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Sample records for reduces insulin content

  1. Reduced malonyl-CoA content in recovery from exercise correlates with improved insulin-stimulated glucose uptake in human skeletal muscle

    DEFF Research Database (Denmark)

    Frøsig, Christian; Roepstorff, Carsten; Brandt, Nina

    2009-01-01

    This study evaluated whether improved insulin-stimulated glucose uptake in recovery from acute exercise coincides with reduced malonyl-CoA (MCoA) content in human muscle. Furthermore, we investigated whether a high-fat diet [65 energy-% (Fat)] would alter the content of MCoA and insulin action...... to be compromised, although to a minor extent, by the Fat diet. Collectively, this study indicates that reduced muscle MCoA content in recovery from exercise may be part of the adaptive response leading to improved insulin action on glucose uptake after exercise in human muscle....

  2. Overfeeding reduces insulin sensitivity and increases oxidative stress, without altering markers of mitochondrial content and function in humans.

    Directory of Open Access Journals (Sweden)

    Dorit Samocha-Bonet

    Full Text Available Mitochondrial dysfunction and increased oxidative stress are associated with obesity and type 2 diabetes. High fat feeding induces insulin resistance and increases skeletal muscle oxidative stress in rodents, but there is controversy as to whether skeletal muscle mitochondrial biogenesis and function is altered.Forty (37 ± 2 y non-obese (25.6 ± 0.6 kg/m(2 sedentary men (n = 20 and women (n = 20 were overfed (+1040 ± 100 kcal/day, 46 ± 1% of energy from fat for 28 days. Hyperinsulinemic-euglycemic clamps were performed at baseline and day 28 of overfeeding and skeletal muscle biopsies taken at baseline, day 3 and day 28 of overfeeding in a sub cohort of 26 individuals (13 men and 13 women that consented to having all 3 biopsies performed. Weight increased on average in the whole cohort by 0.6 ± 0.1 and 2.7 ± 0.3 kg at days 3 and 28, respectively (P<0.0001, without a significant difference in the response between men and women (P = 0.4. Glucose infusion rate during the hyperinsulinemic-euglycemic clamp decreased from 54.8 ± 2.8 at baseline to 50.3 ± 2.5 µmol/min/kg FFM at day 28 of overfeeding (P = 0.03 without a significant difference between men and women (P = 0.4. Skeletal muscle protein carbonyls and urinary F2-isoprostanes increased with overfeeding (P<0.05. Protein levels of muscle peroxisome proliferator-activated receptor gamma coactivator-1α (PGC1α and subunits from complex I, II and V of the electron transport chain were increased at day 3 (all P<0.05 and returned to basal levels at day 28. No changes were detected in muscle citrate synthase activity or ex vivo CO(2 production at either time point.Peripheral insulin resistance was induced by overfeeding, without reducing any of the markers of mitochondrial content that were examined. Oxidative stress was however increased, and may have contributed to the reduction in insulin sensitivity observed.

  3. Reduced skeletal muscle inhibitor of kappaB beta content is associated with insulin resistance in subjects with type 2 diabetes: reversal by exercise training.

    Science.gov (United States)

    Sriwijitkamol, Apiradee; Christ-Roberts, Christine; Berria, Rachele; Eagan, Phyllis; Pratipanawatr, Thongchai; DeFronzo, Ralph A; Mandarino, Lawrence J; Musi, Nicolas

    2006-03-01

    Skeletal muscle insulin resistance plays a key role in the pathogenesis of type 2 diabetes. It recently has been hypothesized that excessive activity of the inhibitor of kappaB (IkappaB)/nuclear factor kappaB (NFkappaB) inflammatory pathway is a mechanism underlying skeletal muscle insulin resistance. However, it is not known whether IkappaB/NFkappaB signaling in muscle from subjects with type 2 diabetes is abnormal. We studied IkappaB/NFkappaB signaling in vastus lateralis muscle from six subjects with type 2 diabetes and eight matched control subjects. Muscle from type 2 diabetic subjects was characterized by a 60% decrease in IkappaB beta protein abundance, an indicator of increased activation of the IkappaB/NFkappaB pathway. IkappaB beta abundance directly correlated with insulin-mediated glucose disposal (Rd) during a hyperinsulinemic (40 mU x m(-2) x min(-1))-euglycemic clamp (r = 0.63, P = 0.01), indicating that increased IkappaB/NFkappaB pathway activity is associated with muscle insulin resistance. We also investigated whether reversal of this abnormality could be a mechanism by which training improves insulin sensitivity. In control subjects, 8 weeks of aerobic exercise training caused a 50% increase in both IkappaB alpha and IkappaB beta protein. In subjects with type 2 diabetes, training increased IkappaB alpha and IkappaB beta protein to levels comparable with that of control subjects, and these increments were accompanied by a 40% decrease in tumor necrosis factor alpha muscle content and a 37% increase in insulin-stimulated glucose disposal. In summary, subjects with type 2 diabetes have reduced IkappaB protein abundance in muscle, suggesting excessive activity of the IkappaB/NFkappaB pathway. Moreover, this abnormality is reversed by exercise training.

  4. Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain.

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    Scherer, Thomas; Lindtner, Claudia; O'Hare, James; Hackl, Martina; Zielinski, Elizabeth; Freudenthaler, Angelika; Baumgartner-Parzer, Sabina; Tödter, Klaus; Heeren, Joerg; Krššák, Martin; Scheja, Ludger; Fürnsinn, Clemens; Buettner, Christoph

    2016-06-01

    Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis. © 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.

  5. Glucocorticoid Antagonism Reduces Insulin Resistance and Associated Lipid Abnormalities in High-Fructose-Fed Mice.

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    Priyadarshini, Emayavaramban; Anuradha, Carani Venkatraman

    2017-02-01

    High intake of dietary fructose causes perturbation in lipid metabolism and provokes lipid-induced insulin resistance. A rise in glucocorticoids (GCs) has recently been suggested to be involved in fructose-induced insulin resistance. The objective of the study was to investigate the effect of GC blockade on lipid abnormalities in insulin-resistant mice. Insulin resistance was induced in mice by administering a high-fructose diet (HFrD) for 60 days. Mifepristone (RU486), a GC antagonist, was administered to HFrD-fed mice for the last 18 days, and the intracellular and extracellular GC levels, the glucocorticoid receptor (GR) activation and the expression of GC-regulated genes involved in lipid metabolism were examined. HFrD elevated the intracellular GC content in both liver and adipose tissue and enhanced the GR nuclear translocation. The plasma GC level remained unchanged. The levels of free fatty acids and triglycerides in plasma were elevated, accompanied by increased plasma insulin and glucose levels and decreased hepatic glycogen content. Treatment with RU486 reduced plasma lipid levels, tissue GC levels and the expression of GC-targeted genes involved in lipid accumulation, and it improved insulin sensitivity. This study demonstrated that HFrD-induced lipid accumulation and insulin resistance are mediated by enhanced GC in liver and adipose tissue and that GC antagonism might reduce fructose-induced lipid abnormalities and insulin resistance. Copyright © 2016 Canadian Diabetes Association. Published by Elsevier Inc. All rights reserved.

  6. Liraglutide, but not vildagliptin, restores normoglycaemia and insulin content in the animal model of type 2 diabetes, Psammomys obesus

    DEFF Research Database (Denmark)

    Vedtofte, Louise; Bodvarsdottir, Thóra B; Gotfredsen, Carsten F

    2010-01-01

    In order to investigate the effect and mechanism of liraglutide and vildagliptin in diabetic Psammomys obesus, we examined proliferation and apoptosis of beta-cells, beta-cell mass (BCM), and pancreatic insulin content after zero, six and fourteen days of treatment compared to control groups. One......, compared to the vehicle-treated animals pancreatic insulin content was normalized in animals treated for six and fourteen days with liraglutide. In contrast, vildagliptin, in doses causing full inhibition of plasma DPP-IV activity, neither reduced blood glucose nor altered HED-induced increases in BCM...... or pancreatic insulin content. These results suggest that liraglutide restores normoglycaemia and improves glycaemic control in P. obesus by increasing their insulin content and improving the function of the beta-cells. In contrast, vildagliptin does not improve glycaemic control in P. obesus nor affect beta...

  7. FOXO1 Content Is Reduced in Cystic Fibrosis and Increases with IGF-I Treatment

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    Arianna Smerieri

    2014-10-01

    Full Text Available Cystic fibrosis-related diabetes is to date the most frequent complication in cystic fibrosis (CF. The mechanisms underlying this condition are not well understood, and a possible role of insulin resistance is debated. We investigated insulin signal transduction in CF. Total insulin receptor, IRS1, p85 PI3K, and AKT contents were substantially normal in CF cells (CFBE41o-, whereas winged helix forkhead (FOXO1 contents were reduced both in baseline conditions and after insulin stimulation. In addition, CF cells showed increased ERK1/2, and reduced β2 arrestin contents. No significant change in SOCS2 was observed. By using a CFTR inhibitor and siRNA, changes in FOXO1 were related to CFTR loss of function. In a CF-affected mouse model, FOXO1 content was reduced in the muscle while no significant difference was observed in liver and adipose tissue compared with wild-type. Insulin-like growth factor 1 (IGF-I increased FOXO1 content in vitro and in vivo in muscle and adipose tissue. In conclusion; we present the first description of reduced FOXO1 content in CF, which is compatible with reduced gluconeogenesis and increased adipogenesis, both features of insulin insensitivity. IGF-I treatment was effective in increasing FOXO1, thereby suggesting that it could be considered as a potential treatment in CF patients possibly to prevent and treat cystic fibrosis-related diabetes.

  8. Reduced Insulin Receptor Expression Enhances Proximal Tubule Gluconeogenesis.

    Science.gov (United States)

    Pandey, Gaurav; Shankar, Kripa; Makhija, Ekta; Gaikwad, Anil; Ecelbarger, Carolyn; Mandhani, Anil; Srivastava, Aneesh; Tiwari, Swasti

    2017-02-01

    Reduced insulin receptor protein levels have been reported in the kidney cortex from diabetic humans and animals. We recently reported that, targeted deletion of insulin receptor (IR) from proximal tubules (PT) resulted in hyperglycemia in non-obese mice. To elucidate the mechanism, we examined human proximal tubule cells (hPTC) and C57BL/6 mice fed with high-fat diet (HFD, 60% fat for 20 weeks). Immunoblotting revealed a significantly lower protein level of IR in HFD compare to normal chow diet (NCD). Furthermore, a blunted rise in p-AKT 308 levels in the kidney cortex of HFD mice was observed in response to acute insulin (0.75 IU/kg body weight, i.p) relative to NCD n = 8/group, P gluconeogenesis. Transcript levels of the gluconeogenic enzyme PEPCK were significantly increased in cAMP/DEXA-stimulated hPTC cells (n = 3, P gluconeogenesis and PEPCK induction was significantly attenuated in IR (siRNA) silenced hPTC (n = 3, P gluconeogenesis. Thus reduced insulin signaling of the proximal tubule may contribute to hyperglycemia in the metabolic syndrome via elevated gluconeogenesis. J. Cell. Biochem. 118: 276-285, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

  9. The Role of Insulin, Insulin Growth Factor, and Insulin-Degrading Enzyme in Brain Aging and Alzheimer's Disease

    OpenAIRE

    Messier, Claude; Teutenberg, Kevin

    2005-01-01

    Most brain insulin comes from the pancreas and is taken up by the brain by what appears to be a receptor-based carrier. Type 2 diabetes animal models associated with insulin resistance show reduced insulin brain uptake and content. Recent data point to changes in the insulin receptor cascade in obesity-related insulin resistance, suggesting that brain insulin receptors also become less sensitive to insulin, which could reduce synaptic plasticity. Insulin transport to the brain is reduced in a...

  10. Exercise Increases Insulin Content and Basal Secretion in Pancreatic Islets in Type 1 Diabetic Mice

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    Han-Hung Huang

    2011-01-01

    Full Text Available Exercise appears to improve glycemic control for people with type 1 diabetes (T1D. However, the mechanism responsible for this improvement is unknown. We hypothesized that exercise has a direct effect on the insulin-producing islets. Eight-week-old mice were divided into four groups: sedentary diabetic, exercised diabetic, sedentary control, and exercised control. The exercised groups participated in voluntary wheel running for 6 weeks. When compared to the control groups, the islet density, islet diameter, and β-cell proportion per islet were significantly lower in both sedentary and exercised diabetic groups and these alterations were not improved with exercise. The total insulin content and insulin secretion were significantly lower in sedentary diabetics compared to controls. Exercise significantly improved insulin content and insulin secretion in islets in basal conditions. Thus, some improvements in exercise-induced glycemic control in T1D mice may be due to enhancement of insulin content and secretion in islets.

  11. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan

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    Nicole M. Templeman

    2017-07-01

    Full Text Available The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1 signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2+/− mice to Ins2+/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2+/− mice. Halving Ins2 lowered circulating insulin by 25%–34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan.

  12. Reduced Circulating Insulin Enhances Insulin Sensitivity in Old Mice and Extends Lifespan.

    Science.gov (United States)

    Templeman, Nicole M; Flibotte, Stephane; Chik, Jenny H L; Sinha, Sunita; Lim, Gareth E; Foster, Leonard J; Nislow, Corey; Johnson, James D

    2017-07-11

    The causal relationships between insulin levels, insulin resistance, and longevity are not fully elucidated. Genetic downregulation of insulin/insulin-like growth factor 1 (Igf1) signaling components can extend invertebrate and mammalian lifespan, but insulin resistance, a natural form of decreased insulin signaling, is associated with greater risk of age-related disease in mammals. We compared Ins2 +/- mice to Ins2 +/+ littermate controls, on a genetically stable Ins1 null background. Proteomic and transcriptomic analyses of livers from 25-week-old mice suggested potential for healthier aging and altered insulin sensitivity in Ins2 +/- mice. Halving Ins2 lowered circulating insulin by 25%-34% in aged female mice, without altering Igf1 or circulating Igf1. Remarkably, decreased insulin led to lower fasting glucose and improved insulin sensitivity in aged mice. Moreover, lowered insulin caused significant lifespan extension, observed across two diverse diets. Our study indicates that elevated insulin contributes to age-dependent insulin resistance and that limiting basal insulin levels can extend lifespan. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

  13. Effect of test meals of varying dietary fiber content on plasma insulin and glucose response.

    Science.gov (United States)

    Potter, J G; Coffman, K P; Reid, R L; Krall, J M; Albrink, M J

    1981-03-01

    To assess the effect of dietary fiber on glucose tolerance four different meals of varying fiber content but identical protein fat and carbohydrate content were fed to eight healthy men aged 22 to 45. Each meal provided 75 g of carbohydrate as liquid glucose formula, as brown rice, pinto beans, or All Bran. The mean plasma glucose and insulin responses were highest following the formula, and least for All Bran and pinto beans. Rice produced nearly as great a rise in insulin and glucose as did the formula. The rank of each meal by content of neutral detergent fiber was nearly the inverse of the rank by magnitude of the insulin response evoked, fiber content being greatest in All Bran (18 g) and pinto beans (16.2 g), low in rice (2.8 g) and absent from the formula. It was concluded that dietary fiber dampened the insulin response to a high carbohydrate meal.

  14. Metformin reduces insulin resistance and the tendency toward ...

    African Journals Online (AJOL)

    Ibrahim Eldaghayes

    2018-05-11

    May 11, 2018 ... insulin concentrations, in addition to urinary cortisol:creatinine ratio, Homeostatic Model Assessment (HOMA) for ... affecting the insulin synthesis and secretion of ... Likewise, no dog with increased Blood Urea Nitrogen.

  15. Role of reduced insulin-stimulated bone blood flow in the pathogenesis of metabolic insulin resistance and diabetic bone fragility.

    Science.gov (United States)

    Hinton, Pamela S

    2016-08-01

    Worldwide, 387 million adults live with type 2 diabetes (T2D) and an additional 205 million cases are projected by 2035. Because T2D has numerous complications, there is significant morbidity and mortality associated with the disease. Identification of early events in the pathogenesis of insulin resistance and T2D might lead to more effective treatments that would mitigate health and monetary costs. Here, we present our hypothesis that impaired bone blood flow is an early event in the pathogenesis of whole-body metabolic insulin resistance that ultimately leads to T2D. Two recent developments in different fields form the basis for this hypothesis. First, reduced vascular function has been identified as an early event in the development of T2D. In particular, before the onset of tissue or whole body metabolic insulin resistance, insulin-stimulated, endothelium-mediated skeletal muscle blood flow is impaired. Insulin resistance of the vascular endothelium reduces delivery of insulin and glucose to skeletal muscle, which leads to tissue and whole-body metabolic insulin resistance. Second is the paradigm-shifting discovery that the skeleton has an endocrine function that is essential for maintenance of whole-body glucose homeostasis. Specifically, in response to insulin signaling, osteoblasts secret osteocalcin, which stimulates pancreatic insulin production and enhances insulin sensitivity in skeletal muscle, adipose, and liver. Furthermore, the skeleton is not metabolically inert, but contributes to whole-body glucose utilization, consuming 20% that of skeletal muscle and 50% that of white adipose tissue. Without insulin signaling or without osteocalcin activity, experimental animals become hyperglycemic and insulin resistant. Currently, it is not known if insulin-stimulated, endothelium-mediated blood flow to bone plays a role in the development of whole body metabolic insulin resistance. We hypothesize that it is a key, early event. Microvascular dysfunction is a

  16. Reduced phosphorylation of brain insulin receptor substrate and Akt proteins in apolipoprotein-E4 targeted replacement mice.

    Science.gov (United States)

    Ong, Qi-Rui; Chan, Elizabeth S; Lim, Mei-Li; Cole, Gregory M; Wong, Boon-Seng

    2014-01-17

    Human ApoE4 accelerates memory decline in ageing and in Alzheimer's disease. Although intranasal insulin can improve cognition, this has little effect in ApoE4 subjects. To understand this ApoE genotype-dependent effect, we examined brain insulin signaling in huApoE3 and huApoE4 targeted replacement (TR) mice. At 32 weeks, lower insulin receptor substrate 1 (IRS1) at S636/639 and Akt phosphorylation at T308 were detected in fasting huApoE4 TR mice as compared to fasting huApoE3 TR mice. These changes in fasting huApoE4 TR mice were linked to lower brain glucose content and have no effect on plasma glucose level. However, at 72 weeks of age, these early changes were accompanied by reduction in IRS2 expression, IRS1 phosphorylation at Y608, Akt phosphorylation at S473, and MAPK (p38 and p44/42) activation in the fasting huApoE4 TR mice. The lower brain glucose was significantly associated with higher brain insulin in the aged huApoE4 TR mice. These results show that ApoE4 reduces brain insulin signaling and glucose level leading to higher insulin content.

  17. The triglyceride content in skeletal muscle is associated with hepatic but not peripheral insulin resistance in elderly twins

    DEFF Research Database (Denmark)

    Grunnet, L G; Laurila, Esa; Hansson, Ola

    2012-01-01

    Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins.......Total muscle triglyceride (MT) content has been associated with insulin resistance. We investigated the predictors and impact of MT on relevant metabolic parameters including peripheral and hepatic insulin resistance in elderly twins....

  18. 65Zinc and endogenous zinc content and distribution in islets in relationship to insulin content

    International Nuclear Information System (INIS)

    Figlewicz, D.P.; Forhan, S.E.; Hodgson, A.T.; Grodsky, G.M.

    1984-01-01

    Uptake of 65 Zn and distribution of 65 Zn, total zinc, and insulin were measured in rat islets and islet granules under different conditions of islet culture. Specific activity of islet zinc ( 65 Zn/zinc) was less than 15% that of extracellular zinc even after 48 h. In contrast, once in the islet, 65 Zn approached 70% of equilibrium with granular zinc in 24 h and apparent equilibrium by 48 h. During a 24-h culture, at either high or low glucose, reduction of both islet zinc and insulin occurred. However, zinc depletion was greater than that predicted if zinc loss was proportional to insulin depletion and occurred only from the granular compartment, which represents only one third of the total islet zinc. Extension of culture to 48 h caused additional insulin depletion, but islet zinc was unchanged. Omission of calcium during the 48-h culture caused a predicted increase in insulin retention, presumably by inhibiting secretion; however, zinc retention was not increased proportionately. Pretreatment of rats with tolbutamide caused a massive depletion of insulin stored in isolated islets, with little change in total islet zinc; subsequent culture of these islets resulted in a greater loss of granular zinc than predicted from the small loss of granular insulin. None of the conditions tested affected the percentage of either 65 Zn or total zinc that was distributed in the islet granules. Results show that zinc exists in a metabolically labile islet compartment(s) as well as in secretory granules; and extra-granular zinc, although not directly associated with insulin storage, may act as a reservoir for granular zinc and may regulate insulin synthesis, storage, and secretion in ways as yet unknown

  19. Human skeletal muscle ceramide content is not a major factor in muscle insulin sensitivity

    DEFF Research Database (Denmark)

    Skovbro, M; Baranowski, M; Skov-Jensen, C

    2008-01-01

    -hyperinsulinaemic clamp was performed for 120 and 90 min for step 1 and step 2, respectively. Muscle biopsies were obtained from vastus lateralis at baseline, and after steps 1 and 2. RESULTS: Glucose infusion rates increased in response to insulin infusion, and significant differences were present between groups (T2D......AIMS/HYPOTHESIS: In skeletal muscle, ceramides may be involved in the pathogenesis of insulin resistance through an attenuation of insulin signalling. This study investigated total skeletal muscle ceramide fatty acid content in participants exhibiting a wide range of insulin sensitivities. METHODS......: The middle-aged male participants (n=33) were matched for lean body mass and divided into four groups: type 2 diabetes (T2D, n=8), impaired glucose tolerance (IGT, n=9), healthy controls (CON, n=8) and endurance-trained (TR, n=8). A two step (28 and 80 mU m(-2) min(-1)) sequential euglycaemic...

  20. Is reducing variability of blood glucose the real but hidden target of intensive insulin therapy?

    Science.gov (United States)

    Egi, Moritoki; Bellomo, Rinaldo; Reade, Michael C

    2009-01-01

    Since the first report that intensive insulin therapy reduced mortality in selected surgical critically ill patients, lowering of blood glucose levels has been recommended as a means of improving patient outcomes. In this initial Leuven trial, blood glucose control by protocol using insulin was applied to 98.7% of patients in the intensive group but to only 39.2% (P dimension of glucose management, a possible mechanism by which an intensive insulin protocol exerts its putative beneficial effects, and an important goal of glucose management in the intensive care unit. Clinicians need to be aware of this controversy when considering the application of intensive insulin therapy and interpreting future trials.

  1. Moderate alcohol consumption is associated with improved insulin sensitivity, reduced basal insulin secretion rate and lower fasting glucagon concentration in healthy women

    DEFF Research Database (Denmark)

    Bonnet, F; Disse, E; Laville, M

    2012-01-01

    Moderate alcohol consumption is associated with a reduced risk of type 2 diabetes with a stronger effect in women. As the underlying mechanisms remain poorly characterised, we investigated its relationship with insulin resistance, insulin secretion, clearance of insulin and glucagon concentration....

  2. Inhibition of insulin release by cyproheptadine: Effects on 3',5'-cyclic-AMP-content and /sup 45/Ca-accumulation of incubated mouse islets

    Energy Technology Data Exchange (ETDEWEB)

    Joost, H G; Beckmann, J; Lenzen, S; Hasselblatt, A [Goettingen Univ. (F.R. Germany)

    1976-01-01

    Cyproheptadine (1, 10 and 100 ..mu..m) significantly reduced insulin release from isolated mouse islets in response to glucose. In contrast, 1 mM cyproheptadine induced a large release of insulin into the incubation medium probably due to islet cell damage, since the islets had lost a considerable amount of their protein content. 3',5'-cyclic-AMP-levels of the islets were not significantly affected by 10 ..mu..M cyproheptadine in the presence as well as in the absence of theophylline (10 mM). As the inhibitory effect of cyproheptadine on insulin release was correlated with reduced accumulation of calcium-45, the agent may inhibit insulin release by interfering with the calcium handling of the ..beta..-cell.

  3. Novel Simple Insulin Delivery Device Reduces Barriers to Insulin Therapy in Type 2 Diabetes

    Science.gov (United States)

    Hermanns, Norbert; Lilly, Leslie C.; Mader, Julia K.; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R.

    2015-01-01

    Background: The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. Methods: This single-center, open-label, single-arm study comprised three 2-week periods: baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Validated questionnaires were administered during the baseline and PaQ treatment periods: Barriers to Insulin Treatment questionnaire (BIT), Insulin Treatment Appraisal Scale (ITAS), and Problem Areas in Diabetes scale (PAID). Results: Eighteen patients (age 59 ± 5 years, diabetes duration 15 ± 7 years, 21% female, HbA1c 7.7 ± 0.7%) completed the questionnaires. There was a strong, significant effect of PaQ use in mean BIT total scores (difference [D] = −5.4 ± 0.7.7, P = .01, effect size [d] = 0.70). Patients perceived less stigmatization by insulin injection (D = −2.2 ± 6.2, P = .18, d = 0.35), increased positive outcome (D = 1.9 ± 6.6, P = .17, d = 0.29), and less fear of injections (1.3 ± 4.8, P = .55, d = 0.28). Mean change in ITAS scores after PaQ device use showed a nonsignificant improvement of 1.71 ± 5.63 but moderate effect size (d = 0.30, P = .14). No increase in PAID scores was seen. Conclusions: The results and moderate to large effects sizes suggest that PaQ device use has beneficial and clinically relevant effects to overcoming barriers to and negative appraisal of insulin treatment, without increasing other diabetes-related distress. PMID:25670847

  4. High dietary protein intake, reducing or eliciting insulin resistance?

    NARCIS (Netherlands)

    Rietman, A.; Schwarz, J.; Tome, D.; Kok, F.J.; Mensink, M.R.

    2014-01-01

    Dietary proteins have an insulinotropic effect and thus promote insulin secretion, which indeed leads to enhanced glucose clearance from the blood. In the long term, however, a high dietary protein intake is associated with an increased risk of type 2 diabetes. Moreover, branched-chain amino acids

  5. Bezafibrate ameliorates diabetes via reduced steatosis and improved hepatic insulin sensitivity in diabetic TallyHo mice

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    Andras Franko

    2017-03-01

    Full Text Available Objective: Recently, we have shown that Bezafibrate (BEZ, the pan-PPAR (peroxisome proliferator-activated receptor activator, ameliorated diabetes in insulin deficient streptozotocin treated diabetic mice. In order to study whether BEZ can also improve glucose metabolism in a mouse model for fatty liver and type 2 diabetes, the drug was applied to TallyHo mice. Methods: TallyHo mice were divided into an early (ED and late (LD diabetes progression group and both groups were treated with 0.5% BEZ (BEZ group or standard diet (SD group for 8 weeks. We analyzed plasma parameters, pancreatic beta-cell morphology, and mass as well as glucose metabolism of the BEZ-treated and control mice. Furthermore, liver fat content and composition as well as hepatic gluconeogenesis and mitochondrial mass were determined. Results: Plasma lipid and glucose levels were markedly reduced upon BEZ treatment, which was accompanied by elevated insulin sensitivity index as well as glucose tolerance, respectively. BEZ increased islet area in the pancreas. Furthermore, BEZ treatment improved energy expenditure and metabolic flexibility. In the liver, BEZ ameliorated steatosis, modified lipid composition and increased mitochondrial mass, which was accompanied by reduced hepatic gluconeogenesis. Conclusions: Our data showed that BEZ ameliorates diabetes probably via reduced steatosis, enhanced hepatic mitochondrial mass, improved metabolic flexibility and elevated hepatic insulin sensitivity in TallyHo mice, suggesting that BEZ treatment could be beneficial for patients with NAFLD and impaired glucose metabolism. Keywords: Bezafibrate, Glucose metabolism, Insulin resistance, Lipid metabolism, NAFLD

  6. Vitamin D deficiency is associated with insulin resistance in nondiabetics and reduced insulin production in type 2 diabetics.

    Science.gov (United States)

    Esteghamati, A; Aryan, Z; Esteghamati, Ar; Nakhjavani, M

    2015-04-01

    It is not known whether the association of serum 25-hydroxyvitamin D [25(OH)D] with glycemic measurements of individuals without diabetes is similar to those with diabetes or not. This study is aimed to investigate the association of serum 25(OH)D with glycemic markers of diabetics, nondiabetics, and prediabetics. A case-control study was conducted on age and sex matched 1,195 patients with type 2 DM, 121 prediabetics, and 209 healthy controls. Anthropometric variables, lipid profile, glycemic measurements, and serum 25(OH)D levels were recorded. Serum insulin and C-peptide levels were also measured. All glycemic measurements were compared between diabetics and nondiabetics and prediabetics at different vitamin D status. Patients with DM had lower serum 25(OH)D compared to prediabetics and healthy controls. Endogenous insulin production in response to food intake and in fasting was significantly lower in vitamin D deficient patients with DM compared to those with serum 25(OH)D>40 ng/ml. Diabetic women with serum 25(OH)D40 ng/ml. Healthy individuals with serum 25(OH)D<20 ng/ml had signs of insulin resistance as estimated by significant increase of HOMA-IR, HbA1c, and fasting plasma glucose (FPG). In addition, we found that serum 25(OH)D was inversely associated with insulin resistance. Vitamin D deficiency is associated with insulin resistance in nondiabetics, which is independent of obesity. Furthermore, vitamin D deficiency is associated with reduced insulin production in type 2 diabetics, which was mainly observed in men. Accordingly, a gender disparity also exists in association of serum 25(OH)D with glycemic measurements. © Georg Thieme Verlag KG Stuttgart · New York.

  7. Increased bioactive lipids content in human subcutaneous and epicardial fat tissue correlates with insulin resistance.

    Science.gov (United States)

    Błachnio-Zabielska, Agnieszka U; Baranowski, Marcin; Hirnle, Tomasz; Zabielski, Piotr; Lewczuk, Anna; Dmitruk, Iwona; Górski, Jan

    2012-12-01

    Obesity is a risk factor for metabolic diseases. Intramuscular lipid accumulation of ceramides, diacylglycerols, and long chain acyl-CoA is responsible for the induction of insulin resistance. These lipids are probably implicated in obesity-associated insulin resistance not only in skeletal muscle but also in fat tissue. Only few data are available about ceramide content in human subcutaneous adipose tissue. However, there are no data on DAG and LCACoA content in adipose tissue. The aim of our study was to measure the lipids content in human SAT and epicardial adipose tissue we sought to determine the bioactive lipids content by LC/MS/MS in fat tissue from lean non-diabetic, obese non-diabetic, and obese diabetic subjects and test whether the lipids correlate with HOMA-IR. We found, that total content of measured lipids was markedly higher in OND and OD subjects in both types of fat tissue (for all p lipids content is greater in subcutaneous and epicardial fat tissue and the particular lipids content positively correlates with HOMA-IR.

  8. Reduced Insulin/Insulin-like Growth Factor-1 Signaling and Dietary Restriction Inhibit Translation but Preserve Muscle Mass in Caenorhabditis elegans

    Energy Technology Data Exchange (ETDEWEB)

    Depuydt, Geert; Xie, Fang; Petyuk, Vladislav A.; Shanmugam, Nilesh; Smolders, Arne; Dhondt, Ineke; Brewer, Heather M.; Camp, David G.; Smith, Richard D.; Braeckman, Bart P.

    2013-09-03

    Reduced signaling through the C. elegans insulin/IGF1 like tyrosine kinase receptor daf2 and dietary restriction via bacterial dilution are two well-characterized lifespan-extending interventions that operate in parallel or through (partially) independent mechanisms. Using accurate mass and time tag LCMS/MS quantitative proteomics we detected that the abundance of a large number of ribosomal subunits is decreased in response to dietary restriction as well as in the daf2(e1370) insulin/IGF1 receptor mutant. In addition, general protein synthesis levels in these long-lived worms are repressed. Surprisingly, ribosomal transcript levels were not correlated to actual protein abundance, suggesting that posttranscriptional regulation determines ribosome content. Proteomics also revealed increased presence of many structural muscle cell components in long-lived worms, which appears to result from prioritized preservation of muscle cell volume in nutrient-poor conditions or low insulin-like signaling. Activation of DAF16, but not diet-restriction, stimulates mRNA expression of muscle-related genes to prevent muscle atrophy. Important daf2 specific proteome changes include overexpression of aerobic metabolism enzymes and a general activation of stress responsive and immune defense systems, while increased abundance of many protein subunits of the proteasome core complex is a DR-specific characteristic.

