disposal in skeletal muscle cells and explored its in vivo antihyperglycemic potential. In L6 myotubes, Arnebin-1 stimulated glucose uptake, mediated through the enhanced translocation of the glucose transporter-4 (GLUT4) to plasma membrane, without changing the amount of GLUT4 or GLUT1. These effects of Arnebin-1 were synergistic with that of insulin. The effect of Arnebin-1 on glucose uptake was abolished in presence of wortmannin, and Arnebin-1 significantly stimulated the phosphorylation of Akt and downstream marker GSK-3β. Moreover, treatment with Arnebin-1 lowered postprandial blood glucose levels in streptozotocin-induced diabetic rats, and improved glucose tolerance and suppressed the rises in the fasting blood glucose, serum insulin, triglycerides, and total cholesterol in db/db mice, associated with enhanced expression of the major marker of the PI-3-Kinase-mediated signaling cascade in skeletal muscle. These findings suggest that Arnebin-1 exert antihyperglycemic activity through stimulating glucose disposal in peripheral tissues via PI-3-Kinase-dependent pathway.

  13. Worldwide low-level waste disposal practices

    SciTech Connect

    Towler, O A

    1985-01-01

    Low-level waste disposal practices will be described for ten or more countries. These practices will be compared with expectations for disposal designs for low-level waste regional compacts in the US.

  14. Disposal of NORM waste in salt caverns

    SciTech Connect

    Veil, J.A.; Smith, K.P.; Tomasko, D.; Elcock, D.; Blunt, D.; Williams, G.P.

    1998-07-01

    Some types of oil and gas production and processing wastes contain naturally occurring radioactive materials (NORM). If NORM is present at concentrations above regulatory levels in oil field waste, the waste requires special disposal practices. The existing disposal options for wastes containing NORM are limited and costly. This paper evaluates the legality, technical feasibility, economics, and human health risk of disposing of NORM-contaminated oil field wastes in salt caverns. Cavern disposal of NORM waste is technically feasible and poses a very low human health risk. From a legal perspective, there are no fatal flaws that would prevent a state regulatory agency from approving cavern disposal of NORM. On the basis of the costs charged by caverns currently used for disposal of nonhazardous oil field waste (NOW), NORM waste disposal caverns could be cost competitive with existing NORM waste disposal methods when regulatory agencies approve the practice.

  15. Phytoextraction crop disposal--an unsolved problem.

    PubMed

    Sas-Nowosielska, A; Kucharski, R; Małkowski, E; Pogrzeba, M; Kuperberg, J M; Kryński, K

    2004-01-01

    Several methods of contaminated crop disposal after phytoextraction process (composting, compaction, incineration, ashing, pyrolysis, direct disposal, liquid extraction) have been described. Advantages and disadvantages of methods are presented and discussed. Composting, compaction and pyrolysis are the pretreatment steps, since significant amount of contaminated biomass will still exist after each of the process. Four methods of final disposal were distinguished: incineration, direct disposal, ashing and liquid extraction. Among them, incineration (smelting) is proposed as the most feasible, economically acceptable and environmentally sound.

  16. Glucagon-mediated impairments in hepatic and peripheral tissue nutrient disposal are not aggravated by increased lipid availability

    PubMed Central

    Chen, Sheng-Song; Santomango, Tammy S.; Williams, Phillip E.; Lacy, D. Brooks; McGuinness, Owen P.

    2009-01-01

    Glucose, fat, and glucagon availability are increased in diabetes. The normal response of the liver to chronic increases in glucose availability is to adapt to become a marked consumer of glucose. Yet this fails to occur in diabetes. The aim was to determine whether increased glucagon and lipid interact to impair the adaptation to increased glucose availability. Chronically catheterized well controlled depancreatized conscious dogs (n = 21) received 3 days of continuous parenteral nutrition (TPN) that was either high in glucose [C; 75% nonprotein calories (NPC)] or in lipid (HL; 75% NPC) in the presence or absence of a low dose (one-third basal) chronic intraportal infusion of glucagon (GN; 0.25 ng·kg−1·min−1). During the 3 days of TPN, all groups received the same insulin algorithm; the total amount of glucose infused (GIR) was varied to maintain isoglycemia (∼120 mg/dl). On day 3 of TPN, hepatic metabolism was assessed. Glucose and insulin levels were similar in all groups. GIR was decreased in HL and C + GN (∼30%) and was further decreased in HL + GN (55%). Net hepatic glucose uptake was decreased ∼15% in C + GN, and HL and was decreased ∼50% in HL + GN. Lipid alone or combined with glucagon decreased glucose uptake by peripheral tissues. Despite impairing whole body glucose utilization, HL did not limit whole body energy disposal. In contrast, glucagon suppressed whole body energy disposal irrespective of the diet composition. In summary, failure to appropriately suppress glucagon secretion adds to the dietary fat-induced impairment in both hepatic and peripheral glucose disposal. In addition, unlike increasing the percentage of calories as fat, inappropriate glucagon secretion in the absence of compensatory hyperinsulinemia limits whole body nutrient disposition. PMID:19208853

  17. 32 CFR 644.315 - Disposal priorities.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 32 National Defense 4 2010-07-01 2010-07-01 true Disposal priorities. 644.315 Section 644.315 National Defense Department of Defense (Continued) DEPARTMENT OF THE ARMY (CONTINUED) REAL PROPERTY REAL ESTATE HANDBOOK Disposal § 644.315 Disposal priorities. Consistent with the best interest of the United...

  18. Waste disposal options report. Volume 1

    SciTech Connect

    Russell, N.E.; McDonald, T.G.; Banaee, J.; Barnes, C.M.; Fish, L.W.; Losinski, S.J.; Peterson, H.K.; Sterbentz, J.W.; Wenzel, D.R.

    1998-02-01

    This report summarizes the potential options for the processing and disposal of mixed waste generated by reprocessing spent nuclear fuel at the Idaho Chemical Processing Plant. It compares the proposed waste-immobilization processes, quantifies and characterizes the resulting waste forms, identifies potential disposal sites and their primary acceptance criteria, and addresses disposal issues for hazardous waste.

  19. Concept for Underground Disposal of Nuclear Waste

    NASA Technical Reports Server (NTRS)

    Bowyer, J. M.

    1987-01-01

    Packaged waste placed in empty oil-shale mines. Concept for disposal of nuclear waste economically synergistic with earlier proposal concerning backfilling of oil-shale mines. New disposal concept superior to earlier schemes for disposal in hard-rock and salt mines because less uncertainty about ability of oil-shale mine to contain waste safely for millenium.

  20. Nuclear waste management: storage and disposal aspects

    SciTech Connect

    Patterson, B.D.; Dave, S.A.; O'Connell, W.J.

    1980-01-01

    Long-term disposal of nuclear wastes must resolve difficulties arising chiefly from the potential for contamination of the environment and the risk of misuse. Alternatives available for storage and disposal of wastes are examined in this overview paper. Guidelines and criteria which may govern in the development of methods of disposal are discussed.

  1. Safe Disposal of Highly Reactive Chemicals.

    ERIC Educational Resources Information Center

    Lunn, George; Sansone, Eric B.

    1994-01-01

    Provides specific procedures for the disposal of a variety of highly reactive chemicals and reports the results of a study of their safe disposal. Disposal of some problematic sulfur-containing compounds are included. Procedures are based on a combination of literature review and author development. (LZ)

  2. Concept for Underground Disposal of Nuclear Waste

    NASA Technical Reports Server (NTRS)

    Bowyer, J. M.

    1987-01-01

    Packaged waste placed in empty oil-shale mines. Concept for disposal of nuclear waste economically synergistic with earlier proposal concerning backfilling of oil-shale mines. New disposal concept superior to earlier schemes for disposal in hard-rock and salt mines because less uncertainty about ability of oil-shale mine to contain waste safely for millenium.

  3. Safe Disposal of Highly Reactive Chemicals.

    ERIC Educational Resources Information Center

    Lunn, George; Sansone, Eric B.

    1994-01-01

    Provides specific procedures for the disposal of a variety of highly reactive chemicals and reports the results of a study of their safe disposal. Disposal of some problematic sulfur-containing compounds are included. Procedures are based on a combination of literature review and author development. (LZ)

  4. Your Glucose Meter

    MedlinePlus

    ... Audience For Women Women's Health Topics Your Glucose Meter Share Tweet Linkedin Pin it More sharing options ... Testing Your Blood Sugar and Caring for Your Meter Glucose meters test and record how much sugar ( ...

  5. Glucose test (image)

    MedlinePlus

    ... person with diabetes constantly manages their blood's sugar (glucose) levels. After a blood sample is taken and tested, it is determined whether the glucose levels are low or high. Following your health ...

  6. Glucose-6-phosphate dehydrogenase

    MedlinePlus

    ... this page: //medlineplus.gov/ency/article/003671.htm Glucose-6-phosphate dehydrogenase test To use the sharing features on this page, please enable JavaScript. Glucose-6-phosphate dehydrogenase (G6PD) is a protein that ...

  7. Exercise, GLUT4, and skeletal muscle glucose uptake.

    PubMed

    Richter, Erik A; Hargreaves, Mark

    2013-07-01

    Glucose is an important fuel for contracting muscle, and normal glucose metabolism is vital for health. Glucose enters the muscle cell via facilitated diffusion through the GLUT4 glucose transporter which translocates from intracellular storage depots to the plasma membrane and T-tubules upon muscle contraction. Here we discuss the current understanding of how exercise-induced muscle glucose uptake is regulated. We briefly discuss the role of glucose supply and metabolism and concentrate on GLUT4 translocation and the molecular signaling that sets this in motion during muscle contractions. Contraction-induced molecular signaling is complex and involves a variety of signaling molecules including AMPK, Ca(2+), and NOS in the proximal part of the signaling cascade as well as GTPases, Rab, and SNARE proteins and cytoskeletal components in the distal part. While acute regulation of muscle glucose uptake relies on GLUT4 translocation, glucose uptake also depends on muscle GLUT4 expression which is increased following exercise. AMPK and CaMKII are key signaling kinases that appear to regulate GLUT4 expression via the HDAC4/5-MEF2 axis and MEF2-GEF interactions resulting in nuclear export of HDAC4/5 in turn leading to histone hyperacetylation on the GLUT4 promoter and increased GLUT4 transcription. Exercise training is the most potent stimulus to increase skeletal muscle GLUT4 expression, an effect that may partly contribute to improved insulin action and glucose disposal and enhanced muscle glycogen storage following exercise training in health and disease.

  8. Noninvasive diagnostic devices for diabetes through measuring tear glucose.

    PubMed

    Zhang, Jin; Hodge, William; Hutnick, Cindy; Wang, Xianbin

    2011-01-01

    This article reviews the development of a noninvasive diagnostic for diabetes by detecting ocular glucose. Early diagnosis and daily management are very important to diabetes patients to ensure a healthy life. Commercial blood glucose sensors have been used since the 1970s. Millions of diabetes patients have to prick their finger for a drop of blood 4-5 times a day to check blood glucose levels--almost 1800 times annually. There is a strong need to have a noninvasive device to help patients to manage the disease easily and painlessly. Instead of detecting the glucose in blood, monitoring the glucose level in other body fluids may provide a feasible approach for noninvasive diagnosis and diabetes control. Tear glucose has been studied for several decades. This article reviews studies on ocular glucose and its monitoring methods. Attempts to continuously monitor the concentration of tear glucose by using contact lens-based sensors are discussed as well as our current development of a nanostructured lens-based sensor for diabetes. This disposable biosensor for the detection of tear glucose may provide an alternative method to help patients manage the disease conveniently.

  9. The problem of nitrogen disposal in the obese.

    PubMed

    Alemany, Marià

    2012-06-01

    Amino-N is preserved because of the scarcity and nutritional importance of protein. Excretion requires its conversion to ammonia, later incorporated into urea. Under conditions of excess dietary energy, the body cannot easily dispose of the excess amino-N against the evolutively adapted schemes that prevent its wastage; thus ammonia and glutamine formation (and urea excretion) are decreased. High lipid (and energy) availability limits the utilisation of glucose, and high glucose spares the production of ammonium from amino acids, limiting the synthesis of glutamine and its utilisation by the intestine and kidney. The amino acid composition of the diet affects the production of ammonium depending on its composition and the individual amino acid catabolic pathways. Surplus amino acids enhance protein synthesis and growth, and the synthesis of non-protein-N-containing compounds. But these outlets are not enough; consequently, less-conventional mechanisms are activated, such as increased synthesis of NO∙ followed by higher nitrite (and nitrate) excretion and changes in the microbiota. There is also a significant production of N(2) gas, through unknown mechanisms. Health consequences of amino-N surplus are difficult to fathom because of the sparse data available, but it can be speculated that the effects may be negative, largely because the fundamental N homeostasis is stretched out of normalcy, forcing the N removal through pathways unprepared for that task. The unreliable results of hyperproteic diets, and part of the dysregulation found in the metabolic syndrome may be an unwanted consequence of this N disposal conflict.

  10. Disposable remote zero headspace extractor

    DOEpatents

    Hand, Julie J.; Roberts, Mark P.

    2006-03-21

    The remote zero headspace extractor uses a sampling container inside a stainless steel vessel to perform toxicity characteristics leaching procedure to analyze volatile organic compounds. The system uses an in line filter for ease of replacement. This eliminates cleaning and disassembly of the extractor. All connections are made with quick connect fittings which can be easily replaced. After use, the bag can be removed and disposed of, and a new sampling container is inserted for the next extraction.

  11. The disposal of military aircraft

    NASA Technical Reports Server (NTRS)

    Warner, Edward P

    1922-01-01

    The end of the war saw every belligerent with vast stocks of aircraft and aircraft supplies in all stages of usefulness, much of the material being absolutely new. The question of the best method of getting rid of this accumulation is one which has been agitating those responsible for its disposal for more than three years now, but no wholly satisfactory solution has yet been reached.

  12. SPS salvage and disposal alternatives

    NASA Technical Reports Server (NTRS)

    1980-01-01

    A wide range of salvage options exist for the satellite power system (SPS) satellite, ranging from use in and beyond geosynchronous orbit to use in low Earth orbit to return and use on Earth. The satellite might be used intact to provide for various purposes, it might be cannibalized, or it might be melted down to supply materials for space- or ground-based products. The use of SPS beyond its nominal lifetime provides value that can be deducted from the SPS capital investment cost. It is shown that the present value of the salvage value of the SPS satellites, referenced to the system initial operation data, is likely to be on the order of five to ten percent of its on-orbit capital cost. (Given a 30 year satellite lifetime and a four percent discount rate, the theoretical maximum salvage value is 30.8 percent of the initial capital cost). The SPS demonstration satellite is available some 30 years earlier than the first full-scale SPS satellite and has a likely salvage value on the order of 80 percent of its on site capital cost. In the event that it becomes desirable to dispose of either the demonstration or full-scale SPS satellite, a number of disposal options appear to exist for which intact disposal costs are less than one percent of capital costs.

  13. Promotion of glucose utilization by insulin enhances granulosa cell proliferation and developmental competence of porcine oocyte grown in vitro.

    PubMed

    Itami, Nobuhiko; Munakata, Yasuhisa; Shirasuna, Koumei; Kuwayama, Takehito; Iwata, Hisataka

    2017-02-01

    In vitro culture of the oocyte granulosa cell complexes (OGCs) from early antral follicles (EAFs) shows granulosa cell (GC) proliferation, but to a lesser extent than that observed in vivo during follicle development. As the number of GCs closely relates to energy sufficiency of the oocytes, enhancement of GC proliferation influences oocyte development. GC proliferation depends on glycolysis and insulin-mediated AKT/mTOR signaling pathway; therefore, addition of culture medium containing insulin and glucose may potentially promote GC proliferation and hence improve oocyte development. In the present study, we assessed the effect of exogenous insulin and glucose concentration on GC proliferation and oocyte energy status as well as developmental abilities of porcine oocytes grown in vitro. In the presence of 5.5 mM of glucose (Low), a comparison of 10 versus 20 μg/ml insulin showed that high insulin enhanced GC proliferation but exhausted glucose from the medium, which resulted in low energy status including lipid and adenosine triphosphate of the oocyte. Whereas, in the presence of 20 μg/ml insulin, medium with 11 mM glucose (High) enhanced GC proliferation and oocyte energy status as well as developmental ability up to the blastocyst stage. Considering that there was no difference in OGCs development observed with medium (10 μg/ml insulin) containing 5.5 versus 11 mM glucose, we concluded that the combination of high insulin and glucose enhanced GC proliferation and energy status of oocytes as well as the developmental ability of the oocytes grown in vitro.

  14. All about Blood Glucose

    MedlinePlus

    Toolkit No. 15 All About Blood Glucose Keeping your blood glucose (sugar)in your target range can prevent or delay the health problems ... Diabetes Association, Inc. 1/15 Toolkit No.15: All About Blood Glucose continued team about when and ...

  15. Canagliflozin lowers postprandial glucose and insulin by delaying intestinal glucose absorption in addition to increasing urinary glucose excretion: results of a randomized, placebo-controlled study.

    PubMed

    Polidori, David; Sha, Sue; Mudaliar, Sunder; Ciaraldi, Theodore P; Ghosh, Atalanta; Vaccaro, Nicole; Farrell, Kristin; Rothenberg, Paul; Henry, Robert R

    2013-08-01

    Canagliflozin, a sodium glucose cotransporter (SGLT) 2 inhibitor, is also a low-potency SGLT1 inhibitor. This study tested the hypothesis that intestinal canagliflozin levels postdose are sufficiently high to transiently inhibit intestinal SGLT1, thereby delaying intestinal glucose absorption. This two-period, crossover study evaluated effects of canagliflozin on intestinal glucose absorption in 20 healthy subjects using a dual-tracer method. Placebo or canagliflozin 300 mg was given 20 min before a 600-kcal mixed-meal tolerance test. Plasma glucose, (3)H-glucose, (14)C-glucose, and insulin were measured frequently for 6 h to calculate rates of appearance of oral glucose (RaO) in plasma, endogenous glucose production, and glucose disposal. Compared with placebo, canagliflozin treatment reduced postprandial plasma glucose and insulin excursions (incremental 0- to 2-h area under the curve [AUC0-2h] reductions of 35% and 43%, respectively; P < 0.001 for both), increased 0- to 6-h urinary glucose excretion (UGE0-6h, 18.2 ± 5.6 vs. <0.2 g; P < 0.001), and delayed RaO. Canagliflozin reduced AUC RaO by 31% over 0 to 1 h (geometric means, 264 vs. 381 mg/kg; P < 0.001) and by 20% over 0 to 2 h (576 vs. 723 mg/kg; P = 0.002). Over 2 to 6 h, canagliflozin increased RaO such that total AUC RaO over 0 to 6 h was <6% lower versus placebo (960 vs. 1,018 mg/kg; P = 0.003). A modest (∼10%) reduction in acetaminophen absorption was observed over the first 2 h, but this difference was not sufficient to explain the reduction in RaO. Total glucose disposal over 0 to 6 h was similar across groups. Canagliflozin reduces postprandial plasma glucose and insulin by increasing UGE (via renal SGLT2 inhibition) and delaying RaO, likely due to intestinal SGLT1 inhibition.

  16. Ambulatory glucose profile: Flash glucose monitoring.

    PubMed

    Kalra, Sanjay; Gupta, Yashdeep

    2015-12-01

    Ambulatory glucose profile (AGP) is a novel way of assessing glycaemic levels on a 24 hour basis, through a minimally invasive method, known as flash glucose monitoring. This review describes the unique features of AGP, differentiates it from existing methods of glucose monitoring, and explains how it helps pursue the glycaemic pentad. The review suggests pragmatic usage of this technology, including pre-test, intra-test, and post-test counselling, and lists specific clinical scenarios where the investigation seems to be of immense benefit.

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

    PubMed

    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.

  18. Thalweg disposal: demonstration of an alternative

    SciTech Connect

    Baker, R.M.; McCown, D.L.; Paddock, R.A.; Ditmars, J.D.

    1984-08-01

    Disposal of dredged material in the main channel, or thalweg, is an alternative disposal option for maintenance dredging. The material dredged from the Upper Mississippi River is clean sand and water quality is not a primary concern with regard to thalweg disposal. Modifications of channel morphology and, more importantly, of riverine habitats due to thalweg disposal are the major environmental issues raised. The Rock Island District, Corps of Engineers, is addressing these issues by means of thalweg disposal experiments at three sites on the Upper Mississippi River. In these experiments, dredged sand has been tagged with dyed sand prior to disposal in the thalweg. Monitoring of dyed sand in the bottom sediments in and downstream of the disposal areas at two sites (for periods of 1 and 2 years) has indicated that the dredged sand remains in the thalweg without apparent modification of channel border habitats. 7 references, 5 figures.

  19. Utilization of dietary glucose in the metabolic syndrome

    PubMed Central

    2011-01-01

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

  20. FGF19 action in the brain induces insulin-independent glucose lowering.

    PubMed

    Morton, Gregory J; Matsen, Miles E; Bracy, Deanna P; Meek, Thomas H; Nguyen, Hong T; Stefanovski, Darko; Bergman, Richard N; Wasserman, David H; Schwartz, Michael W

    2013-11-01

    Insulin-independent glucose disposal (referred to as glucose effectiveness [GE]) is crucial for glucose homeostasis and, until recently, was thought to be invariable. However, GE is reduced in type 2 diabetes and markedly decreased in leptin-deficient ob/ob mice. Strategies aimed at increasing GE should therefore be capable of improving glucose tolerance in these animals. The gut-derived hormone FGF19 has previously been shown to exert potent antidiabetic effects in ob/ob mice. In ob/ob mice, we found that systemic FGF19 administration improved glucose tolerance through its action in the brain and that a single, low-dose i.c.v. injection of FGF19 dramatically improved glucose intolerance within 2 hours. Minimal model analysis of glucose and insulin data obtained during a frequently sampled i.v. glucose tolerance test showed that the antidiabetic effect of i.c.v. FGF19 was solely due to increased GE and not to changes of either insulin secretion or insulin sensitivity. The mechanism underlying this effect appears to involve increased metabolism of glucose to lactate. Together, these findings implicate the brain in the antidiabetic action of systemic FGF19 and establish the brain’s capacity to rapidly, potently, and selectively increase insulin-independent glucose disposal.