  9. Liver fat contents, abdominal adiposity and insulin resistance in non-diabetic prevalent hemodialysis patients.

    Science.gov (United States)

    Chen, Hung-Yuan; Lin, Chien-Chu; Chiu, Yen-Ling; Hsu, Shih-Ping; Pai, Mei-Fen; Yang, Ju-Yeh; Wu, Hon-Yen; Peng, Yu-Sen

    2014-01-01

    The liver fat contents and abdominal adiposity correlate well with insulin resistance (IR) in the general population. However, the relationship between liver fat content, abdominal adiposity and IR in non-diabetic hemodialysis (HD) patients remains unclear. This study aimed to clarify the associations among these factors. This is a cross-sectional, observational study. All patients received abdominal ultrasound for liver fat content. Abdominal adiposity was quantified with the conicity index (Ci) and waist circumference (WC). We checked the homeostasis model assessment for insulin resistance index (HOMA-IR) for IR. A total of 112 patients (60 women) were analyzed. Subjects with higher liver fat contents and WC had higher IR indices. But Ci did not correlate with IR indices. In both the multi-variable linear regression model and the logistic regression model, only higher liver fat content predicted a severe IR status. Liver fat contents have a remarkable correlation with IR; however, abdominal adiposity, measured either by Ci or WC, dose not independently correlate with IR in non-diabetic prevalent HD patients. © 2014 S. Karger AG, Basel.

  10. Insulin

    Science.gov (United States)

    ... For Consumers Home For Consumers Consumer Information by Audience For Women Women's Health Topics Insulin Share Tweet ... I start having side effects? What is my target blood sugar level? How often should I check ...

  11. Exendin-4 reduces tau hyperphosphorylation in type 2 diabetic rats via increasing brain insulin level.

    Science.gov (United States)

    Yang, Yan; Ma, Delin; Xu, Weijie; Chen, Fuqiong; Du, Tingting; Yue, Wenzhu; Shao, Shiying; Yuan, Gang

    2016-01-01

    Type 2 diabetes (T2D) is a high risk factor for Alzheimer's disease (AD). Our previous study identified that hyperphosphorylation of tau protein, which is one of the pathophysiologic hallmarks of AD, also occurred in T2D rats' brain; while glucagon-like peptide-1 (GLP-1) mimetics, a type of drug used in T2D, could decrease the phosphorylation of tau, probably via augmenting insulin signaling pathway. The purpose of this study was to further explore the mechanisms that underlie the effect of exendin-4 (ex-4, a GLP-1 receptor agonist) in reducing tau phosphorylation. We found that peripheral ex-4 injection in T2D rats reduced hyperphosphorylation of tau protein in rat hippocampus, probably via increasing hippocampal insulin which activated insulin signaling. Furthermore, we found that ex-4 could neither activate insulin signaling, nor reduce tau phosphorylation in HT22 neuronal cells in the absence of insulin. These results suggested that insulin is required in reduction of tau hyperphosphorylation by ex-4 in brain rats with T2D. Copyright © 2015 Elsevier Inc. All rights reserved.

  12. Elevated insulin and reduced insulin like growth factor binding protein-3/prostate specific antigen ratio with increase in prostate size in Benign Prostatic Hyperplasia.

    Science.gov (United States)

    Sreenivasulu, Karli; Nandeesha, Hanumanthappa; Dorairajan, Lalgudi Narayanan; Rajappa, Medha; Vinayagam, Vickneshwaran

    2017-06-01

    Insulin and insulin like growth factor-1 (IGF-1) have growth promoting effects, while insulin like growth factor binding protein-3 (IGFBP-3) has growth inhibitory effects. The present study was designed to assess the concentrations of insulin, IGF-1, IGFBP-3 and their association with prostate size in patients with BPH. Ninety 90 BPH cases and 90 controls were enrolled in the study. Insulin, IGF-1, IGFBP-3, PSA, testosterone and estradiol were estimated in both the groups. Insulin, IGF-1 and estradiol were increased and IGFBP-3/PSA was decreased in BPH cases when compared with controls. Insulin (r=0.64, p=0.001) and IGF-1 (r=0.22, p=0.03) were positively correlated and IGFBP-3/PSA (r=-0.316, p=0.002) were negatively correlated with prostate size in BPH. Multivariate analysis showed that insulin (p=0.001) and IGFBP-3/PSA (p=0.004) predicts the prostate size in patients with BPH. Insulin was increased and IGFBP-3/PSA was reduced in BPH patients with increased prostate size. At a cutoff concentration of 527.52, IGFBP-3/PSA ratio was found to differentiate benign growth of prostate from normal prostate with 96% sensitivity and 96% specificity. Insulin is elevated and IGFBP-3/PSA is reduced with increase prostate size in BPH cases. Copyright © 2017 Elsevier B.V. All rights reserved.

  13. Thylakoids promote release of the satiety hormone cholecystokinin while reducing insulin in healthy humans

    DEFF Research Database (Denmark)

    Köhnke, Rickard; Lindbo, Agnes; Larsson, Therese

    2009-01-01

    (CCK, leptin and ghrelin), insulin and blood metabolites (glucose and free fatty acids). RESULTS: The CCK level increased, in particular between the 120 min time-point and onwards, the ghrelin level was reduced at 120 min and leptin level increased at 360 min after intake of the thylakoid-enriched meal....... The insulin level was reduced, whereas glucose concentrations were unchanged. Free fatty acids were reduced between time-point 120 min and onwards after the thylakoid meal. CONCLUSIONS: The addition of thylakoids to energy-dense food promotes satiety signals and reduces insulin response during a single meal......OBJECTIVE: The effects of a promising new appetite suppressor named "thylakoids" (membrane proteins derived from spinach leaves) were examined in a single meal in man. Thylakoids inhibit the lipase/colipase hydrolysis of triacylglycerols in vitro and suppress food intake, decrease body-weight gain...

  14. Increased insulin sensitivity and changes in the expression profile of key insulin regulatory genes and beta cell transcription factors in diabetic KKAy-mice after feeding with a soy bean protein rich diet high in isoflavone content.

    Science.gov (United States)

    Nordentoft, I; Jeppesen, P B; Hong, J; Abudula, R; Hermansen, K

    2008-06-25

    High content isoflavone soy protein (SBP) (Abalon) has been found in animal studies to possess beneficial effects on a number of the characteristic features of the insulin resistance syndrome. The aim of this study was to investigate whether SBP exerts beneficial effects on metabolism in the diabetic KKAy-mouse. Furthermore, we investigated the long-term in vivo effect of SBP on the expression profile in islets of key insulin regulatory genes. Twenty KKAy-mice, aged 5 weeks, were divided into 2 groups and treated for 9 weeks with either (A) standard chow diet (control) or (B) chow + 50% SBP. Twenty normal C57BL-mice fed with standard chow diet served as nondiabetic controls (C). Blood samples were collected and analyzed before and after intervention. Gene expression was determined in islets by quantitative real-time RT-PCR and Affymetrix microarray. It was demonstrated that long-term treatment with SBP improves glucose homeostasis, increases insulin sensitivity, and lowers plasma triglycerides in diabetic KKAy-mice. SBP reduces fasting plasma glucose, insulin, triglycerides, and total cholesterol. Furthermore, SBP markedly changes the gene expression profile of key insulin regulatory genes GLUT2, GLUT3, Ins1, Ins2, IGF1, Beta2/Neurod1, cholecystokinin, and LDLr, and proliferative genes in islets isolated from KKAy-mice. After 9 weeks of treatment with SBP, plasma glucose and insulin homeostasis was normalized compared to start levels. The results indicate that SBP improves glucose and insulin sensitivity and up-regulates the expression of key insulin regulatory genes.

  15. Jinlida reduces insulin resistance and ameliorates liver oxidative stress in high-fat fed rats.

    Science.gov (United States)

    Liu, Yixuan; Song, An; Zang, Shasha; Wang, Chao; Song, Guangyao; Li, Xiaoling; Zhu, Yajun; Yu, Xian; Li, Ling; Wang, Yun; Duan, Liyuan

    2015-03-13

    Jinlida (JLD) is a compound preparation formulated on the basis of traditional Chinese medicine and is officially approved for the treatment of type 2 diabetes (T2DM) in China. We aimed to elucidate the mechanism of JLD treatment, in comparison to metformin treatment, on ameliorating insulin sensitivity in insulin resistant rats and to reveal its anti-oxidant properties. Rats were fed with standard or high-fat diet for 6 weeks. After 6 weeks, the high-fat fed rats were subdivided into five groups and orally fed with JLD or metformin for 8 weeks. Fasting blood glucose (FBG), fasting blood insulin, blood lipid and antioxidant enzymes were measured. Intraperitoneal glucose tolerance test (IPGTT) and hyperinsulinemic euglycemic clamp technique were carried out to measure insulin sensitivity. Gene expression of the major signaling pathway molecules that regulate glucose uptake, including insulin receptor (INSR), insulin receptor substrate-1 (IRS-1), phosphoinositide-3-kinase (PI3K), protein kinase beta (AKT), and glucose transporter type 2 (GLUT2), were assessed by quantitative RT-PCR. The totle and phosphorylation expression of IRS-1, AKT, JNK and p38MAPK were determined by Western blot. Treatment with JLD effectively ameliorated the high-fat induced hyperglycemia, hyperinsulinemia and hyperlipidemia. Similar to metformin, the high insulin resistance in high-fat fed rats was significantly decreased by JLD treatment. JLD displayed anti-oxidant effects, coupled with up-regulation of the insulin signaling pathway. The attenuation of hepatic oxidative stress by JLD treatment was associated with reduced phosphorylation protein levels of JNK and p38MAPK. Treatment with JLD could moderate glucose and lipid metabolism as well as reduce hepatic oxidative stress, most likely through the JNK and p38MAPK pathways. Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.

  16. Reducing fat and sodium content in pork sausage | Junior | African ...

    African Journals Online (AJOL)

    Reducing fat and sodium content in pork sausage. Jonhny De Azevedo Maia Junior, Fábio Da Costa Henry, Felipe Roberto Ferreira Amaral Do Valle, Meire Lelis Leal Martins, Célia Raquel Quirino, Rafael Dos Santos Costa ...

  17. Metformin reduces insulin resistance and the tendency toward hyperglycaemia and dyslipidaemia in dogs with hyperadrenocorticism

    Directory of Open Access Journals (Sweden)

    Diego Daniel Miceli

    2018-05-01

    Full Text Available Hypercortisolism induces a state of insulin resistance that can occur concurrently with fasting hyperglycaemia, dyslipidaemia and diabetes mellitus. Metformin reduces hepatic glucose production and insulin resistance of the skeletal muscle and adipose tissue. The aim of this study was to evaluate the effects of metformin on the control of metabolic disorders of dogs with hyperadrenocorticism (HAC. Twenty-three dogs with HAC were randomly divided into two groups, consisting of a control group and a metformin group (10 mg metformin/kg/12 h. Both groups received the same treatment for HAC. At baseline and 3 months, blood glucose, total cholesterol, triglycerides and insulin concentrations, in addition to urinary cortisol:creatinine ratio, Homeostatic Model Assessment (HOMA for insulin sensitivity and β-cell function were measured. Dogs treated with metformin showed significantly reduced glycaemia, cholesterolaemia and triglyceridaemia. They also presented reduced hyperinsulinism and insulin resistance, as well as improved pancreatic β-cell function. The implementation of metformin as an adjuvant therapy is effective for the normalisation of metabolic disorders of dogs with HAC.

  18. Insulin and 20-hydroxyecdysone action in Bombyx mori: Glycogen content and expression pattern of insulin and ecdysone receptors in fat body.

    Science.gov (United States)

    Keshan, Bela; Thounaojam, Bembem; Kh, Sanathoibi D

    2017-01-15

    Insulin and ecdysone signaling play a critical role on the growth and development of insects including Bombyx mori. Our previous study showed that Bombyx larvae reached critical weight for metamorphosis between day 3.5 and 4 of the fifth larval instar. The present study showed that the effect of insulin on the accumulation of glycogen in fat body of Bombyx larvae depends on the critical growth period. When larvae are in active growth period (before reaching critical weight), insulin caused increased accumulation of glycogen, while its treatment in larvae at terminal growth period (after critical period) resulted in an increased mobilization of glycogen. During terminal growth period, insulin and 20-hydroxyecdysone (20E) showed an antagonistic effect on the accumulation of fat body glycogen in fed, food deprived and decapitated larvae as well as in isolated abdomens. Insulin treatment decreased the glycogen content, whereas, 20E increased it. Food deprivation and decapitation caused an increase in the transcript levels of insulin receptor (InR) and this increase in InR expression might be attributed to a decrease in synthesis/secretion of insulin-like peptides, as insulin treatment in these larvae showed a down-regulation in InR expression. However, insulin showed an up-regulation in InR in isolated abdomens and it suggests that in food deprived and decapitated larvae, the exogenous insulin may interact with some head and/or thoracic factors in modulating the expression of InR. Moreover, in fed larvae, insulin-mediated increase in InR expression indicates that its regulation by insulin-like peptides also depends on the nutritional status of the larvae. The treatment of 20E in fed larvae showed an antagonistic effect on the transcript levels since a down-regulation in InR expression was observed. 20E treatment also led to a decreased expression of InR in food deprived and decapitated larvae as well as in isolated abdomens. Insulin and 20E also modulated the

  19. Household methods to reduce {sup 137}Cs contents of mushrooms

    Energy Technology Data Exchange (ETDEWEB)

    Kostiainen, E. [Radiation and Nuclear Safety Authority - STUK, Helsinki (Finland)

    2005-09-15

    High radiocaesium contents in different species of mushrooms have been observed in areas contaminated by radiocaesium deposition after the Chernobyl accident in 1986. There has been no significant reduction in the {sup 137}Cs contents of mushrooms during the past ten years, besides via radioactive decay. The internal radiation dose received via mushrooms can be reduced by processing mushrooms before consumption. Various household methods were studied to find out their efficiency to reduce {sup 137}Cs contents of mushrooms. The methods tested were the same as normally used in cooking. The tests were made for the species of edible mushrooms widely consumed. The retention factors for the treatments tested were in most cases 0.2-0.3. The efficiency of treatments in reducing the {sup 137}Cs contents increased with larger water volumes and prolonged treatment times.

  20. Household methods to reduce 137Cs contents of mushrooms

    International Nuclear Information System (INIS)

    Kostiainen, E.

    2005-01-01

    High radiocaesium contents in different species of mushrooms have been observed in areas contaminated by radiocaesium deposition after the Chernobyl accident in 1986. There has been no significant reduction in the 137 Cs contents of mushrooms during the past ten years, besides via radioactive decay. The internal radiation dose received via mushrooms can be reduced by processing mushrooms before consumption. Various household methods were studied to find out their efficiency to reduce 137 Cs contents of mushrooms. The methods tested were the same as normally used in cooking. The tests were made for the species of edible mushrooms widely consumed. The retention factors for the treatments tested were in most cases 0.2-0.3. The efficiency of treatments in reducing the 137 Cs contents increased with larger water volumes and prolonged treatment times

  1. Reduced Nicotine Content Expectancies Affect Initial Responses to Smoking.

    Science.gov (United States)

    Mercincavage, Melissa; Smyth, Joshua M; Strasser, Andrew A; Branstetter, Steven A

    2016-10-01

    We sought to determine if negative responses to reduced nicotine content (RNC) cigarettes during open-label trials result from smokers' (negative) expectancies. We examined the effects of nicotine content description - independent of actual nicotine content - on subjective responses (craving reduction, withdrawal suppression, mood changes, and sensory ratings) and smoking behaviors (topography measures and carbon monoxide [CO] boost). Thirty-six 12-hour-abstinent daily smokers completed a 3-session crossover trial. During each session, participants smoked their preferred brand cigarette - blinded and described as containing "usual," "low," and "very low" nicotine content - through a topography device and completed CO and subjective response assessments. Although nicotine content was identical, compared to the "usual" content cigarette, participants experienced less craving reduction after smoking the "very low" nicotine cigarette, and rated its smoke as weaker (p marketing and labeling are likely important considerations if a federal nicotine reduction policy is initiated.

  2. Prediction of reducible soil iron content from iron extraction data

    NARCIS (Netherlands)

    Bodegom, van P.M.; Reeven, van J.; Denier van der Gon, H.A.C.

    2003-01-01

    Soils contain various iron compounds that differ in solubility, reducibility and extractability. Moreover, the contribution of the various iron compounds to total iron (Fe) and total Fe concentrations differs highly among soils. As a result, the total reducible Fe content can also differ among

  3. Prolactin effect on the insulin content of albino rats in different physiological states

    International Nuclear Information System (INIS)

    Megahed, Y.M.; Abdel-Wahab, M.F.; El-Mougi, S.M.; El-Sayed, F.B.; Kuwait Univ.)

    1980-01-01

    The metabolic action of prolactin on insulin levels in plasma and pancreas has been studied. Prolactin was injected in a single dose or single daily doses on 4 successive days into albino rats in six different physiological states. Insulin was determined by radioimmunoassay using 125 I insulin. From the results it is concluded that prolactin injected i.p. influences the output of insulin and stimulates the pancreas to secrete insulin into the plasma. (author)

  4. Novel Simple Insulin Delivery Device Reduces Barriers to Insulin Therapy in Type 2 Diabetes: Results From a Pilot Study

    OpenAIRE

    Hermanns, Norbert; Lilly, Leslie C.; Mader, Julia K.; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R.

    2015-01-01

    Background: The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. Methods: This singl...

  5. The changes of serum leptin and insulin contents in elderly male patients with obesity-related hypertension

    International Nuclear Information System (INIS)

    Zhan Hao; Huang Daijuan; Yuan Bin; He Yong; Zhang Yongxue

    2004-01-01

    To study the contents of serum leptin and insulin in elderly male patients with obesity-related hypertension, the levels of serum leptin and insulin in 21 normotensive cases and 41 hypertensive cases of them were determined by RIA. The results showed that the levels of serum leptin and insulin between hypertensives and normotensives in the non-obese groups were not significantly different (P>0.05). Compared with normotensives, the levels of serum leptin and insulin of hypertensives in the obese groups remarkably increased 1.8μg/L and 2.7 mIU/L respectively (P<0.01). The levels of serum leptin and insulin in the patients with obesity - related hypertension were markedly higher than those in the patients with non-obesity-related hypertension and elevated 2.7μg/L and 4.7mIU/L (P<0.01) respectively. Insulin-sensitivity index (ISI) successively decreased in the groups of HBPOb, NBPOb, HBPNOb and NBPNOb (relative ISI 0.50, 0.68, 0.92, 1 respectively). It is concluded that leptin-resistance and insulin-resistance exist in male elderly patients with obesity-related hypertension

  6. C1qTNF-related protein 1 improve insulin resistance by reducing phosphorylation of serine 1101 in insulin receptor substrate 1.

    Science.gov (United States)

    Xin, Yaping; Zhang, Dongming; Fu, Yanqin; Wang, Chongxian; Li, Qingju; Tian, Chenguang; Zhang, Suhe; Lyu, Xiaodong

    2017-08-30

    C1qTNF-related protein 1 (CTRP1) is independently associated with type 2 diabetes. However, the relationship between CTRP1 and insulin resistance is still not established. This study aimed to explore the role of CTRP1 under the situation of insulin resistance in adipose tissue. Plasma CTRP1 level was investigated in type 2 diabetic subjects (n = 35) and non-diabetic subjects (n = 35). The relationship between CTRP1 and phosphorylation of multi insulin receptor substrate 1 (IRS-1) serine (Ser) sites was further explored. Our data showed that Plasma CTRP1 was higher and negative correlation with insulin resistance in diabetic subjects (r = -0.283, p = 0.018). Glucose utilisation test revealed that the glucose utilisation rate of mature adipocytes was improved by CTRP1 in the presence of insulin. CTRP1 was not only related to IRS-1 protein, but also negatively correlated with IRS-1 Ser1101 phosphorylation (r = -0.398, p = 0.031). Furthermore, Phosphorylation levels of IRS-1 Ser1101 were significantly lower after incubation with 40 ng/mL CTRP1 in mature adipocytes than those with no intervention (p insulin resistance by reducing the phosphorylation of IRS-1 Ser1101, induced in the situation of insulin resistance as a feedback adipokine.

  7. Long-term AICAR administration reduces metabolic disturbances and lowers blood pressure in rats displaying features of the insulin resistance syndrome

    DEFF Research Database (Denmark)

    Buhl, Esben Selmer; Jessen, Niels; Pold, Rasmus

    2002-01-01

    , upregulate mitochondrial enzymes in skeletal muscles, and decrease the content of intra-abdominal fat. Furthermore, acute AICAR exposure has been found to reduce sterol and fatty acid synthesis in rat hepatocytes incubated in vitro as well as suppress endogenous glucose production in rats under euglycemic......-treated animals exhibited a tendency toward decreased intra-abdominal fat content. Furthermore, AICAR administration normalized the oral glucose tolerance test and decreased fasting concentrations of glucose and insulin close to the level of the lean animals. Finally, in line with previous findings, AICAR...... treatment was also found to enhance GLUT4 protein expression and to increase maximally insulin-stimulated glucose transport in primarily white fast-twitch muscles. Our data provide strong evidence that long-term administration of AICAR improves glucose tolerance, improves the lipid profile, and reduces...

  8. Weight-sparing effect of insulin detemir: a consequence of central nervous system-mediated reduced energy intake?

    Science.gov (United States)

    Russell-Jones, D; Danne, T; Hermansen, K; Niswender, K; Robertson, K; Thalange, N; Vasselli, J R; Yildiz, B; Häring, H U

    2015-10-01

    Insulin therapy is often associated with adverse weight gain. This is attributable, at least in part, to changes in energy balance and insulin's anabolic effects. Adverse weight gain increases the risk of poor macrovascular outcomes in people with diabetes and should therefore be mitigated if possible. Clinical studies have shown that insulin detemir, a basal insulin analogue, exerts a unique weight-sparing effect compared with other basal insulins. To understand this property, several hypotheses have been proposed. These explore the interplay of efferent and afferent signals between the muscles, brain, liver, renal and adipose tissues in response to insulin detemir and comparator basal insulins. The following models have been proposed: insulin detemir may reduce food intake through direct or indirect effects on the central nervous system (CNS); it may have favourable actions on hepatic glucose metabolism through a selective effect on the liver, or it may influence fluid homeostasis through renal effects. Studies have consistently shown that insulin detemir reduces energy intake, and moreover, it is clear that this shift in energy balance is not a consequence of reduced hypoglycaemia. CNS effects may be mediated by direct action, by indirect stimulation by peripheral mediators and/or via a more physiological counter-regulatory response to insulin through restoration of the hepatic-peripheral insulin gradient. Although the precise mechanism remains unclear, it is likely that the weight-sparing effect of insulin detemir can be explained by a combination of mechanisms. The evidence for each hypothesis is considered in this review. © 2015 The Authors. Diabetes, Obesity and Metabolism published by John Wiley & Sons Ltd.

  9. Third Exposure to a Reduced Carbohydrate Meal Lowers Evening Postprandial Insulin and GIP Responses and HOMA-IR Estimate of Insulin Resistance.

    Science.gov (United States)

    Lin, Po-Ju; Borer, Katarina T

    2016-01-01

    Postprandial hyperinsulinemia, hyperglycemia, and insulin resistance increase the risk of type 2 diabetes (T2D) and cardiovascular disease mortality. Postprandial hyperinsulinemia and hyperglycemia also occur in metabolically healthy subjects consuming high-carbohydrate diets particularly after evening meals and when carbohydrate loads follow acute exercise. We hypothesized the involvement of dietary carbohydrate load, especially when timed after exercise, and mediation by the glucose-dependent insulinotropic peptide (GIP) in this phenomenon, as this incretin promotes insulin secretion after carbohydrate intake in insulin-sensitive, but not in insulin-resistant states. Four groups of eight metabolically healthy weight-matched postmenopausal women were provided with three isocaloric meals (a pre-trial meal and two meals during the trial day) containing either 30% or 60% carbohydrate, with and without two-hours of moderate-intensity exercise before the last two meals. Plasma glucose, insulin, glucagon, GIP, glucagon-like peptide 1 (GLP-1), free fatty acids (FFAs), and D-3-hydroxybutyrate concentrations were measured during 4-h postprandial periods and 3-h exercise periods, and their areas under the curve (AUCs) were analyzed by mixed-model ANOVA, and insulin resistance during fasting and meal tolerance tests within each diet was estimated using homeostasis-model assessment (HOMA-IR). The third low-carbohydrate meal, but not the high-carbohydrate meal, reduced: (1) evening insulin AUC by 39% without exercise and by 31% after exercise; (2) GIP AUC by 48% without exercise and by 45% after exercise, and (3) evening insulin resistance by 37% without exercise and by 24% after exercise. Pre-meal exercise did not alter insulin-, GIP- and HOMA-IR- lowering effects of low-carbohydrate diet, but exacerbated evening hyperglycemia. Evening postprandial insulin and GIP responses and insulin resistance declined by over 30% after three meals that limited daily carbohydrate intake to

  10. Exercise and diet enhance fat oxidation and reduce insulin resistance in older obese adults

    DEFF Research Database (Denmark)

    Solomon, Thomas; Sistrun, Sakita N; Krishnan, Raj K

    2008-01-01

    oxygen consumption (Vo(2max))] with either normal caloric intake (eucaloric group, 1,901 +/- 277 kcal/day, n = 12) or a reduced-calorie diet (hypocaloric group, 1,307 +/- 70 kcal/day, n = 11), as dictated by nutritional counseling. Body composition (decreased fat mass; maintained fat-free mass), aerobic...... fitness (Vo(2max)), leptinemia, insulin sensitivity, and intramyocellular lipid accumulation (IMCL) in skeletal muscle improved in both groups (P hypocaloric group. Following the intervention...

  11. Lipid content and response to insulin are not invariably linked in human muscle cells

    OpenAIRE

    Aguer , Céline; Mercier , Jacques; Kitzmann , Magali

    2009-01-01

    Abstract In type 2 diabetes, a strong correlation between intramyocellular lipid accumulation and insulin resistance exists but whether intramyocellular accumulation is a cause or a consequence of insulin resistance is not clear. Lipid accumulation and response to insulin were evaluated in primary human myotubes derived from non-diabetic subjects and type 2 diabetic patients. Myotubes derived from type 2 diabetic patients had a defective response to insulin without showing a signif...

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

    DEFF Research Database (Denmark)

    Ørtenblad, Niels; Mogensen, Martin; Petersen, Ingrid

    2005-01-01

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

  13. Reducing gas content of coal deposits by means of bacteria

    Energy Technology Data Exchange (ETDEWEB)

    Godlewska-Lipowa, A A; Kozlowski, B

    1981-07-01

    This paper discusses the results of experiments carried out in Poland under laboratory conditions on efficiency of methane control using bacteria from Methanosarcina and Methanomonas groups. Malashenko and Whittenburry culture mediums were used. Bacteria growth in an atmosphere of air and methane (48.2%, 8.6% and 5.21%) was observed. Temperature ranged from 19 to 20 C. Investigations show that the bacteria are characterized by high oxidation activity. Depending on methane concentration in the air the bacteria consume from 75% to 100% of methane during biosynthesis. The bacteria reduce methane and oxygen content and increase carbon dioxide content in the air. Using bacteria methane concentration in the air was reduced from 48.2% to 12.3%, from 8.6% to 0.0% and from 5.21% to 0.01%. (7 refs.) (In Polish)

  14. ATTEMPT TO REDUCE ACRYLAMIDE CONTENT IN ROASTED CHICORY

    Directory of Open Access Journals (Sweden)

    Gabriela Zięć

    2015-02-01

    Full Text Available The aim of this study was to reduce the formation of acrylamide during roasting of chicory roots by soaking the fresh roots in a solution of calcium chloride, by the use of different temperature and time of roasting of dried roots, as well as by the addition of the enzyme (asparaginase during roasting of dried roots. It was shown, that with increasing roasting temperature of chicory roots from 100 - 175 ° C the acrylamide content also increased, while at a temperature of 210 ° C the growth was inhibited. Increasing roasting time from 10 - 25 minutes resulted in an increased acrylamide content. Soaking the roots in the CaCl2 solution for 20 minutes reduced the formation of acrylamide during the roasting approximately by 40%, similarly as the application of asparaginase to the dried roots during the roasting process.

  15. GLUT-4 content in plasma membrane of muscle from patients with non-insulin-dependent diabetes mellitus

    DEFF Research Database (Denmark)

    Lund, S; Vestergaard, H; Andersen, P H

    1993-01-01

    The abundance of GLUT-4 protein in both total crude membrane and plasma membrane fractions of vastus lateralis muscle from 13 obese non-insulin-dependent diabetes mellitus (NIDDM) patients and 14 healthy subjects were examined in the fasting state and after supraphysiological hyperinsulinemia....... In the basal state the immunoreactive mass of GLUT-4 protein both in the crude membrane preparation and in the plasma membrane fraction was similar in NIDDM patients and control subjects. Moreover, in vivo insulin exposure neither for 30 min nor for 4 h had any impact on the content of GLUT-4 protein in plasma...... membranes. With the use of the same methodology, antibody, and achieving the same degree of plasma membrane purification and recovery, we found, however, that intraperitoneal administration of insulin to 7-wk-old rats within 30 min increased the content of GLUT-4 protein more than twofold (P

  16. Four days of simulated shift work reduces insulin sensitivity in humans.

    Science.gov (United States)

    Bescos, R; Boden, M J; Jackson, M L; Trewin, A J; Marin, E C; Levinger, I; Garnham, A; Hiam, D S; Falcao-Tebas, F; Conte, F; Owens, J A; Kennaway, D J; McConell, G K

    2018-06-01

    The aim of this study was to investigate the effects of 4 consecutive simulated night shifts on glucose homeostasis, mitochondrial function and central and peripheral rhythmicities compared with a simulated day shift schedule. Seventeen healthy adults (8M:9F) matched for sleep, physical activity and dietary/fat intake participated in this study (night shift work n = 9; day shift work n = 8). Glucose tolerance and insulin sensitivity before and after 4 nights of shift work were measured by an intravenous glucose tolerance test and a hyperinsulinaemic euglycaemic clamp respectively. Muscles biopsies were obtained to determine insulin signalling and mitochondrial function. Central and peripheral rhythmicities were assessed by measuring salivary melatonin and expression of circadian genes from hair samples respectively. Fasting plasma glucose increased (4.4 ± 0.1 vs. 4.6 ± 0.1 mmol L -1 ; P = .001) and insulin sensitivity decreased (25 ± 7%, P night shift, with no changes following the day shift. Night shift work had no effect on skeletal muscle protein expression (PGC1α, UCP3, TFAM and mitochondria Complex II-V) or insulin-stimulated pAkt Ser473, pTBC1D4Ser318 and pTBC1D4Thr642. Importantly, the metabolic changes after simulated night shifts occurred despite no changes in the timing of melatonin rhythmicity or hair follicle cell clock gene expression across the wake period (Per3, Per1, Nr1d1 and Nr1d2). Only 4 days of simulated night shift work in healthy adults is sufficient to reduce insulin sensitivity which would be expected to increase the risk of T2D. © 2018 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd.

  17. ACSL1 Is Associated With Fetal Programming of Insulin Sensitivity and Cellular Lipid Content.

    Science.gov (United States)

    Joseph, Roy; Poschmann, Jeremie; Sukarieh, Rami; Too, Peh Gek; Julien, Sofi G; Xu, Feng; Teh, Ai Ling; Holbrook, Joanna D; Ng, Kai Lyn; Chong, Yap Seng; Gluckman, Peter D; Prabhakar, Shyam; Stünkel, Walter

    2015-06-01

    Individuals who are born small for gestational age (SGA) have a risk to develop various metabolic diseases during their life course. The biological memory of the prenatal state of growth restricted individuals may be reflected in epigenetic alterations in stem cell populations. Mesenchymal stem cells (MSCs) from the Wharton's jelly of umbilical cord tissue are multipotent, and we generated primary umbilical cord MSC isolates from SGA and normal neonates, which were subsequently differentiated into adipocytes. We established chromatin state maps for histone marks H3K27 acetylation and H3K27 trimethylation and tested whether enrichment of these marks was associated with gene expression changes. After validating gene expression levels for 10 significant chromatin immunoprecipitation sequencing candidate genes, we selected acyl-coenzyme A synthetase 1 (ACSL1) for further investigations due to its key roles in lipid metabolism. The ACSL1 gene was found to be highly associated with histone acetylation in adipocytes differentiated from MSCs with SGA background. In SGA-derived adipocytes, the ACSL1 expression level was also found to be associated with increased lipid loading as well as higher insulin sensitivity. ACSL1 depletion led to changes in expression of candidate genes such as proinflammatory chemokines and down-regulated both, the amount of cellular lipids and glucose uptake. Increased ACSL1, as well as modulated downstream candidate gene expression, may reflect the obese state, as detected in mice fed a high-fat diet. In summary, we believe that ACSL1 is a programmable mediator of insulin sensitivity and cellular lipid content and adipocytes differentiated from Wharton's jelly MSCs recapitulate important physiological characteristics of SGA individuals.

  18. Evaluation of glucose and insulin response to haylage diets with different content of nonstructural carbohydrates in 2 breeds of horses.

    Science.gov (United States)

    Lindåse, S; Müller, C; Nostell, K; Bröjer, J

    2018-04-09

    Information about the effect of nonstructural carbohydrates (NSCs) in forage on the postprandial glucose and insulin response in horses is scarce. This is of interest as postprandial hyperinsulinemia in horses is a risk factor for laminitis. In addition, insulin sensitivity (IS) differs between breeds. The aim was to evaluate the postprandial glucose and insulin response to haylage diets with different NSC content in horses of 2 different breeds and to evaluate the relationship between the postprandial insulin response and measures of IS derived from a frequently sampled intravenous glucose tolerance test (FSIGTT). Standardbreds (n = 9) and Icelandic horses (n = 9) with a mean body condition score of 5.5 ± 0.6 (scale 1-9) were studied. Horses were clinically healthy at the start of the study and had no history of endocrinopathic laminitis. The experiment was conducted as a replicate 3 × 3 Latin square, in which horses were fed haylage diets with low (4.2%), medium (13.6%), and high (18.2%) NSC content of dry matter. Blood sampling was performed before feeding and every 30 min until 300 min after feeding. An FSIGTT was also performed in all horses. The early (first 60 min) and the total (300 min) postprandial glucose and insulin response (area under the curve [AUC]) was higher after a meal of both medium and high NSC haylage in comparison with low NSC haylage when both breeds were combined (P ≤ 0.02). There was a main effect of breed for the early (P ≤ 0.004) but not for the total (P > 0.12) postprandial glucose and insulin response. The IS index was comparable between breeds (P = 0.75). The natural logarithm of the peak concentration, the AUC for the first 60 min and the total AUC for insulin, after a meal of medium and high NSC haylage, were moderately negatively correlated (P haylage with low NSC content (P > 0.054). This study demonstrates that the postprandial insulin response is affected by both the NSC content of haylage and the horse's IS. However

  19. Pioglitazone improves insulin sensitivity, reduces visceral fat and stimulates lipolysis in non diabetic dialyzed patients

    Directory of Open Access Journals (Sweden)

    Anne Zanchi

    2012-06-01

    Full Text Available Insulin resistance is common in dialyzed patients and is associated with increased mortality and protein-energy wasting. The aim of this study was to investigate the effect of pioglitazone (PIO, a powerful insulin sensitizer, on insulin sensitivity, body composition and adipose tissue metabolism, in dialyzed patients. A double blind randomized cross-over study was performed in non diabetic dialysis patients. Each patient followed 2 treatment phases of 16 weeks, starting either with oral PIO 45 mg/d or placebo (PL, and then switched to the other phase. At the end of each phase, patients underwent hyperinsulinemic euglycemic clamps, dual energy X-ray absorptiometry, an abdominal CT, and extensive plasma biochemical analysis. Twelve patients including 8 HD (59.6±4.4 y and 4 PD patients (43.5±3.6 y were recruited. Nine patients completed both phases and 3 patients dropped out (renal transplantation/2 HD and peritonitis/1 PD. PIO was safe and well tolerated. Under PIO, insulin sensitivity improved, as assessed by increased total glucose disposal rate (1.98±0.24 for PIO versus 1.58±0.12 umol/kg/min for PL, p<0.05, and reduced glucose endogenous hepatic production. PIO did not affect post-dialysis body weight, total fat and lean body mass, but significantly reduced visceral adipose tissue (VAT area and the VAT/SAT (subcutaneous adipose tissue ratio. HDL-cholesterol significantly increased. PIO decreased CRP (3.96±1.44 mg/l vs 7.88±2.56, p<0.05, plasma leptin, and dramatically reduced leptin/adiponectin ratio. Glycerol turnover, circulating glycerol and non esterified fatty acids were paradoxically increased. In conclusion, the improvement in insulin sensitivity by PIO, in non diabetic dialyzed patients, was associated with favorable metabolic effects, reduction in inflammation and body fat redistribution. The stimulation of systemic lipolysis was a surprising finding which may reflect adipose tissue remodeling and/or a paradoxical lypolitic

  20. Effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in drug-naive subjects with type 2 diabetes.

    Science.gov (United States)

    Bi, Yan; Zhang, Bing; Xu, Wen; Yang, Huijie; Feng, Wenhuan; Li, Cuiliu; Tong, Guoyu; Li, Ming; Wang, Xin; Shen, Shanmei; Zhu, Bin; Weng, Jianping; Zhu, Dalong

    2014-10-01

    Ectopic accumulation of lipids in nonadipose tissues plays a primary role in the pathogenesis of type 2 diabetes mellitus (T2DM). This study was to examine the effects of exenatide, insulin, and pioglitazone on liver fat content and body fat distributions in T2DM. Thirty-three drug-naive T2DM patients (age 52.7 ± 1.7 years, HbA1c 8.7 ± 0.2 %, body mass index 24.5 ± 0.5 kg/m(2)) were randomized into exenatide, insulin, or pioglitazone for 6 months. Intrahepatic fat (IHF), visceral fat (VF), and subcutaneous fat (SF) were measured using proton nuclear magnetic resonance spectroscopy. Plasma tumor necrosis factor α (TNFα) and adiponectin were assayed by ELISA. HbA1c declined significantly in all three groups. Body weight, waist, and serum triglycerides decreased with exenatide. After interventions, IHF significantly reduced with three treatments (exenatide Δ = -68 %, insulin Δ = -58 %, pioglitazone Δ = -49 %). Exenatide reduced VF (Δ = -36 %) and SF (Δ = -13 %), and pioglitazone decreased VF (Δ = -30 %) with no impact on SF, whereas insulin had no impact on VF or SF. Levels of TNFα (exenatide/insulin/pioglitazone) decreased, and levels of adiponectin (exenatide/pioglitazone) increased. Analysis showed that ΔIHF correlated with ΔHbA1c and Δweight. Besides, ΔIHF correlated with Δtriglycerides and ΔTNFα, but the correlations fell short of significance after BMI adjustment. By linear regression analysis, ΔHbA1c alone explained 41.5 % of the variance of ΔIHF, and ΔHbA1c + Δweight explained 57.6 % of the variance. Liver fat content can be significantly reduced irrespective of using exenatide, insulin, and pioglitazone. Early glycaemic control plays an important role in slowing progression of fatty liver in T2DM.

  1. Reducing the cadmium content of crude phosphates and mineral fertilizers

    Energy Technology Data Exchange (ETDEWEB)

    Plessen, H von; Schimmel, G

    1987-10-01

    Crude sedimentary phosphates generally contain cadmium together with traces of other heavy metals. These Cd traces generally end up in fertilizers produced from the crude phosphates. Processes have therefore been developed to separate the Cd from the crude phosphate or from the crude phosphoric acids arising therefrom as intermediates. In this way, the Cd content of the crude phosphate can be reduced to less the 10% of its original value, and to 50% thereof by extractive treatment with acidic calcium nitrate solution. Older calcination processes for crude phosphate have been improved to give residual Cd contents of 10 to 50% at temperatures of 800 to 1000/sup 0/C. Cadmium can be removed almost quantitatively from crude phosphate by means of dialkyl dithiophosphoric acid esters by extraction, binding to adsorbents, or ion flotation. Cadmium can be extracted from crude acids in high yield by long-chained amines. After partial neutralization of the crude acids, precipitation as cadmium sulphide is also possible.

  2. Meal replacement reduces insulin requirement, HbA1c and weight long-term in type 2 diabetes patients with >100 U insulin per day.

    Science.gov (United States)

    Kempf, K; Schloot, N C; Gärtner, B; Keil, R; Schadewaldt, P; Martin, S

    2014-04-01

    Despite high insulin doses, good glycaemic control is often lacking in type 2 diabetes patients and new therapeutic options are needed. In a proof of principle study, an energy-restricted, protein-rich meal replacement (PRMR) was examined as a means of reducing insulin requirement, HbA1C and body weight. Obese type 2 diabetes patients (n = 22) with >100 U insulin per day replaced, in week 1, the three main meals with 50 g of PRMR (Almased-Vitalkost) each (= 4903 kJ day(-1) ). In weeks 2-4, breakfast and dinner were replaced, and, in weeks 5-12, only dinner was replaced. Clinical parameters were determined at baseline, and after 4, 8 and 12 weeks, as well as after 1.5 years of follow-up. The Wilcoxon signed-rank test was used for the intention-to-treat analysis and the Mann-Whitney U-test for subgroup analyses. The 12-week-programme was completed by 15 participants (68%). After 1 week, the mean insulin dose was reduced from 147 (75) U to 91 (55) U day(-1) (P = 0.0001), and to 65 (32) U (P fasting blood glucose, triglycerides and high-density lipoprotein cholesterol improved significantly. After 1.5 years, insulin requirement and weight remained significantly lower than baseline. Participants who continued PRMR further reduced their HbA1c, weight and insulin dose. Two patients were able to stop insulin therapy altogether. Energy-restricted PRMR was effective in reducing insulin requirement of type 2 diabetes patients with intensified insulin therapy accompanied by a reduction of HbA1c, weight and other cardiometabolic risk factors. With the continuous use of PRMR, glycaemic control might be improved in the long term. © 2013 The British Dietetic Association Ltd.

  3. Isothiocyanate-rich Moringa oleifera extract reduces weight gain, insulin resistance, and hepatic gluconeogenesis in mice.

    Science.gov (United States)

    Waterman, Carrie; Rojas-Silva, Patricio; Tumer, Tugba Boyunegmez; Kuhn, Peter; Richard, Allison J; Wicks, Shawna; Stephens, Jacqueline M; Wang, Zhong; Mynatt, Randy; Cefalu, William; Raskin, Ilya

    2015-06-01

    Moringa oleifera (moringa) is tropical plant traditionally used as an antidiabetic food. It produces structurally unique and chemically stable moringa isothiocyanates (MICs) that were evaluated for their therapeutic use in vivo. C57BL/6L mice fed very high fat diet (VHFD) supplemented with 5% moringa concentrate (MC, delivering 66 mg/kg/d of MICs) accumulated fat mass, had improved glucose tolerance and insulin signaling, and did not develop fatty liver disease compared to VHFD-fed mice. MC-fed group also had reduced plasma insulin, leptin, resistin, cholesterol, IL-1β, TNFα, and lower hepatic glucose-6-phosphatase (G6P) expression. In hepatoma cells, MC and MICs at low micromolar concentrations inhibited gluconeogenesis and G6P expression. MICs and MC effects on lipolysis in vitro and on thermogenic and lipolytic genes in adipose tissue in vivo argued these are not likely primary targets for the anti-obesity and anti-diabetic effects observed. Data suggest that MICs are the main anti-obesity and anti-diabetic bioactives of MC, and that they exert their effects by inhibiting rate-limiting steps in liver gluconeogenesis resulting in direct or indirect increase in insulin signaling and sensitivity. These conclusions suggest that MC may be an effective dietary food for the prevention and treatment of obesity and type 2 diabetes. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  4. Reduced cytotoxicity of insulin-immobilized CdS quantum dots using PEG as a spacer

    Directory of Open Access Journals (Sweden)

    Choi Moon-Jeong

    2011-01-01

    Full Text Available Abstract Cytotoxicity is a severe problem for cadmium sulfide nanoparticles (CSNPs in biological systems. In this study, mercaptoacetic acid-coated CSNPs, typical semiconductor Q-dots, were synthesized in aqueous medium by the arrested precipitation method. Then, amino-terminated polyethylene glycol (PEG was conjugated to the surface of CSNPs (PCSNPs in order to introduce amino groups to the surface. Finally, insulin was immobilized on the surface of PCSNPs (ICSNPs to reduce cytotoxicity as well as to enhance cell compatibility. The presence of insulin on the surface of ICSNPs was confirmed by observing infrared absorptions of amide I and II. The mean diameter of ICSNPs as determined by dynamic light scattering was about 38 nm. Human fibroblasts were cultured in the absence and presence of cadmium sulfide nanoparticles to evaluate cytotoxicity and cell compatibility. The results showed that the cytotoxicity of insulin-immobilized cadmium sulfide nanoparticles was significantly suppressed by usage of PEG as a spacer. In addition, cell proliferation was highly facilitated by the addition of ICSNPs. The ICSNPs used in this study will be potentials to be used in bio-imaging applications.

  5. Naringenin Inhibits Adipogenesis and Reduces Insulin Sensitivity and Adiponectin Expression in Adipocytes

    Directory of Open Access Journals (Sweden)

    Allison J. Richard

    2013-01-01

    Full Text Available Adipose tissue development and function are widely studied to examine the relationship between obesity and the metabolic syndrome. It is well documented that the inability of adipose tissue to properly increase its lipid storage capacity during the obese state can lead to metabolic dysfunction. In a blind screen of 425 botanicals, we identified naringenin as an inhibitor of adipocyte differentiation. Naringenin is one of the most abundant citrus flavonoids, and recent studies have demonstrated antihyperlipidemic capabilities. These studies have largely focused on the effects of naringenin on the liver. Our biochemical studies clearly demonstrate that naringenin inhibits adipogenesis and impairs mature fat cell function. Naringenin specifically inhibited adipogenesis in a dose-dependent fashion as judged by examining lipid accumulation and induction of adipocyte marker protein expression. In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Exposure to naringenin also inhibited adiponectin protein expression in mature murine and human adipocytes. Our studies have revealed that naringenin may have a negative impact on adipocyte-related diseases by limiting differentiation of preadipocytes, by significantly inducing insulin resistance, and by decreasing adiponectin expression in mature fat cells.

  6. A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance.

    Science.gov (United States)

    Bosse, John D; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E Dale; Pereira, Troy J; Dolinsky, Vernon W; Symons, J David; Jalili, Thunder

    2013-06-15

    Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-HF had lower (P vs. 159 ± 3 mmHg) but a similar degree of cardiac hypertrophy (33.4 ± 0.4 vs. 33.1 ± 0.4 heart weight/tibia length, mg/mm). Mesenteric arteries and the entire aorta were used to assess vascular function and endothelial nitric oxide synthase (eNOS) signaling, respectively. Endothelium-dependent (acetylcholine) relaxation of mesenteric arteries was improved (P vs. SHR-C, whereas contraction (potassium chloride, phenylephrine) was reduced (P vs. SHR-C. Plasma glucose, insulin, and homoeostatic model of insulin assessment were lower (P vs. SHR-C, whereas peripheral insulin sensitivity (insulin tolerance test) was similar. After a 10-h fast, insulin stimulation (2 U/kg ip) increased (P vs. SHR-HF. In conclusion, a low-carbohydrate/high-fat diet reduced blood pressure and improved arterial function in SHR without producing signs of insulin resistance or altering insulin-mediated signaling in the heart, skeletal muscle, or vasculature.

  7. Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

    International Nuclear Information System (INIS)

    Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya; Hirose, Takahisa; Kawamori, Ryuzo; Fujitani, Yoshio; Watada, Hirotaka

    2009-01-01

    Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

  8. Effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation depend on treatment dose, treatment duration and meal contents

    Energy Technology Data Exchange (ETDEWEB)

    Arakawa, Masayuki; Ebato, Chie; Mita, Tomoya [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Hirose, Takahisa [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Kawamori, Ryuzo [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Center for Beta Cell Biology and Regeneration, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan); Fujitani, Yoshio, E-mail: fujitani@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Center for Therapeutic Innovations in Diabetes, Juntendo University School of Medicine, Tokyo (Japan); Watada, Hirotaka, E-mail: hwatada@juntendo.ac.jp [Department of Medicine, Metabolism and Endocrinology, Juntendo University School of Medicine, Tokyo (Japan); Sportology Center, Juntendo University School of Medicine, Tokyo (Japan)

    2009-12-18

    Beta-cell proliferation is regulated by various metabolic demands including peripheral insulin resistance, obesity, and hyperglycemia. In addition to enhancement of glucose-induced insulin secretion, agonists for glucagon-like peptide-1 receptor (GLP-1R) stimulate proliferation and inhibit apoptosis of beta-cells, thereby probably preserve beta-cell mass. To evaluate the beta-cell preserving actions of GLP-1R agonists, we assessed the acute and chronic effects of exendin-4 on beta-cell proliferation, mass and glucose tolerance in C57BL/6J mice under various conditions. Short-term administration of high-dose exendin-4 transiently stimulated beta-cell proliferation. Comparative transcriptomic analysis showed upregulation of IGF-1 receptor and its downstream effectors in islets. Treatment of mice with exendin-4 daily for 4 weeks (long-term administration) and feeding high-fat diet resulted in significant inhibition of weight gain and improvement of glucose tolerance with reduced insulin secretion and beta-cell mass. These findings suggest that long-term GLP-1 treatment results in insulin sensitization of peripheral organs, rather than enhancement of beta-cell proliferation and function, particularly when animals are fed high-fat diet. Thus, the effects of exendin-4 on glucose tolerance, insulin secretion, and beta-cell proliferation largely depend on treatment dose, duration of treatment and meal contents. While GLP-1 enhances proliferation of beta-cells in some diabetic mice models, our results suggest that GLP-1 stimulates beta-cell growth only when expansion of beta-cell mass is required to meet metabolic demands.

  9. Novel simple insulin delivery device reduces barriers to insulin therapy in type 2 diabetes: results from a pilot study.

    Science.gov (United States)

    Hermanns, Norbert; Lilly, Leslie C; Mader, Julia K; Aberer, Felix; Ribitsch, Anja; Kojzar, Harald; Warner, Jay; Pieber, Thomas R

    2015-05-01

    The PaQ® insulin delivery system is a simple-to-use patch-on device that provides preset basal rates and bolus insulin on demand. In addition to feasibility of use, safety, and efficacy (reported elsewhere), this study analyzed the impact of PaQ on patient-reported outcomes, including barriers to insulin treatment, diabetes-related distress, and attitudes toward insulin therapy in patients with type 2 diabetes on a stable multiple daily injection (MDI) regimen. This single-center, open-label, single-arm study comprised three 2-week periods: baseline (MDI), transition from MDI to PaQ, and PaQ treatment. Validated questionnaires were administered during the baseline and PaQ treatment periods: Barriers to Insulin Treatment questionnaire (BIT), Insulin Treatment Appraisal Scale (ITAS), and Problem Areas in Diabetes scale (PAID). Eighteen patients (age 59 ± 5 years, diabetes duration 15 ± 7 years, 21% female, HbA1c 7.7 ± 0.7%) completed the questionnaires. There was a strong, significant effect of PaQ use in mean BIT total scores (difference [D] = -5.4 ± 0.7.7, P = .01, effect size [d] = 0.70). Patients perceived less stigmatization by insulin injection (D = -2.2 ± 6.2, P = .18, d = 0.35), increased positive outcome (D = 1.9 ± 6.6, P = .17, d = 0.29), and less fear of injections (1.3 ± 4.8, P = .55, d = 0.28). Mean change in ITAS scores after PaQ device use showed a nonsignificant improvement of 1.71 ± 5.63 but moderate effect size (d = 0.30, P = .14). No increase in PAID scores was seen. The results and moderate to large effects sizes suggest that PaQ device use has beneficial and clinically relevant effects to overcoming barriers to and negative appraisal of insulin treatment, without increasing other diabetes-related distress. © 2015 Diabetes Technology Society.

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

    NARCIS (Netherlands)

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

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

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

    DEFF Research Database (Denmark)

    Brunak, Søren; Holmkvist, J; Banasik, K

    2009-01-01

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

  12. Insulin binding to brain capillaries is reduced in genetically obese, hyperinsulinemic Zucker rats

    International Nuclear Information System (INIS)

    Schwartz, M.W.; Figlewicz, D.F.; Kahn, S.E.; Baskin, D.G.; Greenwood, M.R.; Porte, D. Jr.

    1990-01-01

    In order to study the role of plasma insulin in regulating the binding of insulin to the endothelium of the blood-brain barrier (BBB), insulin binding to a purified preparation of brain capillaries was measured in both genetically obese Zucker rats and lean Zucker controls. We found a reduction of 65% in brain capillary insulin binding site number in the obese compared to lean rats with no change in receptor affinity. Furthermore, specific insulin binding to brain capillaries was negatively correlated (p less than 0.05) to the plasma insulin level, suggesting a role for plasma insulin in regulating insulin binding. A similar relationship was observed between insulin receptor number in liver membranes and the plasma insulin level. We conclude that obese, hyperinsulinemic Zucker rats exhibit a reduction in the number of BBB insulin receptors, which parallels the reduction seen in other peripheral tissues. Since insulin receptors have been hypothesized to participate in the transport of insulin across the BBB, the reduction observed in the obese rats may account for the decrease in cerebrospinal fluid insulin uptake previously demonstrated in these animals

  13. Structural analogs of human insulin-like growth factor I with reduced affinity for serum binding proteins and the type 2 insulin-like growth factor receptor

    International Nuclear Information System (INIS)

    Bayne, M.L.; Applebaum, J.; Chicchi, G.G.; Hayes, N.S.; Green, B.G.; Cascieri, M.A.

    1988-01-01

    Four structural analogs of human insulin-like growth factor I (hIGF-I) have been prepared by site-directed mutagenesis of a synthetic IGF-I gene and subsequent expression and purification of the mutant protein from the conditioned media of transformed yeast. [Phe -1 , Val 1 , Asn 2 , Gln 3 , His 4 , Ser 8 , His 9 , Glu 12 , Tyr 15 , Leu 16 ]IGF-I (B-chain mutant), in which the first 16 amino acids of hIGF-I were replaced with the first 17 amino acids of the B-chain of insulin, has >1000-, 100-, and 2-fold reduced potency for human serum binding proteins, the rat liver type 2 IGF receptor, and the human placental type 1 IGF receptor, respectively. The B-chain mutant also has 4-fold increased affinity for the human placental insulin receptor. [Gln 3 , Ala 4 ] IGF-I has 4-fold reduced affinity for human serum binding proteins, but is equipotent to hIGF-I at the types 1 and 2 IGF and insulin receptors. [Tyr 15 , Leu 16 ] IGH-I has 4-fold reduced affinity for human serum binding proteins and 10-fold increased affinity for the insulin receptor. The peptide in which these four-point mutations are combined, [Gln 3 , Ala 4 , Tyr 15 ,Leu 16 ]IGF-I, has 600-fold reduced affinity for the serum binding proteins. All four of these mutants stimulate DNA synthesis in the rat vascular smooth muscle cell line A10 with potencies reflecting their potency at the type 1 IGF receptor. These studies identify some of the domains of hIGF-I which are responsible for maintaining high affinity binding with the serum binding protein and the type 2 IGF receptor. In addition, These peptides will be useful in defining the role of the type 2 IGF receptor and serum binding proteins in the physiological actions of hIGF-I

  14. Protein and fat meal content increase insulin requirement in children with type 1 diabetes – Role of duration of diabetes

    Directory of Open Access Journals (Sweden)

    M. van der Hoogt

    2017-12-01

    Full Text Available Background and objective: Hyperglycaemia remains a challenge in type 1 diabetes since current regimes used to determine meal insulin requirements prove to be ineffective. This is particularly problematic for meals containing high amounts of protein and fat. We aimed to determine the post-prandial glycaemic response and total insulin need for mixed meals, using sensor-augmented insulin pumps in children with type 1 diabetes. Methods: Twenty-two children with type 1 diabetes, aged 4–17 years on insulin pump therapy completed this home-based, cross-over, randomised controlled trial. Two meals with identical carbohydrate content – one with low fat and protein (LFLP and one with high fat and protein (HFHP contents – were consumed using normal insulin boluses. Blood glucose monitoring was done for 10 h post-meal, with correction bolus insulin given two-hourly if required. Results: The HFHP meal required significantly more total insulin (3.48 vs. 2.7 units as a result of increased post-meal correction insulin requirement (1.2 vs. 0.15 units spread over a longer duration (6 vs. 3 h. The HFHP meals significantly increased the time spent above target glucose level. Duration of diabetes and total daily insulin use significantly influenced the post-prandial blood glucose response to the two meals. Conclusion: When consuming carbohydrate-based mixed meals, children with type 1 diabetes on insulin pump therapy, required significantly more insulin over a longer period of time than the insulin requirement calculated using current regimes. This additional amount required is influenced by the duration of diabetes and total daily insulin use. Keywords: Carbohydrate, Protein and fat, Type 1 diabetes, Glucose, Insulin infusion systems

  15. Adipocyte-specific blockade of gamma-secretase, but not inhibition of Notch activity, reduces adipose insulin sensitivity

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    David P. Sparling

    2016-02-01

    Full Text Available Objective: As the obesity pandemic continues to expand, novel molecular targets to reduce obesity-related insulin resistance and Type 2 Diabetes (T2D continue to be needed. We have recently shown that obesity is associated with reactivated liver Notch signaling, which, in turn, increases hepatic insulin resistance, opening up therapeutic avenues for Notch inhibitors to be repurposed for T2D. Herein, we tested the systemic effects of γ-secretase inhibitors (GSIs, which prevent endogenous Notch activation, and confirmed these effects through creation and characterization of two different adipocyte-specific Notch loss-of-function mouse models through genetic ablation of the Notch transcriptional effector Rbp-Jk (A-Rbpj and the obligate γ-secretase component Nicastrin (A-Nicastrin. Methods: Glucose homeostasis and both local adipose and systemic insulin sensitivity were examined in GSI-treated, A-Rbpj and A-Nicastrin mice, as well as vehicle-treated or control littermates, with complementary in vitro studies in primary hepatocytes and 3T3-L1 adipocytes. Results: GSI-treatment increases hepatic insulin sensitivity in obese mice but leads to reciprocal lowering of adipose glucose disposal. While A-Rbpj mice show normal body weight, adipose development and mass and unchanged adipose insulin sensitivity as control littermates, A-Nicastrin mice are relatively insulin-resistant, mirroring the GSI effect on adipose insulin action. Conclusions: Notch signaling is dispensable for normal adipocyte function, but adipocyte-specific γ-secretase blockade reduces adipose insulin sensitivity, suggesting that specific Notch inhibitors would be preferable to GSIs for application in T2D. Keywords: Notch, γ-secretase complex, Insulin resistance

  16. Kefir reduces insulin resistance and inflammatory cytokine expression in an animal model of metabolic syndrome.

    Science.gov (United States)

    Rosa, Damiana D; Grześkowiak, Łukasz M; Ferreira, Célia L L F; Fonseca, Ana Carolina M; Reis, Sandra A; Dias, Mariana M; Siqueira, Nathane P; Silva, Leticia L; Neves, Clóvis A; Oliveira, Leandro L; Machado, Alessandra B F; Peluzio, Maria do Carmo G

    2016-08-10

    There is growing evidence that kefir can be a promising tool in decreasing the risk of many diseases, including metabolic syndrome (MetS). The aim of the present study was to evaluate the effect of kefir supplementation in the diet of Spontaneously Hypertensive Rats (SHR) in which MetS was induced with monosodium glutamate (MSG), and to determine its effect on metabolic parameters, inflammatory and oxidation marker expression and glycemic index control. Thirty animals were used in this experiment. For the induction of MetS, twenty two-day-old male SHR received five consecutive intradermal injections of MSG. For the Negative Control, ten newborn male SHR received intradermal injections of saline solution (0.9% saline solution). After weaning, animals received standard diet and water ad libitum until reaching 3 months old, for the development of MetS. They were then divided into three groups (n = 10): negative control (NC, 1 mL saline solution per day), positive control (PC, 1 mL saline solution per day) and the Kefir group (1 mL kefir per day). Feeding was carried out by gavage for 10 weeks and the animals received standard food and water ad libitum. Obesity, insulin resistance, pro- and anti-inflammatory markers, and the histology of pancreatic and adipose tissues were among the main variables evaluated. Compared to the PC group, kefir supplementation reduced plasma triglycerides, liver lipids, liver triglycerides, insulin resistance, fasting glucose, fasting insulin, thoracic circumference, abdominal circumference, products of lipid oxidation, pro-inflammatory cytokine expression (IL-1β) and increased anti-inflammatory cytokine expression (IL-10). The present findings indicate that kefir has the potential to benefit the management of MetS.

  17. Silymarin ameliorates fructose induced insulin resistance syndrome by reducing de novo hepatic lipogenesis in the rat.

    Science.gov (United States)

    Prakash, Prem; Singh, Vishal; Jain, Manish; Rana, Minakshi; Khanna, Vivek; Barthwal, Manoj Kumar; Dikshit, Madhu

    2014-03-15

    High dietary fructose causes insulin resistance syndrome (IRS), primarily due to simultaneous induction of genes involved in glucose, lipid and mitochondrial oxidative metabolism. The present study evaluates effect of a hepatoprotective agent, silymarin (SYM) on fructose-induced metabolic abnormalities in the rat and also assessed the associated thrombotic complications. Wistar rats were kept on high fructose (HFr) diet throughout the 12-week study duration (9 weeks of HFr feeding and subsequently 3 weeks of HFr plus SYM oral administration [once daily]). SYM treatment significantly reduced the HFr diet-induced increase expression of peroxisome proliferator-activated receptor gamma coactivator (PGC)-1α/β, peroxisome proliferator-activated receptor (PPAR)-α, forkhead box protein O1 (FOXO1), sterol regulatory element binding protein (SREBP)-1c, liver X receptor (LXR)-β, fatty acid synthase (FAS) and PPARγ genes in rat liver. SYM also reduced HFr diet mediated increase in plasma triglycerides (TG), non-esterified fatty acids (NEFA), uric acid, malondialdehyde (MDA), total nitrite and pro-inflammatory cytokines (C-reactive protein [CRP], interleukin-6 [IL-6], interferon-gamma [IFN-γ] and tumor necrosis factor [TNF]) levels. Moreover, SYM ameliorated HFr diet induced reduction in glucose utilization and endothelial dysfunction. Additionally, SYM significantly reduced platelet activation (adhesion and aggregation), prolonged ferric chloride-induced blood vessel occlusion time and protected against exacerbated myocardial ischemia reperfusion (MI-RP) injury. SYM treatment prevented HFr induced mRNA expression of hepatic PGC-1α/β and also its target transcription factors which was accompanied with recovery in insulin sensitivity and reduced propensity towards thrombotic complications and aggravated MI-RP injury. Copyright © 2014 Elsevier B.V. All rights reserved.

  18. A Single Day of Excessive Dietary Fat Intake Reduces Whole-Body Insulin Sensitivity: The Metabolic Consequence of Binge Eating

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    Siôn A. Parry

    2017-07-01

    Full Text Available Consuming excessive amounts of energy as dietary fat for several days or weeks can impair glycemic control and reduce insulin sensitivity in healthy adults. However, individuals who demonstrate binge eating behavior overconsume for much shorter periods of time; the metabolic consequences of such behavior remain unknown. The aim of this study was to determine the effect of a single day of high-fat overfeeding on whole-body insulin sensitivity. Fifteen young, healthy adults underwent an oral glucose tolerance test before and after consuming a high-fat (68% of total energy, high-energy (78% greater than daily requirements diet for one day. Fasting and postprandial plasma concentrations of glucose, insulin, non-esterified fatty acids, and triglyceride were measured and the Matsuda insulin sensitivity index was calculated. One day of high-fat overfeeding increased postprandial glucose area under the curve (AUC by 17.1% (p < 0.0001 and insulin AUC by 16.4% (p = 0.007. Whole-body insulin sensitivity decreased by 28% (p = 0.001. In conclusion, a single day of high-fat, overfeeding impaired whole-body insulin sensitivity in young, healthy adults. This highlights the rapidity with which excessive consumption of calories through high-fat food can impair glucose metabolism, and suggests that acute binge eating may have immediate metabolic health consequences for the individual.

  19. Knockout of Vasohibin-1 Gene in Mice Results in Healthy Longevity with Reduced Expression of Insulin Receptor, Insulin Receptor Substrate 1, and Insulin Receptor Substrate 2 in Their White Adipose Tissue

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    Eichi Takeda

    2017-01-01

    Full Text Available Vasohibin-1 (Vash1, originally isolated as an endothelium-derived angiogenesis inhibitor, has a characteristic of promoting stress tolerance in endothelial cells (ECs. We therefore speculated that the lack of the vash1 gene would result in a short lifespan. However, to our surprise, vash1−/− mice lived significantly longer with a milder senescence phenotype than wild-type (WT mice. We sought the cause of this healthy longevity and found that vash1−/− mice exhibited mild insulin resistance along with reduced expression of the insulin receptor (insr, insulin receptor substrate 1 (irs-1, and insulin receptor substrate 2 (irs-2 in their white adipose tissue (WAT but not in their liver or skeletal muscle. The expression of vash1 dominated in the WAT among those 3 organs. Importantly, vash1−/− mice did not develop diabetes even when fed a high-fat diet. These results indicate that the expression of vash1 was required for the normal insulin sensitivity of the WAT and that the target molecules for this activity were insr, irs1, and irs2. The lack of vash1 caused mild insulin resistance without the outbreak of overt diabetes and might contribute to healthy longevity.