  1. DOE SPENT NUCLEAR FUEL DISPOSAL CONTAINER

    SciTech Connect

    F. Habashi

    1998-06-26

    The DOE Spent Nuclear Fuel Disposal Container (SNF DC) supports the confinement and isolation of waste within the Engineered Barrier System of the Mined Geologic Disposal System (MGDS). Disposal containers are loaded and sealed in the surface waste handling facilities, transferred to the underground through the access mains, and emplaced in emplacement drifts. The DOE Spent Nuclear Fuel Disposal Container provides long term confinement of DOE SNF waste, and withstands the loading, transfer, emplacement, and retrieval loads and environments. The DOE SNF Disposal Containers provide containment of waste for a designated period of time, and limit radionuclide release thereafter. The disposal containers maintain the waste in a designated configuration, withstand maximum handling and rockfall loads, limit the individual waste canister temperatures after emplacement. The disposal containers also limit the introduction of moderator into the disposal container during the criticality control period, resist corrosion in the expected repository environment, and provide complete or limited containment of waste in the event of an accident. Multiple disposal container designs may be needed to accommodate the expected range of DOE Spent Nuclear Fuel. The disposal container will include outer and inner barrier walls and outer and inner barrier lids. Exterior labels will identify the disposal container and contents. Differing metal barriers will support the design philosophy of defense in depth. The use of materials with different failure mechanisms prevents a single mode failure from breaching the waste package. The corrosion-resistant inner barrier and inner barrier lid will be constructed of a high-nickel alloy and the corrosion-allowance outer barrier and outer barrier lid will be made of carbon steel. The DOE Spent Nuclear Fuel Disposal Containers interface with the emplacement drift environment by transferring heat from the waste to the external environment and by protecting

  2. Calorie restriction leads to greater Akt2 activity and glucose uptake by insulin-stimulated skeletal muscle from old rats

    PubMed Central

    Wang, Haiyan; Arias, Edward B.

    2016-01-01

    Skeletal muscle insulin resistance is associated with many common age-related diseases, but moderate calorie restriction (CR) can substantially elevate glucose uptake by insulin-stimulated skeletal muscle from both young and old rats. The current study evaluated the isolated epitrochlearis muscle from ∼24.5-mo-old rats that were either fed ad libitum (AL) or subjected to CR (consuming ∼65% of ad libitum, AL, intake beginning at ∼22.5 mo old). Some muscles were also incubated with MK-2206, a potent and selective Akt inhibitor. The most important results were that in isolated muscles, CR vs. AL resulted in 1) greater insulin-stimulated glucose uptake 2) that was accompanied by significantly increased insulin-mediated activation of Akt2, as indicated by greater phosphorylation on both Thr309 and Ser474 along with greater Akt2 activity, 3) concomitant with enhanced phosphorylation of several Akt substrates, including an Akt substrate of 160 kDa on Thr642 and Ser588, filamin C on Ser2213 and proline-rich Akt substrate of 40 kDa on Thr246, but not TBC1D1 on Thr596; and 4) each of the CR effects was eliminated by MK-2206. These data provide compelling new evidence linking greater Akt2 activation to the CR-induced elevation of insulin-stimulated glucose uptake by muscle from old animals. PMID:26739650

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

    NASA Astrophysics Data System (ADS)

    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.

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

    PubMed Central

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

    2016-01-01

    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. PMID:27312339

  5. 41 CFR 102-75.250 - What general policy must the disposal agency follow concerning the disposal of surplus property?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... the disposal agency follow concerning the disposal of surplus property? 102-75.250 Section 102-75.250...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.250 What general policy must the disposal agency follow concerning the disposal of surplus...

  6. 41 CFR 102-75.250 - What general policy must the disposal agency follow concerning the disposal of surplus property?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... the disposal agency follow concerning the disposal of surplus property? 102-75.250 Section 102-75.250...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.250 What general policy must the disposal agency follow concerning the disposal of surplus...

  7. 41 CFR 102-75.250 - What general policy must the disposal agency follow concerning the disposal of surplus property?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... the disposal agency follow concerning the disposal of surplus property? 102-75.250 Section 102-75.250...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.250 What general policy must the disposal agency follow concerning the disposal of surplus...

  8. 41 CFR 102-75.250 - What general policy must the disposal agency follow concerning the disposal of surplus property?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... the disposal agency follow concerning the disposal of surplus property? 102-75.250 Section 102-75.250...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.250 What general policy must the disposal agency follow concerning the disposal of surplus...

  9. 41 CFR 102-75.250 - What general policy must the disposal agency follow concerning the disposal of surplus property?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... the disposal agency follow concerning the disposal of surplus property? 102-75.250 Section 102-75.250...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.250 What general policy must the disposal agency follow concerning the disposal of surplus...

  10. Fracking, wastewater disposal, and earthquakes

    NASA Astrophysics Data System (ADS)

    McGarr, Arthur

    2016-03-01

    In the modern oil and gas industry, fracking of low-permeability reservoirs has resulted in a considerable increase in the production of oil and natural gas, but these fluid-injection activities also can induce earthquakes. Earthquakes induced by fracking are an inevitable consequence of the injection of fluid at high pressure, where the intent is to enhance permeability by creating a system of cracks and fissures that allow hydrocarbons to flow to the borehole. The micro-earthquakes induced during these highly-controlled procedures are generally much too small to be felt at the surface; indeed, the creation or reactivation of a large fault would be contrary to the goal of enhancing permeability evenly throughout the formation. Accordingly, the few case histories for which fracking has resulted in felt earthquakes have been due to unintended fault reactivation. Of greater consequence for inducing earthquakes, modern techniques for producing hydrocarbons, including fracking, have resulted in considerable quantities of coproduced wastewater, primarily formation brines. This wastewater is commonly disposed by injection into deep aquifers having high permeability and porosity. As reported in many case histories, pore pressure increases due to wastewater injection were channeled from the target aquifers into fault zones that were, in effect, lubricated, resulting in earthquake slip. These fault zones are often located in the brittle crystalline rocks in the basement. Magnitudes of earthquakes induced by wastewater disposal often exceed 4, the threshold for structural damage. Even though only a small fraction of disposal wells induce earthquakes large enough to be of concern to the public, there are so many of these wells that this source of seismicity contributes significantly to the seismic hazard in the United States, especially east of the Rocky Mountains where standards of building construction are generally not designed to resist shaking from large earthquakes.

  11. Generic Crystalline Disposal Reference Case

    SciTech Connect

    Painter, Scott Leroy; Chu, Shaoping; Harp, Dylan Robert; Perry, Frank Vinton; Wang, Yifeng

    2015-02-20

    A generic reference case for disposal of spent nuclear fuel and high-level radioactive waste in crystalline rock is outlined. The generic cases are intended to support development of disposal system modeling capability by establishing relevant baseline conditions and parameters. Establishment of a generic reference case requires that the emplacement concept, waste inventory, waste form, waste package, backfill/buffer properties, EBS failure scenarios, host rock properties, and biosphere be specified. The focus in this report is on those elements that are unique to crystalline disposal, especially the geosphere representation. Three emplacement concepts are suggested for further analyses: a waste packages containing 4 PWR assemblies emplaced in boreholes in the floors of tunnels (KBS-3 concept), a 12-assembly waste package emplaced in tunnels, and a 32-assembly dual purpose canister emplaced in tunnels. In addition, three failure scenarios were suggested for future use: a nominal scenario involving corrosion of the waste package in the tunnel emplacement concepts, a manufacturing defect scenario applicable to the KBS-3 concept, and a disruptive glaciation scenario applicable to both emplacement concepts. The computational approaches required to analyze EBS failure and transport processes in a crystalline rock repository are similar to those of argillite/shale, with the most significant difference being that the EBS in a crystalline rock repository will likely experience highly heterogeneous flow rates, which should be represented in the model. The computational approaches required to analyze radionuclide transport in the natural system are very different because of the highly channelized nature of fracture flow. Computational workflows tailored to crystalline rock based on discrete transport pathways extracted from discrete fracture network models are recommended.

  12. PPARδ regulates glucose metabolism and insulin sensitivity

    PubMed Central

    Lee, Chih-Hao; Olson, Peter; Hevener, Andrea; Mehl, Isaac; Chong, Ling-Wa; Olefsky, Jerrold M.; Gonzalez, Frank J.; Ham, Jungyeob; Kang, Heonjoong; Peters, Jeffrey M.; Evans, Ronald M.

    2006-01-01

    The metabolic syndrome is a collection of obesity-related disorders. The peroxisome proliferator-activated receptors (PPARs) regulate transcription in response to fatty acids and, as such, are potential therapeutic targets for these diseases. We show that PPARδ (NR1C2) knockout mice are metabolically less active and glucose-intolerant, whereas receptor activation in db/db mice improves insulin sensitivity. Euglycemic–hyperinsulinemic-clamp experiments further demonstrate that a PPARδ-specific agonist suppresses hepatic glucose output, increases glucose disposal, and inhibits free fatty acid release from adipocytes. Unexpectedly, gene array and functional analyses suggest that PPARδ ameliorates hyperglycemia by increasing glucose flux through the pentose phosphate pathway and enhancing fatty acid synthesis. Coupling increased hepatic carbohydrate catabolism with its ability to promote β-oxidation in muscle allows PPARδ to regulate metabolic homeostasis and enhance insulin action by complementary effects in distinct tissues. The combined hepatic and peripheral actions of PPARδ suggest new therapeutic approaches to treat type II diabetes. PMID:16492734

  13. SNS Proton Beam Window Disposal

    NASA Astrophysics Data System (ADS)

    Popova, Irina; Gallmeier, Franz X.; Trotter, Steven

    2017-09-01

    In order to support the disposal of the proton beam window assembly of the Spallation Neutron Source beamline to the target station, waste classification analyses are performed. The window has a limited life-time due to radiation-induced material damage. Analyses include calculation of the radionuclide inventory and shielding analyses for the transport package/container to ensure that the container is compliant with the transportation and waste management regulations. In order to automate this procedure and minimize manual work a script in Perl language was written.

  14. Titanium dioxide-cellulose hybrid nanocomposite based conductometric glucose biosensor

    NASA Astrophysics Data System (ADS)

    Maniruzzaman, Mohammad; Mahadeva, Suresha K.; Khondoker, Abu Hasan; Kim, Jaehwan

    2012-04-01

    This paper investigates the feasibility of conductometric glucose biosensor based on glucose oxidase (GOx) immobilized TiO2-cellulose hybrid nanocomposite. TiO2 nanoparticles were blended with cellulose solution prepared by dissolving cotton pulp with lithium chloride/N, N-dimethylacetamide solvent to fabricate TiO2-cellulose hybrid nanocomposite. The enzyme (GOx) was immobilized into this hybrid material by physical adsorption method. The successful immobilization of GOx into TiO2-cellulose hybrid nanocomposite via covalent bonding between TiO2 and GOx was confirmed by X-ray photoelectron analysis. The linear response of our propose glucose biosensor is obtained in the range of 1-10mM with correlation coefficient of 0.93. Our study demonstrates TiO2-cellulose hybrid material as a potential candidate for an inexpensive, flexible and disposable glucose biosensor.

  15. Glucose-dependent insulinotropic polypeptide confers early phase insulin release to oral glucose in rats: demonstration by a receptor antagonist.

    PubMed

    Lewis, J T; Dayanandan, B; Habener, J F; Kieffer, T J

    2000-10-01

    A novel GIP receptor antagonist was developed to evaluate the acute role of glucose-dependent insulinotropic polypeptide (GIP) in the insulin response to oral glucose in rats. Antisera to an extracellular epitope of the GIP receptor (GIPR) detected immunoreactive GIPR on rat pancreatic beta-cells. Purified GIPR antibody (GIPR Ab) specifically displaced GIP binding to the receptor and blocked GIP-mediated increases in intracellular cAMP. When delivered to rats by ip injection, GIPR Ab had a half-life of approximately 4 days. Treatment with GIPR Ab (1 microg/g BW) blocked the potentiation of glucose-stimulated insulin secretion by GIP (60 pmol) but not glucagon-like peptide-1 (GLP-1, 60 pmol) in anesthetized rats. The insulin response to oral glucose was delayed in conscious unrestrained rats that were pretreated with GIPR Ab. Plasma insulin levels were approximately 35% lower at 10 min in GIPR Ab treated animals compared with controls. As a result, the glucose excursion was greater in the GIPR Ab treated group. Fasting plasma glucose levels were not altered by GIPR Ab. We conclude that release of GIP following oral glucose may act as an anticipatory signal to pancreatic beta-cells to promote rapid release of insulin for glucose disposal.

  16. Estimating postprandial glucose fluxes using hierarchical Bayes modelling.

    PubMed

    Haidar, Ahmad; Potocka, Elizabeth; Boulet, Benoit; Umpleby, A Margot; Hovorka, Roman

    2012-10-01

    A new stochastic computational method was developed to estimate the endogenous glucose production, the meal-related glucose appearance rate (R(a meal)), and the glucose disposal (R(d)) during the meal tolerance test. A prior probability distribution was adopted which assumes smooth glucose fluxes with individualized smoothness level within the context of a Bayes hierarchical model. The new method was contrasted with the maximum likelihood method using data collected in 18 subjects with type 2 diabetes who ingested a mixed meal containing [U-¹³C]glucose. Primed [6,6-²H₂]glucose was infused in a manner that mimicked the expected endogenous glucose production. The mean endogenous glucose production, R(a meal), and R(d) calculated by the new method and maximum likelihood method were nearly identical. However, the maximum likelihood gave constant, nonphysiological postprandial endogenous glucose production in two subjects whilst the new method gave plausible estimates of endogenous glucose production in all subjects. Additionally, the two methods were compared using a simulated triple-tracer experiment in 12 virtual subjects. The accuracy of the estimates of the endogenous glucose production and R(a meal) profiles was similar [root mean square error (RMSE) 1.0±0.3 vs. 1.4±0.7 μmol/kg/min for EGP and 2.6±1.0 vs. 2.9±0.9 μmol/kg/min for R(a meal); new method vs. maximum likelihood method; P=NS, paired t-test]. The accuracy of R(d) estimates was significantly increased by the new method (RMSE 5.3±1.9 vs. 4.2±1.3; new method vs. ML method; P<0.01, paired t-test). We conclude that the new method increases plausibility of the endogenous glucose production and improves accuracy of glucose disposal compared to the maximum likelihood method. Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.

  17. Disposable optics for microscopy diagnostics

    PubMed Central

    Vilmi, Pauliina; Varjo, Sami; Sliz, Rafal; Hannuksela, Jari; Fabritius, Tapio

    2015-01-01

    The point-of-care testing (POCT) is having increasing role on modern health care systems due to a possibility to perform tests for patients conveniently and immediately. POCT includes lot of disposable devices because of the environment they are often used. For a disposable system to be reasonably utilized, it needs to be high in quality but low in price. Optics based POCT systems are interesting approach to be developed, and here we describe a low-cost fabrication process for microlens arrays for microscopy. Lens arrays having average lens diameter of 222 μm with 300 μm lens pitch were fabricated. The lenses were characterized to have standard deviation of 0.06 μm in height and 4.61 μm in diameter. The resolution limit of 3.9μm is demonstrated with real images, and the images were compared with ones made with glass and polycarbonate lens arrays. The image quality is at the same level than with the glass lenses and the manufacturing costs are very low, thus making them suitable for POCT applications. PMID:26586153

  18. Participatory management of waste disposal.

    PubMed

    Noosorn, Narongsak

    2005-05-01

    The general objective of this study was to develop a sustainable waste disposal management model in Yom riverside communities by creating a sense of ownership in the project among the villagers and encourage the community to identify problems based on their socio-cultural background. The participatory approach was applied in developing a continual learning process between the researcher and stakeholders. The Tub Phueng community of Si Samrong, Sukhothai Province was selected as the location for this study. From the population of 240 households in the area, 40 stakeholders were selected to be on the research team. The team found that the waste in this community was comprised of 4 categories: 1. Occupation: discarded insecticide containers used for farming activities; 2. Consumption: plastic bags and wrappers form pre-packed foods; 3. Traditional activities: after holding ceremonies and festivities, the waste was dumped in the river; and 4. Environmental hygiene: waste water from washing, bathing, toileting, cooking and cleaning was directly drained into the Yom River. The sustainable waste disposal model developed to manage these problems included building simple waste-water treatment wells, digging garbage holes, prosecuting people who throw garbage into the river, withdrawing privileges from people who throw garbage into the river, and establishing a garbage center. Most of the villagers were satisfied with the proposed model, looked forward to the expected positive changes, and thought this kind of solution would be easy to put into practice.

  19. Disposable optics for microscopy diagnostics.

    PubMed

    Vilmi, Pauliina; Varjo, Sami; Sliz, Rafal; Hannuksela, Jari; Fabritius, Tapio

    2015-11-20

    The point-of-care testing (POCT) is having increasing role on modern health care systems due to a possibility to perform tests for patients conveniently and immediately. POCT includes lot of disposable devices because of the environment they are often used. For a disposable system to be reasonably utilized, it needs to be high in quality but low in price. Optics based POCT systems are interesting approach to be developed, and here we describe a low-cost fabrication process for microlens arrays for microscopy. Lens arrays having average lens diameter of 222 μm with 300 μm lens pitch were fabricated. The lenses were characterized to have standard deviation of 0.06 μm in height and 4.61 μm in diameter. The resolution limit of 3.9μm is demonstrated with real images, and the images were compared with ones made with glass and polycarbonate lens arrays. The image quality is at the same level than with the glass lenses and the manufacturing costs are very low, thus making them suitable for POCT applications.

  20. Aerosol can waste disposal device

    DOEpatents

    O'Brien, M.D.; Klapperick, R.L.; Bell, C.

    1993-12-21

    Disclosed is a device for removing gases and liquid from containers. The device punctures the bottom of a container for purposes of exhausting gases and liquid from the container without their escaping into the atmosphere. The device includes an inner cup or cylinder having a top portion with an open end for receiving a container and a bottom portion which may be fastened to a disposal or waste container in a substantially leak-proof manner. A piercing device is mounted in the lower portion of the inner cylinder for puncturing the can bottom placed in the inner cylinder. An outer cylinder having an open end and a closed end fits over the top portion of the inner cylinder in telescoping engagement. A force exerted on the closed end of the outer cylinder urges the bottom of a can in the inner cylinder into engagement with the piercing device in the bottom of the inner cylinder to form an opening in the can bottom, thereby permitting the contents of the can to enter the disposal container. 7 figures.

  1. Aerosol can waste disposal device

    DOEpatents

    O'Brien, Michael D.; Klapperick, Robert L.; Bell, Chris

    1993-01-01

    Disclosed is a device for removing gases and liquid from containers. The ice punctures the bottom of a container for purposes of exhausting gases and liquid from the container without their escaping into the atmosphere. The device includes an inner cup or cylinder having a top portion with an open end for receiving a container and a bottom portion which may be fastened to a disposal or waste container in a substantially leak-proof manner. A piercing device is mounted in the lower portion of the inner cylinder for puncturing the can bottom placed in the inner cylinder. An outer cylinder having an open end and a closed end fits over the top portion of the inner cylinder in telescoping engagement. A force exerted on the closed end of the outer cylinder urges the bottom of a can in the inner cylinder into engagement with the piercing device in the bottom of the inner cylinder to form an opening in the can bottom, thereby permitting the contents of the can to enter the disposal container.

  2. Real Estate: Disposal of Real Estate

    DTIC Science & Technology

    1985-05-10

    50,000 or involving more than 500 acres of withdrawn public lands . (3) Holds on real property disposal and withdrawals from excess of property...certificate as shown at figure 6–1. 6–7. Timber Unless otherwise agreed, the BLM disposes of timber on withdrawn public lands . Other standing timber...under COE procedures. The authorized officer of the BLM will dispose of such materials on withdrawn public lands under 30 USC 601. This includes

  3. Responsible Appliance Disposal Program: 2008 Annual Report

    EPA Pesticide Factsheets

    Presents 2008 summary and findings for Responsible Appliance Disposal partners participation in following best practices related to reduction of emissions, prevention of releases of hazardous materials, etc.

  4. Responsible Appliance Disposal Program: 2007 Annual Report

    EPA Pesticide Factsheets

    Presents 2007 summary and findings for Responsible Appliance Disposal partners participation in following best practices related to reduction of emissions, prevention of releases of hazardous materials, etc.

  5. Responsible Appliance Disposal Program: 2013 Annual Report

    EPA Pesticide Factsheets

    Presents 2013 summary and findings for Responsible Appliance Disposal partners participation in following best practices related to reduction of emissions, prevention of releases of hazardous materials, etc.

  6. Responsible Appliance Disposal Program: 2014 Annual Report

    EPA Pesticide Factsheets

    Presents 2014 summary and findings for Responsible Appliance Disposal partners participation in following best practices related to reduction of emissions, prevention of releases of hazardous materials, etc.

  7. Radioactive waste disposal in the marine environment

    NASA Astrophysics Data System (ADS)

    Anderson, D. R.

    In order to find the optimal solution to waste disposal problems, it is necessary to make comparisons between disposal media. It has become obvious to many within the scientific community that the single medium approach leads to over protection of one medium at the expense of the others. Cross media comparisons are being conducted in the Department of Energy ocean disposal programs for several radioactive wastes. Investigations in three areas address model development, comparisons of laboratory tests with field results and predictions, and research needs in marine disposal of radioactive waste. Tabulated data are included on composition of liquid high level waste and concentration of some natural radionuclides in the sea.

  8. Responsible Appliance Disposal Program: 2010 Annual Report

    EPA Pesticide Factsheets

    Presents 2010 summary and findings for Responsible Appliance Disposal partners participation in following best practices related to reduction of emissions, prevention of releases of hazardous materials, etc.

  9. Effects from past solid waste disposal practices.

    PubMed Central

    Johnson, L J; Daniel, D E; Abeele, W V; Ledbetter, J O; Hansen, W R

    1978-01-01

    This paper reviews documented environmental effects experience from the disposal of solid waste materials in the U.S. Selected case histories are discussed that illustrate waste migration and its actual or potential effects on human or environmental health. Principal conclusions resulting from this review were: solid waste materials do migrate beyond the geometric confines of the initial placement location; environmental effects have been experienced from disposal of municipal, agricultural, and toxic chemical wastes; and utilization of presently known science and engineering principles in sitting and operating solid waste disposal facilities would make a significant improvement in the containment capability of shallow land disposal facilities. PMID:367769

  10. Responsible Appliance Disposal Program: 2012 Annual Report

    EPA Pesticide Factsheets

    Presents 2011 summary and findings for Responsible Appliance Disposal partners participation in following best practices related to reduction of emissions, prevention of releases of hazardous materials, etc.

  11. 10 CFR 61.52 - Land disposal facility operation and disposal site closure.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ...) The boundaries and locations of each disposal unit (e.g., trenches) must be accurately located and... forth in the approved site closure plan must be carried out as each disposal unit (e.g., each trench)...