  20. HLA-B*39:06 Efficiently Mediates Type 1 Diabetes in a Mouse Model Incorporating Reduced Thymic Insulin Expression.

    Science.gov (United States)

    Schloss, Jennifer; Ali, Riyasat; Racine, Jeremy J; Chapman, Harold D; Serreze, David V; DiLorenzo, Teresa P

    2018-04-09

    Type 1 diabetes (T1D) is characterized by T cell-mediated destruction of the insulin-producing β cells of the pancreatic islets. Among the loci associated with T1D risk, those most predisposing are found in the MHC region. HLA-B*39:06 is the most predisposing class I MHC allele and is associated with an early age of onset. To establish an NOD mouse model for the study of HLA-B*39:06, we expressed it in the absence of murine class I MHC. HLA-B*39:06 was able to mediate the development of CD8 T cells, support lymphocytic infiltration of the islets, and confer T1D susceptibility. Because reduced thymic insulin expression is associated with impaired immunological tolerance to insulin and increased T1D risk in patients, we incorporated this in our model as well, finding that HLA-B*39:06-transgenic NOD mice with reduced thymic insulin expression have an earlier age of disease onset and a higher overall prevalence as compared with littermates with typical thymic insulin expression. This was despite virtually indistinguishable blood insulin levels, T cell subset percentages, and TCR Vβ family usage, confirming that reduced thymic insulin expression does not impact T cell development on a global scale. Rather, it will facilitate the thymic escape of insulin-reactive HLA-B*39:06-restricted T cells, which participate in β cell destruction. We also found that in mice expressing either HLA-B*39:06 or HLA-A*02:01 in the absence of murine class I MHC, HLA transgene identity alters TCR Vβ usage by CD8 T cells, demonstrating that some TCR Vβ families have a preference for particular class I MHC alleles. Copyright © 2018 by The American Association of Immunologists, Inc.

  1. Thrombospondin1 deficiency reduces obesity-associated inflammation and improves insulin sensitivity in a diet-induced obese mouse model.

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    Yanzhang Li

    Full Text Available Obesity is prevalent worldwide and is associated with insulin resistance. Advanced studies suggest that obesity-associated low-grade chronic inflammation contributes to the development of insulin resistance and other metabolic complications. Thrombospondin 1 (TSP1 is a multifunctional extracellular matrix protein that is up-regulated in inflamed adipose tissue. A recent study suggests a positive correlation of TSP1 with obesity, adipose inflammation, and insulin resistance. However, the direct effect of TSP1 on obesity and insulin resistance is not known. Therefore, we investigated the role of TSP1 in mediating obesity-associated inflammation and insulin resistance by using TSP1 knockout mice.Male TSP1-/- mice and wild type littermate controls were fed a low-fat (LF or a high-fat (HF diet for 16 weeks. Throughout the study, body weight and fat mass increased similarly between the TSP1-/- mice and WT mice under HF feeding conditions, suggesting that TSP1 deficiency does not affect the development of obesity. However, obese TSP1-/- mice had improved glucose tolerance and increased insulin sensitivity compared to the obese wild type mice. Macrophage accumulation and inflammatory cytokine expression in adipose tissue were reduced in obese TSP1-/- mice. Consistent with the local decrease in pro-inflammatory cytokine levels, systemic inflammation was also decreased in the obese TSP1-/- mice. Furthermore, in vitro data demonstrated that TSP1 deficient macrophages had decreased mobility and a reduced inflammatory phenotype.TSP1 deficiency did not affect the development of high-fat diet induced obesity. However, TSP1 deficiency reduced macrophage accumulation in adipose tissue and protected against obesity related inflammation and insulin resistance. Our data demonstrate that TSP1 may play an important role in regulating macrophage function and mediating obesity-induced inflammation and insulin resistance. These data suggest that TSP1 may serve as a

  2. Insulin in the arcuate nucleus of the hypothalamus reduces fat consumption in rats

    NARCIS (Netherlands)

    van Dijk, G; de Groote, C; Chavez, M; van der Werf, Y; Steffens, AB; Strubbe, JH

    1997-01-01

    Data are accumulating that insulin acting in the central nervous system is a physiological regulator of food intake and body weight, presumably via its effect in the hypothalamus. The present study investigated whether infusion of a small dose of insulin into two major hypothalamic insulin-binding

  3. Weight-loss changes PPAR expression, reduces atherosclerosis and improves cardiovascular function in obese insulin-resistant mice

    Energy Technology Data Exchange (ETDEWEB)

    Verreth, Wim; Verhamme, Peter; Pelat, Michael; Ganame, Javier; Bielicki, John K.; Mertens, Ann; Quarck, Rozenn; Benhabiles, Nora; Marguerie, Gerard; Mackness, Bharti; Mackness, Mike; Ninio, Ewa; Herregods, Marie-Christine; Balligand, Jean-Luc; Holvoet, Paul

    2003-09-01

    Weight-loss in obese insulin-resistant, but not in insulin-sensitive, persons reduces CHD risk. It is not known to what extent changes in the adipose gene expression profile are important for reducing CHD risk. We studied the effect of diet restriction-induced weight-loss on gene expression in adipose tissue, atherosclerosis and cardiovascular function in mice with combined leptin and LDL-receptor deficiency. Obesity, hypertriglyceridemia and insulin-resistance are associated with hypertension, impaired left ventricle function and accelerated atherosclerosis in those mice. Diet restriction during 12 weeks caused a 45% weight-loss and changes in the gene expression in adipose tissue of PPARa and PPAR? and of key genes regulating glucose transport and insulin sensitivity, lipid metabolism, oxidative stress and inflammation, most of which are under the transcriptional control of PPARs. These changes were associated with increased insulin-sensitivity, decreased hypertriglyceridemia, reduced mean 24-hour blood pressure and heart rate, restored circadian variations of blood pressure and heart rate, increased ejection fraction, and reduced atherosclerosis. Thus, induction of PPARa and PPAR? in adipose tissue is a key mechanism for reducing atherosclerosis and improving cardiovascular function resulting from weight-loss. Our observations point to the critical role of PPARs in the pathogenesis of cardiovascular features of the metabolic syndrome.

  4. The effects of short-term overfeeding on insulin action in lean and reduced-obese individuals.

    Science.gov (United States)

    Cornier, Marc-Andre; Bergman, Bryan C; Bessesen, Daniel H

    2006-09-01

    Insulin resistance is clearly associated with obesity. However, the role of excess energy intake per se as opposed to increased fat mass in the development of insulin resistance has not been clearly defined. It may be that the nutrient load provided by short-term overfeeding is sufficient to induce measurable changes in insulin action in skeletal muscle and the liver. We examined the effects of 3 days of overfeeding on insulin action and glucose kinetics in 13 lean (body mass index, 20.9 +/- 2.4 kg/m(2); 6 men, 7 women) and 9 reduced-obese (RO) (body mass index, 29.1 +/- 2.2 kg/m(2); 4 men, 5 women) individuals. A two-step euglycemic hyperinsulinemic clamp study (5 and 40 mU m(-2) min(-1)) with a primed, constant infusion of [6,6-(2)H(2)]glucose was performed after 3 days of a weight-maintenance diet and again after 3 days of overfeeding by 50% (50% carbohydrate, 30% fat, 20% protein). At baseline, lean individuals were more insulin sensitive, as measured by glucose infusion rate, than RO individuals (12.08 +/- 0.8 vs 7.62 +/- 1.0 mg x kg(-1) x min(-1), P lean women being more insulin sensitive than lean men (P lean women (13.37 +/- 1.3 to 11.42 +/- 1.0 mg x kg(-1) x min(-1), P lean men or RO individuals. Basal and insulin-stimulated glucose disposal remained unchanged with overfeeding in all groups. Low-dose insulin suppression of endogenous glucose production was impaired after overfeeding in lean women (euenergetic, 1.92 +/- 0.36 to 0.36 +/- 0.16 mg x kg(-1) x min(-1); overfeeding: 2.13 +/- 0.17 to 0.86 +/- 0.12 mg x kg(-1) x min(-1); P = .04) but remained unchanged in the other groups. These findings demonstrate that insulin action is reduced in lean, obese-resistant women after short-term overfeeding primarily because of an inhibition of insulin-mediated suppression of endogenous glucose production, whereas short-term overfeeding does not appear to effect insulin action in lean men and RO individuals. This response may be indirectly involved in the ability of

  5. Starvation increases insulin sensitivity and reduces juvenile hormone synthesis in mosquitoes.

    Directory of Open Access Journals (Sweden)

    Meritxell Perez-Hedo

    Full Text Available The interactions between the insulin signaling pathway (ISP and juvenile hormone (JH controlling reproductive trade-offs are well documented in insects. JH and insulin regulate reproductive output in mosquitoes; both hormones are involved in a complex regulatory network, in which they influence each other and in which the mosquito's nutritional status is a crucial determinant of the network's output. Previous studies reported that the insulin-TOR (target of rapamacyn signaling pathway is involved in the nutritional regulation of JH synthesis in female mosquitoes. The present studies further investigate the regulatory circuitry that controls both JH synthesis and reproductive output in response to nutrient availability.We used a combination of diet restriction, RNA interference (RNAi and insulin treatments to modify insulin signaling and study the cross-talk between insulin and JH in response to starvation. JH synthesis was analyzed using a newly developed assay utilizing fluorescent tags.Our results reveal that starvation decreased JH synthesis via a decrease in insulin signaling in the corpora allata (CA. Paradoxically, starvation-induced up regulation of insulin receptor transcripts and therefore "primed" the gland to respond rapidly to increases in insulin levels. During this response to starvation the synthetic potential of the CA remained unaffected, and the gland rapidly and efficiently responded to insulin stimulation by increasing JH synthesis to rates similar to those of CA from non-starved females.

  6. Acetyl-CoA carboxylase in Reuber hepatoma cells: variation in enzyme activity, insulin regulation, and cellular lipid content.

    Science.gov (United States)

    Bianchi, A; Evans, J L; Nordlund, A C; Watts, T D; Witters, L A

    1992-01-01

    Reuber hepatoma cells are useful cultured lines for the study of insulin action, lipid and lipoprotein metabolism, and the regulation of acetyl-CoA carboxylase (ACC), the rate-limiting enzyme of fatty acid biosynthesis. During investigations in different clonal lines of these cells, we have uncovered marked intercellular variability in the activity, enzyme content, and insulin regulation of ACC paralleled by differences in cellular neutral lipid (triglyceride) content. Two contrasting clonal lines, Fao and H356A-1, have been studied in detail. Several features distinguish these two lines, including differences in ACC activity and enzyme kinetics, the content of the two major hepatic ACC isozymes (Mr 280,000 and 265,000 Da) and their heteroisozymic complex, the extent of ACC phosphorylation, and the ability of ACC to be activated on stimulation by insulin and insulinomimetic agonists. As studied by Nile Red staining and fluorescence-activated cell sorting, these two lines also display marked differences in neutral lipid content, which correlates with both basal levels of ACC activity and inhibition of ACC by the fatty acid analog, 5-(tetradecyloxy)-2-furoic acid (TOFA). These results emphasize the importance of characterization of any particular clonal line of Reuber cells for studies of enzyme regulation, substrate metabolism, and hormone action. With respect to ACC, studies in contrasting clonal lines of Reuber cells could provide valuable clues to understanding both the complex mechanisms of intracellular ACC regulation in the absence and presence of hormones and its regulatory role(s) in overall hepatic lipid metabolism.

  7. Reduced levels of SCD1 accentuate palmitate-induced stress in insulin-producing β-cells

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    Hovsepyan Meri

    2010-09-01

    Full Text Available Abstract Background Stearoyl-CoA desaturase 1 (SCD1 is an ER resident enzyme introducing a double-bond in saturated fatty acids. Global knockout of SCD1 in mouse increases fatty acid oxidation and insulin sensitivity which makes the animal resistant to diet-induced obesity. Inhibition of SCD1 has therefore been proposed as a potential therapy of the metabolic syndrome. Much of the work has focused on insulin target tissue and very little is known about how reduced levels of SCD1 would affect the insulin-producing β-cell, however. The aim of the present study was therefore to investigate how reduced levels of SCD1 affect the β-cell. Results Insulin-secreting MIN6 cells with reduced levels of SCD1 were established by siRNA mediated knockdown. When fatty acid oxidation was measured, no difference between cells with reduced levels of SCD1 and mock-transfected cells were found. Also, reducing levels of SCD1 did not affect insulin secretion in response to glucose. To investigate how SCD1 knockdown affected cellular mechanisms, differentially regulated proteins were identified by a proteomic approach. Cells with reduced levels of SCD1 had higher levels of ER chaperones and components of the proteasome. The higher amounts did not protect the β-cell from palmitate-induced ER stress and apoptosis. Instead, rise in levels of p-eIF2α and CHOP after palmitate exposure was 2-fold higher in cells with reduced levels of SCD1 compared to mock-transfected cells. Accordingly, apoptosis rose to higher levels after exposure to palmitate in cells with reduced levels of SCD1 compared to mock-transfected cells. Conclusions In conclusion, reduced levels of SCD1 augment palmitate-induced ER stress and apoptosis in the β-cell, which is an important caveat when considering targeting this enzyme as a treatment of the metabolic syndrome.

  8. Insulin-like growth factor I reduces lipid oxidation and foam cell formation via downregulation of 12/15-lipoxygenase.

    Science.gov (United States)

    Sukhanov, Sergiy; Snarski, Patricia; Vaughn, Charlotte; Lobelle-Rich, Patricia; Kim, Catherine; Higashi, Yusuke; Shai, Shaw-Yung; Delafontaine, Patrice

    2015-02-01

    We have shown that insulin-like growth factor I (IGF-1) infusion in Apoe(-/-) mice decreased atherosclerotic plaque size and plaque macrophage and lipid content suggesting that IGF-1 suppressed formation of macrophage-derived foam cells. Since 12/15-lipoxygenase (12/15-LOX) plays an important role in OxLDL and foam cell formation, we hypothesized that IGF-1 downregulates 12/15-LOX, thereby suppressing lipid oxidation and foam cell formation. We found that IGF-1 decreased 12/15-LOX plaque immunopositivity and serum OxLDL levels in Apoe(-/-) mice. IGF-1 reduced 12/15-LOX protein and mRNA levels in cultured THP-1 macrophages and IGF-1 also decreased expression of STAT6 transcription factor. IGF-1 reduction in macrophage 12/15-LOX was mediated in part via a PI3 kinase- and STAT6-dependent transcriptional mechanism. IGF-1 suppressed THP-1 macrophage ability to oxidize lipids and form foam cells. IGF-1 downregulated 12/15-LOX in human blood-derived primary macrophages and IGF-1 decreased LDL oxidation induced by these cells. IGF-1 reduced LDL oxidation and formation of foam cells by wild type murine peritoneal macrophages, however these effects were completely blocked in 12/15-LOX-null macrophages suggesting that the ability of IGF-1 to reduce LDL oxidation and foam cells formation is dependent on its ability to downregulate 12/15-LOX. Overall our data demonstrate that IGF-1 reduces lipid oxidation and foam cell formation via downregulation of 12/15-LOX and this mechanism may play a major role in the anti-atherosclerotic effects of IGF-1. Published by Elsevier Ireland Ltd.

  9. Insulin-like Growth Factor I Reduces Lipid Oxidation and Foam Cell Formation via Downregulation of 12/15-lipoxygenase

    Science.gov (United States)

    Sukhanov, Sergiy; Snarski, Patricia; Vaughn, Charlotte; Lobelle-Rich, Patricia; Kim, Catherine; Higashi, Yusuke; Shai, Shaw-Yung; Delafontaine, Patrice

    2014-01-01

    Objective We have shown that insulin-like growth factor I (IGF-1) infusion in Apoe−/− mice decreased atherosclerotic plaque size and plaque macrophage and lipid content suggesting that IGF-1 suppressed formation of macrophage-derived foam cells. Since 12/15-lipoxygenase (12/15-LOX) plays an important role in OxLDL and foam cell formation, we hypothesized that IGF-1 downregulates 12/15-LOX, thereby suppressing lipid oxidation and foam cell formation. Approach and Results We found that IGF-1 decreased 12/15-LOX plaque immunopositivity and serum OxLDL levels in Apoe−/− mice. IGF-1 reduced 12/15-LOX protein and mRNA levels in cultured THP-1 macrophages and IGF-1 also decreased expression of STAT6 transcription factor. IGF-1 reduction in macrophage 12/15-LOX was mediated in part via a PI3 kinase- and STAT6-dependent transcriptional mechanism. IGF-1 suppressed THP-1 macrophage ability to oxidize lipids and form foam cells. IGF-1 downregulated 12/15-LOX in human blood-derived primary macrophages and IGF-1 decreased LDL oxidation induced by these cells. IGF-1 reduced LDL oxidation and formation of foam cells by wild type murine peritoneal macrophages, however these effects were completely blocked in 12/15-LOX-null macrophages suggesting that the ability of IGF-1 to reduce LDL oxidation and foam cells formation is dependent on its ability to downregulate 12/15-LOX. Conclusions Overall our data demonstrate that IGF-1 reduces lipid oxidation and foam cell formation via downregulation of 12/15-LOX and this mechanism may play a major role in the anti-atherosclerotic effects of IGF-1. PMID:25549319

  10. Correlation of serum vitamin E content with insulin resistance and oxidative stress response in patients with type 2 diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Jun Li

    2017-08-01

    Full Text Available Objective: To study the correlation of serum vitamin E content with insulin resistance and oxidative stress response in patients with type 2 diabetes mellitus. Methods: Patients who were diagnosed with type 2 diabetes mellitus in Xining Second People’s Hospital between February 2016 and February 2017 were selected as T2DM group, healthy volunteers who received physical examination during the same period were selected as control group, oral glucose tolerance test was conducted to detect insulin resistance indexes, and fasting venous blood was collected to detect oxidative stress indicators. Results: Serum VitE, 2 h-Ins, 2 h-CP, Trx, Txnip, SOD and GSH-Px levels of T2DM group were significantly lower than those of control group while F-Ins, F-CP, MDA, AOPP, 8-OHdG, AGEs and LOX-1 levels were significantly higher than those of control group; serum VitE level in T2DM patients was positively correlated with serum 2 h-Ins, 2 h-CP, Trx, Txnip, SOD and GSH-Px levels, and negatively correlated with serum F-Ins, F-CP, MDA, AOPP, 8-OHdG, AGEs and LOX-1 levels. Conclusion: The decrease of serum vitamin E in patients with type 2 diabetes mellitus can lead to the aggravation of insulin resistance and the activation of oxidative stress response.

  11. Growth hormone-induced insulin resistance in human subjects involves reduced pyruvate dehydrogenase activity

    DEFF Research Database (Denmark)

    Nellemann, B.; Vendelbo, M.H.; Nielsen, Thomas Svava

    2014-01-01

    Insulin resistance induced by growth hormone (GH) is linked to promotion of lipolysis by unknown mechanisms. We hypothesized that suppression of the activity of pyruvate dehydrogenase in the active form (PDHa) underlies GH-induced insulin resistance similar to what is observed during fasting....

  12. Ghrelin receptor null mice have reduced visceral fat and improved insulin sensitivity during aging

    Science.gov (United States)

    Aging is associated with a higher incidence of Type 2 diabetes; one in five Americans over age 65 has diabetes. Loss of lean mass and accumulation of fat, particularly visceral fat, during aging result in increased insulin resistance. Insulin resistance is a major pathogenic factor for Type 2 diabet...

  13. EGb761, an extract of Ginkgo biloba leaves, reduces insulin resistance in a high-fat-fed mouse model

    Directory of Open Access Journals (Sweden)

    Wei-na Cong

    2011-06-01

    -activated protein kinase, which plays a crucial role in reducing lipotoxicity, from HFD-induced inactivation. We conclude that EGb761 can effectively reduce HFD-induced insulin resistance and ameliorate other symptoms of the metabolic syndrome.

  14. Reduced plasma adiponectin concentrations may contribute to impaired insulin activation of glycogen synthase in skeletal muscle of patients with type 2 diabetes

    DEFF Research Database (Denmark)

    Højlund, K.; Frystyk, J.; Levin, K.

    2006-01-01

    AIMS/HYPOTHESIS: Circulating levels of adiponectin are negatively associated with multiple indices of insulin resistance, and the concentration is reduced in humans with insulin resistance and type 2 diabetes. However, the mechanisms by which adiponectin improves insulin sensitivity remain unclear...... (ten lean, 21 obese and 20 with type 2 diabetes). RESULTS: Plasma adiponectin was significantly reduced in type 2 diabetic compared with obese and lean subjects. In lean and obese subjects, insulin significantly reduced plasma adiponectin, but this response was blunted in patients with type 2 diabetes...... by improving the capacity to switch from lipid to glucose oxidation and to store glucose as glycogen in response to insulin, and that low adiponectin may contribute to impaired insulin activation of GS in skeletal muscle of patients with type 2 diabetes....

  15. Structural differences between rye and wheat breads but not total fiber content may explain the lower postprandial insulin response to rye bread

    DEFF Research Database (Denmark)

    Juntunen, Katri S; Laaksonen, David E; Autio, Karin

    2003-01-01

    and glucose responses. DESIGN: Nineteen healthy postmenopausal women aged 61 +/- 1 y, with a body mass index (in kg/m(2)) of 26.0 +/- 0.6, and with normal glucose tolerance participated in the study. The test products were refined wheat bread (control), endosperm rye bread, traditional rye bread, and high......BACKGROUND: Rye bread has a beneficial effect on the postprandial insulin response in healthy subjects. The role of rye fiber in insulin and glucose metabolism is not known. OBJECTIVE: The aim of the study was to determine the effect of the content of rye fiber in rye breads on postprandial insulin...

  16. Insulin sensitivity is reduced in children with high body-fat regardless of BMI

    DEFF Research Database (Denmark)

    Fairchild, Timothy J; Klakk, Heidi; Heidemann, Malene

    2018-01-01

    BF% was measured by dual-energy X-ray absorptiometry (DXA). Fasting plasma glucose and insulin concentrations were measured and the homoeostatic model assessment of insulin resistance (HOMA-IR) used to assess insulin sensitivity. RESULTS: Approximately 8% of children classified as normal weight...... by BMI had high BF% (NW + Adipose). Children with high BF% had significantly higher insulin (NW + adipose: 32.3%; OW/OB + Adipose: 52.2%) and HOMA-IR scores (NW + Adipose: 32.3%; OW/OB + Adipose: 55.3%) than children classified as NW without high BF% (reference group; NW + NonAdipose). Adjusting for CRF...

  17. Validity of the reduced-sample insulin modified frequently-sampled intravenous glucose tolerance test using the nonlinear regression approach.

    Science.gov (United States)

    Sumner, Anne E; Luercio, Marcella F; Frempong, Barbara A; Ricks, Madia; Sen, Sabyasachi; Kushner, Harvey; Tulloch-Reid, Marshall K

    2009-02-01

    The disposition index, the product of the insulin sensitivity index (S(I)) and the acute insulin response to glucose, is linked in African Americans to chromosome 11q. This link was determined with S(I) calculated with the nonlinear regression approach to the minimal model and data from the reduced-sample insulin-modified frequently-sampled intravenous glucose tolerance test (Reduced-Sample-IM-FSIGT). However, the application of the nonlinear regression approach to calculate S(I) using data from the Reduced-Sample-IM-FSIGT has been challenged as being not only inaccurate but also having a high failure rate in insulin-resistant subjects. Our goal was to determine the accuracy and failure rate of the Reduced-Sample-IM-FSIGT using the nonlinear regression approach to the minimal model. With S(I) from the Full-Sample-IM-FSIGT considered the standard and using the nonlinear regression approach to the minimal model, we compared the agreement between S(I) from the Full- and Reduced-Sample-IM-FSIGT protocols. One hundred African Americans (body mass index, 31.3 +/- 7.6 kg/m(2) [mean +/- SD]; range, 19.0-56.9 kg/m(2)) had FSIGTs. Glucose (0.3 g/kg) was given at baseline. Insulin was infused from 20 to 25 minutes (total insulin dose, 0.02 U/kg). For the Full-Sample-IM-FSIGT, S(I) was calculated based on the glucose and insulin samples taken at -1, 1, 2, 3, 4, 5, 6, 7, 8,10, 12, 14, 16, 19, 22, 23, 24, 25, 27, 30, 40, 50, 60, 70, 80, 90, 100, 120, 150, and 180 minutes. For the Reduced-Sample-FSIGT, S(I) was calculated based on the time points that appear in bold. Agreement was determined by Spearman correlation, concordance, and the Bland-Altman method. In addition, for both protocols, the population was divided into tertiles of S(I). Insulin resistance was defined by the lowest tertile of S(I) from the Full-Sample-IM-FSIGT. The distribution of subjects across tertiles was compared by rank order and kappa statistic. We found that the rate of failure of resolution of S(I) by

  18. Low Nicotine Content Descriptors Reduce Perceived Health Risks and Positive Cigarette Ratings in Participants Using Very Low Nicotine Content Cigarettes.

    Science.gov (United States)

    Denlinger-Apte, Rachel L; Joel, Danielle L; Strasser, Andrew A; Donny, Eric C

    2017-10-01

    Understanding how smokers perceive reduced nicotine content cigarettes will be important if the FDA and global regulatory agencies implement reduced nicotine product standards for cigarettes. Prior research has shown that some smokers incorrectly believe "light" cigarettes are less harmful than regular cigarettes. Similar misunderstandings of health risk could also apply to reduced nicotine cigarettes. To date, most studies of reduced nicotine cigarettes have blinded subjects to the nicotine content. Therefore, little is known about how smokers experience reduced nicotine content cigarettes when they are aware of the reduced content, and how use may be impacted. The present study was a within-subjects experiment with 68 adult daily smokers who smoked two identical very low nicotine content Quest 3 (0.05 mg nicotine yield) cigarettes. Subjects were told that one cigarette contained "average" nicotine content, and the other contained "very low" nicotine content. After smoking each cigarette, subjects completed subjective measures about their smoking experience. Subjects rated the "very low" nicotine cigarette as less harmful to their health overall compared to the "average" nicotine cigarette; this effect held true for specific smoking-related diseases. Additionally, they rated the "very low" nicotine cigarette as having less desirable subjective effects than the "average" nicotine cigarette and predicted having greater interest in quitting smoking in the future if only the "very low" nicotine cigarette was available. Explicit knowledge of very low nicotine content changes smokers' perceptions of very low nicotine content cigarettes, resulting in reduced predicted harm, subjective ratings and predicted future use. Before a reduced nicotine product standard for cigarettes can be implemented, it is important to understand how product information impacts how smokers think about and experience very low nicotine content cigarettes. Prior research has shown that smokers

  19. Role of sialic acid in insulin action and the insulin resistance of diabetes mellitus

    International Nuclear Information System (INIS)

    Salhanick, A.I.; Amatruda, J.M.

    1988-01-01

    Adipocytes treated with neuraminidase show markedly reduced responsiveness to insulin without any alteration in insulin binding. In addition, several studies have separately demonstrated both insulin resistance and decreases in membrane sialic acid content and associated biosynthetic enzymes in diabetes mellitus. In the present study, the authors investigated the role that sialic acid residues may play in insulin action and in the hepatic insulin resistance associated with nonketotic diabetes. Primary cultures of hepatocytes from normal rats treated with neuraminidase demonstrated a dose-dependent decrease in insulin-stimulated lipogenesis. At a concentration of neuraminidase that decreases insulin action by 50%, 23% of total cellular sialic acid content was released. Neuraminidase-releasable sialic acid was significantly decreased in hepatocytes from diabetic rats and this was associated with significant insulin resistance. Treatment of hepatocytes from diabetic rats with cytidine 5'-monophospho-N-acetylneuraminic acid (CMP-NANA) enhanced insulin responsiveness 39%. The enhanced insulin responsiveness induced by CMP-NANA was blocked by cytidine 5'-monophosphate (CMP) suggesting that the CMP-NANA effect was catalyzed by a cell surface sialyl-transferase. CMP reduced neuraminidase-releasable [ 14 C]sialic acid incorporation into hepatocytes by 43%. The data demonstrate a role for cell surface sialic acid residues in hepatic insulin action and support a role for decreased cell surface sialic acid residues in the insulin resistance of diabetes mellitus

  20. Aspartame in conjunction with carbohydrate reduces insulin levels during endurance exercise

    Directory of Open Access Journals (Sweden)

    Siegler Jason

    2012-08-01

    Full Text Available Abstract Background As most sport drinks contain some form of non-nutritive sweetener (e.g. aspartame, and with the variation in blood glucose regulation and insulin secretion reportedly associated with aspartame, a further understanding of the effects on insulin and blood glucose regulation during exercise is warranted. Therefore, the aim of this preliminary study was to profile the insulin and blood glucose responses in healthy individuals after aspartame and carbohydrate ingestion during rest and exercise. Findings Each participant completed four trials under the same conditions (45 min rest + 60 min self-paced intense exercise differing only in their fluid intake: 1 carbohydrate (2% maltodextrin and 5% sucrose (C; 2 0.04% aspartame with 2% maltodextrin and 5% sucrose (CA; 3 water (W; and 4 aspartame (0.04% aspartame with 2% maltodextrin (A. Insulin levels dropped significantly for CA versus C alone (43% between pre-exercise and 30 min, while W and A insulin levels did not differ between these time points. Conclusions Aspartame with carbohydrate significantly lowered insulin levels during exercise versus carbohydrate alone.

  1. Valproic acid reduces insulin-resistance, fat deposition and FOXO1-mediated gluconeogenesis in type-2 diabetic rat.

    Science.gov (United States)

    Khan, Sabbir; Kumar, Sandeep; Jena, Gopabandhu

    2016-06-01

    Recent evidences highlighted the role of histone deacetylases (HDACs) in insulin-resistance, gluconeogenesis and islet function. HDACs can modulate the expression of various genes, which directly or indirectly affect glucose metabolism. This study was aimed to evaluate the role of valproic acid (VPA) on fat deposition, insulin-resistance and gluconeogenesis in type-2 diabetic rat. Diabetes was developed in Sprague-Dawley rats by the combination of high-fat diet and low dose streptozotocin. VPA at the doses of 150 and 300 mg/kg/day and metformin (positive control) 150 mg/kg twice daily for 10 weeks were administered by oral gavage. Insulin-resistance, dyslipidemia and glycemia were evaluated by biochemical estimations, while fat accumulation and structural alteration were assessed by histopathology. Protein expression and insulin signaling were evaluated by western blot and immunohistochemistry. VPA treatment significantly reduced the plasma glucose, HbA1c, insulin-resistance, fat deposition in brown adipose tissue, white adipose tissue and liver, which are comparable to metformin treatment. Further, VPA inhibited the gluconeogenesis and glucagon expression as well as restored the histopathological alterations in pancreas and liver. Our findings provide new insights on the anti-diabetic role of VPA in type-2 diabetes mellitus by the modulation of insulin signaling and forkhead box protein O1 (FOXO1)-mediated gluconeogenesis. Since VPA is a well established clinical drug, the detailed molecular mechanisms of the present findings can be further investigated for possible clinical use. Copyright © 2016 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  2. Correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury

    Directory of Open Access Journals (Sweden)

    Bing-Feng Tian

    2018-07-01

    Full Text Available Objective: To study the correlation of serum GFAP, S100B and NSE contents with posttraumatic oxidative stress response and insulin resistance in patients with traumatic brain injury. Methods: A total of 110 patients with traumatic brain injury who were treated in our hospital between January 2015 and December 2016 were collected as the observation group, and 60 healthy subjects who received physical examination in our hospital during the same period were collected as normal control group. Serum GFAP, S100B and NSE levels as well as oxidative stress index and insulin resistance index levels of two groups of subjects were detected, and Pearson test was used to further evaluate the correlation of serum GFAP, S100B and NSE contents with oxidative stress response and insulin resistance in patients with traumatic brain injury. Results: Serum GFAP, S100B and NSE contents of observation group were significantly higher than those of normal control group; serum oxidative stress indexes MDA, MPO and LPO contents were higher than those of normal control group while SOD and TAC contents were lower than those of normal control group; serum insulin resistance indexes GLU, INS and HOMA-IR levels were higher than those of control group. Pearson test showed that serum GFAP, S100B and NSE contents in patients with traumatic brain injury were directly correlated with post-traumatic oxidative stress and insulin resistance. Conclusion: The serum GFAP, S100B and NSE contents increase in patients with traumatic brain injury, and the increase is directly correlated with the oxidative stress and insulin resistance.

  3. High nitrogen availability reduces polyphenol content in Sphagnum peat.

    Science.gov (United States)

    Bragazza, Luca; Freeman, Chris

    2007-05-15

    Peat mosses of the genus Sphagnum constitute the bulk of living and dead biomass in bogs. These plants contain peculiar polyphenols which hamper litter peat decomposition through their inhibitory activity on microbial breakdown. In the light of the increasing availability of biologically active nitrogen in natural ecosystems, litter derived from Sphagnum mosses is an ideal substrate to test the potential effects of increased atmospheric nitrogen deposition on polyphenol content in litter peat. To this aim, we measured total nitrogen and soluble polyphenol concentration in Sphagnum litter peat collected in 11 European bogs under a chronic gradient of atmospheric nitrogen deposition. Our results demonstrate that increasing nitrogen concentration in Sphagnum litter, as a consequence of increased exogenous nitrogen availability, is accompanied by a decreasing concentration of polyphenols. This inverse relationship is consistent with reports that in Sphagnum mosses, polyphenol and protein biosynthesis compete for the same precursor. Our observation of modified Sphagnum litter chemistry under chronic nitrogen eutrophication has implications in the context of the global carbon balance, because a lower content of decay-inhibiting polyphenols would accelerate litter peat decomposition.

  4. ATTEMPT TO REDUCE ACRYLAMIDE CONTENT IN ROASTED CHICORY

    Directory of Open Access Journals (Sweden)

    Gabriela Zięć

    2015-02-01

    Full Text Available The region of Upper Nitra has been influenced for several decades by the intensive activity of the industry. The Nitra is a river with the most polluted water ecosystems. It was caused by anthropogenic activities in the past decades. In the upper reaches of the river in the cadastral territory of the village Zemianske Kostoľany is located the thermal power plant. There is the sedimentation reservoir, which caused the ecological disaster in 1965. During this accident there was a bursting of the dam and the downstream sedimentation of sludge spill, which contaminated the entire water catchment area of the Nitra river. As a result of an ecological accident occurred to a long-term contamination of the stream but also the adjacent alluvial areas by heavy metals (Hg, As, Pb and others. In the present work, we have focused on ascertaining the level of contamination the adjacent plot of land and seeds of corn in the cadastral territory of Malé Kršteňany. We ascertained the excess of the limit values in the case of Hg on the south side of the agricultural land in Malé Kršteňany, which borders with the stream of the river. The Cd content has exceeded the limit value at the five sampling places, in the case of lead, content does not exceed the limit value. The average mercury concentration in the grain of maize was 0.095 mg.kg-1, which exceeds the limit value by 90.5%. The average cadmium content in maize grain reached the value of 0.06 mg.kg-1. This value does not exceed the limit value. Average lead accumulation in the grain of maize was 0.54 mg.kg-1, which exceeds 2.7 times the limit value. The results of analyzes indicate an increased level of land contamination by mercury and cadmium, which was reflected in an increased level of contamination by monitored metals of crops.

  5. Left ventricular function impairment in patients with normal-weight obesity: contribution of abdominal fat deposition, profibrotic state, reduced insulin sensitivity, and proinflammatory activation.

    Science.gov (United States)

    Kosmala, Wojciech; Jedrzejuk, Diana; Derzhko, Roksolana; Przewlocka-Kosmala, Monika; Mysiak, Andrzej; Bednarek-Tupikowska, Grazyna

    2012-05-01

    Obesity predisposes to left ventricular (LV) dysfunction and heart failure; however, the risk of these complications has not been assessed in patients with a normal body mass index (BMI) but increased body fat content (normal-weight obesity, NWO). We hypothesized that LV performance in NWO may be impaired and sought to investigate potential contributors to cardiac functional abnormalities. One hundred sixty-eight subjects (age, 38±7 years) with BMI affecting the myocardium were classified on the basis of body fat content into 2 groups: with NWO and without NWO. Echocardiographic indices of LV systolic and diastolic function, including myocardial velocities and deformation, serological fibrosis markers, indicators of proinflammatory activation, and metabolic control, were evaluated. Subjects with NWO demonstrated impaired LV systolic and diastolic function, increased fibrosis intensity (assessed by procollagen type I carboxy-terminal propeptide [PICP]), impaired insulin sensitivity, and increased proinflammatory activation as compared with individuals with normal body fat. The independent correlates of LV systolic and diastolic function variables were as follows: for strain, IL-18 (β=-0.17, P<0.006), C-reactive protein (β=-0.20, P<0.002) and abdominal fat deposit (β=-0.20, P<0.003); for tissue S velocity, PICP (β=-0.21, P<0.002) and abdominal fat deposit (β=-0.43, P<0.0001); for tissue E velocity, abdominal fat deposit (β=-0.30, P<0.0001), PICP (β=-0.31, P<0.0001) and homeostasis model assessment of insulin resistance index (HOMA IR; β=-0.20, P<0.002); and for E/e'-PICP, IL-18 (both β=0.18, P<0.01) and HOMA IR (β=0.16, P<0.04). In patients with NWO, subclinical disturbances of LV function are independently associated with the extent of abdominal fat deposit, profibrotic state (as reflected by circulating PICP), reduced insulin sensitivity, and proinflammatory activation.

  6. Crif1 Deficiency Reduces Adipose OXPHOS Capacity and Triggers Inflammation and Insulin Resistance in Mice

    Science.gov (United States)

    Ryu, Min Jeong; Kim, Soung Jung; Kim, Yong Kyung; Choi, Min Jeong; Tadi, Surendar; Lee, Min Hee; Lee, Seong Eun; Chung, Hyo Kyun; Jung, Saet Byel; Kim, Hyun-Jin; Jo, Young Suk; Kim, Koon Soon; Lee, Sang-Hee; Kim, Jin Man; Kweon, Gi Ryang; Park, Ki Cheol; Lee, Jung Uee; Kong, Young Yun; Lee, Chul-Ho; Chung, Jongkyeong; Shong, Minho

    2013-01-01

    Impaired mitochondrial oxidative phosphorylation (OXPHOS) has been proposed as an etiological mechanism underlying insulin resistance. However, the initiating organ of OXPHOS dysfunction during the development of systemic insulin resistance has yet to be identified. To determine whether adipose OXPHOS deficiency plays an etiological role in systemic insulin resistance, the metabolic phenotype of mice with OXPHOS–deficient adipose tissue was examined. Crif1 is a protein required for the intramitochondrial production of mtDNA–encoded OXPHOS subunits; therefore, Crif1 haploinsufficient deficiency in mice results in a mild, but specific, failure of OXPHOS capacity in vivo. Although adipose-specific Crif1-haploinsufficient mice showed normal growth and development, they became insulin-resistant. Crif1-silenced adipocytes showed higher expression of chemokines, the expression of which is dependent upon stress kinases and antioxidant. Accordingly, examination of adipose tissue from Crif1-haploinsufficient mice revealed increased secretion of MCP1 and TNFα, as well as marked infiltration by macrophages. These findings indicate that the OXPHOS status of adipose tissue determines its metabolic and inflammatory responses, and may cause systemic inflammation and insulin resistance. PMID:23516375

  7. n-3 polyunsaturated fatty acid supplementation reduces insulin resistance in hepatitis C virus infected patients: a randomised controlled trial.

    Science.gov (United States)

    Freire, T O; Boulhosa, R S S B; Oliveira, L P M; de Jesus, R P; Cavalcante, L N; Lemaire, D C; Toralles, M B P; Lyra, L G C; Lyra, A C

    2016-06-01

    Insulin resistance promotes liver disease progression and may be associated with a lower response rate in treated hepatitis C virus (HCV) infected patients. n-3 polyunsaturated fatty acid (PUFA) supplementation may reduce insulin resistance. The present study aimed to evaluate the effect of n-3 PUFA supplementation on insulin resistance in these patients. In a randomised, double-blind clinical trial, 154 patients were screened. After applying inclusion criteria, 52 patients [homeostasis model assessment index of insulin resistance (HOMA-IR ≥2.5)] were randomly divided into two groups: n-3 PUFA (n = 25/6000 mg day(-1) of fish oil) or control (n = 27/6000 mg day(-1) of soybean oil). Both groups were supplemented for 12 weeks and underwent monthly nutritional consultation. Biochemical tests were performed at baseline and after intervention. Statistical analysis was performed using the Wilcoxon Mann-Whitney test for comparisons and the Wilcoxon test for paired data. Statistical package r, version 3.02 (The R Project for Statistical Computing) was used and P resistance in genotype 1 HCV infected patients. © 2015 The British Dietetic Association Ltd.

  8. Prowashonupana barley dietary fibre reduces body fat and increases insulin sensitivity in Caenorhabditis elegans model

    Science.gov (United States)

    Gao, Chenfei; King, Michael L.; Fitzpatrick, Zachary L.; Wei, Wenqian; King, Jason F.; Wang, Mingming; Greenway, Frank L.; Finley, John W.; Burton, Jeffrey H.; Johnson, William D.; Keenan, Michael J.; Enright, Frederick M.; Martin, Roy J.; Zheng, Jolene

    2016-01-01

    Prowashonupana barley (PWB) is high in β-glucan with moderate content of resistant starch. PWB reduced intestinal fat deposition (IFD) in wild type Caenorhabditis elegans (C. elegans, N2), and in sir-2.1 or daf-16 null mutants, and sustained a surrogate marker of lifespan, pharyngeal pumping rate (PPR), in N2, sir-2.1, daf-16, or daf-16/daf-2 mutants. Hyperglycaemia (2% glucose) reversed or reduced the PWB effect on IFD in N2 or daf-16/daf-2 mutants with a sustained PPR. mRNA expression of cpt-1, cpt-2, ckr-1, and gcy-8 were dose-dependently reduced in N2 or daf-16 mutants, elevated in daf-16/daf-2 mutants with reduction in cpt-1, and unchanged in sir-2.1 mutants. mRNA expressions were increased by hyperglycaemia in N2 or daf-16/daf-2 mutants, while reduced in sir-2.1 or daf-16 mutants. The effects of PWB in the C. elegans model appeared to be primarily mediated via sir-2.1, daf-16, and daf-16/daf-2. These data suggest that PWB and β-glucans may benefit hyperglycaemia-impaired lipid metabolism. PMID:27721901

  9. Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents.

    Science.gov (United States)

    Lira, Fábio S; Rosa, Jose C; Pimentel, Gustavo D; Santos, Ronaldo V; Carnier, June; Sanches, Priscila L; de Piano, Aline; de Souza, Claudio T; Tock, Lian; Tufik, Sergio; de Mello, Marco T; Seelaender, Marília; Oller do Nascimento, Claudia M; Oyama, Lila M; Dâmaso, Ana R

    2012-09-18

    The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15-19 y) with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR). The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

  10. Long-term interdisciplinary therapy reduces endotoxin level and insulin resistance in obese adolescents

    Directory of Open Access Journals (Sweden)

    Lira Fábio S

    2012-09-01

    Full Text Available Abstract Aim The purpose of the present study was to assess the dietary fat intake, glucose, insulin, Homeostasis model assessment for insulin resistance HOMA-IR, and endotoxin levels and correlate them with adipokine serum concentrations in obese adolescents who had been admitted to long-term interdisciplinary weight-loss therapy. Design The present study was a longitudinal clinical intervention of interdisciplinary therapy. Adolescents (n = 18, aged 15–19 y with a body mass index > 95th percentile were admitted and evaluated at baseline and again after 1 year of interdisciplinary therapy. We collected blood samples, and IL-6, adiponectin, and endotoxin concentrations were measured by ELISA. Food intake was measured using 3-day diet records. In addition, we assessed glucose and insulin levels as well as the homeostasis model assessment for insulin resistance (HOMA-IR. Results The most important finding from the present investigation was that the long-term interdisciplinary lifestyle therapy decreased dietary fat intake and endotoxin levels and improved HOMA-IR. We observed positive correlations between dietary fat intake and endotoxin levels, insulin levels, and the HOMA-IR. In addition, endotoxin levels showed positive correlations with IL-6 levels, insulin levels and the HOMA-IR. Interestingly, we observed a negative correlation between serum adiponectin and both dietary fat intake and endotoxin levels. Conclusions The present results indicate an association between dietary fat intake and endotoxin level, which was highly correlated with a decreased pro-inflammatory state and an improvement in HOMA-IR. In addition, this benefits effect may be associated with an increased adiponectin level, which suggests that the interdisciplinary therapy was effective in improving inflammatory pathways.

  11. Interleukin-18 activates skeletal muscle AMPK and reduces weight gain and insulin resistance in mice

    DEFF Research Database (Denmark)

    Madsen, Birgitte Lindegaard; Matthews, Vance B; Brandt, Claus

    2013-01-01

    Circulating interleukin (IL)-18 is elevated in obesity, but paradoxically causes hypophagia. We hypothesized that IL-18 may attenuate high fat diet induced insulin resistance by activating AMP activated protein kinase (AMPK). We studied mice with a global deletion of the α isoform of the IL-18...... receptor (IL-18R(-/-)), fed a standard chow or high fat diet (HFD). We next performed gain of function experiments in skeletal muscle, in vitro, ex vivo and in vivo. We show that IL-18 is implicated in metabolic homeostasis, inflammation and insulin resistance via mechanisms involving the activation...

  12. Intestinal remodelling in mink fed with reduced protein content

    DEFF Research Database (Denmark)

    Chen, Pengmin; Zhao, Jingbo; Nielsen, Vivi Hunnicke

    2009-01-01

    Low protein intake occurs in humans in relation to diseases, starvation and post-operatively. Low-protein diets may affect the gastrointestinal structure and mechanical function. The aim was to study the passive biomechanical properties and tissue remodelling of the intestine in minks on reduced...... protein diets. Twenty-seven male minks were divided into three groups receiving different protein level in the diet for 6 weeks: High protein level (group H, 55% energy from protein), moderate protein level (group M, 30% energy from protein) and low protein level (group L, 15% energy from protein) (n=9...... groups. Feeding the low-protein diet shifted the stress-strain curves to the right for the circumferential direction, indicating the wall become softer in the circumferential direction. However, no significant difference was observed in the longitudinal direction for any of the intestinal segments...

  13. Diamel Therapy in Polycystic Ovary Syndrome Reduces Hyperinsulinaemia, Insulin Resistance, and Hyperandrogenaemia

    Directory of Open Access Journals (Sweden)

    Arturo Hernández-Yero

    2012-01-01

    Full Text Available For to determine the effect of Diamel on the insulin resistance, insulin sensitivity, and sexual hormones results in women with polycystic ovary syndrome (PCOS. A study was carried out on 37 patients with this disorder. A triple-blind clinical trial was designed in which the Diamel food supplement was compared with a placebo. The women with reproductive ages were randomly distributed in two groups, with 18 and 19 women respectively, and they took Diamel or placebo and were followed up during 6 months with clinical and biochemical evaluation. A significant decrease in the HOMA-IR from the initial value at six months was observed in the group with Diamel. The insulin sensitivity improved considerably in this group. The rate of menstrual recovery was higher in the group with Diamel, and two patients from this group obtained pregnancy. The hormone levels shows a significant decrease in testosterone at 3 months in the group with Diamel compared with the control group. The LH also decreases in the same group when comparing the start with 6 months.We concluded that the Diamel decreases insulin resistance and improves sensitivity to this hormone in women with PCOS, with improvement in the levels of LH and testosterone.

  14. Cocoa reduces blood pressure and insulin resistance and improves endothelium-dependent vasodilation in hypertensives.

    Science.gov (United States)

    Grassi, Davide; Necozione, Stefano; Lippi, Cristina; Croce, Giuseppe; Valeri, Letizia; Pasqualetti, Paolo; Desideri, Giovambattista; Blumberg, Jeffrey B; Ferri, Claudio

    2005-08-01

    Consumption of flavanol-rich dark chocolate (DC) has been shown to decrease blood pressure (BP) and insulin resistance in healthy subjects, suggesting similar benefits in patients with essential hypertension (EH). Therefore, we tested the effect of DC on 24-hour ambulatory BP, flow-mediated dilation (FMD), and oral glucose tolerance tests (OGTTs) in patients with EH. After a 7-day chocolate-free run-in phase, 20 never-treated, grade I patients with EH (10 males; 43.7+/-7.8 years) were randomized to receive either 100 g per day DC (containing 88 mg flavanols) or 90 g per day flavanol-free white chocolate (WC) in an isocaloric manner for 15 days. After a second 7-day chocolate-free period, patients were crossed over to the other treatment. Noninvasive 24-hour ambulatory BP, FMD, OGTT, serum cholesterol, and markers of vascular inflammation were evaluated at the end of each treatment. The homeostasis model assessment of insulin resistance (HOMA-IR), quantitative insulin sensitivity check index (QUICKI), and insulin sensitivity index (ISI) were calculated from OGTT values. Ambulatory BP decreased after DC (24-hour systolic BP -11.9+/-7.7 mm Hg, Pbenefit if included as part of a healthy diet for patients with EH.

  15. Macrophage mTORC1 disruption reduces inflammation and insulin resistance in obese mice

    NARCIS (Netherlands)

    Jiang, Hongfeng; Westerterp, Marit; Wang, Chunjiong; Zhu, Yi; Ai, Ding

    2014-01-01

    Inflammatory factors secreted by macrophages play an important role in obesity-related insulin resistance. Being at the crossroads of a nutrient-hormonal signalling network, the mammalian target of rapamycin complex 1 (mTORC1) controls important functions in the regulation of energy balance and

  16. Intermittent fasting reduces body fat but exacerbates hepatic insulin resistance in young rats regardless of high protein and fat diets.

    Science.gov (United States)

    Park, Sunmin; Yoo, Kyung Min; Hyun, Joo Suk; Kang, Suna

    2017-02-01

    Intermittent fasting (IMF) is a relatively new dietary approach to weight management, although the efficacy and adverse effects have not been full elucidated and the optimal diets for IMF are unknown. We tested the hypothesis that a one-meal-per-day intermittent fasting with high fat (HF) or protein (HP) diets can modify energy, lipid, and glucose metabolism in normal young male Sprague-Dawley rats with diet-induced obesity or overweight. Male rats aged 5 weeks received either HF (40% fat) or HP (26% protein) diets ad libitum (AL) or for 3 h at the beginning of the dark cycle (IMF) for 5 weeks. Epidydimal fat pads and fat deposits in the leg and abdomen were lower with HP and IMF. Energy expenditure at the beginning of the dark cycle, especially from fat oxidation, was higher with IMF than AL, possibly due to greater activity levels. Brown fat content was higher with IMF. Serum ghrelin levels were higher in HP-IMF than other groups, and accordingly, cumulative food intake was also higher in HP-IMF than HF-IMF. HF-IMF exhibited higher area under the curve (AUC) of serum glucose at the first part (0-40 min) during oral glucose tolerance test, whereas AUC of serum insulin levels in both parts were higher in IMF and HF. During intraperitoneal insulin tolerance test, serum glucose levels were higher with IMF than AL. Consistently, hepatic insulin signaling (GLUT2, pAkt) was attenuated and PEPCK expression was higher with IMF and HF than other groups, and HOMA-IR revealed significantly impaired attenuated insulin sensitivity in the IMF groups. However, surprisingly, hepatic and skeletal muscle glycogen storage was higher in IMF groups than AL. The higher glycogen storage in the IMF groups was associated with the lower expression of glycogen phosphorylase than the AL groups. In conclusion, IMF especially with HF increased insulin resistance, possibly by attenuating hepatic insulin signaling, and lowered glycogen phosphorylase expression despite decreased fat mass in young

  17. Disruption of KEX1 gene reduces the proteolytic degradation of secreted two-chain Insulin glargine in Pichia pastoris.

    Science.gov (United States)

    Sreenivas, Suma; Krishnaiah, Sateesh M; Shyam Mohan, Anil H; Mallikarjun, Niveditha; Govindappa, Nagaraja; Chatterjee, Amarnath; Sastry, Kedarnath N

    2016-02-01

    Insulin glargine is a slow acting analog of insulin used in diabetes therapy. It is produced by recombinant DNA technology in different hosts namely E. coli and Pichia pastoris. In our previous study, we have described the secretion of fully folded two-chain Insulin glargine into the medium by over-expression of Kex2 protease. The enhanced levels of the Kex2 protease was responsible for the processing of the glargine precursor with in the host. Apart from the two-chain glargine product we observed a small proportion of arginine clipped species. This might be due to the clipping of arginine present at the C-terminus of the B-chain as it is exposed upon Kex2 cleavage. The carboxypeptidase precursor Kex1 is known to be responsible for clipping of C-terminal lysine or arginine of the proteins or peptides. In order to address this issue we created a Kex1 knock out in the host using Cre/loxP mechanism of targeted gene deletion. When two-chain glargine was expressed in the Kex1 knock out host of P. pastoris GS115 the C-terminal clipped species reduced by ∼80%. This modification further improved the process by reducing the levels of product related impurities. Copyright © 2015 Elsevier Inc. All rights reserved.

  18. Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

    KAUST Repository

    Lavoie, Suzie

    2016-04-21

    Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

  19. Glutamate Cysteine Ligase—Modulatory Subunit Knockout Mouse Shows Normal Insulin Sensitivity but Reduced Liver Glycogen Storage

    KAUST Repository

    Lavoie, Suzie; Steullet, Pascal; Kulak, Anita; Preitner, Frederic; Do, Kim Q.; Magistretti, Pierre J.

    2016-01-01

    Glutathione (GSH) deficits have been observed in several mental or degenerative illness, and so has the metabolic syndrome. The impact of a decreased glucose metabolism on the GSH system is well-known, but the effect of decreased GSH levels on the energy metabolism is unclear. The aim of the present study was to investigate the sensitivity to insulin in the mouse knockout (KO) for the modulatory subunit of the glutamate cysteine ligase (GCLM), the rate-limiting enzyme of GSH synthesis. Compared to wildtype (WT) mice, GCLM-KO mice presented with reduced basal plasma glucose and insulin levels. During an insulin tolerance test, GCLM-KO mice showed a normal fall in glycemia, indicating normal insulin secretion. However, during the recovery phase, plasma glucose levels remained lower for longer in KO mice despite normal plasma glucagon levels. This is consistent with a normal counterregulatory hormonal response but impaired mobilization of glucose from endogenous stores. Following a resident-intruder stress, during which stress hormones mobilize glucose from hepatic glycogen stores, KO mice showed a lower hyperglycemic level despite higher plasma cortisol levels when compared to WT mice. The lower hepatic glycogen levels observed in GCLM-KO mice could explain the impaired glycogen mobilization following induced hypoglycemia. Altogether, our results indicate that reduced liver glycogen availability, as observed in GCLM-KO mice, could be at the origin of their lower basal and challenged glycemia. Further studies will be necessary to understand how a GSH deficit, typically observed in GCLM-KO mice, leads to a deficit in liver glycogen storage.

  20. Insulin reduces neuronal excitability by turning on GABA(A channels that generate tonic current.

    Directory of Open Access Journals (Sweden)

    Zhe Jin

    Full Text Available Insulin signaling to the brain is important not only for metabolic homeostasis but also for higher brain functions such as cognition. GABA (γ-aminobutyric acid decreases neuronal excitability by activating GABA(A channels that generate phasic and tonic currents. The level of tonic inhibition in neurons varies. In the hippocampus, interneurons and dentate gyrus granule cells normally have significant tonic currents under basal conditions in contrast to the CA1 pyramidal neurons where it is minimal. Here we show in acute rat hippocampal slices that insulin (1 nM "turns on" new extrasynaptic GABA(A channels in CA1 pyramidal neurons resulting in decreased frequency of action potential firing. The channels are activated by more than million times lower GABA concentrations than synaptic channels, generate tonic currents and show outward rectification. The single-channel current amplitude is related to the GABA concentration resulting in a single-channel GABA affinity (EC(50 in intact CA1 neurons of 17 pM with the maximal current amplitude reached with 1 nM GABA. They are inhibited by GABA(A antagonists but have novel pharmacology as the benzodiazepine flumazenil and zolpidem are inverse agonists. The results show that tonic rather than synaptic conductances regulate basal neuronal excitability when significant tonic conductance is expressed and demonstrate an unexpected hormonal control of the inhibitory channel subtypes and excitability of hippocampal neurons. The insulin-induced new channels provide a specific target for rescuing cognition in health and disease.

  1. Phthalates might interfere with testicular function by reducing testosterone and insulin-like factor 3 levels.

    Science.gov (United States)

    Chang, Wei-Hsiang; Li, Sih-Syuan; Wu, Meng-Hsing; Pan, Hsien-An; Lee, Ching-Chang

    2015-11-01

    Do phthalates create a male reproductive hormone imbalance by down-regulating the secretion of testosterone and insulin-like factor 3 (INSL3)? Our study suggests that exposure to phthalates is related to a reduction in the secretion of testosterone and INSL3 in adult males. There is evidence that exposure to phthalates, an abundant group of industrial plasticizers, negatively affects testosterone biosynthesis, but little is known about the mechanism in men. The hypothesis that exposure to phthalates reduces the levels of testosterone and INSL3, a marker of Leydig cell function, is underexplored. This case-control study of 176 men ran from 2010 to 2012. Infertile men were recruited through infertility clinics in Taiwan, fertile men were recruited from childbirth preparation classes and all were categorized based on the World Health Organization definition of infertility and by the diagnoses of obstetricians. Urinary concentrations of 11 phthalate metabolites were measured, along with serum levels of FSH, LH, total testosterone (TT), estradiol, sex hormone-binding globulin and Inhibin B. Androgen status indices including free testosterone (fT) and the free androgen index (FAI) were calculated. The circulating INSL3 level was evaluated using a radioimmunoassay. Non-parametric analyses, trend tests and linear regression models were used. Urinary mono-n-butyl phthalate (MnBP), mono-(2-ethylhexyl) phthalate (MEHP) and mono-2-ethyl-5-carboxypentyl phthalate were significantly higher in infertile than in fertile men. Serum Inhibin B, the Inhibin B : FSH ratio, the TT : LH ratio and INSL3 were significantly lower in infertile men. In multiple regression models controlled for potential confounders, there is an inverse association between urinary levels of mono-methyl phthalate (MMP), mono-iso-butyl phthalate (MiBP), MEHP, MEHP% and serum TT (P = 0.001, 0.007, 0.042 and 0.012, respectively). The inverse associations were also found between urinary levels of MiBP, monobenzyl

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

    DEFF Research Database (Denmark)

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

    2011-01-01

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

  3. Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

    Directory of Open Access Journals (Sweden)

    Shahriar Koochekpour

    Full Text Available Reduction or depletion of mitochondrial DNA (mtDNA has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA and Caucasian American (CA men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients 7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

  4. Reduced mitochondrial DNA content associates with poor prognosis of prostate cancer in African American men.

    Science.gov (United States)

    Koochekpour, Shahriar; Marlowe, Timothy; Singh, Keshav K; Attwood, Kristopher; Chandra, Dhyan

    2013-01-01

    Reduction or depletion of mitochondrial DNA (mtDNA) has been associated with cancer progression. Although imbalanced mtDNA content is known to occur in prostate cancer, differences in mtDNA content between African American (AA) and Caucasian American (CA) men are not defined. We provide the first evidence that tumors in AA men possess reduced level of mtDNA compared to CA men. The median tumor mtDNA content was reduced in AA men. mtDNA content was also reduced in normal prostate tissues of AA men compared to CA men, suggesting a possible predisposition to cancer in AA men. mtDNA content was also reduced in benign prostatic hyperplasia (BPH) tissue from AA men. Tumor and BPH tissues from patients ≥ 60 years of age possess reduced mtDNA content compared to patients 7 compared to ≤ 7, whereas reduced mtDNA content was observed in tumors of Gleason grade >7 compared to ≤ 7. Together, our data suggest that AA men possess lower mtDNA levels in normal and tumor tissues compared to CA men, which could contribute to higher risk and more aggressive prostate cancer in AA men.

  5. Reduced nicotine content cigarettes, e-cigarettes and the cigarette end game

    Science.gov (United States)

    Benowitz, Neal L.; Donny, Eric C.; Hatsukami, Dorothy K.

    2017-01-01

    The reduced nicotine content cigarette and the emergence of non-combusted nicotine products like e-cigarettes should be viewed not as alternatives but as complementary components of regulatory interventions that could virtually end combusted tobacco use. PMID:27555354

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

    Science.gov (United States)

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

    2009-04-01

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

  7. Reduced plasma aldosterone concentrations in randomly selected patients with insulin-dependent diabetes mellitus.

    LENUS (Irish Health Repository)

    Cronin, C C

    2012-02-03

    Abnormalities of the renin-angiotensin system have been reported in patients with diabetes mellitus and with diabetic complications. In this study, plasma concentrations of prorenin, renin, and aldosterone were measured in a stratified random sample of 110 insulin-dependent (Type 1) diabetic patients attending our outpatient clinic. Fifty-four age- and sex-matched control subjects were also examined. Plasma prorenin concentration was higher in patients without complications than in control subjects when upright (geometric mean (95% confidence intervals (CI): 75.9 (55.0-105.6) vs 45.1 (31.6-64.3) mU I-1, p < 0.05). There was no difference in plasma prorenin concentration between patients without and with microalbuminuria and between patients without and with background retinopathy. Plasma renin concentration, both when supine and upright, was similar in control subjects, in patients without complications, and in patients with varying degrees of diabetic microangiopathy. Plasma aldosterone was suppressed in patients without complications in comparison to control subjects (74 (58-95) vs 167 (140-199) ng I-1, p < 0.001) and was also suppressed in patients with microvascular disease. Plasma potassium was significantly higher in patients than in control subjects (mean +\\/- standard deviation: 4.10 +\\/- 0.36 vs 3.89 +\\/- 0.26 mmol I-1; p < 0.001) and plasma sodium was significantly lower (138 +\\/- 4 vs 140 +\\/- 2 mmol I-1; p < 0.001). We conclude that plasma prorenin is not a useful early marker for diabetic microvascular disease. Despite apparently normal plasma renin concentrations, plasma aldosterone is suppressed in insulin-dependent diabetic patients.