  12. 10 CFR 61.52 - Land disposal facility operation and disposal site closure.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ...) The boundaries and locations of each disposal unit (e.g., trenches) must be accurately located and... forth in the approved site closure plan must be carried out as each disposal unit (e.g., each trench)...

  13. 10 CFR 61.52 - Land disposal facility operation and disposal site closure.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ...) The boundaries and locations of each disposal unit (e.g., trenches) must be accurately located and... forth in the approved site closure plan must be carried out as each disposal unit (e.g., each trench)...

  14. 10 CFR 61.52 - Land disposal facility operation and disposal site closure.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ...) The boundaries and locations of each disposal unit (e.g., trenches) must be accurately located and... forth in the approved site closure plan must be carried out as each disposal unit (e.g., each trench)...

  15. 10 CFR 61.52 - Land disposal facility operation and disposal site closure.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ...) The boundaries and locations of each disposal unit (e.g., trenches) must be accurately located and... forth in the approved site closure plan must be carried out as each disposal unit (e.g., each trench)...

  16. GLUT2, glucose sensing and glucose homeostasis.

    PubMed

    Thorens, Bernard

    2015-02-01

    The glucose transporter isoform GLUT2 is expressed in liver, intestine, kidney and pancreatic islet beta cells, as well as in the central nervous system, in neurons, astrocytes and tanycytes. Physiological studies of genetically modified mice have revealed a role for GLUT2 in several regulatory mechanisms. In pancreatic beta cells, GLUT2 is required for glucose-stimulated insulin secretion. In hepatocytes, suppression of GLUT2 expression revealed the existence of an unsuspected glucose output pathway that may depend on a membrane traffic-dependent mechanism. GLUT2 expression is nevertheless required for the physiological control of glucose-sensitive genes, and its inactivation in the liver leads to impaired glucose-stimulated insulin secretion, revealing a liver-beta cell axis, which is likely to be dependent on bile acids controlling beta cell secretion capacity. In the nervous system, GLUT2-dependent glucose sensing controls feeding, thermoregulation and pancreatic islet cell mass and function, as well as sympathetic and parasympathetic activities. Electrophysiological and optogenetic techniques established that Glut2 (also known as Slc2a2)-expressing neurons of the nucleus tractus solitarius can be activated by hypoglycaemia to stimulate glucagon secretion. In humans, inactivating mutations in GLUT2 cause Fanconi-Bickel syndrome, which is characterised by hepatomegaly and kidney disease; defects in insulin secretion are rare in adult patients, but GLUT2 mutations cause transient neonatal diabetes. Genome-wide association studies have reported that GLUT2 variants increase the risks of fasting hyperglycaemia, transition to type 2 diabetes, hypercholesterolaemia and cardiovascular diseases. Individuals with a missense mutation in GLUT2 show preference for sugar-containing foods. We will discuss how studies in mice help interpret the role of GLUT2 in human physiology.

  17. The glucose oxidase-peroxidase assay for glucose

    USDA-ARS?s Scientific Manuscript database

    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...

  18. Alcatraz Disposal Site Investigation. Report 3. San Francisco Bay- Alcatraz Disposal Site Erodibility

    DTIC Science & Technology

    1987-05-01

    MISCELLANEOUS PAPER HL-86-1 ALCATRAZ DISPOSAL SITE INVESTIGATION in Report 3 91X FILE COP’Y SAN FRANCISCO BAY- ALCATRAZ DISPOSAL SITE ERODIBILITY (V...Street ELEMENT NO NO NO ACCESSION NO San Francisco, CA 94105-1905 ________________ 11 TITLE (include Security Classification) Alcatraz Disposal Site...Investigation; Report 3, San Francisco Day- Alcatraz Disposal Site Teeter, Allen M. 13a TYPE OF REPORT 113b TIME COVERED 114 DATE OF REPORT (Year, A4oiith

  19. Lipopolysaccharides-mediated increase in glucose-stimulated insulin secretion: involvement of the GLP-1 pathway.

    PubMed

    Nguyen, Anh Thoai; Mandard, Stéphane; Dray, Cédric; Deckert, Valérie; Valet, Philippe; Besnard, Philippe; Drucker, Daniel J; Lagrost, Laurent; Grober, Jacques

    2014-02-01

    Lipopolysaccharides (LPS) of the cell wall of gram-negative bacteria trigger inflammation, which is associated with marked changes in glucose metabolism. Hyperglycemia is frequently observed during bacterial infection and it is a marker of a poor clinical outcome in critically ill patients. The aim of the current study was to investigate the effect of an acute injection or continuous infusion of LPS on experimentally induced hyperglycemia in wild-type and genetically engineered mice. The acute injection of a single dose of LPS produced an increase in glucose disposal and glucose-stimulated insulin secretion (GSIS). Continuous infusion of LPS through mini-osmotic pumps was also associated with increased GSIS. Finally, manipulation of LPS detoxification by knocking out the plasma phospholipid transfer protein (PLTP) led to increased glucose disposal and GSIS. Overall, glucose tolerance and GSIS tests supported the hypothesis that mice treated with LPS develop glucose-induced hyperinsulinemia. The effects of LPS on glucose metabolism were significantly altered as a result of either the accumulation or antagonism of glucagon-like peptide 1 (GLP-1). Complementary studies in wild-type and GLP-1 receptor knockout mice further implicated the GLP-1 receptor-dependent pathway in mediating the LPS-mediated changes in glucose metabolism. Hence, enhanced GLP-1 secretion and action underlies the development of glucose-mediated hyperinsulinemia associated with endotoxemia.

  20. Glucose Sensing by Skeletal Myocytes Couples Nutrient Signaling to Systemic Homeostasis.

    PubMed

    Meng, Zhuo-Xian; Gong, Jianke; Chen, Zhimin; Sun, Jingxia; Xiao, Yuanyuan; Wang, Lin; Li, Yaqiang; Liu, Jianfeng; Xu, X Z Shawn; Lin, Jiandie D

    2017-05-04

    Skeletal muscle is a major site of postprandial glucose disposal. Inadequate insulin action in skeletal myocytes contributes to hyperglycemia in diabetes. Although glucose is known to stimulate insulin secretion by β cells, whether it directly engages nutrient signaling pathways in skeletal muscle to maintain systemic glucose homeostasis remains largely unexplored. Here we identified the Baf60c-Deptor-AKT pathway as a target of muscle glucose sensing that augments insulin action in skeletal myocytes. Genetic activation of this pathway improved postprandial glucose disposal in mice, whereas its muscle-specific ablation impaired insulin action and led to postprandial glucose intolerance. Mechanistically, glucose triggers KATP channel-dependent calcium signaling, which promotes HDAC5 phosphorylation and nuclear exclusion, leading to Baf60c induction and insulin-independent AKT activation. This pathway is engaged by the anti-diabetic sulfonylurea drugs to exert their full glucose-lowering effects. These findings uncover an unexpected mechanism of glucose sensing in skeletal myocytes that contributes to homeostasis and therapeutic action. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. 10 CFR 61.51 - Disposal site design for land disposal.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... extent practicable water infiltration, to direct percolating or surface water away from the disposed... must direct surface water drainage away from disposal units at velocities and gradients which will not result in erosion that will require ongoing active maintenance in the future. (6) The disposal site...

  2. DOSE ASSESSMENTS FROM THE DISPOSAL OF LOW-ACTIVITY WASTES IN RCRA-C DISPOSAL CELLS

    EPA Science Inventory

    Modeling the long-term performance of the RCRA-C disposal cell and potential doses to off-site receptors is used to derive maximum radionuclide specific concentrations in the wastes that would enable these wastes to be disposed of safely using the RCRA-C disposal cell technology....

  3. DOSE ASSESSMENTS FROM THE DISPOSAL OF LOW-ACTIVITY WASTES IN RCRA-C DISPOSAL CELLS

    EPA Science Inventory

    Modeling the long-term performance of the RCRA-C disposal cell and potential doses to off-site receptors is used to derive maximum radionuclide specific concentrations in the wastes that would enable these wastes to be disposed of safely using the RCRA-C disposal cell technology....

  4. NEP processing, operations, and disposal

    NASA Technical Reports Server (NTRS)

    Stancati, Mike

    1993-01-01

    Several recent studies by ASAO/NPO staff members at LeRC and by other organizations have highlighted the potential benefits of using Nuclear Electric Propulsion (NEP) as the primary transportation means for some of the proposed missions of the Space Exploration Initiative. These include the potential to reduce initial mass in orbit and Mars transit time. Modular NEP configurations also introduce fully redundant main propulsion to Mars flight systems adding several abort or fall back options not otherwise available. Recent studies have also identified mission operations, such as on orbital assembly, refurbishment, and reactor disposal, as important discriminators for propulsion system evaluation. This study is intended to identify and assess 'end-to-end' operational issues associated with using NEP for transporting crews and cargo between Earth and Mars. We also include some consideration of lunar cargo transfer as well.

  5. Magnesite disposal of carbon dioxide

    SciTech Connect

    Lackner, K.S.; Butt, D.P.; Wendt, C.H.

    1997-08-01

    In this paper we report our progress on developing a method for carbon dioxide disposal whose purpose it is to maintain coal energy competitive even is environmental and political pressures will require a drastic reduction in carbon dioxide emissions. In contrast to most other methods, our approach is not aiming at a partial solution of the problem, or at buying time for phasing out fossil energy. Instead, its purpose is to obtain a complete and economic solution of the problem, and thus maintain access to the vast fossil energy reservoir. A successful development of this technology would guarantee energy availability for many centuries even if world economic growth the most optimistic estimates that have been put forward. Our approach differs from all others in that we are developing an industrial process which chemically binds the carbon dioxide in an exothermic reaction into a mineral carbonate that is thermodynamically stable and environmentally benign.

  6. Deep Borehole Disposal Safety Analysis.

    SciTech Connect

    Freeze, Geoffrey A.; Stein, Emily; Price, Laura L.; MacKinnon, Robert J.; Tillman, Jack Bruce

    2016-10-01

    This report presents a preliminary safety analysis for the deep borehole disposal (DBD) concept, using a safety case framework. A safety case is an integrated collection of qualitative and quantitative arguments, evidence, and analyses that substantiate the safety, and the level of confidence in the safety, of a geologic repository. This safety case framework for DBD follows the outline of the elements of a safety case, and identifies the types of information that will be required to satisfy these elements. At this very preliminary phase of development, the DBD safety case focuses on the generic feasibility of the DBD concept. It is based on potential system designs, waste forms, engineering, and geologic conditions; however, no specific site or regulatory framework exists. It will progress to a site-specific safety case as the DBD concept advances into a site-specific phase, progressing through consent-based site selection and site investigation and characterization.

  7. Nuclear waste disposal educational forum

    SciTech Connect

    Not Available

    1982-10-18

    In keeping with a mandate from the US Congress to provide opportunities for consumer education and information and to seek consumer input on national issues, the Department of Energy's Office of Consumer Affairs held a three-hour educational forum on the proposed nuclear waste disposal legislation. Nearly one hundred representatives of consumer, public interest, civic and environmental organizations were invited to attend. Consumer affairs professionals of utility companies across the country were also invited to attend the forum. The following six papers were presented: historical perspectives; status of legislation (Senate); status of legislation (House of Representatives); impact on the legislation on electric utilities; impact of the legislation on consumers; implementing the legislation. All six papers have been abstracted and indexed for the Energy Data Base.

  8. A disposable blood cyanide sensor.

    PubMed

    Tian, Yong; Dasgupta, Purnendu K; Mahon, Sari B; Ma, Jian; Brenner, Matthew; Wang, Jian-Hua; Boss, Gerry R

    2013-03-20

    Deaths due to smoke inhalation in fires are often due to poisoning by HCN. Rapid administration of antidotes can result in complete resuscitation of the patient but judicious dosing requires the knowledge of the level of cyanide exposure. Rapid sensitive means for blood cyanide quantitation are needed. Hydroxocyanocobinamide (OH(CN)Cbi) reacts with cyanide rapidly; this is accompanied by a large spectral change. The disposable device consists of a pair of nested petri dish bottoms and a single top that fits the outer bottom dish. The top cover has a diametrically strung porous polypropylene membrane tube filled with aqueous OH(CN)Cbi. One end of the tube terminates in an amber (583nm) light emitting diode; the other end in a photodiode via an acrylic optical fiber. An aliquot of the blood sample is put in the inner dish, the assembly covered and acid is added through a port in the cover. Evolved HCN diffuses into the OH(CN)Cbi solution and the absorbance in the long path porous membrane tube cell is measured within 160 s. The LOD was 0.047, 1.0, 0.15, 5.0 and 2.2 μM, respectively, for water (1 mL), bovine blood (100 μL, 1 mL), and rabbit blood (20 μL, 50 μL). RSDs were<10% in all cases and the linear range extended from 0.5 to 200 μM. The method was validated against a microdiffusion approach and applied to the measurement of cyanide in rabbit and human blood. The disposable device permits field measurement of blood cyanide in <4 min. Copyright © 2013 Elsevier B.V. All rights reserved.

  9. A Disposable Blood Cyanide Sensor

    PubMed Central

    Tian, Yong; Dasgupta, Purnendu K.; Mahon, Sari B.; Ma, Jian; Brenner, Matthew; Wang, Jian-Hua; Boss, Gerry R.

    2013-01-01

    Deaths due to smoke inhalation in fires are often due to poisoning by HCN. Rapid administration of antidotes can result in complete resuscitation of the patient but judicious dosing requires the knowledge of the level of cyanide exposure. Rapid sensitive means for blood cyanide quantitation are needed. Hydroxocyanocobinamide (OH(CN)Cbi) reacts with cyanide rapidly; this is accompanied by a large spectral change. The disposable device consists of a pair of nested petri dish bottoms and a single top that fits the outer bottom dish. The top cover has a diametrically strung porous polypropylene membrane tube filled with aqueous OH(CN)Cbi. One end of the tube terminates in an amber (583 nm) light emitting diode; the other end in a photodiode via an acrylic optical fiber. An aliquot of the blood sample is put in the inner dish, the assembly covered and acid is added through a port in the cover. Evolved HCN diffuses into the OH(CN)Cbi solution and the absorbance in the long path porous membrane tube cell is measured within 160s. The LOD was 0.047, 1.0, 0.15, 5.0 and 2.2 μM, respectively, for water (1 mL), bovine blood (100 μL, 1 mL), and rabbit blood (20μL, 50 μL). RSDs were < 10% in all cases and the linear range extended from 0.5 to 200 μM. The method was validated against a microdiffusion approach and applied to the measurement of cyanide in rabbit and human blood. The disposable device permits field measurement of blood cyanide in < 4 min. PMID:23473259

  10. Effectiveness of GNSS disposal strategies

    NASA Astrophysics Data System (ADS)

    Alessi, E. M.; Rossi, A.; Valsecchi, G. B.; Anselmo, L.; Pardini, C.; Colombo, C.; Lewis, H. G.; Daquin, J.; Deleflie, F.; Vasile, M.; Zuiani, F.; Merz, K.

    2014-06-01

    The management of the Global Navigation Satellite Systems (GNSS) and of the Medium Earth Orbit (MEO) region as a whole is a subject that cannot be deferred, due to the growing exploitation and launch rate in that orbital regime. The advent of the European Galileo and the Chinese Beidou constellations significantly added complexity to the system and calls for an adequate global view on the four constellations present in operation. The operation procedures, including maintenance and disposal practices, of the constellations currently deployed were analyzed in order to asses a proper reference simulation scenario. The complex dynamics of the MEO region with all the geopotential and lunisolar resonances was studied to better identify the proper end-of-life orbit for every proposed strategy, taking into account and, whenever possible, exploiting the orbital dynamics in this peculiar region of space. The possibility to exploit low thrust propulsion or non gravitational perturbations with passive de-orbiting devices (and a combination of the two) was analyzed, in view of possible applications in the design of the future generations of the constellations satellites. Several upgrades in the long-term evolution software SDM and DAMAGE were undertaken to properly handle the constellation simulations in every aspect from constellation maintenance to orbital dynamics. A thorough approach considering the full time evolving covariance matrix associated with every object was implemented in SDM to compute the collision risk and associated maneuver rate for the constellation satellites. Once the software upgrades will be completed, the effectiveness of the different disposal strategies will be analyzed in terms of residual collision risk and avoidance maneuvers rate. This work was performed under the ESA/GSP Contract no. 4000107201/12/F/MOS.

  11. Glucose: detection and analysis

    USDA-ARS?s Scientific Manuscript database

    Glucose is an aldosic monosaccharide that is centrally entrenched in the processes of photosynthesis and respiration, serving as an energy reserve and metabolic fuel in most organisms. As both a monomer and as part of more complex structures such as polysaccharides and glucosides, glucose also pla...

  12. Capillary blood glucose monitoring.

    PubMed

    Wallymahmed, M

    This article, the first in a series of articles relating to clinical skills in nursing, outlines the procedure of capillary blood glucose monitoring. This is a convenient way of monitoring blood glucose patterns and can be a useful aid in guiding treatment changes in patients with type 1 and type 2 diabetes, especially during periods of illness or frequent hypoglycaemia.

  13. Failure of Hyperglycemia and Hyperinsulinemia to Compensate for Impaired Metabolic Response to an Oral Glucose Load

    PubMed Central

    Hussain, M; Janghorbani, M; Schuette, S; Considine, RV; Chisholm, RL; Mather, KJ

    2014-01-01

    Objective To evaluate whether the augmented insulin and glucose response to a glucose challenge is sufficient to compensate for defects in glucose utilization in obesity and type 2 diabetes, using a breath test measurement of integrated glucose metabolism. Methods Non-obese, obese normoglycemic and obese Type 2 diabetic subjects were studied on 2 consecutive days. A 75g oral glucose load spiked with 13C-glucose was administered, measuring exhaled breath 13CO2 as an integrated measure of glucose metabolism and oxidation. A hyperinsulinemic euglycemic clamp was performed, measuring whole body glucose disposal rate. Body composition was measured by DEXA. Multivariable analyses were performed to evaluate the determinants of the breath 13CO2. Results Breath 13CO2 was reduced in obese and type 2 diabetic subjects despite hyperglycemia and hyperinsulinemia. The primary determinants of breath response were lean mass, fat mass, fasting FFA concentrations, and OGTT glucose excursion. Multiple approaches to analysis showed that hyperglycemia and hyperinsulinemia were not sufficient to compensate for the defect in glucose metabolism in obesity and diabetes. Conclusions Augmented insulin and glucose responses during an OGTT are not sufficient to overcome the underlying defects in glucose metabolism in obesity and diabetes. PMID:25511878

  14. Sewage Disposal in Port Harcourt, Nigeria.

    ERIC Educational Resources Information Center

    Ayotamuno, M. J.

    1993-01-01

    This survey of the Port Harcourt, Nigeria, sewage disposal system exemplifies sewage disposal in the developing world. Results reveal that some well-constructed and maintained drains, as well as many open drains and septic tanks, expose women and children to the possibility of direct contact with parasitic organisms and threaten water resources.…

  15. 50 CFR 300.109 - Gear disposal.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 50 Wildlife and Fisheries 11 2014-10-01 2014-10-01 false Gear disposal. 300.109 Section 300.109... Antarctic Marine Living Resources § 300.109 Gear disposal. (a) The operator of a harvesting vessel may not... fishing vessels or gear, or that may catch fish or cause damage to any marine resource, including...

  16. 50 CFR 300.109 - Gear disposal.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 50 Wildlife and Fisheries 9 2011-10-01 2011-10-01 false Gear disposal. 300.109 Section 300.109... Antarctic Marine Living Resources § 300.109 Gear disposal. (a) The operator of a harvesting vessel may not... fishing vessels or gear, or that may catch fish or cause damage to any marine resource, including...

  17. 50 CFR 300.109 - Gear disposal.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 50 Wildlife and Fisheries 11 2012-10-01 2012-10-01 false Gear disposal. 300.109 Section 300.109... Antarctic Marine Living Resources § 300.109 Gear disposal. (a) The operator of a harvesting vessel may not... fishing vessels or gear, or that may catch fish or cause damage to any marine resource, including...

  18. 50 CFR 300.109 - Gear disposal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 50 Wildlife and Fisheries 11 2013-10-01 2013-10-01 false Gear disposal. 300.109 Section 300.109... Antarctic Marine Living Resources § 300.109 Gear disposal. (a) The operator of a harvesting vessel may not... fishing vessels or gear, or that may catch fish or cause damage to any marine resource, including...

  19. Sewage Disposal in Port Harcourt, Nigeria.

    ERIC Educational Resources Information Center

    Ayotamuno, M. J.

    1993-01-01

    This survey of the Port Harcourt, Nigeria, sewage disposal system exemplifies sewage disposal in the developing world. Results reveal that some well-constructed and maintained drains, as well as many open drains and septic tanks, expose women and children to the possibility of direct contact with parasitic organisms and threaten water resources.…

  20. Crystalline and Crystalline International Disposal Activities

    SciTech Connect

    Viswanathan, Hari S.; Chu, Shaoping; Reimus, Paul William; Makedonska, Nataliia; Hyman, Jeffrey De'Haven; Karra, Satish; Dittrich, Timothy M.

    2015-12-21

    This report presents the results of work conducted between September 2014 and July 2015 at Los Alamos National Laboratory in the crystalline disposal and crystalline international disposal work packages of the Used Fuel Disposition Campaign (UFDC) for DOE-NE’s Fuel Cycle Research and Development program.

  1. Medications at School: Disposing of Pharmaceutical Waste

    ERIC Educational Resources Information Center

    Taras, Howard; Haste, Nina M.; Berry, Angela T.; Tran, Jennifer; Singh, Renu F.

    2014-01-01

    Background: This project quantified and categorized medications left unclaimed by students at the end of the school year. It determined the feasibility of a model medication disposal program and assessed school nurses' perceptions of environmentally responsible medication disposal. Methods: At a large urban school district all unclaimed…

  2. Subseabed disposal program. Volume 1: Summary

    NASA Astrophysics Data System (ADS)

    Hinga, K. R.

    1982-02-01

    This is the seventh annual report describing the results of the investigations of the Subseabed Disposal Program. The program, international in scope, is evaluating the feasibility of disposing of high-level radioactive wastes by burial in certain geologically stable and economically valueless sediments of the deep sea floor.

  3. Tritium waste disposal technology in the US

    SciTech Connect

    Albenesius, E.L.; Towler, O.A.

    1983-01-01

    Tritium waste disposal methods in the US range from disposal of low specific activity waste along with other low-level waste in shallow land burial facilities, to disposal of kilocurie amounts in specially designed triple containers in 65' deep augered holes located in an aird region of the US. Total estimated curies disposed of are 500,000 in commercial burial sites and 10 million curies in defense related sites. At three disposal sites in humid areas, tritium has migrated into the ground water, and at one arid site tritium vapor has been detected emerging from the soil above the disposal area. Leaching tests on tritium containing waste show that tritium in the form of HTO leaches readily from most waste forms, but that leaching rates of tritiated water into polymer impregnated concrete are reduced by as much as a factor of ten. Tests on improved tritium containment are ongoing. Disposal costs for tritium waste are 7 to 10 dollars per cubic foot for shallow land burial of low specific activity tritium waste, and 10 to 20 dollars per cubic foot for disposal of high specific activity waste. The cost of packaging the high specific activity waste is 150 to 300 dollars per cubic foot. 18 references.

  4. Petroleum Engineering Techniques for HLW Disposal

    SciTech Connect

    van den Broek, W. M. G. T.

    2002-02-25

    This paper describes why petroleum engineering techniques are of importance and can be used for underground disposal of HLW (high-level radioactive waste). It is focused on rock salt as a geological host medium in combination with disposal of the HLW canisters in boreholes drilled from the surface. Both permanent disposal and disposal with the option to retrieve the waste are considered. The paper starts with a description of the disposal procedure. Next disposal in deep boreholes is treated. Then the possible use of deviated boreholes and of multiple boreholes is discussed. Also waste isolation aspects and the implications of the HLW heat generation are treated. It appears that the use of deep boreholes can be beneficial, and also that--to a certain extent--borehole deviation offers possibilities. The benefits of using multiple boreholes are questionable for permanent disposal, while this technique cannot be applied for retrievable disposal. For the use of casing material, the additional temperature rise due to the HLW heat generation must be taken into account.

  5. Medications at School: Disposing of Pharmaceutical Waste

    ERIC Educational Resources Information Center

    Taras, Howard; Haste, Nina M.; Berry, Angela T.; Tran, Jennifer; Singh, Renu F.

    2014-01-01

    Background: This project quantified and categorized medications left unclaimed by students at the end of the school year. It determined the feasibility of a model medication disposal program and assessed school nurses' perceptions of environmentally responsible medication disposal. Methods: At a large urban school district all unclaimed…

  6. 21 CFR 1250.79 - Garbage disposal.

    Code of Federal Regulations, 2010 CFR

    2010-04-01

    ... 21 Food and Drugs 8 2010-04-01 2010-04-01 false Garbage disposal. 1250.79 Section 1250.79 Food and... SANITATION Servicing Areas for Land and Air Conveyances § 1250.79 Garbage disposal. (a) Water-tight, readily cleanable, nonabsorbent containers with close-fitting covers shall be used to receive and store garbage. (b...

  7. 21 CFR 1250.79 - Garbage disposal.

    Code of Federal Regulations, 2013 CFR

    2013-04-01

    ... 21 Food and Drugs 8 2013-04-01 2013-04-01 false Garbage disposal. 1250.79 Section 1250.79 Food and... SANITATION Servicing Areas for Land and Air Conveyances § 1250.79 Garbage disposal. (a) Water-tight, readily cleanable, nonabsorbent containers with close-fitting covers shall be used to receive and store garbage. (b...

  8. 21 CFR 1250.79 - Garbage disposal.

    Code of Federal Regulations, 2014 CFR

    2014-04-01

    ... 21 Food and Drugs 8 2014-04-01 2014-04-01 false Garbage disposal. 1250.79 Section 1250.79 Food and... SANITATION Servicing Areas for Land and Air Conveyances § 1250.79 Garbage disposal. (a) Water-tight, readily cleanable, nonabsorbent containers with close-fitting covers shall be used to receive and store garbage. (b...

  9. 21 CFR 1250.79 - Garbage disposal.

    Code of Federal Regulations, 2011 CFR

    2011-04-01

    ... 21 Food and Drugs 8 2011-04-01 2011-04-01 false Garbage disposal. 1250.79 Section 1250.79 Food and... SANITATION Servicing Areas for Land and Air Conveyances § 1250.79 Garbage disposal. (a) Water-tight, readily cleanable, nonabsorbent containers with close-fitting covers shall be used to receive and store garbage. (b...

  10. 21 CFR 1250.79 - Garbage disposal.

    Code of Federal Regulations, 2012 CFR

    2012-04-01

    ... 21 Food and Drugs 8 2012-04-01 2012-04-01 false Garbage disposal. 1250.79 Section 1250.79 Food and... SANITATION Servicing Areas for Land and Air Conveyances § 1250.79 Garbage disposal. (a) Water-tight, readily cleanable, nonabsorbent containers with close-fitting covers shall be used to receive and store garbage. (b...

  11. 7 CFR 3203.10 - Disposal.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... Regulations of the Department of Agriculture (Continued) OFFICE OF PROCUREMENT AND PROPERTY MANAGEMENT... PURSUANT TO SECTION 14220 OF THE 2008 FARM BILL § 3203.10 Disposal. When property received under this part is no longer needed by the recipient, it must be disposed of in an environmentally sound manner...

  12. 45 CFR 671.12 - Waste disposal.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... provisions of this section, shall, to the maximum extent practicable, not be disposed of onto sea ice, ice... and domestic liquid wastes may be discharged directly into the sea, taking into account the... treatment processes are used, the by-product of such treatment may be disposed of into the sea...

  13. 45 CFR 671.12 - Waste disposal.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... provisions of this section, shall, to the maximum extent practicable, not be disposed of onto sea ice, ice... and domestic liquid wastes may be discharged directly into the sea, taking into account the... treatment processes are used, the by-product of such treatment may be disposed of into the sea...

  14. 45 CFR 671.12 - Waste disposal.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... provisions of this section, shall, to the maximum extent practicable, not be disposed of onto sea ice, ice... and domestic liquid wastes may be discharged directly into the sea, taking into account the... treatment processes are used, the by-product of such treatment may be disposed of into the sea...

  15. 45 CFR 671.12 - Waste disposal.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... provisions of this section, shall, to the maximum extent practicable, not be disposed of onto sea ice, ice... and domestic liquid wastes may be discharged directly into the sea, taking into account the... treatment processes are used, the by-product of such treatment may be disposed of into the sea...

  16. 45 CFR 671.12 - Waste disposal.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... provisions of this section, shall, to the maximum extent practicable, not be disposed of onto sea ice, ice... and domestic liquid wastes may be discharged directly into the sea, taking into account the... treatment processes are used, the by-product of such treatment may be disposed of into the sea...

  17. 32 CFR 644.395 - Coordination on disposal problems.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... problem adversely affecting a specific disposal project or the overall program for disposal or property. ... 32 National Defense 4 2011-07-01 2011-07-01 false Coordination on disposal problems. 644.395... PROPERTY REAL ESTATE HANDBOOK Disposal Predisposal Action § 644.395 Coordination on disposal problems. If...

  18. Rab4b Is a Small GTPase Involved in the Control of the Glucose Transporter GLUT4 Localization in Adipocyte

    PubMed Central

    Kaddai, Vincent; Gonzalez, Teresa; Keslair, Frédérique; Grémeaux, Thierry; Bonnafous, Stéphanie; Gugenheim, Jean; Tran, Albert; Gual, Philippe; Le Marchand-Brustel, Yannick; Cormont, Mireille

    2009-01-01

    Background Endosomal small GTPases of the Rab family, among them Rab4a, play an essential role in the control of the glucose transporter GLUT4 trafficking, which is essential for insulin-mediated glucose uptake. We found that adipocytes also expressed Rab4b and we observed a consistent decrease in the expression of Rab4b mRNA in human and mice adipose tissue in obese diabetic states. These results led us to study this poorly characterized Rab member and its potential role in glucose transport. Methodology/Principal Findings We used 3T3-L1 adipocytes to study by imaging approaches the localization of Rab4b and to determine the consequence of its down regulation on glucose uptake and endogenous GLUT4 location. We found that Rab4b was localized in endosomal structures in preadipocytes whereas in adipocytes it was localized in GLUT4 and in VAMP2-positive compartments, and also in endosomal compartments containing the transferrin receptor (TfR). When Rab4b expression was decreased with specific siRNAs by two fold, an extent similar to its decrease in obese diabetic subjects, we observed a small increase (25%) in basal deoxyglucose uptake and a more sustained increase (40%) in presence of submaximal and maximal insulin concentrations. This increase occurred without any change in GLUT4 and GLUT1 expression levels and in the insulin signaling pathways. Concomitantly, GLUT4 but not TfR amounts were increased at the plasma membrane of basal and insulin-stimulated adipocytes. GLUT4 seemed to be targeted towards its non-endosomal sequestration compartment. Conclusion/Significance Taken our results together, we conclude that Rab4b is a new important player in the control of GLUT4 trafficking in adipocytes and speculate that difference in its expression in obese diabetic states could act as a compensatory effect to minimize the glucose transport defect in their adipocytes. PMID:19590752

  19. p75 neurotrophin receptor regulates glucose homeostasis and insulin sensitivity

    PubMed Central

    Baeza-Raja, Bernat; Li, Pingping; Le Moan, Natacha; Sachs, Benjamin D.; Schachtrup, Christian; Davalos, Dimitrios; Vagena, Eirini; Bridges, Dave; Kim, Choel; Saltiel, Alan R.; Olefsky, Jerrold M.; Akassoglou, Katerina

    2012-01-01

    Insulin resistance is a key factor in the etiology of type 2 diabetes. Insulin-stimulated glucose uptake is mediated by the glucose transporter 4 (GLUT4), which is expressed mainly in skeletal muscle and adipose tissue. Insulin-stimulated translocation of GLUT4 from its intracellular compartment to the plasma membrane is regulated by small guanosine triphosphate hydrolases (GTPases) and is essential for the maintenance of normal glucose homeostasis. Here we show that the p75 neurotrophin receptor (p75NTR) is a regulator of glucose uptake and insulin resistance. p75NTR knockout mice show increased insulin sensitivity on normal chow diet, independent of changes in body weight. Euglycemic-hyperinsulinemic clamp studies demonstrate that deletion of the p75NTR gene increases the insulin-stimulated glucose disposal rate and suppression of hepatic glucose production. Genetic depletion or shRNA knockdown of p75NTR in adipocytes or myoblasts increases insulin-stimulated glucose uptake and GLUT4 translocation. Conversely, overexpression of p75NTR in adipocytes decreases insulin-stimulated glucose transport. In adipocytes, p75NTR forms a complex with the Rab5 family GTPases Rab5 and Rab31 that regulate GLUT4 trafficking. Rab5 and Rab31 directly interact with p75NTR primarily via helix 4 of the p75NTR death domain. Adipocytes from p75NTR knockout mice show increased Rab5 and decreased Rab31 activities, and dominant negative Rab5 rescues the increase in glucose uptake seen in p75NTR knockout adipocytes. Our results identify p75NTR as a unique player in glucose metabolism and suggest that signaling from p75NTR to Rab5 family GTPases may represent a unique therapeutic target for insulin resistance and diabetes. PMID:22460790

  20. Branched short-chain fatty acids modulate glucose and lipid metabolism in primary adipocytes

    PubMed Central

    Heimann, Emilia; Nyman, Margareta; Pålbrink, Ann-Ki; Lindkvist-Petersson, Karin; Degerman, Eva

    2016-01-01

    ABSTRACT Short-chain fatty acids (SCFAs), e.g. acetic acid, propionic acid and butyric acid, generated through colonic fermentation of dietary fibers, have been shown to reach the systemic circulation at micromolar concentrations. Moreover, SCFAs have been conferred anti-obesity properties in both animal models and human subjects. Branched SCFAs (BSCFAs), e.g., isobutyric and isovaleric acid, are generated by fermentation of branched amino acids, generated from undigested protein reaching colon. However, BSCFAs have been sparsely investigated when referring to effects on energy metabolism. Here we primarily investigate the effects of isobutyric acid and isovaleric acid on glucose and lipid metabolism in primary rat and human adipocytes. BSCFAs inhibited both cAMP-mediated lipolysis and insulin-stimulated de novo lipogenesis at 10 mM, whereas isobutyric acid potentiated insulin-stimulated glucose uptake by all concentrations (1, 3 and 10 mM) in rat adipocytes. For human adipocytes, only SCFAs inhibited lipolysis at 10 mM. In both in vitro models, BSCFAs and SCFAs reduced phosphorylation of hormone sensitive lipase, a rate limiting enzyme in lipolysis. In addition, BSCFAs and SCFAs, in contrast to insulin, inhibited lipolysis in the presence of wortmannin, a phosphatidylinositide 3-kinase inhibitor and OPC3911, a phosphodiesterase 3 inhibitor in rat adipocytes. Furthermore, BSCFAs and SCFAs reduced insulin-mediated phosphorylation of protein kinase B. To conclude, BSCFAs have effects on adipocyte lipid and glucose metabolism that can contribute to improved insulin sensitivity in individuals with disturbed metabolism. PMID:27994949

  1. A BOD monitoring disposable reactor with alginate-entrapped bacteria.

    PubMed

    Villalobos, Patricio; Acevedo, Cristian A; Albornoz, Fernando; Sánchez, Elizabeth; Valdés, Erika; Galindo, Raúl; Young, Manuel E

    2010-10-01

    Biochemical oxygen demand (BOD) is a measure of the amount of dissolved oxygen that is required for the biochemical oxidation of the organic compounds in 5 days. New biosensor-based methods have been conducted for a faster determination of BOD. In this study, a mathematical model to evaluate the feasibility of using a BOD sensor, based on disposable alginate-entrapped bacteria, for monitoring BOD in situ was applied. The model considers the influences of alginate bead size and bacterial concentration. The disposable biosensor can be adapted according to specific requirements depending on the organic load contained in the wastewater. Using Klein and Washausen parameter in a Lineweaver-Burk plot, the glucose diffusivity was calculated in 6.4 × 10(-10) (m2/s) for beads of 1 mm in diameter and slight diffusion restrictions were observed (n = 0.85). Experimental results showed a correlation (p < 0.05) between the respirometric peak and the standard BOD test. The biosensor response was representative of BOD.

  2. Improper sharp disposal practices among diabetes patients in home care settings: Need for concern?

    PubMed Central

    Majumdar, Anindo; Sahoo, Jayaprakash; Roy, Gautam; Kamalanathan, Sadishkumar

    2015-01-01

    In the recent years, outbreaks of blood-borne infections have been reported from assisted living facilities, which were traced back to improper blood glucose monitoring practices. Needle-stick injuries have been implicated in many such cases. This directly raises concerns over sharp disposal practices of diabetic patients self-managing their condition in home care settings. With India being home to a huge diabetic population, this issue, if neglected, can cause substantial damage to the health of the population and a marked economic loss. This article discusses the sharp disposal practices prevalent among diabetes patients, the importance of proper sharp disposal, barriers to safe disposal of sharps, and the options available for doing the same. For adopting an environmentally safe wholesome approach, disposal of plastics generated as a result of diabetes self-care at home is important as well. The article also looks at the possible long-term solutions to these issues that are sustainable in an Indian context. PMID:25932402

  3. 41 CFR 102-75.255 - What are disposal agencies' specific responsibilities concerning the disposal of surplus property?

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... agencies' specific responsibilities concerning the disposal of surplus property? 102-75.255 Section 102-75...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.255 What are disposal agencies' specific responsibilities concerning the disposal of surplus...

  4. 41 CFR 102-75.255 - What are disposal agencies' specific responsibilities concerning the disposal of surplus property?

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... agencies' specific responsibilities concerning the disposal of surplus property? 102-75.255 Section 102-75...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.255 What are disposal agencies' specific responsibilities concerning the disposal of surplus...

  5. 41 CFR 102-75.255 - What are disposal agencies' specific responsibilities concerning the disposal of surplus property?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... agencies' specific responsibilities concerning the disposal of surplus property? 102-75.255 Section 102-75...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.255 What are disposal agencies' specific responsibilities concerning the disposal of surplus...

  6. 41 CFR 102-75.255 - What are disposal agencies' specific responsibilities concerning the disposal of surplus property?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... agencies' specific responsibilities concerning the disposal of surplus property? 102-75.255 Section 102-75...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.255 What are disposal agencies' specific responsibilities concerning the disposal of surplus...

  7. 41 CFR 102-75.255 - What are disposal agencies' specific responsibilities concerning the disposal of surplus property?

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... agencies' specific responsibilities concerning the disposal of surplus property? 102-75.255 Section 102-75...) FEDERAL MANAGEMENT REGULATION REAL PROPERTY 75-REAL PROPERTY DISPOSAL Surplus Real Property Disposal § 102-75.255 What are disposal agencies' specific responsibilities concerning the disposal of surplus...

  8. Glucose screening tests during pregnancy

    MedlinePlus

    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 ...

  9. Disposal configuration options for future uses of greater confinement disposal at the Nevada Test Site

    SciTech Connect

    Price, L.

    1994-09-01

    The US Department of Energy (DOE) is responsible for disposing of a variety of radioactive and mixed wastes, some of which are considered special-case waste because they do not currently have a clear disposal option. The DOE`s Nevada Field Office contracted with Sandia National Laboratories to investigate the possibility of disposing of some of this special-case waste at the Nevada Test Site (NTS). As part of this investigation, a review of a near-surface and subsurface disposal options that was performed to develop alternative disposal configurations for special-case waste disposal at the NTS. The criteria for the review included (1) configurations appropriate for disposal at the NTS; (2) configurations for disposal of waste at least 100 ft below the ground surface; (3) configurations for which equipment and technology currently exist; and (4) configurations that meet the special requirements imposed by the nature of special-case waste. Four options for subsurface disposal of special-case waste are proposed: mined consolidated rock, mined alluvium, deep pits or trenches, and deep boreholes. Six different methods for near-surface disposal are also presented: earth-covered tumuli, above-grade concrete structures, trenches, below-grade concrete structures, shallow boreholes, and hydrofracture. Greater confinement disposal (GCD) in boreholes at least 100 ft deep, similar to that currently practiced at the GCD facility at the Area 5 Radioactive Waste Management Site at the NTS, was retained as the option that met the criteria for the review. Four borehole disposal configurations are proposed with engineered barriers that range from the native alluvium to a combination of gravel and concrete. The configurations identified will be used for system analysis that will be performed to determine the disposal configurations and wastes that may be suitable candidates for disposal of special-case wastes at the NTS.

  10. Brown Adipose Tissue Improves Whole-Body Glucose Homeostasis and Insulin Sensitivity in Humans

    PubMed Central

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Annamalai, Palam; Enerbäck, Sven; Lidell, Martin E.; Saraf, Manish K.; Labbe, Sebastien M.; Hurren, Nicholas M.; Yfanti, Christina; Chao, Tony; Andersen, Clark R.; Cesani, Fernando; Hawkins, Hal

    2014-01-01

    Brown adipose tissue (BAT) has attracted scientific interest as an antidiabetic tissue owing to its ability to dissipate energy as heat. Despite a plethora of data concerning the role of BAT in glucose metabolism in rodents, the role of BAT (if any) in glucose metabolism in humans remains unclear. To investigate whether BAT activation alters whole-body glucose homeostasis and insulin sensitivity in humans, we studied seven BAT-positive (BAT+) men and five BAT-negative (BAT−) men under thermoneutral conditions and after prolonged (5–8 h) cold exposure (CE). The two groups were similar in age, BMI, and adiposity. CE significantly increased resting energy expenditure, whole-body glucose disposal, plasma glucose oxidation, and insulin sensitivity in the BAT+ group only. These results demonstrate a physiologically significant role of BAT in whole-body energy expenditure, glucose homeostasis, and insulin sensitivity in humans, and support the notion that BAT may function as an antidiabetic tissue in humans. PMID:25056438

  11. 32 CFR 644.503 - Methods of disposal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... ESTATE HANDBOOK Disposal Disposal of Standing Timber, Crops, and Embedded Gravel, Sand and Stone § 644.503 Methods of disposal. Standing timber, crops, sand, gravel, or stone-quarried products, authorized...

  12. 43 CFR 4730.2 - Disposal of remains.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... HORSES AND BURROS Destruction of Wild Horses or Burros and Disposal of Remains § 4730.2 Disposal of remains. Remains of wild horses or burros that die after capture shall be disposed of in accordance with...

  13. 43 CFR 4730.2 - Disposal of remains.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... HORSES AND BURROS Destruction of Wild Horses or Burros and Disposal of Remains § 4730.2 Disposal of remains. Remains of wild horses or burros that die after capture shall be disposed of in accordance with...

  14. 43 CFR 4730.2 - Disposal of remains.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... HORSES AND BURROS Destruction of Wild Horses or Burros and Disposal of Remains § 4730.2 Disposal of remains. Remains of wild horses or burros that die after capture shall be disposed of in accordance with...

  15. 43 CFR 4730.2 - Disposal of remains.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... HORSES AND BURROS Destruction of Wild Horses or Burros and Disposal of Remains § 4730.2 Disposal of remains. Remains of wild horses or burros that die after capture shall be disposed of in accordance with...

  16. 32 CFR 644.503 - Methods of disposal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... ESTATE HANDBOOK Disposal Disposal of Standing Timber, Crops, and Embedded Gravel, Sand and Stone § 644.503 Methods of disposal. Standing timber, crops, sand, gravel, or stone-quarried products, authorized...

  17. 32 CFR 644.503 - Methods of disposal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... ESTATE HANDBOOK Disposal Disposal of Standing Timber, Crops, and Embedded Gravel, Sand and Stone § 644.503 Methods of disposal. Standing timber, crops, sand, gravel, or stone-quarried products, authorized...

  18. 32 CFR 644.503 - Methods of disposal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... ESTATE HANDBOOK Disposal Disposal of Standing Timber, Crops, and Embedded Gravel, Sand and Stone § 644.503 Methods of disposal. Standing timber, crops, sand, gravel, or stone-quarried products, authorized...

  19. Salt caverns for oil field waste disposal.

    SciTech Connect

    Veil, J.; Ford, J.; Rawn-Schatzinger, V.; Environmental Assessment; RMC, Consultants, Inc.