  8. Arsenite reduces insulin secretion in rat pancreatic β-cells by decreasing the calcium-dependent calpain-10 proteolysis of SNAP-25

    International Nuclear Information System (INIS)

    Diaz-Villasenor, Andrea; Burns, Anna L.; Salazar, Ana Maria; Sordo, Monserrat; Hiriart, Marcia; Cebrian, Mariano E.; Ostrosky-Wegman, Patricia

    2008-01-01

    An increase in the prevalence of type 2 diabetes has been consistently observed among residents of high arsenic exposure areas. We have previously shown that in rat pancreatic β-cells, low arsenite doses impair the secretion of insulin without altering its synthesis. To further study the mechanism by which arsenite reduces insulin secretion, we evaluated the effects of arsenite on the calcium-calpain pathway that triggers insulin exocytosis in RINm5F cells. Cell cycle and proliferation analysis were also performed to complement the characterization. Free [Ca 2+ ]i oscillations needed for glucose-stimulated insulin secretion were abated in the presence of subchronic low arsenite doses (0.5-2 μM). The global activity of calpains increased with 2 μM arsenite. However, during the secretion of insulin stimulated with glucose (15.6 mM), 1 μM arsenite decreased the activity of calpain-10, measured as SNAP-25 proteolysis. Both proteins are needed to fuse insulin granules with the membrane to produce insulin exocytosis. Arsenite also induced a slowdown in the β cell line proliferation in a dose-dependent manner, reflected by a reduction of dividing cells and in their arrest in G2/M. Data obtained showed that one of the mechanisms by which arsenite impairs insulin secretion is by decreasing the oscillations of free [Ca 2+ ]i, thus reducing calcium-dependent calpain-10 partial proteolysis of SNAP-25. The effects in cell division and proliferation observed with arsenite exposure can be an indirect consequence of the decrease in insulin secretion

  9. Concentrated insulins: the new basal insulins

    Directory of Open Access Journals (Sweden)

    Lamos EM

    2016-03-01

    Full Text Available Elizabeth M Lamos,1 Lisa M Younk,2 Stephen N Davis3 1Division of Endocrinology, Diabetes and Nutrition, 2Department of Medicine, University of Maryland School of Medicine, 3Department of Medicine, University of Maryland Medical Center, Baltimore, MD, USA Introduction: Insulin therapy plays a critical role in the treatment of type 1 and type 2 diabetes mellitus. However, there is still a need to find basal insulins with 24-hour coverage and reduced risk of hypoglycemia. Additionally, with increasing obesity and insulin resistance, the ability to provide clinically necessary high doses of insulin at low volume is also needed. Areas covered: This review highlights the published reports of the pharmacokinetic (PK and glucodynamic properties of concentrated insulins: Humulin-R U500, insulin degludec U200, and insulin glargine U300, describes the clinical efficacy, risk of hypoglycemic, and metabolic changes observed, and finally, discusses observations about the complexity of introducing a new generation of concentrated insulins to the therapeutic market. Conclusion: Humulin-R U500 has a similar onset but longer duration of action compared with U100 regular insulin. Insulin glargine U300 has differential PK/pharmacodynamic effects when compared with insulin glargine U100. In noninferiority studies, glycemic control with degludec U200 and glargine U300 is similar to insulin glargine U100 and nocturnal hypoglycemia is reduced. Concentrated formulations appear to behave as separate molecular entities when compared with earlier U100 insulin analog compounds. In the review of available published data, newer concentrated basal insulins may offer an advantage in terms of reduced intraindividual variability as well as reducing the injection burden in individuals requiring high-dose and large volume insulin therapy. Understanding the PK and pharmacodynamic properties of this new generation of insulins is critical to safe dosing, dispensing, and administration

  10. Plasma BDNF Is Reduced among Middle-Aged and Elderly Women with Impaired Insulin Function: Evidence of a Compensatory Mechanism

    Science.gov (United States)

    Arentoft, Alyssa; Sweat, Victoria; Starr, Vanessa; Oliver, Stephen; Hassenstab, Jason; Bruehl, Hannah; Tirsi, Aziz; Javier, Elizabeth; McHugh, Pauline F.; Convit, Antonio

    2009-01-01

    Brain-derived neurotrophic factor (BDNF) plays a regulatory role in neuronal differentiation and synaptic plasticity and has been linked to glucose regulation and cognition. Associations among plasma BDNF, cognition, and insulin function were explored. Forty-one participants with impaired insulin function (IIF), ranging from insulin resistance to…

  11. Denervation and high-fat diet reduce insulin signaling in T-tubules in skeletal muscle of living mice

    DEFF Research Database (Denmark)

    Lauritzen, Hans P M; Ploug, Thorkil; Ai, Hua

    2008-01-01

    OBJECTIVE: Insulin stimulates muscle glucose transport by translocation of GLUT4 to sarcolemma and T-tubules. Despite muscle glucose uptake playing a major role in insulin resistance and type 2 diabetes, the temporal and spatial changes in insulin signaling and GLUT4 translocation during these co...

  12. Insulin resistance is associated with lower arterial blood flow and reduced cortical perfusion in cognitively asymptomatic middle-aged adults

    Science.gov (United States)

    Hoscheidt, Siobhan M; Kellawan, J Mikhail; Berman, Sara E; Rivera-Rivera, Leonardo A; Krause, Rachel A; Oh, Jennifer M; Beeri, Michal S; Rowley, Howard A; Wieben, Oliver; Carlsson, Cynthia M; Asthana, Sanjay; Johnson, Sterling C; Schrage, William G

    2016-01-01

    Insulin resistance (IR) is associated with poor cerebrovascular health and increased risk for dementia. Little is known about the unique effect of IR on both micro- and macrovascular flow particularly in midlife when interventions against dementia may be most effective. We examined the effect of IR as indexed by the Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) on cerebral blood flow in macro- and microvessels utilizing magnetic resonance imaging (MRI) among cognitively asymptomatic middle-aged individuals. We hypothesized that higher HOMA-IR would be associated with reduced flow in macrovessels and lower cortical perfusion. One hundred and twenty cognitively asymptomatic middle-aged adults (57 ± 5 yrs) underwent fasting blood draw, phase contrast-vastly undersampled isotropic projection reconstruction (PC VIPR) MRI, and arterial spin labeling (ASL) perfusion. Higher HOMA-IR was associated with lower arterial blood flow, particularly within the internal carotid arteries (ICAs), and lower cerebral perfusion in several brain regions including frontal and temporal lobe regions. Higher blood flow in bilateral ICAs predicted greater cortical perfusion in individuals with lower HOMA-IR, a relationship not observed among those with higher HOMA-IR. Findings provide novel evidence for an uncoupling of macrovascular blood flow and microvascular perfusion among individuals with higher IR in midlife. PMID:27488909

  13. Reduced Insulin/IGF-1 Signaling Restores the Dynamic Properties of Key Stress Granule Proteins during Aging

    Directory of Open Access Journals (Sweden)

    Marie C. Lechler

    2017-01-01

    Full Text Available Summary: Low-complexity “prion-like” domains in key RNA-binding proteins (RBPs mediate the reversible assembly of RNA granules. Individual RBPs harboring these domains have been linked to specific neurodegenerative diseases. Although their aggregation in neurodegeneration has been extensively characterized, it remains unknown how the process of aging disturbs RBP dynamics. We show that a wide variety of RNA granule components, including stress granule proteins, become highly insoluble with age in C. elegans and that reduced insulin/insulin-like growth factor 1 (IGF-1 daf-2 receptor signaling efficiently prevents their aggregation. Importantly, stress-granule-related RBP aggregates are associated with reduced fitness. We show that heat shock transcription factor 1 (HSF-1 is a main regulator of stress-granule-related RBP aggregation in both young and aged animals. During aging, increasing DAF-16 activity restores dynamic stress-granule-related RBPs, partly by decreasing the buildup of other misfolded proteins that seed RBP aggregation. Longevity-associated mechanisms found to maintain dynamic RBPs during aging could be relevant for neurodegenerative diseases. : Lechler et al. show that RNA-binding proteins (RBPs including stress granule proteins are prone to aggregate with age in C. elegans. Aggregation of stress granule RBPs with “prion-like” domains is associated with reduced fitness. Their aggregation is prevented by longevity pathways and promoted by the aggregation of other misfolded proteins. Keywords: neurodegenerative diseases, Caenorhabditis elegans, protein aggregation, aging, RNA-binding proteins, stress granules, HSF-1, DAF-2, longevity

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

    Directory of Open Access Journals (Sweden)

    Johan Holmkvist

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

  15. Four weeks of treatment with liraglutide reduces insulin dose without loss of glycemic control in type 1 diabetic patients with and without residual beta-cell function

    DEFF Research Database (Denmark)

    Kielgast, Urd; Krarup, Thure; Holst, Jens Juul

    2011-01-01

    OBJECTIVE To investigate the effect of 4 weeks of treatment with liraglutide on insulin dose and glycemic control in type 1 diabetic patients with and without residual ß-cell function. RESEARCH DESIGN AND METHODS Ten type 1 diabetic patients with residual ß-cell function (C-peptide positive) and 19.......1]; P Treatment with liraglutide in type 1 diabetic patients reduces insulin dose with improved or unaltered glycemic control....... activity was performed before (week 0) and during (week 4) treatment. Differences in insulin dose; HbA(1c); time spent with blood glucose 10, and 3.9-9.9 mmol/L; and body weight were evaluated. RESULTS Insulin dose decreased from 0.50 ± 0.06 to 0.31 ± 0.08 units/kg per day (P

  16. Genetic Analysis of Reduced γ-Tocopherol Content in Ethiopian Mustard Seeds.

    Science.gov (United States)

    García-Navarro, Elena; Fernández-Martínez, José M; Pérez-Vich, Begoña; Velasco, Leonardo

    2016-01-01

    Ethiopian mustard (Brassica carinata A. Braun) line BCT-6, with reduced γ-tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced γ-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both γ- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of γ-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of γ-tocopherol is required.

  17. Genetic Analysis of Reduced γ-Tocopherol Content in Ethiopian Mustard Seeds

    Directory of Open Access Journals (Sweden)

    Elena García-Navarro

    2016-01-01

    Full Text Available Ethiopian mustard (Brassica carinata A. Braun line BCT-6, with reduced γ-tocopherol content in the seeds, has been previously developed. The objective of this research was to conduct a genetic analysis of seed tocopherols in this line. BCT-6 was crossed with the conventional line C-101 and the F1, F2, and BC plant generations were analyzed. Generation mean analysis using individual scaling tests indicated that reduced γ-tocopherol content fitted an additive-dominant genetic model with predominance of additive effects and absence of epistatic interactions. This was confirmed through a joint scaling test and additional testing of the goodness of fit of the model. Conversely, epistatic interactions were identified for total tocopherol content. Estimation of the minimum number of genes suggested that both γ- and total tocopherol content may be controlled by two genes. A positive correlation between total tocopherol content and the proportion of γ-tocopherol was identified in the F2 generation. Additional research on the feasibility of developing germplasm with high tocopherol content and reduced concentration of γ-tocopherol is required.

  18. Drosophila Longevity Assurance Conferred by Reduced Insulin Receptor Substrate Chico Partially Requires d4eBP.

    Directory of Open Access Journals (Sweden)

    Hua Bai

    Full Text Available Mutations of the insulin/IGF signaling (IIS pathway extend Drosophila lifespan. Based on genetic epistasis analyses, this longevity assurance is attributed to downstream effects of the FOXO transcription factor. However, as reported FOXO accounts for only a portion of the observed longevity benefit, suggesting there are additional outputs of IIS to mediate aging. One candidate is target of rapamycin complex 1 (TORC1. Reduced TORC1 activity is reported to slow aging, whereas reduced IIS is reported to repress TORC1 activity. The eukaryotic translation initiation factor 4E binding protein (4E-BP is repressed by TORC1, and activated 4E-BP is reported to increase Drosophila lifespan. Here we use genetic epistasis analyses to test whether longevity assurance mutants of chico, the Drosophila insulin receptor substrate homolog, require Drosophila d4eBP to slow aging. In chico heterozygotes, which are robustly long-lived, d4eBP is required but not sufficient to slow aging. Remarkably, d4eBP is not required or sufficient for chico homozygotes to extend longevity. Likewise, chico heterozygote females partially require d4eBP to preserve age-dependent locomotion, and both chico genotypes require d4eBP to improve stress-resistance. Reproduction and most measures of growth affected by either chico genotype are always independent of d4eBP. In females, chico heterozygotes paradoxically produce more rather than less phosphorylated 4E-BP (p4E-BP. Altered IRS function within the IIS pathway of Drosophila appears to have partial, conditional capacity to regulate aging through an unconventional interaction with 4E-BP.

  19. Sitagliptin down-regulates retinol-binding protein 4 and reduces insulin resistance in gestational diabetes mellitus: a randomized and double-blind trial.

    Science.gov (United States)

    Sun, Xia; Zhang, Zhendong; Ning, Hui; Sun, Hong; Ji, Xianghong

    2017-06-01

    Gestational diabetes mellitus (GDM) is a condition that affects increasing number of pregnant women worldwide. Sitagliptin was reported to alleviate symptoms of type 2 diabetes mellitus by reducing serum levels of retinol-binding protein 4 (RBP-4). We investigated the effectiveness of sitagliptin on insulin sensitivity parameters in GDM patients. Pregnant GDM women in the 2nd trimester were recruited for this study. Participants were then assigned randomly to sitagliptin treatment group or placebo treatment group, and administered sitagliptin or placebo daily for 16 weeks. Glucose and insulin profiles, as well as serum RBP-4 level, were measured at both baseline and end of the study. After 16 weeks of treatment, participants in the STL group exhibited significantly improved levels of fasting plasma glucose and serum insulin, homeostasis model of assessment of β cell function (HOMA-β) and insulin resistance (HOMA-IR), compared with those in the placebo group. Serum levels of RBP-4 were also markedly decreased in the sitagliptin treatment group, and more importantly it was positively correlated with improved insulin resistance parameters. Our study supports a potentially promising role of sitagliptin in improving insulin resistance by decreasing RBP-4 in GDM-affected women.

  20. Insulin-induced inhibition of gluconeogenesis genes, including glutamic pyruvic transaminase 2, is associated with reduced histone acetylation in a human liver cell line.

    Science.gov (United States)

    Honma, Kazue; Kamikubo, Michiko; Mochizuki, Kazuki; Goda, Toshinao

    2017-06-01

    Hepatic glutamic pyruvic transaminase (GPT; also known as alanine aminotransferase) is a gluconeogenesis enzyme that catalyzes conversions between alanine and pyruvic acid. It is also used as a blood biomarker for hepatic damage. In this study, we investigated whether insulin regulates GPT expression, as it does for other gluconeogenesis genes, and if this involves the epigenetic modification of histone acetylation. Human liver-derived HepG2 cells were cultured with 0.5-100nM insulin for 8h, and the mRNA expression of GPT, glutamic-oxaloacetic transaminase (GOT), γ-glutamyltransferase (GGT), PCK1, G6PC and FBP1 was measured. We also investigated the extent of histone acetylation around these genes. Insulin suppressed the mRNA expression of gluconeogenesis genes (GPT2, GOT1, GOT2, GGT1, GGT2, G6PC, and PCK1) in HepG2 cells in a dose-dependent manner. mRNA levels of GPT2, but not GPT1, were decreased by insulin. Histone acetylation was also reduced around GPT2, G6PC, and PCK1 in response to insulin. The expression of GPT2 and other gluconeogenesis genes such as G6PC and PCK1 was suppressed by insulin, in association with decreases in histone H3 and H4 acetylation surrounding these genes. Copyright © 2017 Elsevier Inc. All rights reserved.

  1. Reduced Systemic Levels of IL-10 Are Associated with the Severity of Obstructive Sleep Apnea and Insulin Resistance in Morbidly Obese Humans

    Directory of Open Access Journals (Sweden)

    Sonia Leon-Cabrera

    2015-01-01

    Full Text Available Obstructive sleep apnea (OSA has been related to elevation of inflammatory cytokines and development of insulin resistance in morbidly obese (MO subjects. However, it is still unclear whether the systemic concentration of anti-inflammatory mediators is also affected in MO subjects directly related to the severity of OSA and level of insulin resistance. Normal weight and MO subjects were subjected to overnight polysomnography in order to establish the severity of OSA, according to the apnea-hypopnea index (AHI. Blood samples were obtained for estimation of total cholesterol and triglycerides, insulin, glucose, insulin resistance, tumor necrosis factor alpha (TNF-α, interleukin 12 (IL12, and interleukin 10 (IL-10. Serum levels of IL-10 were significantly lower in MO subjects with OSA than in MO and control individuals without OSA. Besides being inversely associated with serum TNF-α and IL-12, decreased IL-10 levels were significantly related to increased AHI, hyperinsulinemia, and insulin resistance. Serum IL-10 is significantly reduced in morbidly obese subjects with severe OSA while also showing a clear relationship with a state of hyperinsulinemia and insulin resistance probably regardless of obesity in the present sample. It may be of potential clinical interest to identify the stimulatory mechanisms of IL-10 in obese individuals with OSA.

  2. [Effectiveness of increased contents of dietary fiber in early stages of non-insulin-dependent diabetes mellitus].

    Science.gov (United States)

    Krashenitsa, G M; Botvineva, L A; Mogila, A V

    1994-01-01

    Patients with early NIDDM were put on routine diet N 9 (food fiber 25 g/day) and test diet (food fiber 55 g/day). The diet of both groups (group 1 and 2, respectively) was supplemented with oral mineral water Essentuki 17. High-fiber diets proved to be effective for the above patients as they induced positive trends in NIDDM clinical symptoms, body weight, lowering of basal insulin, an increase in insulin immediate pool. There was also a reduction of insulinemia and hyperglycemia later in the course of glucose tolerance test. The above shifts were more pronounced in 2 patients.

  3. Vitamin D deficiency impairs glucose-stimulated insulin secretion and increases insulin resistance by reducing PPAR-γ expression in nonobese Type 2 diabetic rats.

    Science.gov (United States)

    Park, Sunmin; Kim, Da Sol; Kang, Suna

    2016-01-01

    Human studies have provided relatively strong associations of poor vitamin D status with Type 2 diabetes but do not explain the nature of the association. Here, we explored the physiological pathways that may explain how vitamin D status modulates energy, lipid and glucose metabolisms in nonobese Type 2 diabetic rats. Goto-Kakizaki (GK) rats were fed high-fat diets containing 25 (VD-low), 1000 (VD-normal) or 10,000 (VD-high) cholecalciferol-IU/kg diet for 8 weeks. Energy expenditure, insulin resistance, insulin secretory capacity and lipid metabolism were measured. Serum 25-OH-D levels, an index of vitamin D status, increased dose dependently with dietary vitamin D. VD-low resulted in less fat oxidation without a significant difference in energy expenditure and less lean body mass in the abdomen and legs comparison to the VD-normal group. In comparison to VD-low, VD-normal had lower serum triglycerides and intracellular fat accumulation in the liver and skeletal muscles which was associated with down-regulation of the mRNA expressions of sterol regulatory element binding protein-1c and fatty acid synthase and up-regulation of gene expressions of peroxisome proliferator-activated receptors (PPAR)-α and carnitine palmitoyltransferase-1. In euglycemic hyperinsulinemic clamp, whole-body and hepatic insulin resistance was exacerbated in the VD-low group but not in the VD-normal group, possibly through decreasing hepatic insulin signaling and PPAR-γ expression in the adipocytes. In 3T3-L1 adipocytes 1,25-(OH)2-D (10 nM) increased triglyceride accumulation by elevating PPAR-γ expression and treatment with a PPAR-γ antagonist blocked the triglyceride deposition induced by 1,25-(OH)2-D treatment. VD-low impaired glucose-stimulated insulin secretion in hyperglycemic clamp and decreased β-cell mass by decreasing β-cell proliferation. In conclusion, vitamin D deficiency resulted in the dysregulation of glucose metabolism in GK rats by simultaneously increasing insulin

  4. Reducing the CP content in broiler feeds: impact on animal performance, meat quality and nitrogen utilization.

    Science.gov (United States)

    Belloir, P; Méda, B; Lambert, W; Corrent, E; Juin, H; Lessire, M; Tesseraud, S

    2017-11-01

    Reducing the dietary CP content is an efficient way to limit nitrogen excretion in broilers but, as reported in the literature, it often reduces performance, probably because of an inadequate provision in amino acids (AA). The aim of this study was to investigate the effect of decreasing the CP content in the diet on animal performance, meat quality and nitrogen utilization in growing-finishing broilers using an optimized dietary AA profile based on the ideal protein concept. Two experiments (1 and 2) were performed using 1-day-old PM3 Ross male broilers (1520 and 912 for experiments 1 and 2, respectively) using the minimum AA:Lys ratios proposed by Mack et al. with modifications for Thr and Arg. The digestible Thr (dThr): dLys ratio was increased from 63% to 68% and the dArg:dLys ratio was decreased from 112% to 108%. In experiment 1, the reduction of dietary CP from 19% to 15% (five treatments) did not alter feed intake or BW, but the feed conversion ratio was increased for the 16% and 15% CP diets (+2.4% and +3.6%, respectively), while in experiment 2 (three treatments: 19%, 17.5% and 16% CP) there was no effect of dietary CP on performance. In both experiments, dietary CP content did not affect breast meat yield. However, abdominal fat content (expressed as a percentage of BW) was increased by the decrease in CP content (up to +0.5 and +0.2 percentage point, in experiments 1 and 2, respectively). In experiment 2, meat quality traits responded to dietary CP content with a higher ultimate pH and lower lightness and drip loss values for the low CP diets. Nitrogen retention efficiency increased when reducing CP content in both experiments (+3.5 points/CP percentage point). The main consequence of this higher efficiency was a decrease in nitrogen excretion (-2.5 g N/kg BW gain) and volatilization (expressed as a percentage of excretion: -5 points/CP percentage point). In conclusion, this study demonstrates that with an adapted AA profile, it is possible to reduce

  5. High-fat diet with stress impaired islets' insulin secretion by reducing plasma estradiol and pancreatic GLUT2 protein levels in rats' proestrus phase.

    Science.gov (United States)

    Salimi, M; Zardooz, H; Khodagholi, F; Rostamkhani, F; Shaerzadeh, F

    2016-10-01

    This study was conducted to determine whether two estrus phases (proestrus and diestrus) in female rats may influence the metabolic response to a high-fat diet and/or stress, focusing on pancreatic insulin secretion and content. Animals were divided into high-fat and normal diet groups, then each group was subdivided into stress and non-stress groups, and finally, each one of these was divided into proestrus and diestrus subgroups. At the end of high-fat diet treatment, foot-shock stress was applied to the animals. Then, blood samples were taken to measure plasma factors. Finally, the pancreas was removed for determination of glucose transporter 2 (GLUT2) protein levels and assessment of insulin content and secretion of the isolated islets. In the normal and high-fat diet groups, stress increased plasma corticosterone concentration in both phases. In both study phases, high-fat diet consumption decreased estradiol and increased leptin plasma levels. In the high-fat diet group in response to high glucose concentration, a reduction in insulin secretion was observed in the proestrus phase compared with the same phase in the normal diet group in the presence and absence of stress. Also, high-fat diet decreased the insulin content of islets in the proestrus phase compared with the normal diet. High-fat diet and/or stress caused a reduction in islet GLUT2 protein levels in both phases. In conclusion, it seems possible that high-fat diet alone or combined with foot-shock, predispose female rats to impaired insulin secretion, at least in part, by interfering with estradiol levels in the proestrus phase and decreasing pancreatic GLUT2 protein levels.

  6. Application of Titanium Compounds to Reduce Fluoride Ion in Water Resources with High Fluoride Ion Contents

    Directory of Open Access Journals (Sweden)

    Fariborz Riahi

    2005-06-01

    Full Text Available The present work describes studies on the sorption of fluoride ions from water by titanium compounds used in water treatment to reduce fluoride content in water resources. There are different methods of reducing fluoride ion in water, each associated with specific problems such as secondary contamination, environmental contamination, high costs, or the need for primary and secondary treatment. In this study, application of titanium sulfate and Metatitanic acid produced from titanium ore concentrate (ileminite is investigated in the removal of fluoride ion and the possibility of complete purification of fluorine containing wastewater is examined to determine the optimal conditions. Metatitanic acid has a great sorption property for fluoride ion. Also titanium sulfate is a suitable and more effective material for this purpose. Efficiency of this material in reducing fluoride ion content is 99.9% and it is possible to refresh sorbet material for reuse without problems arising from Ti+4 ion contamination.

  7. The Finnish Diabetes Risk Score is associated with insulin resistance but not reduced beta-cell function, by classical and model-based estimates

    NARCIS (Netherlands)

    Brodovicz, K.G.; Dekker, J.M.; Rijkelijkhuizen, J.M.; Rhodes, T.; Mari, A.; Alssema, M.J.; Nijpels, G.; Williams-Herman, D.E.; Girman, C.J.

    2011-01-01

    Aims The Finnish Diabetes Risk Score (FINDRISC) is widely used for risk stratification in Type2 diabetes prevention programmes. Estimates of β-cell function vary widely in people without diabetes and reduced insulin secretion has been described in people at risk for diabetes. The aim of this

  8. Evaluation of Jump into Action: A Program to Reduce the Risk of Non-Insulin Dependent Diabetes Mellitus in School Children on the Texas-Mexico Border.

    Science.gov (United States)

    Holcomb, J. David; Lira, Juanita; Kingery, Paul M.; Smith, D. W.; Lane, Dorothy; Goodway, Jackie

    1998-01-01

    Evaluated Jump into Action, a non-insulin dependent diabetes mellitus (NIDDM)-prevention program that encouraged students to eat well and exercise regularly to reduce NIDDM risks. Surveys of predominantly Hispanic fifth graders and their teachers at Texas-Mexico border schools indicated that the program increased NIDDM-prevention knowledge and…

  9. Reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet impairs the incretin effect in healthy subjects

    DEFF Research Database (Denmark)

    Hansen, K B; Vilsbøll, T; Bagger, J I

    2010-01-01

    The loss of incretin effect in patients with type 2 diabetes mellitus may be secondary to impaired glucose homeostasis. We investigated whether reduced glucose tolerance and insulin resistance induced by steroid treatment, relative physical inactivity, and high-calorie diet in healthy young males...

  10. Basal-bolus insulin therapy reduces maternal triglycerides in gestational diabetes without modifying cholesteryl ester transfer protein activity.

    Science.gov (United States)

    Olmos, Pablo R; Borzone, Gisella R

    2017-09-01

    Macrosomia in the offspring of overweight/obese mothers with glucose-controlled gestational diabetes mellitus (GDM) is due to excessive rise of maternal triglycerides (TG). We aimed to ascertain whether basal-bolus insulin therapy (BBIT), or other components of the treatment, could reduce TG in GDM. We studied the records of 131 singleton pregnancies with GDM, using stepwise multiple linear regression, Mann-Whitney, χ 2 , and Jonckheere-Terpstra tests. As maternal TG increased steadily during normal pregnancy, these were transformed as z-scores. The atherogenic index of plasma (AIP) was calculated as a measure of cholesteryl ester transfer protein activity. Multiple regression showed that only BBIT (but neither limitation of weight gain nor metformin) reduced maternal TG z-scores (P = 0.011). When the 131 pregnancies were split into two groups - without BBIT (n = 58; HbA1c = 5.3 ± 0.3%) and with BBIT (n = 73; HbA1c = 5.4 ± 0.6; P = 0.2005) - we observed that BBIT (n = 73) reduced maternal TG z-scores in a dose-related fashion (Jonckheere-Terpstra P = 0.03817). The atherogenic index of plasma remained within normal range in both groups. BBIT (but not weight gain control nor metformin) reduced maternal TG in mothers with glucose-controlled GDM. This beneficial effect of BBIT was not related to changes in the cholesteryl ester transfer protein activity. © 2017 Japan Society of Obstetrics and Gynecology.

  11. Predictive Low-Glucose Insulin Suspension Reduces Duration of Nocturnal Hypoglycemia in Children Without Increasing Ketosis.

    Science.gov (United States)

    Buckingham, Bruce A; Raghinaru, Dan; Cameron, Fraser; Bequette, B Wayne; Chase, H Peter; Maahs, David M; Slover, Robert; Wadwa, R Paul; Wilson, Darrell M; Ly, Trang; Aye, Tandy; Hramiak, Irene; Clarson, Cheril; Stein, Robert; Gallego, Patricia H; Lum, John; Sibayan, Judy; Kollman, Craig; Beck, Roy W

    2015-07-01

    Nocturnal hypoglycemia can cause seizures and is a major impediment to tight glycemic control, especially in young children with type 1 diabetes. We conducted an in-home randomized trial to assess the efficacy and safety of a continuous glucose monitor-based overnight predictive low-glucose suspend (PLGS) system. In two age-groups of children with type 1 diabetes (11-14 and 4-10 years of age), a 42-night trial for each child was conducted wherein each night was assigned randomly to either having the PLGS system active (intervention night) or inactive (control night). The primary outcome was percent time <70 mg/dL overnight. Median time at <70 mg/dL was reduced by 54% from 10.1% on control nights to 4.6% on intervention nights (P < 0.001) in 11-14-year-olds (n = 45) and by 50% from 6.2% to 3.1% (P < 0.001) in 4-10-year-olds (n = 36). Mean overnight glucose was lower on control versus intervention nights in both age-groups (144 ± 18 vs. 152 ± 19 mg/dL [P < 0.001] and 153 ± 14 vs. 160 ± 16 mg/dL [P = 0.004], respectively). Mean morning blood glucose was 159 ± 29 vs. 176 ± 28 mg/dL (P < 0.001) in the 11-14-year-olds and 154 ± 25 vs. 158 ± 22 mg/dL (P = 0.11) in the 4-10-year-olds, respectively. No differences were found between intervention and control in either age-group in morning blood ketosis. In 4-14-year-olds, use of a nocturnal PLGS system can substantially reduce overnight hypoglycemia without an increase in morning ketosis, although overnight mean glucose is slightly higher. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  12. Beneficial role of vitamin K supplementation on insulin sensitivity, glucose metabolism, and the reduced risk of type 2 diabetes: A review.

    Science.gov (United States)

    Manna, Prasenjit; Kalita, Jatin

    2016-01-01

    Micronutrients are gaining acceptance as an important nutritional therapy for the prevention and/or management of diabetes and its associated health risks. Although a very small quantity of micronutrients are required for specific functions in our bodies, moderate deficiencies can lead to serious health issues. Impaired insulin sensitivity and glucose intolerance play a major role in the development of diabetic pathophysiology. Vitamin K is well known for its function in blood coagulation. Moreover, several human studies reported the beneficial role of vitamin K supplementation in improving insulin sensitivity and glucose tolerance, preventing insulin resistance, and reducing the risk of type 2 diabetes (T2 D). Both animal and human studies have suggested that vitamin K-dependent protein (osteocalcin [OC]), regulation of adipokine levels, antiinflammatory properties, and lipid-lowering effects may mediate the beneficial function of vitamin K in insulin sensitivity and glucose tolerance. This review for the first time provides an overview of the currently available preclinical and clinical evidences on the effect of vitamin K supplementation in the management of insulin sensitivity and glucose tolerance. The outcome of this review will increase understanding for the development of a novel adjuvant therapy to achieve better control of glycemia and improve the lives of diabetic patients. Copyright © 2016 Elsevier Inc. All rights reserved.

  13. Improved insulin sensitivity after exercise training is linked to reduced plasma C14:0 ceramide in obesity and type 2 diabetes.

    Science.gov (United States)

    Kasumov, Takhar; Solomon, Thomas P J; Hwang, Calvin; Huang, Hazel; Haus, Jacob M; Zhang, Renliang; Kirwan, John P

    2015-07-01

    To assess the effect of exercise training on insulin sensitivity and plasma ceramides in obesity and type 2 diabetes (T2D). Twenty-four adults with obesity and normal glucose tolerance (NGT, n = 14) or diabetes (n = 10) were studied before and after a 12-week supervised exercise-training program (5 days/week, 1 h/day, 80-85% of maximum heart rate). Changes in body composition were assessed using hydrostatic weighing and computed tomography. Peripheral tissue insulin sensitivity was assessed by a 40 mU/m(2) /min hyperinsulinemic euglycemic clamp. Plasma ceramides (C14:0, C16:0, C18:0, C18:1, C20:0, C24:0, and C24:1) were quantified using electrospray ionization tandem mass spectrometry after separation with HPLC. Plasma ceramides were similar for the subjects with obesity and NGT and the subjects with diabetes, despite differences in glucose tolerance. Exercise significantly reduced body weight and adiposity and increased peripheral insulin sensitivity in both groups (P exercise training-induced improvements in insulin sensitivity, and plasma C14:0 ceramide may provide a specific target for investigating lipid-related insulin resistance in obesity and T2D. © 2015 The Obesity Society.

  14. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle.

    Science.gov (United States)

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid content in skeletal muscle was measured. Genes and proteins of the AMPK signaling pathway were analyzed by real time RT-PCR and Western blot. Adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) and other genes involved in mitochondrial function and fat oxidation were analyzed by real time RT-PCR. Histological staining was also performed. JLD or pioglitazone administration ameliorated fasting plasma levels of glucose, insulin, triglyceride (TG), total cholesterol (TC), ALT, AST and non-esterified fatty acid (NEFA) (P < 0.05). Treatment with JLD or pioglitazone significantly reverted muscle lipid content (P < 0.05). JLD (1.5 g/kg) significantly increased plasma adiponectin concentration by 60.17% and increased AMPK and acetyl-CoA carboxylase (ACC) phosphorylation in skeletal muscle (P < 0.05). JLD administration increased levels of ADIPOR1 and ADIPOR2 by 1.48 and 1.29 respectively. Levels of genes involved in mitochondrial function and fat oxidation were increased. This study provides the molecular mechanism by which JLD ameliorates HFD-induced insulin resistance in rats.

  15. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    OpenAIRE

    Atar Herziger; Amel Benzerga; Jana Berkessel; Niken L. Dinartika; Matija Franklin; Kamilla K. Steinnes; Felicia Sundström

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing soc...