    2000-07-01

    Salt caverns used for oil field waste disposal are created in salt formations by solution mining. When created, caverns are filled with brine. Wastes are introduced into the cavern by pumping them under low pressure. Each barrel of waste injected to the cavern displaces a barrel of brine to the surface. The brine is either used for drilling mud or is disposed of in an injection well. Figure 8 shows an injection pump used at disposal cavern facilities in west Texas. Several types of oil field waste may be pumped into caverns for disposal. These include drilling muds, drill cuttings, produced sands, tank bottoms, contaminated soil, and completion and stimulation wastes. Waste blending facilities are constructed at the site of cavern disposal to mix the waste into a brine solution prior to injection. Overall advantages of salt cavern disposal include a medium price range for disposal cost, large capacity and availability of salt caverns, limited surface land requirement, increased safety, and ease of establishment of individual state regulations.

  20. Consideration of privatization of solid waste disposal

    SciTech Connect

    Harrison, W.K.

    1995-09-01

    Martin County is responsible by law for the solid waste disposal needs of all County residents. In the State of Florida, counties have the responsibility of providing solid waste disposal services. Florida Statutes 403.706 divides the responsibility among local governments as follows: {open_quotes}The governing body of a County has the responsibility and power to provide for the operation of solid waste disposal facilities to meet the needs of all incorporated and unincorporated areas of the County. In accordance with this section, municipalities are responsible for collecting and transporting solid waste from their jurisdictions to a solid waste disposal facility operated by a county or operated under a contract with a county.{close_quotes} Solid waste disposal is a mandatory obligation primarily because of public health and safety concerns. In addition to contributing to environmental damage, dumping (as opposed to landfilling) contributes to infestations of insects and rodents that carry disease to the human population. Although the County may choose to provide solid waste disposal service indirectly, the ultimate responsibility for the service will remain with the County. If a contractor fails to provide the service, the County will be legally responsible to the State and to County residents for correcting the failure. This report discussess issues associated with the privatization of solid waste disposal.

  1. Peristaltic pumps for waste disposal

    SciTech Connect

    Griffith, G.W.

    1992-09-01

    Laboratory robots are capable of generating large volumes of hazardous liquid wastes when they are used to perform chemical analyses of metal finishing solutions. A robot at Allied-Signal Inc., Kansas City Division, generates 30 gallons of acid waste each month. This waste contains mineral acids, heavy metals, metal fluorides, and other materials. The waste must be contained in special drums that are closed to the atmosphere. The initial disposal method was to have the robot pour the waste into a collecting funnel, which contained a liquid-sensing valve to admit the waste into the drum. Spills were inevitable, splashing occurred, and the special valve often didn`t work well. The device also occupied a large amount of premium bench space. Peristaltic pumps are made to handle hazardous liquids quickly and efficiently. A variable-speed pump, equipped with a quick-loading pump head, was mounted below the robot bench near the waste barrel. The pump inlet tube was mounted above the bench within easy reach of the robot, while the outlet tube was connected directly to the barrel. During operation, the robot brings the waste liquid up to the pump inlet tube and activates the pump. When the waste has been removed, the pump stops. The procedure is quick, simple, inexpensive, safe, and reliable.

  2. Peristaltic pumps for waste disposal

    SciTech Connect

    Griffith, G.W.

    1992-09-01

    Laboratory robots are capable of generating large volumes of hazardous liquid wastes when they are used to perform chemical analyses of metal finishing solutions. A robot at Allied-Signal Inc., Kansas City Division, generates 30 gallons of acid waste each month. This waste contains mineral acids, heavy metals, metal fluorides, and other materials. The waste must be contained in special drums that are closed to the atmosphere. The initial disposal method was to have the robot pour the waste into a collecting funnel, which contained a liquid-sensing valve to admit the waste into the drum. Spills were inevitable, splashing occurred, and the special valve often didn't work well. The device also occupied a large amount of premium bench space. Peristaltic pumps are made to handle hazardous liquids quickly and efficiently. A variable-speed pump, equipped with a quick-loading pump head, was mounted below the robot bench near the waste barrel. The pump inlet tube was mounted above the bench within easy reach of the robot, while the outlet tube was connected directly to the barrel. During operation, the robot brings the waste liquid up to the pump inlet tube and activates the pump. When the waste has been removed, the pump stops. The procedure is quick, simple, inexpensive, safe, and reliable.

  3. System for disposing of sludge

    SciTech Connect

    Williams, R.M.

    1991-05-28

    This patent describes improvement in a system for disposing of sludge by using the sludge as a primary source of fuel for its disposition by combustion thereof. The system comprises: processing a mass of liquified sludge to reduce the solids to a predetermined size for use as the fuel and concurrently separating a substantial portion of the contained liquid as a water vapor; delivering the processes solids and liquid to the combustor such that the combustor contains the solids and the liquids in the processed mass for conversion of the solids to ash and the conversion of the liquids to vapor; admitting a portion of the ambient air to the burner to support combustion of the solids, and another portion of ambient air to the combustor for removing the vapor at a temperature below the temperature at which the solids are reduced to ash; utilizing a part of the removed vapor to initiate evaporization of the liquid in the processed mass, and a part of the removed vapor to elevate the temperature of the ambient air admitted to the burner and to the combustor; releasing the part of the removed vapor used to elevate the temperature of the admitted ambient air to the ambient atmosphere; and removing the ash substantially free of vapor.

  4. Processing Irradiated Beryllium For Disposal

    SciTech Connect

    T. J. Tranter; R. D. Tillotson; N. R. Mann; G. R. Longhurst

    2005-11-01

    The purpose of this research was to develop a process for decontaminating irradiated beryllium that will allow it to be disposed of through normal radwaste channels. Thus, the primary objectives of this ongoing study are to remove the transuranic (TRU) isotopes to less than 100 nCi/g and remove {sup 60}Co, and {sup 137}Cs, to levels that will allow the beryllium to be contact handled. One possible approach that appears to have the most promise is aqueous dissolution and separation of the isotopes by selected solvent extraction followed by precipitation, resulting in a granular form for the beryllium that may be fixed to prevent it from becoming respirable and therefore hazardous. Beryllium metal was dissolved in nitric and fluorboric acids. Isotopes of {sup 241}Am, {sup 239}Pu, {sup 85}Sr, and {sup 137}Cs were then added to make a surrogate beryllium waste solution. A series of batch contacts was performed with the spiked simulant using chlorinated cobalt dicarbollide (CCD) and polyethylene glycol diluted with sulfone to extract the isotopes of Cs and Sr. Another series of batch contacts was performed using a combination of octyl (phenyl)-N,N-diisobutylcarbamoylmethylphosphine oxide (CMPO) in tributyl phosphate (TBP) diluted with dodecane for extracting the isotopes of Pu and Am. The results indicate that greater than 99.9% removal can be achieved for each isotope with only three contact stages.

  5. Large Component Removal/Disposal

    SciTech Connect

    Wheeler, D. M.

    2002-02-27

    This paper describes the removal and disposal of the large components from Maine Yankee Atomic Power Plant. The large components discussed include the three steam generators, pressurizer, and reactor pressure vessel. Two separate Exemption Requests, which included radiological characterizations, shielding evaluations, structural evaluations and transportation plans, were prepared and issued to the DOT for approval to ship these components; the first was for the three steam generators and one pressurizer, the second was for the reactor pressure vessel. Both Exemption Requests were submitted to the DOT in November 1999. The DOT approved the Exemption Requests in May and July of 2000, respectively. The steam generators and pressurizer have been removed from Maine Yankee and shipped to the processing facility. They were removed from Maine Yankee's Containment Building, loaded onto specially designed skid assemblies, transported onto two separate barges, tied down to the barges, th en shipped 2750 miles to Memphis, Tennessee for processing. The Reactor Pressure Vessel Removal Project is currently under way and scheduled to be completed by Fall of 2002. The planning, preparation and removal of these large components has required extensive efforts in planning and implementation on the part of all parties involved.

  6. Monitor blood glucose - slideshow

    MedlinePlus

    ... Series—Monitoring blood glucose: Using a self-test meter To use the sharing features on this page, ... 5 out of 5 Overview Set up the meter according to the specific directions that come with ...

  7. Hyperglycemia (High Blood Glucose)

    MedlinePlus

    ... Doctors, Nurses & More Oral Health & Hygiene Women A1C Insulin Pregnancy 8 Tips for Caregivers Health Insurance Health ... glucose happens when the body has too little insulin or when the body can't use insulin ...

  8. Glucose urine test

    MedlinePlus

    Urine sugar test; Urine glucose test; Glucosuria test; Glycosuria test ... After you provide a urine sample, it is tested right away. The health care provider uses a dipstick made with a color-sensitive pad. The ...

  9. Continuous Glucose Monitoring

    MedlinePlus

    ... to download data from the devices to a computer for tracking and analysis of patterns and trends, ... use CGM systems can download data to a computer to see patterns and trends in their glucose ...

  10. Glucose: Detection and analysis.

    PubMed

    Galant, A L; Kaufman, R C; Wilson, J D

    2015-12-01

    Glucose is an aldosic monosaccharide that is centrally entrenched in the processes of photosynthesis and respiration, serving as an energy reserve and metabolic fuel in most organisms. As both a monomer and as part of more complex structures such as polysaccharides and glucosides, glucose also plays a major role in modern food products, particularly where flavor and or structure are concerned. Over the years, many diverse methods for detecting and quantifying glucose have been developed; this review presents an overview of the most widely employed and historically significant, including copper iodometry, HPLC, GC, CZE, and enzyme based systems such as glucose meters. The relative strengths and limitations of each method are evaluated, and examples of their recent application in the realm of food chemistry are discussed.

  11. Vascular Glucose Sensor Symposium

    PubMed Central

    Joseph, Jeffrey I; Torjman, Marc C.; Strasma, Paul J.

    2015-01-01

    Hyperglycemia, hypoglycemia, and glycemic variability have been associated with increased morbidity, mortality, length of stay, and cost in a variety of critical care and non–critical care patient populations in the hospital. The results from prospective randomized clinical trials designed to determine the risks and benefits of intensive insulin therapy and tight glycemic control have been confusing; and at times conflicting. The limitations of point-of-care blood glucose (BG) monitoring in the hospital highlight the great clinical need for an automated real-time continuous glucose monitoring system (CGMS) that can accurately measure the concentration of glucose every few minutes. Automation and standardization of the glucose measurement process have the potential to significantly improve BG control, clinical outcome, safety and cost. PMID:26078254

  12. Recombinant glucose uptake system

    DOEpatents

    Ingrahm, Lonnie O.; Snoep, Jacob L.; Arfman, Nico

    1997-01-01

    Recombinant organisms are disclosed that contain a pathway for glucose uptake other than the pathway normally utilized by the host cell. In particular, the host cell is one in which glucose transport into the cell normally is coupled to PEP production. This host cell is transformed so that it uses an alternative pathway for glucose transport that is not coupled to PEP production. In a preferred embodiment, the host cell is a bacterium other than Z. mobilis that has been transformed to contain the glf and glk genes of Z. mobilis. By uncoupling glucose transport into the cell from PEP utilization, more PEP is produced for synthesis of products of commercial importance from a given quantity of biomass supplied to the host cells.

  13. Future trends which will influence waste disposal.

    PubMed Central

    Wolman, A

    1978-01-01

    The disposal and management of solid wastes are ancient problems. The evolution of practices naturally changed as populations grew and sites for disposal became less acceptable. The central search was for easy disposal at minimum costs. The methods changed from indiscriminate dumping to sanitary landfill, feeding to swine, reduction, incineration, and various forms of re-use and recycling. Virtually all procedures have disabilities and rising costs. Many methods once abandoned are being rediscovered. Promises for so-called innovations outstrip accomplishments. Markets for salvage vary widely or disappear completely. The search for conserving materials and energy at minimum cost must go on forever. PMID:570105

  14. Utilities continue to wrestle with radwaste disposal

    SciTech Connect

    Strauss, S.D.

    1983-12-01

    The continuing doldrums in nuclear generation as an industry is a matter of public knowledge. The level of commercial activity related to nuclear energy, however, is another matter entirely, with waste disposal holding the spotlight. While the ultimate disposal of high-level waste (spent fuel, essentially) is the dramatic headline producer, it is the low-level radioactive wastes that dominate radwaste planning and design activities at nuclear utilities. Dwindling waste-disposal sites and economic considerations have spotlighted the need for volume minimization for at least a half-dozen years.

  15. Disposal of medical waste: a legal perspective.

    PubMed

    Du Toit, Karen; Bodenstein, Johannes

    2013-09-03

    The Constitution of the Republic of South Africa provides that everyone has the right to an environment that is not harmful to their health and well-being. The illegal dumping of hazardous waste poses a danger to the environment when pollutants migrate into water sources and ultimately cause widespread infection or toxicity, endangering the health of humans who might become exposed to infection and toxins. To give effect to the Constitution, the safe disposal of hazardous waste is governed by legislation in South Africa. Reports of the illegal disposal of waste suggest a general lack of awareness and training in regard to the safe disposal of medical waste. 

  16. Glucose metabolism and hyperglycemia.

    PubMed

    Giugliano, Dario; Ceriello, Antonio; Esposito, Katherine

    2008-01-01

    Islet dysfunction and peripheral insulin resistance are both present in type 2 diabetes and are both necessary for the development of hyperglycemia. In both type 1 and type 2 diabetes, large, prospective clinical studies have shown a strong relation between time-averaged mean values of glycemia, measured as glycated hemoglobin (HbA1c), and vascular diabetic complications. These studies are the basis for the American Diabetes Association's current recommended treatment goal that HbA1c should be <7%. The measurement of the HbA1c concentration is considered the gold standard for assessing long-term glycemia; however, it does not reveal any information on the extent or frequency of blood glucose excursions, but provides an overall mean value only. Postprandial hyperglycemia occurs frequently in patients with diabetes receiving active treatment and can occur even when metabolic control is apparently good. Interventional studies indicate that reducing postmeal glucose excursions is as important as controlling fasting plasma glucose in persons with diabetes and impaired glucose tolerance. Evidence exists for a causal relation between postmeal glucose increases and microvascular and macrovascular outcomes; therefore, it is not surprising that treatment with different compounds that have specific effects on postprandial glucose regulation is accompanied by a significant improvement of many pathways supposed to be involved in diabetic complications, including oxidative stress, endothelial dysfunction, inflammation, and nuclear factor-kappaB activation. The goal of therapy should be to achieve glycemic status as near to normal as safely possible in all 3 components of glycemic control: HbA1c, fasting glucose, and postmeal glucose peak.

  17. An acoustic glucose sensor.

    PubMed

    Hu, Ruifen; Stevenson, Adrian C; Lowe, Christopher R

    2012-05-15

    In vivo glucose monitoring is required for tighter glycaemic control. This report describes a new approach to construct a miniature implantable device based on a magnetic acoustic resonance sensor (MARS). A ≈ 600-800 nm thick glucose-responsive poly(acrylamide-co-3-acrylamidophenylboronic acid) (poly(acrylamide-co-3-APB)) film was polymerised on the quartz disc (12 mm in diameter and 0.25 mm thick) of the MARS. The swelling/shrinking of the polymer film induced by the glucose binding to the phenylboronate caused changes in the resonance amplitude of the quartz disc in the MARS. A linear relationship between the response of the MARS and the glucose concentration in the range ≈ 0-15 mM was observed, with the optimum response of the MARS sensor being obtained when the polymer films contained ≈ 20 mol% 3-APB. The MARS glucose sensor also functioned under flow conditions (9 μl/min) with a response almost identical to the sensor under static or non-flow conditions. The results suggest that the MARS could offer a promising strategy for developing a small subcutaneously implanted continuous glucose monitor.

  18. The infusion of glucose in ewes during the luteal phase increases the number of follicles but reduces oestradiol production and some correlates of metabolic function in the large follicles.

    PubMed

    Gallet, Claire; Dupont, Joëlle; Campbell, Bruce K; Monniaux, Danielle; Guillaume, Daniel; Scaramuzzi, Rex J

    2011-09-01

    Short-term nutritional supplementation stimulates folliculogenesis in ewes probably by insulin-mediated actions of glucose in the follicle. The aim of this study was to determine the effect of glucose on follicle number and granulosa levels of Aromatase P450 and phosphorylated Akt and AMPK. Twelve Ile-de-France ewes were allocated to two groups; one (n=7) infused with saline and the other (n=5) with glucose (10mM/h) for 72h in the luteal phase. At the end of infusion, ovaries were collected and all follicles >1mm in diameter were dissected to recover granulosa cells. Aromatase P450 and phosphorylated Akt and AMPK were analysed by Western blotting of granulosa cell lysates. Blood plasmas collected before and during the infusions were analysed for progesterone, oestradiol, LH, FSH, glucose, insulin and IGF-I. The infusion of glucose significantly increased follicle number but, significantly reduced Aromatase P450 and phosphorylated Akt and AMPK in granulosa cells. The circulating concentration of glucose rose significantly 3h after the start of the glucose infusion and remained elevated until 27h then fell; the circulating concentration of insulin rose significantly by 3h and remained elevated. The circulating concentration of oestradiol fell significantly by 32h and remained low; the circulating concentrations of LH and FSH were unaffected. These data show that short-term infusion of glucose stimulated follicular growth but decreased Aromatase P450 in granulosa cells. The reduced levels of phosphorylated Akt and AMPK suggest that the phosphatidylinositol 3-kinase pathway has been inhibited by high concentrations of glucose. These data also suggest that there may be functional cross-talk between FSH and insulin signalling in granulosa cells.

  19. Spent fuel characteristics & disposal considerations

    SciTech Connect

    Oversby, V.M.

    1996-06-01

    The fuel used in commercial nuclear power reactors is uranium, generally in the form of an oxide. The gas-cooled reactors developed in England use metallic uranium enclosed in a thin layer of Magnox. Since this fuel must be processed into a more stable form before disposal, we will not consider the characteristics of the Magnox spent fuel. The vast majority of the remaining power reactors in the world use uranium dioxide pellets in Zircaloy cladding as the fuel material. Reactors that are fueled with uranium dioxide generally use water as the moderator. If ordinary water is used, the reactors are called Light Water Reactors (LWR), while if water enriched in the deuterium isotope of hydrogen is used, the reactors are called Heavy Water reactors. The LWRs can be either pressurized reactors (PWR) or boiling water reactors (BWR). Both of these reactor types use uranium that has been enriched in the 235 isotope to about 3.5 to 4% total abundance. There may be minor differences in the details of the spent fuel characteristics for PWRs and BWRs, but for simplicity we will not consider these second-order effects. The Canadian designed reactor (CANDU) that is moderated by heavy water uses natural uranium without enrichment of the 235 isotope as the fuel. These reactors run at higher linear power density than LWRs and produce spent fuel with lower total burn-up than LWRs. Where these difference are important with respect to spent fuel management, we will discuss them. Otherwise, we will concentrate on spent fuel from LWRs.

  20. Marine disposal of radioactive wastes

    NASA Astrophysics Data System (ADS)

    Woodhead, D. S.

    1980-03-01

    In a general sense, the main attraction of the marine environment as a repository for the wastes generated by human activities lies in the degree of dispersion and dilution which is readily attainable. However, the capacity of the oceans to receive wastes without unacceptable consequences is clearly finite and this is even more true of localized marine environments such as estuaries, coastal waters and semi-enclosed seas. Radionuclides have always been present in the marine environment and marine organisms and humans consuming marine foodstuffs have always been exposed, to some degree, to radiation from this source. The hazard associated with ionizing radiations is dependent upon the absorption of energy from the radiation field within some biological entity. Thus any disposal of radioactive wastes into the marine environment has consequences, the acceptability of which must be assessed in terms of the possible resultant increase in radiation exposure of human and aquatic populations. In the United Kingdom the primary consideration has been and remains the safe-guarding of public health. The control procedures are therefore designed to minimize as far as practicable the degree of human exposure within the overall limits recommended as acceptable by the International Commission on Radiological Protection. There are several approaches through which control could be exercised and the strengths and weaknesses of each are considered. In this review the detailed application of the critical path technique to the control of the discharge into the north-east Irish Sea from the fuel reprocessing plant at Windscale is given as a practical example. It will be further demonstrated that when human exposure is controlled in this way no significant risk attaches to the increased radiation exposure experienced by populations of marine organisms in the area.

  1. Arsenic Treatment Residuals: Quantities, Characteristics and Disposal

    EPA Science Inventory

    This presentation provides information on the quantities, the characteristics and the disposal options for the common arsenic removal technologies. The technologies consist of adsorption media, iron removal, coagulation/filtration and ion exchange. The information for the prese...

  2. Disposal of controlled substances. Final rule.

    PubMed

    2014-09-09

    This rule governs the secure disposal of controlled substances by registrants and ultimate users. These regulations will implement the Secure and Responsible Drug Disposal Act of 2010 by expanding the options available to collect controlled substances from ultimate users for the purpose of disposal, including: Take-back events, mail-back programs, and collection receptacle locations. These regulations contain specific language allowing law enforcement to voluntarily continue to conduct take-back events, administer mail-back programs, and maintain collection receptacles. These regulations will allow authorized manufacturers, distributors, reverse distributors, narcotic treatment programs (NTPs), hospitals/clinics with an on-site pharmacy, and retail pharmacies to voluntarily administer mail-back programs and maintain collection receptacles. In addition, this rule expands the authority of authorized hospitals/clinics and retail pharmacies to voluntarily maintain collection receptacles at long-term care facilities. This rule also reorganizes and consolidates previously existing regulations on disposal, including the role of reverse distributors.

  3. How to Dispose of Unused Medicines

    MedlinePlus

    ... your city’s or county government’s household trash and recycling service to learn about medication disposal options and ... regulations and laws, contact your local trash and recycling facility. This article appears on FDA's Consumer Updates ...

  4. Method of Disposing of Corrosive Gases

    DOEpatents

    Burford, W.B. III; Anderson, H.C.

    1950-07-11

    Waste gas containing elemental fluorine is disposed of in the disclosed method by introducing the gas near the top of a vertical chamber under a downward spray of caustic soda solution which contains a small amount of sodium sulfide.

  5. Arsenic Treatment Residuals: Quantities, Characteristics and Disposal

    EPA Science Inventory

    This presentation provides information on the quantities, the characteristics and the disposal options for the common arsenic removal technologies. The technologies consist of adsorption media, iron removal, coagulation/filtration and ion exchange. The information for the prese...

  6. Assessment of Preferred Depleted Uranium Disposal Forms

    SciTech Connect

    Croff, A.G.; Hightower, J.R.; Lee, D.W.; Michaels, G.E.; Ranek, N.L.; Trabalka, J.R.

    2000-06-01

    The Department of Energy (DOE) is in the process of converting about 700,000 metric tons (MT) of depleted uranium hexafluoride (DUF6) containing 475,000 MT of depleted uranium (DU) to a stable form more suitable for long-term storage or disposal. Potential conversion forms include the tetrafluoride (DUF4), oxide (DUO2 or DU3O8), or metal. If worthwhile beneficial uses cannot be found for the DU product form, it will be sent to an appropriate site for disposal. The DU products are considered to be low-level waste (LLW) under both DOE orders and Nuclear Regulatory Commission (NRC) regulations. The objective of this study was to assess the acceptability of the potential DU conversion products at potential LLW disposal sites to provide a basis for DOE decisions on the preferred DU product form and a path forward that will ensure reliable and efficient disposal.

  7. Waste disposal options report. Volume 2

    SciTech Connect

    Russell, N.E.; McDonald, T.G.; Banaee, J.; Barnes, C.M.; Fish, L.W.; Losinski, S.J.; Peterson, H.K.; Sterbentz, J.W.; Wenzel, D.R.

    1998-02-01

    Volume 2 contains the following topical sections: estimates of feed and waste volumes, compositions, and properties; evaluation of radionuclide inventory for Zr calcine; evaluation of radionuclide inventory for Al calcine; determination of k{sub eff} for high level waste canisters in various configurations; review of ceramic silicone foam for radioactive waste disposal; epoxides for low-level radioactive waste disposal; evaluation of several neutralization cases in processing calcine and sodium-bearing waste; background information for EFEs, dose rates, watts/canister, and PE-curies; waste disposal options assumptions; update of radiation field definition and thermal generation rates for calcine process packages of various geometries-HKP-26-97; and standard criteria of candidate repositories and environmental regulations for the treatment and disposal of ICPP radioactive mixed wastes.

  8. Disposal of radioactive iodine in space

    NASA Technical Reports Server (NTRS)

    Burns, R. E.; Defield, J. G.

    1978-01-01

    The possibility of space disposal of iodine waste from nuclear power reactors is investigated. The space transportation system utilized relies upon the space shuttle, a liquid hydrogen/liquid oxygen orbit transfer vehicle, and a solid propellant final stage. The iodine is assumed to be in the form of either an iodide or an iodate, and calculations assume that the final destination is either solar orbit or solar system escape. It is concluded that space disposal of iodine is feasible.

  9. Disposal of Chemotherapeutic Agent -- Contaminated Waste

    DTIC Science & Technology

    1989-03-01

    Human interface is limited to manual loading and unloading to protect the operator and to prevent malfunction as a result of operator error. The system...wastes are not vet controlled but should be prevented from entering thp drinking water recycling chain. These wastes contain halogenated hydrocarbons that...This design promises to safely dispose of these types of wastes. No technical problems were encountered which would prevent this disposal process

  10. Disposal facility data for the interim performance

    SciTech Connect

    Eiholzer, C.R.

    1995-05-15

    The purpose of this report is to identify and provide information on the waste package and disposal facility concepts to be used for the low-level waste tank interim performance assessment. Current concepts for the low-level waste form, canister, and the disposal facility will be used for the interim performance assessment. The concept for the waste form consists of vitrified glass cullet in a sulfur polymer cement matrix material. The waste form will be contained in a 2 {times} 2 {times} 8 meter carbon steel container. Two disposal facility concepts will be used for the interim performance assessment. These facility concepts are based on a preliminary disposal facility concept developed for estimating costs for a disposal options configuration study. These disposal concepts are based on vault type structures. None of the concepts given in this report have been approved by a Tank Waste Remediation Systems (TWRS) decision board. These concepts will only be used in th interim performance assessment. Future performance assessments will be based on approved designs.

  11. Cavern/Vault Disposal Concepts and Thermal Calculations for Direct Disposal of 37-PWR Size DPCs

    SciTech Connect

    Hardin, Ernest; Hadgu, Teklu; Clayton, Daniel James

    2015-03-01

    This report provides two sets of calculations not presented in previous reports on the technical feasibility of spent nuclear fuel (SNF) disposal directly in dual-purpose canisters (DPCs): 1) thermal calculations for reference disposal concepts using larger 37-PWR size DPC-based waste packages, and 2) analysis and thermal calculations for underground vault-type storage and eventual disposal of DPCs. The reader is referred to the earlier reports (Hardin et al. 2011, 2012, 2013; Hardin and Voegele 2013) for contextual information on DPC direct disposal alternatives.

  12. Glucose Uptake and Triacylglycerol Synthesis Are Increased in Barth Syndrome Lymphoblasts.

    PubMed

    Mejia, Edgard M; Zinko, James C; Hauff, Kristin D; Xu, Fred Y; Ravandi, Amir; Hatch, Grant M

    2017-02-01

    Barth syndrome (BTHS) is an X-linked genetic disease resulting in loss of cardiolipin (Ptd2Gro). Patients may be predisposed to hypoglycemia and exhibit increases in whole-body glucose disposal rates and a higher fat mass percentage. We examined the reasons for this in BTHS lymphoblasts. BTHS lymphoblasts exhibited a 60% increase (p < 0.004) in 2-[1,2-(3)H(N)]deoxy-D-glucose uptake, a 40% increase (p < 0.01) in glucose transporter-3 protein expression, an increase in phosphorylated-adenosine monophosphate kinase (AMPK) and a 58% increase (p < 0.001) in the phosphorylated-AMPK/AMPK ratio compared to controls. In addition, BTHS lymphoblasts exhibited a 90% (p < 0.001) increase in D-[U-(14)C]glucose incorporated into 1,2,3-triacyl-sn-glycerol (TAG) and a 29% increase (p < 0.025) in 1,2-diacyl-sn-glycerol acyltransferase-2 activity compared to controls. Thus, BTHS lymphoblasts exhibit increased glucose transport and increased glucose utilization for TAG synthesis. These results may, in part, explain why BTHS patients exhibit an increase in whole-body glucose disposal rates, may be predisposed to hypoglycemia and exhibit a higher fat mass percentage.

  13. Nonoxidative Free Fatty Acid Disposal Is Greater in Young Women than Men

    PubMed Central

    Koutsari, Christina; Basu, Rita; Rizza, Robert A.; Nair, K. Sreekumaran; Khosla, Sundeep

    2011-01-01

    Context: Large increases in systemic free fatty acid (FFA) availability in the absence of a corresponding increase in fatty acid oxidation can create a host of metabolic abnormalities. These adverse responses are thought to be the result of fatty acids being shunted into hepatic very low-density lipoprotein-triglyceride production and/or intracellular lipid storage and signaling pathways because tissues are forced to increase nonoxidative FFA disposal. Objective: The objective of the study was to examine whether variations in postabsorptive nonoxidative FFA disposal within the usual range predict insulin resistance and hypertriglyceridemia. Design: We measured: systemic FFA turnover using a continuous iv infusion of [9–10, 3H]palmitate; substrate oxidation with indirect calorimetry combined with urinary nitrogen excretion; whole-body and peripheral insulin sensitivity with the labeled iv glucose tolerance test minimal model. Setting: the study was conducted at the Mayo Clinic General Clinical Research Center. Participants: Participants included healthy, postabsorptive, nonobese adults (21 women and 21 men). Interventions: There were no interventions. Main Outcome Measures: Nonoxidative FFA disposal (micromoles per minute), defined as the FFA disappearance rate minus fatty acid oxidation. Results: Women had 64% greater nonoxidative FFA disposal rate than men but a better lipid profile and similar insulin sensitivity. There was no significant correlation between nonoxidative FFA disposal and whole-body sensitivity, peripheral insulin sensitivity, or fasting serum triglyceride concentrations in men or women. Conclusions: Healthy nonobese women have greater rates of nonoxidative FFA disposal than men, but this does not appear to relate to adverse health consequences. Understanding the sex-specific interaction between adipose tissue lipolysis and peripheral FFA removal will help to discover new approaches to treat FFA-induced abnormalities. PMID:21123445

  14. A glucose sensor protein for continuous glucose monitoring.

    PubMed

    Veetil, Jithesh V; Jin, Sha; Ye, Kaiming

    2010-12-15

    In vivo continuous glucose monitoring has posed a significant challenge to glucose sensor development due to the lack of reliable techniques that are non- or at least minimally-invasive. In this proof-of-concept study, we demonstrated the development of a new glucose sensor protein, AcGFP1-GBPcys-mCherry, and an optical sensor assembly, capable of generating quantifiable FRET (fluorescence resonance energy transfer) signals for glucose monitoring. Our experimental data showed that the engineered glucose sensor protein can generate measurable FRET signals in response to glucose concentrations varying from 25 to 800 μM. The sensor developed based on this protein had a shelf-life of up to 3 weeks. The sensor response was devoid of interference from compounds like galactose, fructose, lactose, mannose, and mannitol when tested at physiologically significant concentrations of these compounds. This new glucose sensor protein can potentially be used to develop implantable glucose sensors for continuous glucose monitoring.

  15. 32 CFR 644.394 - Protection of disposal information.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 32 National Defense 4 2011-07-01 2011-07-01 false Protection of disposal information. 644.394... PROPERTY REAL ESTATE HANDBOOK Disposal Predisposal Action § 644.394 Protection of disposal information. To... to Army or Air Force requirements. (The Air Force preliminary real estate disposal directive is not...

  16. 10 CFR 20.2005 - Disposal of specific wastes.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 10 Energy 1 2014-01-01 2014-01-01 false Disposal of specific wastes. 20.2005 Section 20.2005 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2005 Disposal of specific wastes. (a) A licensee may dispose of the following licensed material as if it...

  17. 10 CFR 20.2005 - Disposal of specific wastes.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 10 Energy 1 2010-01-01 2010-01-01 false Disposal of specific wastes. 20.2005 Section 20.2005 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2005 Disposal of specific wastes. (a) A licensee may dispose of the following licensed material as if it...

  18. 36 CFR 13.1604 - Solid waste disposal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Solid waste disposal. 13.1604... Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be located within...

  19. 36 CFR 13.1912 - Solid waste disposal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Solid waste disposal. 13.1912....1912 Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be...

  20. 10 CFR 20.2005 - Disposal of specific wastes.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 10 Energy 1 2013-01-01 2013-01-01 false Disposal of specific wastes. 20.2005 Section 20.2005 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2005 Disposal of specific wastes. (a) A licensee may dispose of the following licensed material as if it...

  1. 36 CFR 13.1604 - Solid waste disposal.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 36 Parks, Forests, and Public Property 1 2014-07-01 2014-07-01 false Solid waste disposal. 13.1604... Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be located within...

  2. 10 CFR 20.2005 - Disposal of specific wastes.

    Code of Federal Regulations, 2011 CFR

    2011-01-01

    ... 10 Energy 1 2011-01-01 2011-01-01 false Disposal of specific wastes. 20.2005 Section 20.2005 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2005 Disposal of specific wastes. (a) A licensee may dispose of the following licensed material as if it...

  3. 36 CFR 13.1912 - Solid waste disposal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Solid waste disposal. 13.1912....1912 Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be...

  4. 36 CFR 13.1912 - Solid waste disposal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 36 Parks, Forests, and Public Property 1 2012-07-01 2012-07-01 false Solid waste disposal. 13.1912....1912 Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be...

  5. 36 CFR 13.1604 - Solid waste disposal.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 36 Parks, Forests, and Public Property 1 2013-07-01 2013-07-01 false Solid waste disposal. 13.1604... Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be located within...

  6. 10 CFR 20.2005 - Disposal of specific wastes.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 10 Energy 1 2012-01-01 2012-01-01 false Disposal of specific wastes. 20.2005 Section 20.2005 Energy NUCLEAR REGULATORY COMMISSION STANDARDS FOR PROTECTION AGAINST RADIATION Waste Disposal § 20.2005 Disposal of specific wastes. (a) A licensee may dispose of the following licensed material as if it...

  7. 30 CFR 817.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Disposal of noncoal mine wastes. 817.89 Section... ACTIVITIES § 817.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  8. 30 CFR 816.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Disposal of noncoal mine wastes. 816.89 Section... ACTIVITIES § 816.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  9. 30 CFR 817.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... 30 Mineral Resources 3 2012-07-01 2012-07-01 false Disposal of noncoal mine wastes. 817.89 Section... ACTIVITIES § 817.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  10. 30 CFR 816.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Disposal of noncoal mine wastes. 816.89 Section... ACTIVITIES § 816.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  11. 30 CFR 817.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2014 CFR

    2014-07-01

    ... 30 Mineral Resources 3 2014-07-01 2014-07-01 false Disposal of noncoal mine wastes. 817.89 Section... ACTIVITIES § 817.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  12. 30 CFR 816.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 30 Mineral Resources 3 2010-07-01 2010-07-01 false Disposal of noncoal mine wastes. 816.89 Section... ACTIVITIES § 816.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  13. 30 CFR 817.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Disposal of noncoal mine wastes. 817.89 Section... ACTIVITIES § 817.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  14. 30 CFR 817.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Disposal of noncoal mine wastes. 817.89 Section... ACTIVITIES § 817.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  15. 30 CFR 816.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 30 Mineral Resources 3 2011-07-01 2011-07-01 false Disposal of noncoal mine wastes. 816.89 Section... ACTIVITIES § 816.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  16. 30 CFR 816.89 - Disposal of noncoal mine wastes.

    Code of Federal Regulations, 2013 CFR

    2013-07-01

    ... 30 Mineral Resources 3 2013-07-01 2013-07-01 false Disposal of noncoal mine wastes. 816.89 Section... ACTIVITIES § 816.89 Disposal of noncoal mine wastes. (a) Noncoal mine wastes including, but not limited to... disposal of noncoal mine wastes shall be in a designated disposal site in the permit area or a...

  17. 48 CFR 45.605 - Inventory disposal reports.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 1 2010-10-01 2010-10-01 false Inventory disposal reports... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 45.605 Inventory disposal reports. The plant clearance officer shall promptly prepare an SF 1424, Inventory Disposal Report,...

  18. 48 CFR 45.605 - Inventory disposal reports.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 1 2011-10-01 2011-10-01 false Inventory disposal reports... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal 45.605 Inventory disposal reports. The plant clearance officer shall promptly prepare an SF 1424, Inventory Disposal Report,...

  19. 48 CFR 1345.604 - Disposal of surplus property.

    Code of Federal Regulations, 2013 CFR

    2013-10-01

    ... 48 Federal Acquisition Regulations System 5 2013-10-01 2013-10-01 false Disposal of surplus... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal § 1345.604 Disposal of surplus property. Surplus property shall be disposed of in accordance with procedures outlined in the DOC Personal Property...

  20. 48 CFR 1345.604 - Disposal of surplus property.

    Code of Federal Regulations, 2012 CFR

    2012-10-01

    ... 48 Federal Acquisition Regulations System 5 2012-10-01 2012-10-01 false Disposal of surplus... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal § 1345.604 Disposal of surplus property. Surplus property shall be disposed of in accordance with procedures outlined in the DOC Personal Property...

  1. 48 CFR 1345.604 - Disposal of surplus property.

    Code of Federal Regulations, 2011 CFR

    2011-10-01

    ... 48 Federal Acquisition Regulations System 5 2011-10-01 2011-10-01 false Disposal of surplus... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal § 1345.604 Disposal of surplus property. Surplus property shall be disposed of in accordance with procedures outlined in the DOC Personal Property...

  2. 48 CFR 1345.604 - Disposal of surplus property.

    Code of Federal Regulations, 2010 CFR

    2010-10-01

    ... 48 Federal Acquisition Regulations System 5 2010-10-01 2010-10-01 false Disposal of surplus... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal § 1345.604 Disposal of surplus property. Surplus property shall be disposed of in accordance with procedures outlined in the DOC Personal Property...

  3. 48 CFR 1345.604 - Disposal of surplus property.

    Code of Federal Regulations, 2014 CFR

    2014-10-01

    ... 48 Federal Acquisition Regulations System 5 2014-10-01 2014-10-01 false Disposal of surplus... MANAGEMENT GOVERNMENT PROPERTY Reporting, Reutilization, and Disposal § 1345.604 Disposal of surplus property. Surplus property shall be disposed of in accordance with procedures outlined in the DOC Personal Property...

  4. 36 CFR 13.1008 - Solid waste disposal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Solid waste disposal. 13.1008... § 13.1008 Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be...

  5. 36 CFR 13.1604 - Solid waste disposal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Solid waste disposal. 13.1604... Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be located within one...

  6. 36 CFR 13.1912 - Solid waste disposal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 1 2011-07-01 2011-07-01 false Solid waste disposal. 13.1912....1912 Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be located...

  7. 36 CFR 228.57 - Types of disposal.

    Code of Federal Regulations, 2012 CFR

    2012-07-01

    ... Disposal of Mineral Materials Types and Methods of Disposal § 228.57 Types of disposal. Except as provided in § 228.41(b), disposal of mineral materials may be made by: (a) Competitive sale to the highest... contract. (1) For removal of materials to be used in connection with a public works improvement program on...

  8. 12 CFR 717.83 - Disposal of consumer information.

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 12 Banks and Banking 7 2013-01-01 2013-01-01 false Disposal of consumer information. 717.83... FAIR CREDIT REPORTING Duties of Users of Consumer Reports Regarding Address Discrepancies and Records Disposal § 717.83 Disposal of consumer information. (a) In general. You must properly dispose of any...

  9. 12 CFR 717.83 - Disposal of consumer information.

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 12 Banks and Banking 7 2012-01-01 2012-01-01 false Disposal of consumer information. 717.83... FAIR CREDIT REPORTING Duties of Users of Consumer Reports Regarding Address Discrepancies and Records Disposal § 717.83 Disposal of consumer information. (a) In general. You must properly dispose of any...

  10. 12 CFR 717.83 - Disposal of consumer information.

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 12 Banks and Banking 7 2014-01-01 2014-01-01 false Disposal of consumer information. 717.83... FAIR CREDIT REPORTING Duties of Users of Consumer Reports Regarding Address Discrepancies and Records Disposal § 717.83 Disposal of consumer information. (a) In general. You must properly dispose of any...

  11. 40 CFR 761.97 - Export for disposal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 40 Protection of Environment 30 2010-07-01 2010-07-01 false Export for disposal. 761.97 Section... PROHIBITIONS Transboundary Shipments of PCBs for Disposal § 761.97 Export for disposal. (a) General provisions. No person may export PCBs or PCB Items for disposal without an exemption, except that: (1) PCBs...

  12. 36 CFR 228.57 - Types of disposal.

    Code of Federal Regulations, 2011 CFR

    2011-07-01

    ... 36 Parks, Forests, and Public Property 2 2011-07-01 2011-07-01 false Types of disposal. 228.57 Section 228.57 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.57 Types of disposal. Except as provided...

  13. 36 CFR 228.57 - Types of disposal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 2 2010-07-01 2010-07-01 false Types of disposal. 228.57 Section 228.57 Parks, Forests, and Public Property FOREST SERVICE, DEPARTMENT OF AGRICULTURE MINERALS Disposal of Mineral Materials Types and Methods of Disposal § 228.57 Types of disposal. Except as provided...

  14. 36 CFR 13.1008 - Solid waste disposal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Solid waste disposal. 13.1008... § 13.1008 Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be...

  15. 36 CFR 13.1604 - Solid waste disposal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Solid waste disposal. 13.1604... Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be located within one...

  16. 36 CFR 13.1912 - Solid waste disposal.

    Code of Federal Regulations, 2010 CFR

    2010-07-01

    ... 36 Parks, Forests, and Public Property 1 2010-07-01 2010-07-01 false Solid waste disposal. 13.1912....1912 Solid waste disposal. (a) A solid waste disposal site may accept non-National Park Service solid waste generated within the boundaries of the park area. (b) A solid waste disposal site may be located...

  17. 12 CFR 717.83 - Disposal of consumer information.

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 12 Banks and Banking 6 2010-01-01 2010-01-01 false Disposal of consumer information. 717.83... FAIR CREDIT REPORTING Duties of Users of Consumer Reports Regarding Address Discrepancies and Records Disposal § 717.83 Disposal of consumer information. (a) In general. You must properly dispose of...

  18. Tear glucose detection combining microfluidic thread based device, amperometric biosensor and microflow injection analysis.

    PubMed

    Agustini, Deonir; Bergamini, Márcio F; Marcolino-Junior, Luiz Humberto

    2017-12-15

    The tear glucose analysis is an important alternative for the indirect, simple and less invasive monitoring of blood glucose levels. However, the high cost and complex manufacturing process of tear glucose analyzers combined with the need to exchange the sensor after each analysis in the disposable tests prevent widespread application of the tear in glucose monitoring. Here, we present the integration of a biosensor made by the electropolymerization of poly(toluidine blue O) (PTB) and glucose oxidase (GOx) with an electroanalytical microfluidic device of easy assembly based on cotton threads, low cost materials and measurements by microflow injection analysis (µFIA) through passive pumping for performing tear glucose analyses in a simple, rapid and inexpensive way. A high stability between the analyses (RSD = 2.54%) and among the different systems (RSD = 3.13%) was obtained for the determination of glucose, in addition to a wide linear range between 0.075 and 7.5mmolL(-1) and a limit of detection of 22.2µmolL(-1). The proposed method was efficiently employed in the determination of tear glucose in non-diabetic volunteers, obtaining a close correlation with their blood glucose levels, simplifying and reducing the costs of the analyses, making the tear glucose monitoring more accessible for the population. Copyright © 2017 Elsevier B.V. All rights reserved.

  19. Measurement of insulin sensitivity indices using 13C-glucose and gas chromatography/combustion/isotope ratio mass spectrometry.

    PubMed

    Clapperton, Allan T; Coward, W Andrew; Bluck, Leslie J C

    2002-01-01

    Important aspects of glucose metabolism can be quantified by using the minimal model of glucose kinetics to interpret the results of intravenous glucose tolerance tests. The power of this methodology can be greatly increased by the addition of stable isotopically labelled tracer to the glucose bolus dose. This allows the separation of glucose disposal from endogenous glucose production and also increases the precision of the estimates of the physiological parameters measured. Until now the tracer of choice has been deuteriated glucose and the analytical technique has been gas chromatography/mass spectrometry (GC/MS). The consequence of this choice is that nearly 2 g of labelled material are needed and this makes the test expensive. We have investigated the use of (13)C-labelled glucose as the tracer in combination with gas chromatography/combustion/isotope ratio mass spectrometry (GC/C/IRMS) as the analytical technique. This methodology offers superior analytical precision when compared with the conventional method and so the amount of tracer used, and hence the cost, can be reduced considerably. Healthy non-obese male volunteers were recruited for a standard intravenous glucose tolerance test (IVGTT) protocol but 6,6-(2)H-glucose and 1-(13)C-glucose were administered simultaneously. Tracer/tracee ratios were derived from isotope ratio measurements of plasma glucose using both GC/MS and GC/C/IRMS. The results of these determinations indicated that the two tracers behaved identically under the test protocol. The combination of these results with plasma glucose and insulin concentration data allowed determination of the minimal model parameters S*g and S*i. The parameter relating to insulin-assisted glucose disposal, S*i, was found to be the same in the two techniques, but this was not the case for the non-insulin-dependent parameter S*g.