  16. Melatonin-Mediated Intracellular Insulin during 2-Deoxy-d-glucose Treatment Is Reduced through Autophagy and EDC3 Protein in Insulinoma INS-1E Cells

    Directory of Open Access Journals (Sweden)

    Han Sung Kim

    2016-01-01

    Full Text Available 2-DG triggers glucose deprivation without altering other nutrients or metabolic pathways and then activates autophagy via activation of AMPK and endoplasmic reticulum (ER stress. We investigated whether 2-DG reduced intracellular insulin increased by melatonin via autophagy/EDC3 in insulinoma INS-1E cells. p-AMPK and GRP78/BiP level were significantly increased by 2-DG in the presence/absence of melatonin, but IRE1α level was reduced in 2-DG treatment. Levels of p85α, p110, p-Akt (Ser473, Thr308, and p-mTOR (Ser2481 were also significantly reduced by 2-DG in the presence/absence of melatonin. Mn-SOD increased with 2-DG plus melatonin compared to groups treated with/without melatonin alone. Bcl-2 was decreased and Bax increased with 2-DG plus melatonin. LC3II level increased with 2-DG treatment in the presence/absence of melatonin. Intracellular insulin production increased in melatonin plus 2-DG but reduced in treatment with 2-DG with/without melatonin. EDC3 was increased by 2-DG in the presence/absence of melatonin. Rapamycin, an mTOR inhibitor, increased GRP78/BiP and EDC3 levels in a dose-dependent manner and subsequently resulted in a decrease in intracellular production of insulin. These results suggest that melatonin-mediated insulin synthesis during 2-DG treatment involves autophagy and EDC3 protein in rat insulinoma INS-1E cells and subsequently results in a decrease in intracellular production of insulin.

  17. Sodium phenylbutyrate, a drug with known capacity to reduce endoplasmic reticulum stress, partially alleviates lipid-induced insulin resistance and beta-cell dysfunction in humans.

    Science.gov (United States)

    Xiao, Changting; Giacca, Adria; Lewis, Gary F

    2011-03-01

    Chronically elevated free fatty acids contribute to insulin resistance and pancreatic β-cell failure. Among numerous potential factors, the involvement of endoplasmic reticulum (ER) stress has been postulated to play a mechanistic role. Here we examined the efficacy of the chemical chaperone, sodium phenylbutyrate (PBA), a drug with known capacity to reduce ER stress in animal models and in vitro, on lipid-induced insulin resistance and β-cell dysfunction in humans. Eight overweight or obese nondiabetic men underwent four studies each, in random order, 4 to 6 weeks apart. Two studies were preceded by 2 weeks of oral PBA (7.5 g/day), followed by a 48-h i.v. infusion of intralipid/heparin or saline, and two studies were preceded by placebo treatment, followed by similar infusions. Insulin secretion rates (ISRs) and sensitivity (S(I)) were assessed after the 48-h infusions by hyperglycemic and hyperinsulinemic-euglycemic clamps, respectively. Lipid infusion reduced S(I), which was significantly ameliorated by pretreatment with PBA. Absolute ISR was not affected by any treatment; however, PBA partially ameliorated the lipid-induced reduction in the disposition index (DI = ISR × S(I)), indicating that PBA prevented lipid-induced β-cell dysfunction. These results suggest that PBA may provide benefits in humans by ameliorating the insulin resistance and β-cell dysfunction induced by prolonged elevation of free fatty acids.

  18. Reduced viscosity Barley β-Glucan versus placebo: a randomized controlled trial of the effects on insulin sensitivity for individuals at risk for diabetes mellitus

    Directory of Open Access Journals (Sweden)

    Schmelzer Wade

    2011-08-01

    Full Text Available Abstract Background Prior studies suggest soluble fibers may favorably affect glucose/insulin metabolism. Methods This prospective, randomized, placebo controlled, double blind, parallel group trial evaluated 50 generally healthy subjects without prior diagnosis of diabetes mellitus (44 completers, who were administered beverages containing placebo (control, lower dose (3 g/d, or higher dose (6 g/d reduced viscosity barley β-glucan (BBG extract. Subjects (68% women mean age 56 years, Body Mass Index (BMI 32 kg/m2 and baseline fasting plasma glucose 102 mg/dl were instructed to follow a weight-maintaining Therapeutic Lifestyle Changes (TLC diet and consumed three 11 oz study beverages daily with meals for 12 weeks. The four primary study endpoint measures were plasma glucose and insulin [each fasting and post-Oral Glucose Tolerance Testing (OGTT]. Results Compared to placebo, administration of 3 g/d BBG over 12 weeks significantly reduced glucose incremental Area Under the Curve (iAUC measures during OGTT and 6 g/d BBG over 12 weeks significantly reduced fasting insulin as well as the related homeostasis model assessment of insulin resistance (HOMA-IR. Beverages were generally well tolerated with no serious adverse experiences and no significant differences between groups for adverse experiences. Per protocol instruction, subjects maintained body weight. Conclusions These findings suggest 6 g/d BBG consumed in a beverage over 12 weeks may improve insulin sensitivity among hyperglycemic individuals with no prior diagnosis of diabetes mellitus, and who experience no change in body weight. Trial Registration ClinicalTrials.gov Identifier: NCT01375803.

  19. Lemon detox diet reduced body fat, insulin resistance, and serum hs-CRP level without hematological changes in overweight Korean women.

    Science.gov (United States)

    Kim, Mi Joung; Hwang, Jung Hyun; Ko, Hyun Ji; Na, Hye Bock; Kim, Jung Hee

    2015-05-01

    The lemon detox program is a very low-calorie diet which consists of a mixture of organic maple and palm syrups, and lemon juice for abstinence period of 7 days. We hypothesized that the lemon detox program would reduce body weight, body fat mass, thus lowering insulin resistance and known risk factors of cardiovascular disease. We investigated anthropometric indices, insulin sensitivity, levels of serum adipokines, and inflammatory markers in overweight Korean women before and after clinical intervention trial. Eighty-four premenopausal women were randomly divided into 3 groups: a control group without diet restriction (Normal-C), a pair-fed placebo diet group (Positive-C), and a lemon detox diet group (Lemon-D). The intervention period was 11 days total: 7 days with the lemon detox juice or the placebo juice, and then 4 days with transitioning food. Changes in body weight, body mass index, percentage body fat, and waist-hip ratio were significantly greater in the Lemon-D and Positive-C groups compared to the Normal-C group. Serum insulin level, homeostasis model assessment insulin resistance scores, leptin, and adiponectin levels decreased in the Lemon-D and Positive-C groups. Serum high-sensitive C-reactive protein (hs-CRP) levels were also reduced only in the Lemon-D group. Hemoglobin and hematocrit levels remained stable in the Lemon-D group while they decreased in the Positive-C and Normal-C groups. Therefore, we suppose that the lemon detox program reduces body fat and insulin resistance through caloric restriction and might have a potential beneficial effect on risk factors for cardiovascular disease related to circulating hs-CRP reduction without hematological changes. Copyright © 2015 Elsevier Inc. All rights reserved.

  20. A Bit String Content Aware Chunking Strategy for Reduced CPU Energy on Cloud Storage

    Directory of Open Access Journals (Sweden)

    Bin Zhou

    2015-01-01

    Full Text Available In order to achieve energy saving and reduce the total cost of ownership, green storage has become the first priority for data center. Detecting and deleting the redundant data are the key factors to the reduction of the energy consumption of CPU, while high performance stable chunking strategy provides the groundwork for detecting redundant data. The existing chunking algorithm greatly reduces the system performance when confronted with big data and it wastes a lot of energy. Factors affecting the chunking performance are analyzed and discussed in the paper and a new fingerprint signature calculation is implemented. Furthermore, a Bit String Content Aware Chunking Strategy (BCCS is put forward. This strategy reduces the cost of signature computation in chunking process to improve the system performance and cuts down the energy consumption of the cloud storage data center. On the basis of relevant test scenarios and test data of this paper, the advantages of the chunking strategy are verified.

  1. Options for reducing oil content of sludge from a petroleum wastewater treatment plant.

    Science.gov (United States)

    Kwon, Tae-Soon; Lee, Jae-Young

    2015-10-01

    Wastewater treatment plants at petroleum refineries often produce substantial quantities of sludge with relatively high concentrations of oil. Disposal of this waste is costly, in part because the high oil content requires use of secure disposal methods akin to handling of hazardous wastes. This article examines the properties of oily sludge and evaluates optional methods for reducing the oil content of this sludge to enable use of lower cost disposal methods. To reduce the oil content or break the structure of oily sludge, preliminary lab-scale experiments involving mechanical treatment, surfactant extraction, and oxidation are conducted. By applying surfactants, approximately 36% to 45% of oils are extracted from oily sludge. Of this, about 33% of oils are rapidly oxidised via radiation by an electron beam within 10 s of exposure. The Fenton reaction is effective for destruction of oily sludge. It is also found that 56% of oils were removed by reacting oily sludge with water containing ozone of 0.5 mg l(-1) over a period of 24 h. Oxidation using ozone thus can also be effectively used as a pretreatment for oily sludge. © The Author(s) 2015.

  2. Elevated Chitin Content Reduces the Susceptibility of Candida Species to Caspofungin

    Science.gov (United States)

    Walker, Louise A.; Gow, Neil A. R.

    2013-01-01

    The echinocandin antifungal drugs inhibit synthesis of the major fungal cell wall polysaccharide β(1,3)-glucan. Echinocandins have good efficacy against Candida albicans but reduced activity against other Candida species, in particular Candida parapsilosis and Candida guilliermondii. Treatment of Candida albicans with a sub-MIC level of caspofungin has been reported to cause a compensatory increase in chitin content and to select for sporadic echinocandin-resistant FKS1 point mutants that also have elevated cell wall chitin. Here we show that elevated chitin in response to caspofungin is a common response in various Candida species. Activation of chitin synthesis was observed in isolates of C. albicans, Candida tropicalis, C. parapsilosis, and C. guilliermondii and in some isolates of Candida krusei in response to caspofungin treatment. However, Candida glabrata isolates demonstrated no exposure-induced change in chitin content. Furthermore, isolates of C. albicans, C. krusei, C. parapsilosis, and C. guilliermondii which were stimulated to have higher chitin levels via activation of the calcineurin and protein kinase C (PKC) signaling pathways had reduced susceptibility to caspofungin. Isolates containing point mutations in the FKS1 gene generally had higher chitin levels and did not demonstrate a further compensatory increase in chitin content in response to caspofungin treatment. These results highlight the potential of increased chitin synthesis as a potential mechanism of tolerance to caspofungin for the major pathogenic Candida species. PMID:23089748

  3. Glucose-reducing effect of the ORMD-0801 oral insulin preparation in patients with uncontrolled type 1 diabetes: a pilot study.

    Directory of Open Access Journals (Sweden)

    Roy Eldor

    Full Text Available The unpredictable behavior of uncontrolled type 1 diabetes often involves frequent swings in blood glucose levels that impact maintenance of a daily routine. An intensified insulin regimen is often unsuccessful, while other therapeutic options, such as amylin analog injections, use of continuous glucose sensors, and islet or pancreas transplantation are of limited clinical use. In efforts to provide patients with a more compliable treatment method, Oramed Pharmaceuticals tested the capacity of its oral insulin capsule (ORMD-0801, 8 mg insulin in addressing this resistant clinical state. Eight Type I diabetes patients with uncontrolled diabetes (HbA1c: 7.5-10% were monitored throughout the 15-day study period by means of a blind continuous glucose monitoring device. Baseline patient blood glucose behavior was monitored and recorded over a five-day pretreatment screening period. During the ensuing ten-day treatment phase, patients were asked to conduct themselves as usual and to self-administer an oral insulin capsule three times daily, just prior to meal intake. CGM data sufficient for pharmacodynamics analyses were obtained from 6 of the 8 subjects. Treatment with ORMD-0801 was associated with a significant 24.4% reduction in the frequencies of glucose readings >200 mg/dL (60.1 ± 7.9% pretreatment vs. 45.4 ± 4.9% during ORMD-0801 treatment; p = 0.023 and a significant mean 16.6% decrease in glucose area under the curve (AUC (66055 ± 5547 mg/dL/24 hours vs. 55060 ± 3068 mg/dL/24 hours, p = 0.023, with a greater decrease during the early evening hours. In conclusion, ORMD-0801 oral insulin capsules in conjunction with subcutaneous insulin injections, well tolerated and effectively reduced glycemia throughout the day.Clinicaltrials.gov NCT00867594.

  4. The economic impact of strengthening fuel quality regulation-reducing sulfur content in diesel fuel

    International Nuclear Information System (INIS)

    Chang, H.J.; Cho, G.L.; Kim, Y.D.

    2006-01-01

    This paper investigates the impact of strengthening vehicle emission regulation on economic activities. The government attempts to use three regulation measures to protect air quality from transportation emission. The measures include the aggregate limit (bubbles), the vehicle emission standard, and the fuel quality standard. Especially, we focus on the economic impact of reducing sulfur content in diesel fuel quality standard. Sulfur content in diesel fuel is one of the main factors in worsening local air quality. The emission from diesel vehicle accounts for 51.8% of total vehicle emission in Korea. If sulfur content reduction regulation is implemented, then the petroleum industry should build more facility to produce low sulfur content diesel, leading to additional production costs and increasing prices and decreasing outputs. We use computable general equilibrium model to analyze how the sulfur reduction regulation affects economic activities and trace out local emission reduction cost and GDP loss. And we suggest the tax-recycling mechanism to mitigate the negative economic costs due to the sulfur reduction regulation

  5. Insulin receptor degradation is accelerated in cultured lymphocytes from patients with genetic syndromes of extreme insulin resistance

    International Nuclear Information System (INIS)

    McElduff, A.; Hedo, J.A.; Taylor, S.I.; Roth, J.; Gorden, P.

    1984-01-01

    The insulin receptor degradation rate was examined in B lymphocytes that were obtained from peripheral blood of normal subjects and patients with several syndromes of extreme insulin resistance. The insulin receptors were surface labeled using Na 125 I/lactoperoxidase and the cells were returned to incubate in growth media. After varying periods of incubation, aliquots of cells were solubilized and the cell content of labeled receptor subunits were measured by immunoprecipitation with anti-receptor antibodies and NaDodSO4/polyacrylamide gel electrophoresis. In cell lines from four patients in whom the number of insulin receptors was reduced by greater than 90%, the rate of receptor loss was greater than normal (t1/2 equals 3.8 +/- 0.9 h vs. 6.5 +/- 1.2 h; mean +/- SD, P less than 0.01). However, a similar acceleration in receptor degradation was seen in cells from five patients with extreme insulin resistance but low-normal insulin receptor concentration (t1/2 equals 4.4 +/- 0.9 h). Thus, all the patients with genetic syndromes of insulin resistance had accelerated receptor degradation, regardless of their receptor concentration. By contrast, insulin receptors on cultured lymphocytes that were obtained from patients with extreme insulin resistance secondary to autoantibodies to the insulin receptor had normal receptor degradation (t1/2 equals 6.1 +/- 1.9 h). We conclude that (a) accelerated insulin receptor degradation is an additional feature of cells from patients with genetic forms of insulin resistance; (b) that accelerated insulin receptor degradation may explain the low-normal receptor concentrations that were seen in some patients with extreme insulin resistance; and (c) that accelerated degradation does not explain the decreased receptor concentration in patients with very low insulin receptor binding and, therefore, by inference, a defect in receptor synthesis must be present in this subgroup

  6. Peripheral insulin resistance and impaired insulin signaling contribute to abnormal glucose metabolism in preterm baboons.

    Science.gov (United States)

    Blanco, Cynthia L; McGill-Vargas, Lisa L; Gastaldelli, Amalia; Seidner, Steven R; McCurnin, Donald C; Leland, Michelle M; Anzueto, Diana G; Johnson, Marney C; Liang, Hanyu; DeFronzo, Ralph A; Musi, Nicolas

    2015-03-01

    Premature infants develop hyperglycemia shortly after birth, increasing their morbidity and death. Surviving infants have increased incidence of diabetes as young adults. Our understanding of the biological basis for the insulin resistance of prematurity and developmental regulation of glucose production remains fragmentary. The objective of this study was to examine maturational differences in insulin sensitivity and the insulin-signaling pathway in skeletal muscle and adipose tissue of 30 neonatal baboons using the euglycemic hyperinsulinemic clamp. Preterm baboons (67% gestation) had reduced peripheral insulin sensitivity shortly after birth (M value 12.5 ± 1.5 vs 21.8 ± 4.4 mg/kg · min in term baboons) and at 2 weeks of age (M value 12.8 ± 2.6 vs 16.3 ± 4.2, respectively). Insulin increased Akt phosphorylation, but these responses were significantly lower in preterm baboons during the first week of life (3.2-fold vs 9.8-fold). Preterm baboons had lower glucose transporter-1 protein content throughout the first 2 weeks of life (8%-12% of term). In preterm baboons, serum free fatty acids (FFAs) did not decrease in response to insulin, whereas FFAs decreased by greater than 80% in term baboons; the impaired suppression of FFAs in the preterm animals was paired with a decreased glucose transporter-4 protein content in adipose tissue. In conclusion, peripheral insulin resistance and impaired non-insulin-dependent glucose uptake play an important role in hyperglycemia of prematurity. Impaired insulin signaling (reduced Akt) contributes to the defect in insulin-stimulated glucose disposal. Counterregulatory hormones are not major contributors.

  7. Labelling of insulin with 99mTc and its evaluation in rabbits

    International Nuclear Information System (INIS)

    Bhelose, A.; Raju, A.; Ramamoorthy, N.; George, R.; Soni, P.S.

    1998-01-01

    Full text: In order to assess the feasibility of administering insulin into the respiratory tract as aerosol and determining its efficacy for drug treatment, as an alternative to intramuscular injection, we have studied the labelling of insulin with 99m Tc. 99m Tc insulin was evaluated in rabbits by i.v. injection. Reduction of insulin was carried out with 2 mercaptoethanol (2-ME) at different molar ratios of 3250:1 to 100:1 of insulin 2-ME. The reduced insulin was purified over Sephadex G-75 (7 x 1 cm) column. The fractions were identified and estimated for insulin content by spectrophotometry (280 nm). The labelling of this reduced, purified insulin was carried out using the standard Sn-GHA kit of BRIT. The R.C. purity was determined using ITLC/ normal saline which was found to be 68% at molar ratio 3250:1 of insulin:2-ME and increased to >85% at 100:1 insulin:2-ME. Bioactivity of insulin, after labelling was confirmed by injecting i.v. 99m Tc-insulin in rabbits. The blood sugar level dropped from 96 mg % to 88 % within 30 min which indicated that no significant alteration to the biomolecule structure took place during labelling. This approach thus seems to be promising and further studies with 99m Tc-insulin aerosols are warranted to establish the efficacy

  8. Content

    DEFF Research Database (Denmark)

    Keiding, Tina Bering

    secondary levels. In subject matter didactics, the question of content is more developed, but it is still mostly confined to teaching on lower levels. As for higher education didactics, discussions on selection of content are almost non-existent on the programmatic level. Nevertheless, teachers are forced...... curriculum, in higher education, and to generate analytical categories and criteria for selection of content, which can be used for systematic didactical reflection. The larger project also concerns reflection on and clarification of the concept of content, including the relation between content at the level......Aim, content and methods are fundamental categories of both theoretical and practical general didactics. A quick glance in recent pedagogical literature on higher education, however, reveals a strong preoccupation with methods, i.e. how teaching should be organized socially (Biggs & Tang, 2007...

  9. Insulin receptors

    International Nuclear Information System (INIS)

    Kahn, C.R.; Harrison, L.C.

    1988-01-01

    This book contains the proceedings on insulin receptors. Part A: Methods for the study of structure and function. Topics covered include: Method for purification and labeling of insulin receptors, the insulin receptor kinase, and insulin receptors on special tissues

  10. Hydrocolloid-Based Coatings are Effective at Reducing Acrylamide and Oil Content of French Fries

    Directory of Open Access Journals (Sweden)

    Asmaa Al-Asmar

    2018-04-01

    Full Text Available French fries are popular products worldwide. However, this product is a sufferable source of high acrylamide due to high temperature and low moisture. The main objective of this study was to evaluate the effect of grass pea flour (GPF, transglutaminase (TGase-treated (GPF + TGase, chitosan (CH, and pectin (PEC hydrocolloid coating solutions on the formation of acrylamide, water retention as well as on oil content. In addition, the Daily Intake (DI and Margin of Exposure (MOE were calculated to estimate variations in risk assessment by applying coating solutions before frying. Our results showed that the highest acrylamide content was detected in the control sample, reaching a value of 2089 µg kg−1. Hydrocolloid coating solutions were demonstrated to be an effective way to reduce acrylamide formation, with the percentage of acrylamide reduction equal to 48% for PEC, >38% for CH, ≥37% for GPF + TGase, and >31% for GPF, respectively. We hypothesized that the coatings were able to increase the water retention and, thus reduce the Maillard reaction, which is responsible for acrylamide formation. In fact, the MOE value for coated French fries was increase, resulting in being closer to the safety level to avoid carcinogenic risk. Moreover, our coatings were effective in reducing oil uptake.

  11. Improvements in or relating to processes for reducing the oxygen content of metal oxides

    International Nuclear Information System (INIS)

    James, R.H.; Spooner, J.A.

    1980-01-01

    A process is described for reducing the oxygen content of a metal oxide material (such as an intimate mixture of uranium and plutonium oxides or a mixed oxide of uranium and plutonium) by contacting the material with a hydrogen-containing gas at an elevated temperature, wherein the material is contained in a plurality of carbon crucibles, each crucible having apertured ends and being otherwise a closed vessel, the crucibles being moved through a heated zone in end-to-end contact and thereby forming a duct through which the gas is passed counter-current to the direction of movement of the crucibles. (author)

  12. Reduced content of chloroatranol and atranol in oak moss absolute significantly reduces the elicitation potential of this fragrance material.

    Science.gov (United States)

    Andersen, Flemming; Andersen, Kirsten H; Bernois, Armand; Brault, Christophe; Bruze, Magnus; Eudes, Hervé; Gadras, Catherine; Signoret, Anne-Cécile J; Mose, Kristian F; Müller, Boris P; Toulemonde, Bernard; Andersen, Klaus Ejner

    2015-02-01

    Oak moss absolute, an extract from the lichen Evernia prunastri, is a valued perfume ingredient but contains extreme allergens. To compare the elicitation properties of two preparations of oak moss absolute: 'classic oak moss', the historically used preparation, and 'new oak moss', with reduced contents of the major allergens atranol and chloroatranol. The two preparations were compared in randomized double-blinded repeated open application tests and serial dilution patch tests in 30 oak moss-sensitive volunteers and 30 non-allergic control subjects. In both test models, new oak moss elicited significantly less allergic contact dermatitis in oak moss-sensitive subjects than classic oak moss. The control subjects did not react to either of the preparations. New oak moss is still a fragrance allergen, but elicits less allergic contact dermatitis in previously oak moss-sensitized individuals, suggesting that new oak moss is less allergenic to non-sensitized individuals. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  13. Reduced Stress and Improved Sleep Quality Caused by Green Tea Are Associated with a Reduced Caffeine Content

    Directory of Open Access Journals (Sweden)

    Keiko Unno

    2017-07-01

    Full Text Available Caffeine, one of the main components in green tea, can interfere with sleep and block the effect of theanine. Since theanine, the main amino acid in tea leaves, has significant anti-stress effects in animals and humans, we examined the effects of green tea with lowered caffeine content, i.e., low-caffeine green tea (LCGT, on stress and quality of sleep of middle–aged individuals (n = 20, mean age 51.3 ± 6.7 years in a double-blind crossover design. Standard green tea (SGT was used as the control. These teas (≥300 mL/day, which were eluted with room temperature water, were consumed over a period of seven days after a single washout term. The level of salivary α-amylase activity (sAA, a stress marker, was significantly lower in participants that consumed LCGT (64.7 U/mL than in those that consumed SGT (73.9 U/mL. Sleep quality was higher in participants that consumed a larger quantity of LCGT. In addition, a self-diagnostic check for accumulated fatigue was significantly lower in those participants that consumed LCGT than SGT. These results indicate that LCGT intake can reduce stress in middle-aged individuals and improve their quality of sleep. The reduction in caffeine is suggested to be a valid reason for enhancing the anti-stress effect of green tea.

  14. Reduced Stress and Improved Sleep Quality Caused by Green Tea Are Associated with a Reduced Caffeine Content.

    Science.gov (United States)

    Unno, Keiko; Noda, Shigenori; Kawasaki, Yohei; Yamada, Hiroshi; Morita, Akio; Iguchi, Kazuaki; Nakamura, Yoriyuki

    2017-07-19

    Caffeine, one of the main components in green tea, can interfere with sleep and block the effect of theanine. Since theanine, the main amino acid in tea leaves, has significant anti-stress effects in animals and humans, we examined the effects of green tea with lowered caffeine content, i.e., low-caffeine green tea (LCGT), on stress and quality of sleep of middle-aged individuals ( n = 20, mean age 51.3 ± 6.7 years) in a double-blind crossover design. Standard green tea (SGT) was used as the control. These teas (≥300 mL/day), which were eluted with room temperature water, were consumed over a period of seven days after a single washout term. The level of salivary α-amylase activity (sAA), a stress marker, was significantly lower in participants that consumed LCGT (64.7 U/mL) than in those that consumed SGT (73.9 U/mL). Sleep quality was higher in participants that consumed a larger quantity of LCGT. In addition, a self-diagnostic check for accumulated fatigue was significantly lower in those participants that consumed LCGT than SGT. These results indicate that LCGT intake can reduce stress in middle-aged individuals and improve their quality of sleep. The reduction in caffeine is suggested to be a valid reason for enhancing the anti-stress effect of green tea.

  15. GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients: is insulin resistance in type 2 diabetes a slow, type 1 fiber disease?

    DEFF Research Database (Denmark)

    Gaster, M; Staehr, P; Beck-Nielsen, H

    2001-01-01

    To gain further insight into the mechanisms underlying muscle insulin resistance, the influence of obesity and type 2 diabetes on GLUT4 immunoreactivity in slow and fast skeletal muscle fibers was studied. Through a newly developed, very sensitive method using immunohistochemistry combined...... with morphometry, GLUT4 density was found to be significantly higher in slow compared with fast fibers in biopsy specimens from lean and obese subjects. In contrast, in type 2 diabetic subjects, GLUT4 density was significantly lower in slow compared with fast fibers. GLUT4 density in slow fibers from diabetic...... was reduced to 77% in the obese subjects and to 61% in type 2 diabetic patients compared with the control subjects. We propose that a reduction in the fraction of slow-twitch fibers, combined with a reduction in GLUT4 expression in slow fibers, may reduce the insulin-sensitive GLUT4 pool in type 2 diabetes...

  16. A nutritional intervention to reduce the calorie content of meals served at psychiatric rehabilitation programs.

    Science.gov (United States)

    Casagrande, Sarah Stark; Dalcin, Arlene; McCarron, Phyllis; Appel, Lawrence J; Gayles, Debra; Hayes, Jennifer; Daumit, Gail

    2011-12-01

    To assess the effectiveness of an intervention to reduce the calorie content of meals served at two psychiatric rehabilitation programs. Intervention staff assisted kitchen staff with ways to reduce calories and improve the nutritional quality of meals. Breakfast and lunch menus were collected before and after a 6-month intervention period. ESHA software was used to determine total energy and nutrient profiles of meals. Total energy of served meals significantly decreased by 28% at breakfast and 29% at lunch for site 1 (P breakfast for site 2 (P = 0.018). Total sugars significantly decreased at breakfast for both sites (P ≤ 0.001). In general, sodium levels were high before and after the intervention period. The nutrition intervention was effective in decreasing the total energy and altering the composition of macro-nutrients of meals. These results highlight an unappreciated opportunity to improve diet quality in patients attending psychiatric rehabilitation programs.

  17. Effect of reduced cobalt contents on hot isostatically pressed powder metallurgy U-700 alloys

    Science.gov (United States)

    Harf, F. H.

    1982-01-01

    The effect of reducing the cobalt content of prealloyed powders of UDIMET 700 (U-700) alloys to 12.7, 8.6, 4.3, and 0% was examined. The powders were hot isostatically pressed into billets, which were given heat treatments appropriate for turbine disks, namely partial solutioning at temperatures below the gamma prime solvus and four step aging treatments. Chemical analyses, metallographic examinations, and X-ray diffraction measurements were performed on the materials. Minor effects on gamma prime content and on room temperature and 650 C tensile properties were observed. Creep rupture lives at 650 C reached a maximum at the 8.4% concentration, while at 760 C a maximum in life was reached at the 4.3% cobalt level. Minimum creep rates increased with decreasing cobalt content at both test temperatures. Extended exposures at 760 and 815 C resulted in decreased tensile strengths and rupture lives for all alloys. Evidence of sigma phase formation was also found.

  18. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    Directory of Open Access Journals (Sweden)

    Atar Herziger

    2017-06-01

    Full Text Available Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism in an empirical research design. The project will test (a whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b whether self-transcendence (i.e., biospheric and self-enhancement (i.e., egoistic and hedonic values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating, while priming the relevant values and goals (self-transcendence or self-enhancement. These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions.

  19. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption

    Science.gov (United States)

    Herziger, Atar; Benzerga, Amel; Berkessel, Jana; Dinartika, Niken L.; Franklin, Matija; Steinnes, Kamilla K.; Sundström, Felicia

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism) in an empirical research design. The project will test (a) whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b) whether self-transcendence (i.e., biospheric) and self-enhancement (i.e., egoistic and hedonic) values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating), while priming the relevant values and goals (self-transcendence or self-enhancement). These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions. PMID:28649220

  20. A Study Protocol for Testing the Effectiveness of User-Generated Content in Reducing Excessive Consumption.

    Science.gov (United States)

    Herziger, Atar; Benzerga, Amel; Berkessel, Jana; Dinartika, Niken L; Franklin, Matija; Steinnes, Kamilla K; Sundström, Felicia

    2017-01-01

    Excessive consumption is on the rise, as is apparent in growing financial debt and global greenhouse gas emissions. Voluntary simplicity, a lifestyle choice of reduced consumption and sustainable consumer behavior, provides a potential solution for excessive consumers. However, voluntary simplicity is unpopular, difficult to adopt, and under researched. The outlined research project will test a method of promoting voluntary simplicity via user-generated content, thus mimicking an existing social media trend (Minimalism) in an empirical research design. The project will test (a) whether the Minimalism trend could benefit consumers interested in reducing their consumption, and (b) whether self-transcendence (i.e., biospheric) and self-enhancement (i.e., egoistic and hedonic) values and goals have a similar impact in promoting voluntary simplicity. A one-week intervention program will test the efficacy of watching user-generated voluntary simplicity videos in reducing non-essential consumption. Each of the two intervention conditions will present participants with similar tutorial videos on consumption reduction (e.g., decluttering, donating), while priming the relevant values and goals (self-transcendence or self-enhancement). These interventions will be compared to a control condition, involving no user-generated content. Participants will undergo baseline and post-intervention evaluations of: voluntary simplicity attitudes and behaviors, buying and shopping behaviors, values and goals in reducing consumption, and life satisfaction. Experience sampling will monitor affective state during the intervention. We provide a detailed stepwise procedure, materials, and equipment necessary for executing this intervention. The outlined research design is expected to contribute to the limited literature on voluntary simplicity, online behavioral change interventions, and the use of social marketing principles in consumer interventions.

  1. Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity.

    Science.gov (United States)

    Vieira Potter, Victoria J; Strissel, Katherine J; Xie, Chen; Chang, Eugene; Bennett, Grace; Defuria, Jason; Obin, Martin S; Greenberg, Andrew S

    2012-09-01

    Menopause promotes central obesity, adipose tissue (AT) inflammation, and insulin resistance (IR). Both obesity and the loss of estrogen can activate innate and adaptive immune cells (macrophages, T cells). The respective impacts of weight gain and loss of ovarian hormones on AT inflammation and IR are poorly understood. Here we determined the temporal kinetics of fat accretion, AT inflammation, and IR over a 26-wk time course in ovariectomized (OVX) mice, a model of menopause. OVX and sham-operated (SHM) C57BL6 mice were fed a normal chow diet. Weight, body composition (magnetic resonance imaging), total and regional adiposity, activity, food intake, AT crown-like structures, biohumoral measures, and insulin sensitivity (insulin tolerance testing and homeostatic model assessment) were determined at wk 12, 20, and 26. Macrophages and T cells from perigonadal AT were immunophenotyped by fluorescence-associated cell sorting, and perigonadal adipose tissue (PGAT) gene expression was quantified by quantitative PCR. OVX mice (≈ 31 g) became fatter than SHM mice (≈ 26 g) by wk 12, but mice were equally insulin sensitive. PGAT of OVX mice contained more T cells but expressed higher levels of M2-MΦ (arginase-1) and T cell-regulatory (cytotoxic T-lymphocyte antigen 4) genes. At wk 20, both OVX and SHM mice weighed approximately 35 g and were equally insulin sensitive with comparable amounts of PGAT and total body fat. OVX mice became less insulin sensitive than SHM mice by wk 26, coincident with the down-regulation of PGAT arginase-1 (-20-fold) and cytotoxic T-lymphocyte antigen 4 (2-fold) and up-regulation of M1/Th1 genes CD11c (+2-fold), IL12p40 (+2-fold), and interferon-γ (+78-fold). Ovarian hormone loss in mice induces PGAT inflammation and IR by mechanisms that can be uncoupled from OVX-induced obesity.