  20. Evaluation of a Self-Administered Oral Glucose Tolerance Test

    PubMed Central

    Bethel, M. Angelyn; Price, Hermione C.; Sourij, Harald; White, Sarah; Coleman, Ruth L.; Ring, Arne; Kennedy, Irene E.C.; Tucker, Lynne; Holman, Rury R.

    2013-01-01

    OBJECTIVE To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. RESEARCH DESIGN AND METHODS Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. RESULTS The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. CONCLUSIONS Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes. PMID:23321216

  1. Evaluation of a self-administered oral glucose tolerance test.

    PubMed

    Bethel, M Angelyn; Price, Hermione C; Sourij, Harald; White, Sarah; Coleman, Ruth L; Ring, Arne; Kennedy, Irene E C; Tucker, Lynne; Holman, Rury R

    2013-06-01

    To assess the feasibility of using a disposable, self-administered, capillary blood sampling oral glucose tolerance test (OGTT) device in a community setting. Eighteen healthy and 12 type 2 diabetic volunteers underwent six 75-g OGTTs using a prototype device in the following three settings: unaided at home (twice); unaided but observed in clinic (twice); and performed by a nurse with simultaneous laboratory glucose assays of 0- and 120-min venous plasma samples (twice). The device displayed no results. A detachable data recorder returned to the clinic provided plasma-equivalent 0- and 120-min glucose values and key parameters, including test date, start and end times, and time taken to consume the glucose drink. The device was universally popular with participants and was perceived as easy to use, and the ability to test at home was well liked. Device failures meant that 0- and 120-min glucose values were obtained for only 141 (78%) of the 180 OGTTs performed, independent of setting. Device glucose measurements showed a mean bias compared with laboratory-measured values of +0.9 at 5.0 mmol/L increasing to +4.4 at 15.0 mmol/L. Paired device glucose values were equally reproducible across settings, with repeat testing showing no training effect regardless of setting order. Self-administered OGTTs can be performed successfully by untrained individuals in a community setting. With improved device reliability and appropriate calibration, this novel technology could be used in routine practice to screen people who might need a formal OGTT to confirm the presence of impaired glucose tolerance or diabetes.

  2. Sensing of Salivary Glucose Using Nano-Structured Biosensors

    PubMed Central

    Du, Yunqing; Zhang, Wenjun; Wang, Ming L.

    2016-01-01

    The anxiety and pain associated with frequent finger pricking has always been troublesome for diabetics measuring blood glucose (BG) in their daily lives. For this reason, a reliable glucose monitoring system that allows noninvasive measurements is highly desirable. Our main objective is to develop a biosensor that can detect low-level glucose in saliva (physiological range 0.5–20 mg/dL). Salivary glucose (SG) sensors were built using a layer-by-layer self-assembly of single-walled carbon nanotubes, chitosan, gold nanoparticles, and glucose oxidase onto a screen-printed platinum electrode. An electrochemical method was utilized for the quantitative detection of glucose in both buffer solution and saliva samples. A standard spectrophotometric technique was used as a reference method to validate the glucose content of each sample. The disposable glucose sensors have a detection limit of 0.41 mg/dL, a sensitivity of 0.24 μA·s·dL·mg−1, a linear range of 0.5–20 mg/dL in buffer solution, and a response time of 30 s. A study of 10 healthy subjects was conducted, and SG levels between 1.1 to 10.1 mg/dL were successfully detected. The results revealed that the noninvasive SG monitoring could be an alternative for diabetes self-management at home. This paper is not intended to replace regular BG tests, but to study SG itself as an indicator for the quality of diabetes care. It can potentially help patients control and monitor their health conditions, enabling them to comply with prescribed treatments for diabetes. PMID:26999233

  3. Sensing of Salivary Glucose Using Nano-Structured Biosensors.

    PubMed

    Du, Yunqing; Zhang, Wenjun; Wang, Ming L

    2016-03-17

    The anxiety and pain associated with frequent finger pricking has always been troublesome for diabetics measuring blood glucose (BG) in their daily lives. For this reason, a reliable glucose monitoring system that allows noninvasive measurements is highly desirable. Our main objective is to develop a biosensor that can detect low-level glucose in saliva (physiological range 0.5-20 mg/dL). Salivary glucose (SG) sensors were built using a layer-by-layer self-assembly of single-walled carbon nanotubes, chitosan, gold nanoparticles, and glucose oxidase onto a screen-printed platinum electrode. An electrochemical method was utilized for the quantitative detection of glucose in both buffer solution and saliva samples. A standard spectrophotometric technique was used as a reference method to validate the glucose content of each sample. The disposable glucose sensors have a detection limit of 0.41 mg/dL, a sensitivity of 0.24 μA·s·dL·mg(-1), a linear range of 0.5-20 mg/dL in buffer solution, and a response time of 30 s. A study of 10 healthy subjects was conducted, and SG levels between 1.1 to 10.1 mg/dL were successfully detected. The results revealed that the noninvasive SG monitoring could be an alternative for diabetes self-management at home. This paper is not intended to replace regular BG tests, but to study SG itself as an indicator for the quality of diabetes care. It can potentially help patients control and monitor their health conditions, enabling them to comply with prescribed treatments for diabetes.

  4. Sodium-glucose cotransport

    PubMed Central

    Poulsen, Søren Brandt; Fenton, Robert A.; Rieg, Timo

    2017-01-01

    Purpose of review Sodium-glucose cotransporters (SGLTs) are important mediators of glucose uptake across apical cell membranes. SGLT1 mediates almost all sodium-dependent glucose uptake in the small intestine, while in the kidney SGLT2, and to a lesser extent SGLT1, account for more than 90% and nearly 3%, respectively, of glucose reabsorption from the glomerular ultrafiltrate. Although the recent availability of SGLT2 inhibitors for the treatment of diabetes mellitus has increased the number of clinical studies, this review has a focus on mechanisms contributing to the cellular regulation of SGLTs. Recent findings Studies have focused on the regulation of SGLT expression under different physiological/pathophysiological conditions, for example diet, age or diabetes mellitus. Several studies provide evidence of SGLT regulation via cyclic adenosine monophosphate/protein kinase A, protein kinase C, glucagon-like peptide 2, insulin, leptin, signal transducer and activator of transcription-3 (STAT3), phosphoinositide-3 kinase (PI3K)/Akt, mitogen-activated protein kinases (MAPKs), nuclear factor-kappaB (NF-kappaB), with-no-K[Lys] kinases/STE20/SPS1-related proline/alanine-rich kinase (Wnk/SPAK) and regulatory solute carrier protein 1 (RS1) pathways. Summary SGLT inhibitors are important drugs for glycemic control in diabetes mellitus. Although the contribution of SGLT1 for absorption of glucose from the intestine as well as SGLT2/SGLT1 for renal glucose reabsorption has been comprehensively defined, this review provides an up-to-date outline for the mechanistic regulation of SGLT1/SGLT2. PMID:26125647

  5. Continuous Glucose Monitoring

    PubMed Central

    Fritschi, Cynthia; Quinn, Laurie; Penckofer, Sue; Surdyk, Patricia M.

    2010-01-01

    Purpose The purpose of this descriptive study was to document the experience of wearing a continuous glucose monitoring (CGM) device in women with type 2 diabetes (T2DM). The availability of CGM has provided patients and clinicians with the opportunity to describe the immediate effects of diet, exercise, and medications on blood glucose levels; however, there are few data examining patients’ experiences and acceptability of using CGM. Methods Thirty-five women with T2DM wore a CGM for 3 days. Semistructured interviews were conducted to capture the self-described experience of wearing a CGM. Three open-ended questions were used to guide the participants’ self-reflection. Interviews were transcribed and analyzed. Results The women verbalized both positive and negative aspects of needing to check their blood glucose more frequently and wearing the monitor. After viewing the results, most women were surprised by the magnitude and frequency of blood glucose excursions. They immediately examined their behaviors during the time they wore the CGM. Independent problem-solving skills became apparent as they attempted to identify reasons for hyperglycemia by retracing food intake, physical activity, and stress experiences during the period of CGM. Most important, the majority of women stated they were interested in changing their diabetes-related self-care behaviors, especially eating and exercise behaviors, after reviewing their CGM results. Conclusions CGM is generally acceptable to women with T2DM and offers patients and their health care practitioners a possible alternative to routine glucose monitoring for assessing the effects of real-life events on blood glucose levels. PMID:20016057

  6. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning

    PubMed Central

    Weiss, Ram; Dufour, Sylvie; Taksali, Sara E; Tambortlane, William V; Petersen, Kitt F; Bonadonna, Riccardo C; Boselli, Linda; Barbetta, Gina; Alle, Karin; Rife, Francis; Savoye, Mary; Dziura, James; Sherwin, Robert; Shulman, Gerald I; Caprio, Sonia

    2010-01-01

    Summary Background Impaired glucose tolerance is common among obese adolescents, but the changes in insulin sensitivity and secretion that lead to this prediabetic state are unknown. We investigated whether altered partitioning of myocellular and abdominal fat relates to abnormalities in glucose homoeostasis in obese adolescents with prediabetes. Methods We studied 14 obese children with impaired glucose tolerance and 14 with normal glucose tolerance, of similar ages, sex distribution, and degree of obesity. Insulin sensitivity and secretion were assessed by the euglycaemichyperinsulinaemic clamp and the hyperglycaemic clamp. Intramyocellular lipid was assessed by proton nuclear magnetic resonance spectroscopy and abdominal fat distribution by magnetic resonance imaging. Findings Peripheral glucose disposal was significantly lower in individuals with impaired than in those with normal glucose tolerance (mean 35·4 [SE 4·0] vs 60·6 [7·2] μmoles per kg lean body mass per min; p=0·023) owing to a reduction in non-oxidative glucose disposal metabolism (storage). Individuals with impaired glucose tolerance had higher intramyocellular lipid content (3·04 [0·43] vs 1·99 [0·19]%, p=0·03), lower abdominal subcutaneous fat (460 [47] vs 626 [39] cm2, p=0·04), and slightly higher visceral fat than the controls (70 [11] vs 47 [6] cm2, p=0·065), resulting in a higher ratio of visceral to subcutaneous fat (0·15 [0·02] vs 0·07 [0·01], p=0·002). Intramyocellular and visceral lipid contents were inversely related to the glucose disposal and non-oxidative glucose metabolism and positively related to the 2 h plasma glucose concentration. Interpretation In obese children and adolescents with prediabetes, intramyocellular and intra-abdominal lipid accumulation is closely linked to the development of severe peripheral insulin resistance. PMID:14511928

  7. Prediabetes in obese youth: a syndrome of impaired glucose tolerance, severe insulin resistance, and altered myocellular and abdominal fat partitioning.

    PubMed

    Weiss, Ram; Dufour, Sylvie; Taksali, Sara E; Tamborlane, William V; Petersen, Kitt F; Bonadonna, Riccardo C; Boselli, Linda; Barbetta, Gina; Allen, Karin; Rife, Francis; Savoye, Mary; Dziura, James; Sherwin, Robert; Shulman, Gerald I; Caprio, Sonia

    2003-09-20

    Impaired glucose tolerance is common among obese adolescents, but the changes in insulin sensitivity and secretion that lead to this prediabetic state are unknown. We investigated whether altered partitioning of myocellular and abdominal fat relates to abnormalities in glucose homoeostasis in obese adolescents with prediabetes. We studied 14 obese children with impaired glucose tolerance and 14 with normal glucose tolerance, of similar ages, sex distribution, and degree of obesity. Insulin sensitivity and secretion were assessed by the euglycaemic-hyperinsulinaemic clamp and the hyperglycaemic clamp. Intramyocellular lipid was assessed by proton nuclear magnetic resonance spectroscopy and abdominal fat distribution by magnetic resonance imaging. Peripheral glucose disposal was significantly lower in individuals with impaired than in those with normal glucose tolerance (mean 35.4 [SE 4.0] vs 60.6 [7.2] micromoles per kg lean body mass per min; p=0.023) owing to a reduction in non-oxidative glucose disposal metabolism (storage). Individuals with impaired glucose tolerance had higher intramyocellular lipid content (3.04 [0.43] vs 1.99 [0.19]%, p=0.03), lower abdominal subcutaneous fat (460 [47] vs 626 [39] cm2, p=0.04), and slightly higher visceral fat than the controls (70 [11] vs 47 [6] cm2, p=0.065), resulting in a higher ratio of visceral to subcutaneous fat (0.15 [0.02] vs 0.07 [0.01], p=0.002). Intramyocellular and visceral lipid contents were inversely related to the glucose disposal and non-oxidative glucose metabolism and positively related to the 2 h plasma glucose concentration. In obese children and adolescents with prediabetes, intramyocellular and intra-abdominal lipid accumulation is closely linked to the development of severe peripheral insulin resistance.

  8. Subseabed Disposal Program Plan. Volume I. Overview

    SciTech Connect

    1981-07-01

    The primary objective of the Subseabed Disposal Program (SDP) is to assess the scientific, environmental, and engineering feasibility of disposing of processed and packaged high-level nuclear waste in geologic formations beneath the world's oceans. High-level waste (HLW) is considered the most difficult of radioactive wastes to dispose of in oceanic geologic formations because of its heat and radiation output. From a scientific standpoint, the understanding developed for the disposal of such HLW can be used for other nuclear wastes (e.g., transuranic - TRU - or low-level) and materials from decommissioned facilities, since any set of barriers competent to contain the heat and radiation outputs of high-level waste will also contain such outputs from low-level waste. If subseabed disposal is found to be feasible for HLW, then other factors such as cost will become more important in considering subseabed emplacement for other nuclear wastes. A secondary objective of the SDP is to develop and maintain a capability to assess and cooperate with the seabed nuclear waste disposal programs of other nations. There are, of course, a number of nations with nuclear programs, and not all of these nations have convenient access to land-based repositories for nuclear waste. Many are attempting to develop legislative and scientific programs that will avoid potential hazards to man, threats to other ocean uses, and marine pollution, and they work together to such purpose in meetings of the international NEA/Seabed Working Group. The US SDP, as the first and most highly developed R and D program in the area, strongly influences the development of subseabed-disposal-related policy in such nations.

  9. Redundancy in Glucose Sensing

    PubMed Central

    Sharifi, Amin; Varsavsky, Andrea; Ulloa, Johanna; Horsburgh, Jodie C.; McAuley, Sybil A.; Krishnamurthy, Balasubramanian; Jenkins, Alicia J.; Colman, Peter G.; Ward, Glenn M.; MacIsaac, Richard J.; Shah, Rajiv; O’Neal, David N.

    2015-01-01

    Background: Current electrochemical glucose sensors use a single electrode. Multiple electrodes (redundancy) may enhance sensor performance. We evaluated an electrochemical redundant sensor (ERS) incorporating two working electrodes (WE1 and WE2) onto a single subcutaneous insertion platform with a processing algorithm providing a single real-time continuous glucose measure. Methods: Twenty-three adults with type 1 diabetes each wore two ERSs concurrently for 168 hours. Post-insertion a frequent sampling test (FST) was performed with ERS benchmarked against a glucose meter (Bayer Contour Link). Day 4 and 7 FSTs were performed with a standard meal and venous blood collected for reference glucose measurements (YSI and meter). Between visits, ERS was worn with capillary blood glucose testing ≥8 times/day. Sensor glucose data were processed prospectively. Results: Mean absolute relative deviation (MARD) for ERS day 1-7 (3,297 paired points with glucose meter) was (mean [SD]) 10.1 [11.5]% versus 11.4 [11.9]% for WE1 and 12.0 [11.9]% for WE2; P < .0001. ERS Clarke A and A+B were 90.2% and 99.8%, respectively. ERS day 4 plus day 7 MARD (1,237 pairs with YSI) was 9.4 [9.5]% versus 9.6 [9.7]% for WE1 and 9.9 [9.7]% for WE2; P = ns. ERS day 1-7 precision absolute relative deviation (PARD) was 9.9 [3.6]% versus 11.5 [6.2]% for WE1 and 10.1 [4.4]% for WE2; P = ns. ERS sensor display time was 97.8 [6.0]% versus 91.0 [22.3]% for WE1 and 94.1 [14.3]% for WE2; P < .05. Conclusions: Electrochemical redundancy enhances glucose sensor accuracy and display time compared with each individual sensing element alone. ERS performance compares favorably with ‘best-in-class’ of non-redundant sensors. PMID:26499476

  10. 7 CFR 1484.36 - How do Cooperators dispose of disposable property?

    Code of Federal Regulations, 2013 CFR

    2013-01-01

    ... 7 Agriculture 10 2013-01-01 2013-01-01 false How do Cooperators dispose of disposable property? 1484.36 Section 1484.36 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS PROGRAMS TO HELP DEVELOP FOREIGN...

  11. 7 CFR 1484.36 - How do Cooperators dispose of disposable property?

    Code of Federal Regulations, 2010 CFR

    2010-01-01

    ... 7 Agriculture 10 2010-01-01 2010-01-01 false How do Cooperators dispose of disposable property? 1484.36 Section 1484.36 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE LOANS, PURCHASES, AND OTHER OPERATIONS PROGRAMS TO...

  12. 7 CFR 1484.36 - How do Cooperators dispose of disposable property?

    Code of Federal Regulations, 2014 CFR

    2014-01-01

    ... 7 Agriculture 10 2014-01-01 2014-01-01 false How do Cooperators dispose of disposable property? 1484.36 Section 1484.36 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS PROGRAMS TO HELP DEVELOP FOREIGN...

  13. 7 CFR 1484.36 - How do Cooperators dispose of disposable property?

    Code of Federal Regulations, 2012 CFR

    2012-01-01

    ... 7 Agriculture 10 2012-01-01 2012-01-01 false How do Cooperators dispose of disposable property? 1484.36 Section 1484.36 Agriculture Regulations of the Department of Agriculture (Continued) COMMODITY CREDIT CORPORATION, DEPARTMENT OF AGRICULTURE EXPORT PROGRAMS PROGRAMS TO HELP DEVELOP FOREIGN...

  14. Reducing Liver Fat by Low Carbohydrate Caloric Restriction Targets Hepatic Glucose Production in Non-Diabetic Obese Adults with Non-Alcoholic Fatty Liver Disease

    PubMed Central

    Yu, Haoyong; Jia, Weiping; Guo, ZengKui

    2014-01-01

    Non-alcoholic fatty liver disease (NAFLD) impairs liver functions, the organ responsible for the regulation of endogenous glucose production and thus plays a key role in glycemic homeostasis. Therefore, interventions designed to normalize liver fat content are needed to improve glucose metabolism in patients affected by NAFLD such as obesity. Objective: this investigation is designed to determine the effects of caloric restriction on hepatic and peripheral glucose metabolism in obese humans with NAFLD. Methods: eight non-diabetic obese adults were restricted for daily energy intake (800 kcal) and low carbohydrate (<10%) for 8 weeks. Body compositions, liver fat and hepatic glucose production (HGP) and peripheral glucose disposal before and after the intervention were determined. Results: the caloric restriction reduced liver fat content by 2/3 (p = 0.004). Abdominal subcutaneous and visceral fat, body weight, BMI, waist circumference and fasting plasma triglyceride and free fatty acid concentrations all significantly decreased (p < 0.05). The suppression of post-load HGP was improved by 22% (p = 0.002) whereas glucose disposal was not affected (p = 0.3). Fasting glucose remained unchanged and the changes in the 2-hour plasma glucose and insulin concentration were modest and statistically insignificant (p > 0.05). Liver fat is the only independent variable highly correlated to HGP after the removal of confounders. Conclusion: NAFLD impairs HGP but not peripheral glucose disposal; low carbohydrate caloric restriction effectively lowers liver fat which appears to directly correct the HGP impairment. PMID:25411646

  15. Contamination of disposable tonometer prisms during tonometry.

    PubMed

    Rajak, S N; Paul, J; Sharma, V; Vickers, S

    2006-03-01

    Due to the theoretical possibility of prion transmission in applanation tonometry, many ophthalmological units in the United Kingdom now use disposable tonometer prisms. We have investigated the potential for bacterial and viral transmission from the health practitioner to the patient via disposable prisms. All staff who perform applanation tonometry at the Sussex Eye Hospital (SEH) received a questionnaire to evaluate if the applanating face of the prism is touched during tonometry and the ease of use of the disposable prism compared to the reusable prisms that were previously used. We then cultured prisms handled by a random sample of staff members for common bacteria. Finally, we constructed a model to investigate the possibility of interpatient adenoviral transmission via disposable tonometer prisms. The questionnaire revealed that almost 50% of the staff admit to touching the applanating face of the tonometer prism prior to applanation. Cultures of the prisms grew a range of bacteria including Staphylococcus epidermidis, Staphylococcus aureus, and Bacillus species. The viral model suggested that adenovirus could be transmitted by applanation tonometry. The use of disposable prisms for applanation tonometry may reduce the risk of prion transmission but is not bacteriologically or virologically aseptic. This is a potential infection risk to patients.

  16. Salt sensitivity is associated with insulin resistance in essential hypertension.

    PubMed

    Fuenmayor, N; Moreira, E; Cubeddu, L X

    1998-04-01

    The relationship between salt sensitivity and insulin resistance was investigated in nondiabetic, nonobese (body mass index < or = 28) untreated patients with uncomplicated, mild-to-moderate essential hypertension. Alterations in insulin-mediated glucose disposal were assessed by means of the insulin suppression test. Subjects were classified as salt sensitive and salt resistant according to their blood pressure response to low and high salt intake. Fasting serum glucose levels were within normal limits and did not differ between salt sensitive and salt resistant hypertensives, irrespectively of the level of salt intake. Fasting serum insulin levels increased in salt sensitive patients when on a high intake of salt. The insulin suppression test revealed the existence of marked differences in insulin-mediated glucose uptake between salt sensitive and salt resistant hypertensives. Much higher steady-state glucose values (nanomoles of glucose/ liter) were obtained during the insulin suppression test in salt sensitive than in salt-resistant hypertensives (7.4+/-1.6 v 3.5+/-0.1 under low salt; and 12.5+/-1.1 v 4.3+/-0.1 under high salt intake). The product of glucose times insulin obtained at steady state during low and high salt intakes were 2.5 and 5 times greater, respectively, in salt sensitive than in salt resistant hypertensives. Therefore, the impairment in insulin-mediated glucose disposal observed in salt sensitive hypertensives was present both under low salt (60 to 70 mEq/day) and high salt intake (300 mEq/day). However, it was exacerbated under high salt intake. These results suggest that untreated salt sensitive hypertensives have a considerable impairment in insulin-mediated glucose disposal because of a state of insulin resistance. High salt intake increased BP, induced hyperinsulinemia, and worsened insulin-mediated glucose disposal only in salt sensitive patients. We propose that salt sensitivity contributes, separately from hypertension, to insulin

  17. ENVIRONMENTALLY SOUND DISPOSAL OF RADIOACTIVE MATERIALS AT A RCRA HAZARDOUS WASTE DISPOSAL FACILITY

    SciTech Connect

    Romano, Stephen; Welling, Steven; Bell, Simon

    2003-02-27

    The use of hazardous waste disposal facilities permitted under the Resource Conservation and Recovery Act (''RCRA'') to dispose of low concentration and exempt radioactive materials is a cost-effective option for government and industry waste generators. The hazardous and PCB waste disposal facility operated by US Ecology Idaho, Inc. near Grand View, Idaho provides environmentally sound disposal services to both government and private industry waste generators. The Idaho facility is a major recipient of U.S. Army Corps of Engineers FUSRAP program waste and received permit approval to receive an expanded range of radioactive materials in 2001. The site has disposed of more than 300,000 tons of radioactive materials from the federal government during the past five years. This paper presents the capabilities of the Grand View, Idaho hazardous waste facility to accept radioactive materials, site-specific acceptance criteria and performance assessment, radiological safety and environmental monitoring program information.

  18. Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis

    PubMed Central

    Lansey, Melissa N.; Walker, Natalie N.; Hargett, Stefan R.; Stevens, Joseph R.

    2012-01-01

    Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160−/−) mice. We observed increased and normal basal glucose uptake in isolated AS160−/− adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160−/− extensor digitorum longus muscles. In plasma membranes isolated from AS160−/− adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160−/− adipocytes and normal in AS160−/− soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160−/− skeletal muscles and liver but not in AS160−/− adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis. PMID:23011063

  19. Deletion of Rab GAP AS160 modifies glucose uptake and GLUT4 translocation in primary skeletal muscles and adipocytes and impairs glucose homeostasis.

    PubMed

    Lansey, Melissa N; Walker, Natalie N; Hargett, Stefan R; Stevens, Joseph R; Keller, Susanna R

    2012-11-15

    Tight control of glucose uptake in skeletal muscles and adipocytes is crucial to glucose homeostasis and is mediated by regulating glucose transporter GLUT4 subcellular distribution. In cultured cells, Rab GAP AS160 controls GLUT4 intracellular retention and release to the cell surface and consequently regulates glucose uptake into cells. To determine AS160 function in GLUT4 trafficking in primary skeletal muscles and adipocytes and investigate its role in glucose homeostasis, we characterized AS160 knockout (AS160(-/-)) mice. We observed increased and normal basal glucose uptake in isolated AS160(-/-) adipocytes and soleus, respectively, while insulin-stimulated glucose uptake was impaired and GLUT4 expression decreased in both. No such abnormalities were found in isolated AS160(-/-) extensor digitorum longus muscles. In plasma membranes isolated from AS160(-/-) adipose tissue and gastrocnemius/quadriceps, relative GLUT4 levels were increased under basal conditions and remained the same after insulin treatment. Concomitantly, relative levels of cell surface-exposed GLUT4, determined with a glucose transporter photoaffinity label, were increased in AS160(-/-) adipocytes and normal in AS160(-/-) soleus under basal conditions. Insulin augmented cell surface-exposed GLUT4 in both. These observations suggest that AS160 is essential for GLUT4 intracellular retention and regulation of glucose uptake in adipocytes and skeletal muscles in which it is normally expressed. In vivo studies revealed impaired insulin tolerance in the presence of normal (male) and impaired (female) glucose tolerance. Concurrently, insulin-elicited increases in glucose disposal were abolished in all AS160(-/-) skeletal muscles and liver but not in AS160(-/-) adipose tissues. This suggests AS160 as a target for differential manipulation of glucose homeostasis.

  20. Glucose Tolerance and Hyperkinesis.

    ERIC Educational Resources Information Center

    Langseth, Lillian; Dowd, Judith

    Examined were medical records of 265 hyperkinetic children (7-9 years old). Clinical blood chemistries, hematology, and 5-hour glucose tolerance test (GTT) results indicated that hematocrit levels were low in 27% of the Ss, eosinophil levels were abnormally high in 86% of the Ss, and GTT results were abnormal in a maority of Ss. (CL)

  1. Glucose Tolerance and Hyperkinesis.

    ERIC Educational Resources Information Center

    Langseth, Lillian; Dowd, Judith

    Examined were medical records of 265 hyperkinetic children (7-9 years old). Clinical blood chemistries, hematology, and 5-hour glucose tolerance test (GTT) results indicated that hematocrit levels were low in 27% of the Ss, eosinophil levels were abnormally high in 86% of the Ss, and GTT results were abnormal in a maority of Ss. (CL)

  2. Implantable continuous glucose sensors.

    PubMed

    Renard, Eric

    2008-08-01

    Because of the limits of wearable needle-type or microdialysis-based enzymatic sensors in clinical use, fully implantable glucose monitoring systems (IGMS) represent a promising alternative. Long-term use reducing impact of invasiveness due to implantation, less frequent calibration needs because of a more stable tissue environment around the sensor and potential easier inclusion in a closed-loop insulin delivery system are the expected benefits of IGMS. First experiences with subcutaneous and intravenous IGMS have been recently collected in pilot studies. While no severe adverse events have been reported, biointerface issues have been responsible for the failures of IGMS. Tissue reactions around implanted subcutaneous devices and damages of intravenous sensors due to shearing forces of blood flow impaired IGMS function and longevity. In functioning systems, accuracy of glucose measurement reached satisfactory levels for average durations of about 120 days with subcutaneous IGMS and 259 days with intravenous sensors. Moreover, sensor information could help to improve time spent in normal glucose range when provided to patients wearing subcutaneous IGMS and allowed safe and effective closed-loop glucose control when intravenous sensors were connected to implanted pumps using intra-peritoneal insulin delivery. These data could open a favourable perspective for IGMS after improvement of biointerface conditions and if compatible with an affordable cost.

  3. Continuous Glucose Monitoring

    MedlinePlus

    ... to reduce the burden of monitoring and managing blood glucose. An artificial pancreas based on mechanical devices requires at least ... MiniMed Paradigm REAL-Time System—is not an artificial pancreas, but it does ... pricking a fingertip to obtain a blood sample and using a glu cose meter to ...

  4. AMP-activated protein kinase (AMPK)α2 plays a role in determining the cellular fate of glucose in insulin-resistant mouse skeletal muscle

    PubMed Central

    Lee-Young, R.S.; Bonner, J.S.; Mayes, W.H.; Iwueke, I.; Barrick, B.A.; Hasenour, C.M.; Kang, L.; Wasserman, D.H.

    2014-01-01

    Aims/hypothesis We determined whether: (1) an acute lipid infusion impairs skeletal muscle AMP-activated protein kinase (AMPK)α2 activity, increases inducible nitric oxide synthase (iNOS) and causes peripheral insulin resistance in conscious, unstressed, lean mice; and (2) restoration of AMPKα2 activity during the lipid infusion attenuates the increase in iNOS and reverses the defect in insulin sensitivity in vivo. Methods Chow-fed, 18-week-old C57BL/6J male mice were surgically catheterised. After 5 days they received: (1) a 5 h infusion of 5 ml kg−1 h−1 Intralipid + 6U/h heparin (Lipid treatment) or saline (Control); (2) Lipid treatment or Control, followed by a 2 h hyperinsulinaemic–euglycaemic clamp (insulin clamp; 4 mU kg−1 min−1); and (3) infusion of the AMPK activator, 5-aminoimidazole-4-carboxamide 1-β-d-ribofuranoside (AICAR) (1 mg kg−1 min−1), or saline during Lipid treatment, followed by a 2 h insulin clamp. In a separate protocol, mice producing a muscle-specific kinase-dead AMPKα2 subunit (α2-KD) underwent an insulin clamp to determine the role of AMPKα2 in insulin-mediated muscle glucose metabolism. Results Lipid treatment decreased AMPKα2 activity, increased iNOS abundance/activation and reduced whole-body insulin sensitivity in vivo. AICAR increased AMPKα2 activity twofold; this did not suppress iNOS or improve whole-body or tissue-specific rates of glucose uptake during Lipid treatment. AICAR caused a marked increase in insulin-mediated glycogen synthesis in skeletal muscle. Consistent with this latter result, lean α2-KD mice exhibited impaired insulinstimulated glycogen synthesis even though muscle glucose uptake was not affected. Conclusions/interpretation Acute induction of insulin resistance via lipid infusion in healthy mice impairs AMPKα2, increases iNOS and causes insulin resistance in vivo. However, these changes do not appear to be interrelated. Rather, a functionally active AMPKα2 subunit is required for insulin

  5. Johnston Atoll Chemical Agent Disposal System (JACADS)

    SciTech Connect

    Not Available

    1990-06-01

    This Final Second Supplemental Environmental Impact Statement (SSEIS) to the Johnston Atoll Chemical Agent Disposal System (JACADS) Environmental Impact Statement (EIS) assesses the effects of receiving, storing, and ultimately destructing the United States stockpile of lethal unitary chemical munitions currently stored in the Federal Republic of Germany (FRG) (European stockpile) at the Army's JACADS facility located on Johnston Atoll in the Pacific Ocean. This Final SSEIS addresses the effects of the following proposed European stockpile activities: the transport of the European stockpile from the territorial limit to Johnston Island, the unloading of munitions from transportation ships, the on-island munitions transport and handling, on-island munitions storage, the disposal of munitions in the JACADS facility, the disposal of incineration wastes, and alternatives to the proposed action. This document also updates information in the 1983 EIS and the 1988 SEIS, as appropriate. 46 refs., 10 figs., 9 tabs.

  6. Workshop on disposable fuel cells. Final report

    SciTech Connect

    Smyrl, W.H.

    1996-12-01

    The objective of the present workshop was to assess the feasibility of a low-power disposable fuel cell. The technological basis for the concept was evaluated along with the barriers that must be overcome for its development. The scope was limited to systems with a useful life of 500 hours or less and a power production of 1 kilowatt or less. Tabulated results reveal that such a system would have advantages related to mass over competitive batteries or other power systems, and this workshop compared other characteristics of such systems as well. Disposable devices infer that a major consideration will be the cost, but there is also implied a limited environment burden. The consensus of the participants was that a disposable fuel cell (DFC) is a viable concept and that there is merit pursuing its development.

  7. Colors in Disposable Diapers: Addressing Myths.

    PubMed

    Evans, Eric B; Helmes, C Tucker; Kirsch, Taryn; Ruble, Karen M

    2014-08-01

    Colors are frequently added to disposable diapers to enhance the diapering experience. The colors in the interior of diapers are composed of nonsensitizing pigments that are bound during the fiber-making process into the fibers of the nonwoven that covers the absorbent core materials. In the past, the use of color in diapers has been called into question based on the presumed use of disperse dyes, known sensitizers in the textile industry, and erroneous reports in literature. In fact, disperse dyes are not used in leading disposable diapers; the colors used in these disposable diapers are nonsensitizing pigments with favorable safety profiles. Numerous safety tests, such as skin patch tests with pigments used on diaper backsheets, have found no evidence of skin irritation or sensitization.

  8. Oklahoma's recent earthquakes and saltwater disposal.

    PubMed

    Walsh, F Rall; Zoback, Mark D

    2015-06-01

    Over the past 5 years, parts of Oklahoma have experienced marked increases in the number of small- to moderate-sized earthquakes. In three study areas that encompass the vast majority of the recent seismicity, we show that the increases in seismicity follow 5- to 10-fold increases in the rates of saltwater disposal. Adjacent areas where there has been relatively little saltwater disposal have had comparatively few recent earthquakes. In the areas of seismic activity, the saltwater disposal principally comes from "produced" water, saline pore water that is coproduced with oil and then injected into deeper sedimentary formations. These formations appear to be in hydraulic communication with potentially active faults in crystalline basement, where nearly all the earthquakes are occurring. Although most of the recent earthquakes have posed little danger to the public, the possibility of triggering damaging earthquakes on potentially active basement faults cannot be discounted.

  9. Qualifying radioactive waste forms for geologic disposal

    SciTech Connect

    Jardine, L.J.; Laidler, J.J.; McPheeters, C.C.

    1994-09-01

    We have developed a phased strategy that defines specific program-management activities and critical documentation for producing radioactive waste forms, from pyrochemical processing of spent nuclear fuel, that will be acceptable for geologic disposal by the US Department of Energy. The documentation of these waste forms begins with the decision to develop the pyroprocessing technology for spent fuel conditioning and ends with production of the last waste form for disposal. The need for this strategy is underscored by the fact that existing written guidance for establishing the acceptability for disposal of radioactive waste is largely limited to borosilicate glass forms generated from the treatment of aqueous reprocessing wastes. The existing guidance documents do not provide specific requirements and criteria for nonstandard waste forms such as those generated from pyrochemical processing operations.

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

    SciTech Connect

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

    2013-02-15

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

  11. Municipal solid wastes and their disposal.

    PubMed Central

    Stone, R

    1978-01-01

    A brief overview is given of the sources, characteristics, and toxic constituents of municipal solid wastes. Several methods are presented for handling, treating, and disposal of solid wastes. Monitoring the landfill site is necessary; there has been a trend to recognize that municipal solid wastes may be hazardous and to provide separate secure handling, treatment, and disposal for their dangerous constituents. Under current state and Federal regulations, permits are being required to assure that proper handling of conventional solid wastes and more hazardous constituents are carefully managed. PMID:738240

  12. Reusable acoustic tweezers for disposable devices

    PubMed Central

    Guo, Feng; Xie, Yuliang; Li, Sixing; Lata, James; Ren, Liqiang; Mao, Zhangming; Ren, Baiyang; Wu, Mengxi; Ozcelik, Adem

    2015-01-01

    We demonstrate acoustic tweezers used for disposable devices. Rather than forming an acoustic resonance, we locally transmitted standing surface acoustic waves into a removable, independent polydimethylsiloxane (PDMS)-glass hybridized microfluidic superstrate device for micromanipulation. By configuring and regulating the displacement nodes on a piezoelectric substrate, cells and particles were effectively patterned and transported into said superstrate, accordingly. With the label-free and contactless nature of acoustic waves, the presented technology could offer a simple, accurate, low-cost, biocompatible, and disposable method for applications in the fields of point-of-care diagnostics and fundamental biomedical studies. PMID:26507411

  13. Electrochemical apparatus comprising modified disposable rectangular cuvette

    DOEpatents

    Dattelbaum, Andrew M; Gupta, Gautam; Morris, David E

    2013-09-10

    Electrochemical apparatus includes a disposable rectangular cuvette modified with at least one hole through a side and/or the bottom. Apparatus may include more than one cuvette, which in practice is a disposable rectangular glass or plastic cuvette modified by drilling the hole(s) through. The apparatus include two plates and some means of fastening one plate to the other. The apparatus may be interfaced with a fiber optic or microscope objective, and a spectrometer for spectroscopic studies. The apparatus are suitable for a variety of electrochemical experiments, including surface electrochemistry, bulk electrolysis, and flow cell experiments.

  14. Co-disposal of mixed waste materials

    SciTech Connect

    Phillips, S.J.; Alexander, R.G.; Crane, P.J.; England, J.L.; Kemp, C.J.; Stewart, W.E.

    1993-08-01

    Co-disposal of process waste streams with hazardous and radioactive materials in landfills results in large, use-efficiencies waste minimization and considerable cost savings. Wasterock, produced from nuclear and chemical process waste streams, is segregated, treated, tested to ensure regulatory compliance, and then is placed in mixed waste landfills, burial trenches, or existing environmental restoration sites. Large geotechnical unit operations are used to pretreat, stabilize, transport, and emplace wasterock into landfill or equivalent subsurface structures. Prototype system components currently are being developed for demonstration of co-disposal.

  15. Improving surface coal refuse disposal site inspections

    SciTech Connect

    Meister, R.A.; Hoffman, R.L.

    1980-06-01

    The study on improving surface coal refuse disposal site inspections included surface inspections of 15 refuse disposal sites. Monthly aerial photos were taken of the sites and computer methods were used to determine elevation changes. Photogrammetric techniques that were used are described in detail. A comparison of the results of each of these inspection techniques is included. A detailed evaluation of the photogrammetric techniques was made and conclusions were drawn concerning the advantages and disadvantages of using aerial photography and photogrammetry as part of the inspection procedure. Operators' opinions of the aerial photography methods are included.

  16. Environmental restoration waste materials co-disposal

    SciTech Connect

    Phillips, S.J.; Alexander, R.G.; England, J.L.; Kirdendall, J.R.; Raney, E.A.; Stewart, W.E.; Dagan, E.B.; Holt, R.G.

    1993-09-01

    Co-disposal of radioactive and hazardous waste is a highly efficient and cost-saving technology. The technology used for final treatment of soil-washing size fractionization operations is being demonstrated on simulated waste. Treated material (wasterock) is used to stabilize and isolate retired underground waste disposal structures or is used to construct landfills or equivalent surface or subsurface structures. Prototype equipment is under development as well as undergoing standardized testing protocols to prequalify treated waste materials. Polymer and hydraulic cement solidification agents are currently used for geotechnical demonstration activities.

  17. Relative risk assessment of cruise ships biosolids disposal alternatives.

    PubMed

    Avellaneda, Pedro M; Englehardt, James D; Olascoaga, Josefina; Babcock, Elizabeth A; Brand, Larry; Lirman, Diego; Rogge, Wolfgang F; Solo-Gabriele, Helena; Tchobanoglous, George

    2011-10-01

    A relative risk assessment of biosolids disposal alternatives for cruise ships is presented in this paper. The area of study encompasses islands and marine waters of the Caribbean Sea. The objective was to evaluate relative human health and ecological risks of (a) dewatering/incineration, (b) landing the solids for disposal, considering that in some countries land-disposed solids might be discharged in the near-shore environment untreated, and (c) deep ocean disposal. Input to the Bayesian assessment consisted of professional judgment based on available literature and modeling information, data on constituent concentrations in cruise ship biosolids, and simulations of constituent concentrations in Caribbean waters assuming ocean disposal. Results indicate that human health and ecological risks associated with land disposal and shallow ocean disposal are higher than those of the deep ocean disposal and incineration. For incineration, predicted ecological impacts were lower relative to deep ocean disposal before considering potential impacts of carbon emissions.

  18. The glucose sensor protein glucokinase is expressed in glucagon-producing alpha-cells.

    PubMed Central

    Heimberg, H; De Vos, A; Moens, K; Quartier, E; Bouwens, L; Pipeleers, D; Van Schaftingen, E; Madsen, O; Schuit, F

    1996-01-01

    Expression of glucokinase in hepatocytes and pancreatic 6-cells is of major physiologic importance to mammalian glucose homeostasis. Liver glucokinase catalyzes the first committed step in the disposal of glucose, and beta-cell glucokinase catalyzes a rate-limiting step required for glucose-regulated insulin release. The present study reports the expression of glucokinase in rat glucagon-producing alpha-cells, which are negatively regulated by glucose. Purified rat alpha-cells express glucokinase mRNA and protein with the same transcript length, nucleotide sequence, and immunoreactivity as the beta-cell isoform. Glucokinase activity accounts for more than 50% of glucose phosphorylation in extracts of alpha-cells and for more than 90% of glucose utilization in intact cells. The glucagon-producing tumor MSL-G-AN also contained glucokinase mRNA, protein, and enzymatic activity. These data indicate that glucokinase may serve as a metabolic glucose sensor in pancreatic alpha-cells and, hence, mediate a mechanism for direct regulation of glucagon release by extracellular glucose. Since these cells do not express Glut2, we suggest that glucose sensing does not necessarily require the coexpression of Glut2 and glucokinase. Images Fig. 1 Fig. 2 Fig. 3 Fig. 4 PMID:8692940

  19. The disposal of orphan wastes using the greater confinement disposal concept

    SciTech Connect

    Bonano, E.J.; Chu, M.S.Y.; Price, L.L.; Conrad, S.H.; Dickman, P.T.

    1991-02-01

    In the United States, radioactive wastes are conventionally classified as high-level wastes, transuranic wastes, or low-level wastes. Each of these types of wastes, by law, has a ``home`` for their final disposal; i.e., high-level wastes are destined for disposal at the proposed repository at Yucca Mountain, transuranic waste for the proposed Waste Isolation Pilot Plant, and low-level waste for shallow-land disposal sites. However, there are some radioactive wastes within the United States Department of Energy (DOE) complex that do not meet the criteria established for disposal of either high-level waste, transuranic waste, or low-level waste. The former are called ``special-case`` or ``orphan`` wastes. This paper describes an ongoing project sponsored by the DOE`s Nevada Operations Office for the disposal of orphan wastes at the Radioactive Waste Management Site at Area 5 of the Nevada Test Site using the greater confinement disposal (GCD) concept. The objectives of the GCD project are to evaluate the safety of the site for disposal of orphan wastes by assessing compliance with pertinent regulations through performance assessment, and to examine the feasibility of this disposal concept as a cost-effective, safe alternative for management of orphan wastes within the DOE complex. Decisions on the use of GCD or other alternate disposal concepts for orphan wastes can be expected to be addressed in a Programmatic Environmental Impact Statement being prepared by DOE. The ultimate decision to use GCD will require a Record of Decision through the National Environmental Policy Act (NEPA) process. 20 refs., 3 figs., 2 tabs.

  20. Glucose and Aging

    NASA Astrophysics Data System (ADS)

    Ely, John T. A.

    2008-04-01

    When a human's enzymes attach glucose to proteins they do so at specific sites on a specific molecule for a specific purpose that also can include ascorbic acid (AA) at a high level such as 1 gram per hour during exposure. In an AA synthesizing animal the manifold increase of AA produced in response to illness is automatic. In contrast, the human non-enzymatic process adds glucose haphazardly to any number of sites along available peptide chains. As Cerami clarified decades ago, extensive crosslinking of proteins contributes to loss of elasticity in aging tissues. Ascorbic acid reduces the random non-enyzmatic glycation of proteins. Moreover, AA is a cofactor for hydroxylase enzymes that are necessary for the production and replacement of collagen and other structural proteins. We will discuss the relevance of ``aging is scurvy'' to the biochemistry of human aging.