  2. Carbohydrate modified diet & insulin sensitizers reduce body weight & modulate metabolic syndrome measures in EMPOWIR (enhance the metabolic profile of women with insulin resistance: a randomized trial of normoglycemic women with midlife weight gain.

    Directory of Open Access Journals (Sweden)

    Harriette R Mogul

    Full Text Available Progressive midlife weight gain is associated with multiple adverse health outcomes and may represent an early manifestation of insulin resistance in a distinct subset of women. Emerging data implicate hyperinsulinema as a proximate cause of weight gain and support strategies that attenuate insulin secretion.To assess a previously reported novel hypocaloric carbohydrate modified diet alone (D, and in combination with metformin (M and metformin plus low-dose rosiglitazone (MR, in diverse women with midlife weight gain (defined as >20lbs since the twenties, normal glucose tolerance, and hyperinsulinemia.46 women, mean age 46.6±1.0, BMI 30.5±0.04 kg/m2, 54.5% white, 22.7% black, 15.9% Hispanic, at 2 university medical centers.A dietary intervention designed to reduce insulin excursions was implemented in 4 weekly nutritional group workshops prior to randomization.Change in 6-month fasting insulin. Pre-specified secondary outcomes were changes in body weight, HOMA-IR, metabolic syndrome (MS measures, leptin, and adiponectin.Six-month fasting insulin declined significantly in the M group: 12.5 to 8.0 µU/ml, p = .026. Mean 6-month weight decreased significantly and comparably in D, M, and MR groups: 4.7, 5.4, and 5.5% (p's.049, .002, and.032. HOMA-IR decreased in M and MR groups (2.5 to 1.6 and 1.9 to 1.3, p's = .054, .013. Additional improvement in MS measures included reduced waist circumference in D and MR groups and increased HDL in the D and M groups. Notably, mean fasting leptin did not decline in a subset of subjects with weight loss (26.15±2.01 ng/ml to 25.99±2.61 ng/ml, p = .907. Adiponectin increased significantly in the MR group (11.1±1.0 to 18.5±7.4, p<.001 Study medications were well tolerated.These findings suggest that EMPOWIR's easily implemented dietary interventions, alone and in combination with pharmacotherapies that target hyperinsulinemia, merit additional investigation in larger, long-term studies

  3. Yeast Starter as a Biotechnological Tool for Reducing Copper Content in Wine

    Directory of Open Access Journals (Sweden)

    Angela Capece

    2018-01-01

    Full Text Available Copper is widely used in agriculture as a traditional fungicide in organic farming to control downy mildew on grapes, consequently it is possible to find this metal during all stages of the vinification process. Low amounts of copper play a key role on the function of key cell enzymes, whereas excess quantities can exert amount-dependent cytotoxicity, resulting in general cellular damage. Nowadays the excessive copper ions in wines is removed by addition of adsorbents, but these additives can influence the sensory characteristics of wine, as well as detrimental to the health of consumers. It is well known that high concentrations of Cu2+ can be toxic to yeasts, inhibiting growth and activity, causing sluggish fermentation and reducing alcohol production. In this study, 47 S. cerevisiae strains were tested for copper tolerance by two different tests, growth on copper added medium and fermentative activity in copper added grape must. The results obtained by the two different tests were comparable and the high strain variability found was used to select four wild strains, possessing this characteristic at the highest (PP1-13 and A20 and the lowest level (MPR2-24 and A13. The selected strains were tested in synthetic and natural grape must fermentation for ability to reduce copper content in wine. The determination of copper content in wines and yeast cells revealed that at the lowest copper residual in wine corresponded the highest content in yeast cells, indicating a strong strain ability to reduce the copper content in wine. This effect was inversely correlated with strain copper resistance and the most powerful strain in copper reduction was the most sensitive strain, MPR2-24. This wild strain was finally tested as starter culture in cellar pilot scale fermentation in comparison to a commercial starter, confirming the behavior exhibited at lab scale. The use of this wild strain to complete the alcoholic fermentation and remove the copper from

  4. Sensory and microbiological evaluation of uncured fresh chicken sausage with reduced fat content

    Directory of Open Access Journals (Sweden)

    Anna Cecilia Venturini

    2011-09-01

    Full Text Available The purpose of this study was to evaluate the acceptability and the microbiological safety of uncured fresh chicken sausages with reduced fat content, considering the scientific evidence that correlated cancer and cardiovascular diseases to this diet. Two formulations of uncured fresh chicken sausage were processed using different concentrations of cochineal carmine pigment, rosemary extracts and synthetic antioxidants, which are used to give color, appearance and pleasant flavor to the products. Then, instrumental color (L*, a*, b*, C* and h*, microbial contamination and sensory tests (ranking and acceptance were used to evaluate the quality of the uncured chicken sausages. The instrumental color (chroma and hue and the sensory properties of the A and B uncured sausages were similar to the commercial cured sausage (C. However, the sensory color and appearance of samples A and B were statistically higher than those of the commercial uncured sausages D, which are prepared without the addition of nitrite or pigments. The results showed that it is possible to produce safe and high-quality uncured fresh chicken sausage with reduced fat content, using natural pigments and antioxidants.

  5. Pectinesterase inhibitor from jelly-fig (Ficus awkeotsang Makino) achenes reduces methanol content in carambola wine.

    Science.gov (United States)

    Wu, James Swi-Bea; Wu, Ming-Chang; Jiang, Chii-Ming; Hwang, Ya-Ping; Shen, Szu-Chuan; Chang, Hung-Min

    2005-11-30

    Crude pectinesterase (PE) inhibitor (PEI) extracted from jelly-fig achenes (JFA) (Ficus awakeosang Makino) was added to carambola (Averrhoa carambola L.) puree to determine the change in methanol production during fermentation. Addition of pectin or microbial pectic enzyme to puree increased dose-dependently the methanol content in fermented products. Decreasing ratio (from 1:0 to 1:19, v:v) of pectic enzyme to diluted crude PEI solution in the puree-enzyme mixture decreased the PE activity remarkably. Except for transmittance (%T), addition of crude PEI to puree did not affect apparently the physical and chemical properties of wine; however, it reduced methanol content in the control from 256 to 58 ppm. The degree of esterification (DE) of pectin in starting puree was approximately 70%. It decreased to approximately 27% in the control group and reduced slightly to approximately 67% in fermented puree with crude PEI added after 14 days of fermentation. This reveals that crude PEI solution was potent in inhibiting intrinsic carambola PE activity and appeared to be a potential alternative for methanol reduction in wines.

  6. Cryptochrome and phytochrome cooperatively but independently reduce active gibberellin content in rice seedlings under light irradiation.

    Science.gov (United States)

    Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

    2012-09-01

    In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4-OsGA2ox7). For further examination of the regulation of these genes, we established a series of cryptochrome-deficient lines through reverse genetic screening from a Tos17 mutant population and construction of knockdown lines based on an RNA interference technique. By using these lines and phytochrome mutants, we elucidated that cryptochrome 1 (cry1), consisting of two species in rice plants (cry1a and cry1b), is indispensable for robust induction of the GA2ox genes. On the other hand, repression of the GA20ox genes is mediated by phytochromes. In addition, we found that the phytochromes also mediate the repression of a gibberellin 3-oxidase gene (OsGA3ox2) in the light. These results imply that, in rice seedlings, phytochromes mediate the repression of gibberellin biosynthesis capacity, while cry1 mediates the induction of gibberellin inactivation capacity. The cry1 action was demonstrated to be dominant in the reduction of active gibberellin content, but, in rice seedlings, the cumulative effects of these independent actions reduced active gibberellin content in the light. This pathway design in which different types of photoreceptors independently but cooperatively regulate active gibberellin content is unique from the viewpoint of dicot research. This redundancy should provide robustness to the response in rice plants.

  7. Development of transgenic Brassica juncea lines for reduced seed sinapine content by perturbing phenylpropanoid pathway genes.

    Directory of Open Access Journals (Sweden)

    Sachin Kajla

    Full Text Available Sinapine is a major anti-nutritive compound that accumulates in the seeds of Brassica species. When ingested, sinapine imparts gritty flavuor in meat and milk of animals and fishy odor to eggs of brown egg layers, thereby compromising the potential use of the valuable protein rich seed meal. Sinapine content in Brassica juncea germplasm ranges from 6.7 to 15.1 mg/g of dry seed weight (DSW which is significantly higher than the prescribed permissible level of 3.0 mg/g of DSW. Due to limited natural genetic variability, conventional plant breeding approach for reducing the sinapine content has largely been unsuccessful. Hence, transgenic approach for gene silencing was adopted by targeting two genes-SGT and SCT, encoding enzymes UDP- glucose: sinapate glucosyltransferase and sinapoylglucose: choline sinapoyltransferase, respectively, involved in the final two steps of sinapine biosynthetic pathway. These two genes were isolated from B. juncea and eight silencing constructs were developed using three different RNA silencing approaches viz. antisense RNA, RNAi and artificial microRNA. Transgenics in B. juncea were developed following Agrobacterium-mediated transformation. From a total of 1232 independent T0 transgenic events obtained using eight silencing constructs, 25 homozygous lines showing single gene inheritance were identified in the T2 generation. Reduction of seed sinapine content in these lines ranged from 15.8% to 67.2%; the line with maximum reduction had sinapine content of 3.79 mg/g of DSW. The study also revealed that RNAi method was more efficient than the other two methods used in this study.

  8. A chimpanzee recognizes synthetic speech with significantly reduced acoustic cues to phonetic content.

    Science.gov (United States)

    Heimbauer, Lisa A; Beran, Michael J; Owren, Michael J

    2011-07-26

    A long-standing debate concerns whether humans are specialized for speech perception, which some researchers argue is demonstrated by the ability to understand synthetic speech with significantly reduced acoustic cues to phonetic content. We tested a chimpanzee (Pan troglodytes) that recognizes 128 spoken words, asking whether she could understand such speech. Three experiments presented 48 individual words, with the animal selecting a corresponding visuographic symbol from among four alternatives. Experiment 1 tested spectrally reduced, noise-vocoded (NV) synthesis, originally developed to simulate input received by human cochlear-implant users. Experiment 2 tested "impossibly unspeechlike" sine-wave (SW) synthesis, which reduces speech to just three moving tones. Although receiving only intermittent and noncontingent reward, the chimpanzee performed well above chance level, including when hearing synthetic versions for the first time. Recognition of SW words was least accurate but improved in experiment 3 when natural words in the same session were rewarded. The chimpanzee was more accurate with NV than SW versions, as were 32 human participants hearing these items. The chimpanzee's ability to spontaneously recognize acoustically reduced synthetic words suggests that experience rather than specialization is critical for speech-perception capabilities that some have suggested are uniquely human. Copyright © 2011 Elsevier Ltd. All rights reserved.

  9. Toward understanding insulin fibrillation.

    Science.gov (United States)

    Brange, J; Andersen, L; Laursen, E D; Meyn, G; Rasmussen, E

    1997-05-01

    Formation of insulin fibrils is a physical process by which partially unfolded insulin molecules interact with each other to form linear aggregates. Shielding of hydrophobic domains is the main driving force for this process, but formation of intermolecular beta-sheet may further stabilize the fibrillar structure. Conformational displacement of the B-chain C-terminal with exposure of nonpolar, aliphatic core residues, including A2, A3, B11, and B15, plays a crucial role in the fibrillation process. Recent crystal analyses and molecular modeling studies have suggested that when insulin fibrillates this exposed domain interacts with a hydrophobic surface domain formed by the aliphatic residues A13, B6, B14, B17, and B18, normally buried when three insulin dimers form a hexamer. In rabbit immunization experiments, insulin fibrils did not elicit an increased immune response with respect to formation of IgG insulin antibodies when compared with native insulin. In contrast, the IgE response increased with increasing content of insulin in fibrillar form. Strategies and practical approaches to prevent insulin from forming fibrils are reviewed. Stabilization of the insulin hexameric structure and blockage of hydrophobic interfaces by addition of surfactants are the most effective means of counteracting insulin fibrillation.

  10. Clinical significance of changes of serum insulin-like growth factors contents in patients with cirrhosis of liver

    International Nuclear Information System (INIS)

    Hu Haiqiang; Lei Qiufang; Ye Peihong; Li Xiaohong; Gao Wenjin; Wang Mingtao

    2006-01-01

    Objective: To investigate the association between the serum contents of IGF-I, IGF-II and liver dysfunction (as classified with Child-Pugh grades). Methods: Liver function test profiles as well as serum IGF-I, IGF-II contents ( with IRMA) were studied in 46 patients with liver cirrhosis and 32 controls. Results: According to the degree of liver dysfunction, these 46 patients with cirrhosis could be classified as: Child Grade A, n=17; Child B, n=20; and Child C, n=9. The serum IGF-I and IGF-II contents in the cirrhotic patients were significantly lower than those in the controls (P<0.001). The levels dropped along with the progression of child classification grades. Changes of IGF-II were more sensitive than those of IGF-I. Conclusion: Serum IGF-I and IGF-II contents were closely associated with degree of liver dysfunction and might be of prognostic significance. (authors)

  11. The ontogeny of insulin signaling in the preterm baboon model.

    Science.gov (United States)

    Blanco, Cynthia L; Liang, Hanyu; Joya-Galeana, Joaquin; DeFronzo, Ralph A; McCurnin, Donald; Musi, Nicolas

    2010-05-01

    Hyperglycemia, a prevalent condition in premature infants, is thought to be a consequence of incomplete suppression of endogenous glucose production and reduced insulin-stimulated glucose disposal in peripheral tissues. However, the molecular basis for these conditions remains unclear. To test the hypothesis that the insulin transduction pathway is underdeveloped with prematurity, fetal baboons were delivered, anesthetized, and euthanized at 125 d gestational age (GA), 140 d GA, or near term at 175 d GA. Vastus lateralis muscle and liver tissues were obtained, and protein content of insulin signaling molecules [insulin receptor (IR)-beta, IR substate-1, p85 subunit of phosphatidylinositol 3-kinase, Akt, and AS160] and glucose transporters (GLUT)-1 and GLUT4 was measured by Western blotting. Muscle from 125 d GA baboons had markedly reduced GLUT1 protein content (16% of 140 d GA and 9% of 175 d GA fetuses). GLUT4 and AS160 also were severely reduced in 125 d GA fetal muscle (43% of 175 d GA and 35% of 175 d GA, respectively). In contrast, the protein content of IR-beta, IR substate-1, and Akt was elevated by 1.7-, 5.2-, and 1.9-fold, respectively, in muscle from 125 d GA baboons when compared with 175 d GA fetuses. No differences were found in the content of insulin signaling proteins in liver. In conclusion, significant gestational differences exist in the protein content of several insulin signaling proteins in the muscle of fetal baboons. Reduced muscle content of key glucose transport-regulating proteins (GLUT1, GLUT4, AS160) could play a role in the pathogenesis of neonatal hyperglycemia and reduced insulin-stimulated glucose disposal.

  12. Vitamin E and vitamin C do not reduce insulin sensitivity but inhibit mitochondrial protein expression in exercising obese rats

    Science.gov (United States)

    Controversy exists as to whether supplementation with the antioxidants vitamin E (VE) and vitamin C (VC) blocks adaptation to exercise. Exercise is a first-line means to treat obesity and its complications. While diet-induced obesity alters mitochondrial (MT) function and induces insulin resistance ...

  13. A 12-Week Aerobic Exercise Program Reduces Hepatic Fat Accumulation and Insulin Resistance in Obese, Hispanic Adolescents

    NARCIS (Netherlands)

    van der Heijden, Gert-Jan; Wang, Zhiyue J.; Chu, Zili D.; Sauer, Pieter J. J.; Haymond, Morey W.; Rodriguez, Luisa M.; Sunehag, Agneta L.

    2010-01-01

    The rise in obesity-related morbidity in children and adolescents requires urgent prevention and treatment strategies. Currently, only limited data are available on the effects of exercise programs on insulin resistance, and visceral, hepatic, and intramyocellular fat accumulation. We hypothesized

  14. Reduced insulin exocytosis in human pancreatic β-cells with gene variants linked to type 2 diabetes

    DEFF Research Database (Denmark)

    Rosengren, Anders H; Braun, Matthias; Mahdi, Taman

    2012-01-01

    The majority of genetic risk variants for type 2 diabetes (T2D) affect insulin secretion, but the mechanisms through which they influence pancreatic islet function remain largely unknown. We functionally characterized human islets to determine secretory, biophysical, and ultrastructural features ...

  15. Salinity Inhibits Rice Seed Germination by Reducing α-Amylase Activity via Decreased Bioactive Gibberellin Content

    Directory of Open Access Journals (Sweden)

    Li Liu

    2018-03-01

    Full Text Available Seed germination plays important roles in the establishment of seedlings and their subsequent growth; however, seed germination is inhibited by salinity, and the inhibitory mechanism remains elusive. Our results indicate that NaCl treatment inhibits rice seed germination by decreasing the contents of bioactive gibberellins (GAs, such as GA1 and GA4, and that this inhibition can be rescued by exogenous bioactive GA application. To explore the mechanism of bioactive GA deficiency, the effect of NaCl on GA metabolic gene expression was investigated, revealing that expression of both GA biosynthetic genes and GA-inactivated genes was up-regulated by NaCl treatment. These results suggest that NaCl-induced bioactive GA deficiency is caused by up-regulated expression of GA-inactivated genes, and the up-regulated expression of GA biosynthetic genes might be a consequence of negative feedback regulation of the bioactive GA deficiency. Moreover, we provide evidence that NaCl-induced bioactive GA deficiency inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression. Additionally, exogenous bioactive GA rescues NaCl-inhibited seed germination by enhancing α-amylase activity. Thus, NaCl treatment reduces bioactive GA content through promotion of bioactive GA inactivation, which in turn inhibits rice seed germination by decreasing α-amylase activity via down-regulation of α-amylase gene expression.

  16. Insulin and insulin signaling play a critical role in fat induction of insulin resistance in mouse

    Science.gov (United States)

    Ning, Jie; Hong, Tao; Yang, Xuefeng; Mei, Shuang; Liu, Zhenqi; Liu, Hui-Yu

    2011-01-01

    The primary player that induces insulin resistance has not been established. Here, we studied whether or not fat can cause insulin resistance in the presence of insulin deficiency. Our results showed that high-fat diet (HFD) induced insulin resistance in C57BL/6 (B6) mice. The HFD-induced insulin resistance was prevented largely by the streptozotocin (STZ)-induced moderate insulin deficiency. The STZ-induced insulin deficiency prevented the HFD-induced ectopic fat accumulation and oxidative stress in liver and gastrocnemius. The STZ-induced insulin deficiency prevented the HFD- or insulin-induced increase in hepatic expression of long-chain acyl-CoA synthetases (ACSL), which are necessary for fatty acid activation. HFD increased mitochondrial contents of long-chain acyl-CoAs, whereas it decreased mitochondrial ADP/ATP ratio, and these HFD-induced changes were prevented by the STZ-induced insulin deficiency. In cultured hepatocytes, we observed that expressions of ACSL1 and -5 were stimulated by insulin signaling. Results in cultured cells also showed that blunting insulin signaling by the PI3K inhibitor LY-294002 prevented fat accumulation, oxidative stress, and insulin resistance induced by the prolonged exposure to either insulin or oleate plus sera that normally contain insulin. Finally, knockdown of the insulin receptor prevented the oxidative stress and insulin resistance induced by the prolonged exposure to insulin or oleate plus sera. Together, our results show that insulin and insulin signaling are required for fat induction of insulin resistance in mice and cultured mouse hepatocytes. PMID:21586696

  17. Metformin and insulin receptors

    International Nuclear Information System (INIS)

    Vigneri, R.; Gullo, D.; Pezzino, V.

    1984-01-01

    The authors evaluated the effect of metformin (N,N-dimethylbiguanide), a biguanide known to be less toxic than phenformin, on insulin binding to its receptors, both in vitro and in vivo. Specific 125 I-insulin binding to cultured IM-9 human lymphocytes and MCF-7 human breast cancer cells was determined after preincubation with metformin. Specific 125 I-insulin binding to circulating monocytes was also evaluated in six controls, eight obese subjects, and six obese type II diabetic patients before and after a short-term treatment with metformin. Plasma insulin levels and blood glucose were also measured on both occasions. Metformin significantly increased insulin binding in vitro to both IM-9 lymphocytes and MCF-7 cells; the maximum increment was 47.1% and 38.0%, respectively. Metformin treatment significantly increased insulin binding in vivo to monocytes of obese subjects and diabetic patients. Scatchard analysis indicated that the increased binding was mainly due to an increase in receptor capacity. Insulin binding to monocytes of normal controls was unchanged after metformin as were insulin levels in all groups; blood glucose was significantly reduced after metformin only in diabetic patients. These data indicate that metformin increases insulin binding to its receptors in vitro and in vivo. The effect in vivo is observed in obese subjects and in obese type II diabetic patients, paralleling the clinical effectiveness of this antidiabetic agent, and is not due to receptor regulation by circulating insulin, since no variation in insulin levels was recorded

  18. Replacing Fish Oil with Vegetable Oils in Salmon Feed Increases Hepatic Lipid Accumulation and Reduces Insulin Sensitivity in Mice

    DEFF Research Database (Denmark)

    Midtbø, Lisa Kolden

    Background: Due to a growing global aquaculture production, fish oil (FO) and fish meal (FM) are partly replaced with vegetable ingredients in aqua feed for Atlantic salmon. These replacements in the feed lead to an altered fatty acid composition in the salmon fillet. We aimed to investigate how...... these changes affects obesity development and insulin sensitivity in mice eating the salmon. In addition, we wanted to investigate how the background diet affects the antiobesity effect of FO. Results: Western diets (WDs) were produced containing salmon fed either FO (WD-FO), or with partly replacement (80......%) of FO with different vegetable oils (VOs); rape seed oil (WDRO), olive oil (WD-OO) or soybean oil (WD-SO). These diets were given to C57BL/6J mice, and mice had higher hepatic lipid accumulation and lower insulin sensitivity when given WD-SO compared with WD-FO. Mice given WD-SO had higher hepatic...

  19. Reduced sarcoplasmic reticulum content of releasable Ca2+ in rat soleus muscle fibres after eccentric contractions

    DEFF Research Database (Denmark)

    Nielsen, J S; Sahlin, K; Ørtenblad, N

    2007-01-01

    AIM: The purpose was to evaluate the effects of fatiguing eccentric contractions (EC) on calcium (Ca2+) handling properties in mammalian type I muscles. We hypothesized that EC reduces both endogenous sarcoplasmic reticulum (SR) content of releasable Ca2+ (eSRCa2+) and myofibrillar Ca2+ sensitivity....... METHODS: Isolated rat soleus muscles performed 30 EC bouts. Single fibres were isolated from the muscle and after mechanical removal of sarcolemma used to measure eSRCa2+, rate of SR Ca2+ loading and myofibrillar Ca2+ sensitivity. RESULTS: Following EC maximal force in whole muscle was reduced by 30......% and 16/100 Hz force ratio by 33%. The eSRCa2+ in fibres from non-stimulated muscles was 45 +/- 5% of the maximal loading capacity. After EC, eSRCa2+ per fibre CSA decreased by 38% (P = 0.05), and the maximal capacity of SR Ca2+ loading was depressed by 32%. There were no effects of EC on either...

  20. Reduced nicotine content cigarette advertising: How false beliefs and subjective ratings affect smoking behavior.

    Science.gov (United States)

    Mercincavage, Melissa; Saddleson, Megan L; Gup, Emily; Halstead, Angela; Mays, Darren; Strasser, Andrew A

    2017-04-01

    Tobacco advertising can create false beliefs about health harms that are reinforced by product design features. Reduced nicotine content (RNC) cigarettes may reduce harm, but research has not addressed advertising influences. This study examined RNC cigarette advertising effects on false harm beliefs, and how these beliefs - along with initial subjective ratings of RNC cigarettes - affect subsequent smoking behaviors. We further explored whether subjective ratings moderate associations between false beliefs and behavior. Seventy-seven daily, non-treatment-seeking smokers (66.2% male) participated in the first 15days of a randomized, controlled, open-label RNC cigarette trial. Participants viewed an RNC cigarette advertisement at baseline before completing a 5-day period of preferred brand cigarette use, followed by a 10-day period of RNC cigarette use (0.6mg nicotine yield). Participants provided pre- and post-advertisement beliefs, and subjective ratings and smoking behaviors for cigarettes smoked during laboratory visits. Viewing the advertisement increased beliefs that RNC cigarettes contain less nicotine and are healthier than regular cigarettes (p'saffected smoking behaviors. Significant interactions of strength and taste ratings with beliefs (p'ssmokers with less negative initial subjective ratings, greater false beliefs were associated with greater RNC cigarette consumption. Smokers may misconstrue RNC cigarettes as less harmful than regular cigarettes. These beliefs, in conjunction with favorable subjective ratings, may increase product use. Copyright © 2017 Elsevier B.V. All rights reserved.

  1. DHEA supplementation in ovariectomized rats reduces impaired glucose-stimulated insulin secretion induced by a high-fat diet

    Directory of Open Access Journals (Sweden)

    Katherine Veras

    2014-01-01

    Full Text Available Dehydroepiandrosterone (DHEA and the dehydroepiandrosterone sulfate (DHEA-S are steroids produced mainly by the adrenal cortex. There is evidence from both human and animal models suggesting beneficial effects of these steroids for obesity, diabetes mellitus, hypertension, and osteoporosis, conditions associated with the post-menopausal period. Accordingly, we hypothesized that DHEA supplementation in ovariectomized (OVX female rats fed a high-fat diet would maintain glucose-induced insulin secretion (GSIS and pancreatic islet function. OVX resulted in a 30% enlargement of the pancreatic islets area compared to the control rats, which was accompanied by a 50% reduction in the phosphorylation of AKT protein in the pancreatic islets. However, a short-term high-fat diet induced insulin resistance, accompanied by impaired GSIS in isolated pancreatic islets. These effects were reversed by DHEA treatment, with improved insulin sensitivity to levels similar to the control group, and with increased serine phosphorylation of the AKT protein. These data confirm the protective effect of DHEA on the endocrine pancreas in a situation of diet-induced overweight and low estrogen concentrations, a phenotype similar to that of the post-menopausal period.

  2. HPMC supplementation reduces abdominal fat content, intestinal permeability, inflammation, and insulin resistance in diet-induced obese mice

    Science.gov (United States)

    Cationic hydroxyethyl cellulose (cHEC) , was fed to hamsters to determine if this new soluble fiber had an effect on hypercholesterolemia and dyslipidemia associated with cardiovascular disease. In this study, Golden Syrian hamsters were supplemented with 3-8% cHEC or microcrystalline cellulose (MC...

  3. Expression of a bacterial 3-dehydroshikimate dehydratase reduces lignin content and improves biomass saccharification efficiency.

    Science.gov (United States)

    Eudes, Aymerick; Sathitsuksanoh, Noppadon; Baidoo, Edward E K; George, Anthe; Liang, Yan; Yang, Fan; Singh, Seema; Keasling, Jay D; Simmons, Blake A; Loqué, Dominique

    2015-12-01

    Lignin confers recalcitrance to plant biomass used as feedstocks in agro-processing industries or as source of renewable sugars for the production of bioproducts. The metabolic steps for the synthesis of lignin building blocks belong to the shikimate and phenylpropanoid pathways. Genetic engineering efforts to reduce lignin content typically employ gene knockout or gene silencing techniques to constitutively repress one of these metabolic pathways. Recently, new strategies have emerged offering better spatiotemporal control of lignin deposition, including the expression of enzymes that interfere with the normal process for cell wall lignification. In this study, we report that expression of a 3-dehydroshikimate dehydratase (QsuB from Corynebacterium glutamicum) reduces lignin deposition in Arabidopsis cell walls. QsuB was targeted to the plastids to convert 3-dehydroshikimate - an intermediate of the shikimate pathway - into protocatechuate. Compared to wild-type plants, lines expressing QsuB contain higher amounts of protocatechuate, p-coumarate, p-coumaraldehyde and p-coumaryl alcohol, and lower amounts of coniferaldehyde, coniferyl alcohol, sinapaldehyde and sinapyl alcohol. 2D-NMR spectroscopy and pyrolysis-gas chromatography/mass spectrometry (pyro-GC/MS) reveal an increase of p-hydroxyphenyl units and a reduction of guaiacyl units in the lignin of QsuB lines. Size-exclusion chromatography indicates a lower degree of lignin polymerization in the transgenic lines. Therefore, our data show that the expression of QsuB primarily affects the lignin biosynthetic pathway. Finally, biomass from these lines exhibits more than a twofold improvement in saccharification efficiency. We conclude that the expression of QsuB in plants, in combination with specific promoters, is a promising gain-of-function strategy for spatiotemporal reduction of lignin in plant biomass. © 2015 The Authors. Plant Biotechnology Journal published by Society for Experimental Biology and The

  4. Taurine ameliorates hyperglycemia and dyslipidemia by reducing insulin resistance and leptin level in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term diabetes

    Science.gov (United States)

    Oh, Da Hee; Kim, Jung Yeon; Lee, Bong Gn; You, Jeong Soon; Chang, Kyung Ja; Chung, Hyunju; Yoo, Myung Chul; Yang, Hyung-In; Kang, Ja-Heon; Hwang, Yoo Chul; Ahn, Kue Jeong; Chung, Ho-Yeon

    2012-01-01

    This study aimed to determine whether taurine supplementation improves metabolic disturbances and diabetic complications in an animal model for type 2 diabetes. We investigated whether taurine has therapeutic effects on glucose metabolism, lipid metabolism, and diabetic complications in Otsuka Long-Evans Tokushima fatty (OLETF) rats with long-term duration of diabetes. Fourteen 50-week-old OLETF rats with chronic diabetes were fed a diet supplemented with taurine (2%) or a non-supplemented control diet for 12 weeks. Taurine reduced blood glucose levels over 12 weeks, and improved OGTT outcomes at 6 weeks after taurine supplementation, in OLETF rats. Taurine significantly reduced insulin resistance but did not improve β-cell function or islet mass. After 12 weeks, taurine significantly decreased serum levels of lipids such as triglyceride, cholesterol, high density lipoprotein cholesterol, and low density lipoprotein cholesterol. Taurine significantly reduced serum leptin, but not adiponectin levels. However, taurine had no therapeutic effect on damaged tissues. Taurine ameliorated hyperglycemia and dyslipidemia, at least in part, by improving insulin sensitivity and leptin modulation in OLETF rats with long-term diabetes. Additional study is needed to investigate whether taurine has the same beneficial effects in human diabetic patients. PMID:23114424

  5. Pharmacological Evaluation of Total Alkaloids from Nux Vomica: Effect of Reducing Strychnine Contents

    Directory of Open Access Journals (Sweden)

    Jun Chen

    2014-04-01

    Full Text Available The aim of the study was to investigate the possibility of improving the therapeutic efficacy of the total alkaloid fraction (TAF extracted from processed nux vomica by reducing the strychnine contents. Most strychnine was removed from TAF to obtain the modified total alkaloid fraction (MTAF. The toxicity and pharmacokinetics of TAF and MTAF were further investigated and compared besides their antitumor, analgesic and anti-inflammatory activities. The results showed that the ratios of brucine to strychnine were 1:2.05 and 2.2:1 for TAF and MTAF, respectively, and the toxicity of TAF was about 3.17-fold higher than that of MTAF. Compared to brucine alone, the elimination of brucine was found to be inhibited by other alkaloids in TAF or MTAF except strychnine. Significantly increased pharmacological activities when administered by the oral route were obtained with MTAF in comparison to TAF and nux vomica powder (NVP. In summary, MTAF might replace NVP and TAF in the clinical application of Chinese medicine to obtain much higher efficacy.

  6. Reduced abscisic acid content is responsible for enhanced sucrose accumulation by potassium nutrition in vegetable soybean seeds.

    Science.gov (United States)

    Tu, Bingjie; Liu, Changkai; Tian, Bowen; Zhang, Qiuying; Liu, Xiaobing; Herbert, Stephen J

    2017-05-01

    In order to understand the physiological mechanism of potassium (K) application in enhancing sugar content of vegetable soybean seeds, pot experiments were conducted in 2014 and 2015 with two vegetable soybean (Glycine max L. Merr.) cultivars (c.v. Zhongkemaodou 1 and c.v. 121) under normal rate of nitrogen and phosphorus application. Three potassium (K) fertilization treatments were imposed: No K application (K0), 120 kg K 2 SO 4 ha -1 at seeding (K1), and 120 kg K 2 SO 4 ha -1 at seedling + 1% K 2 SO 4 foliar application at flowering (K2). Contents of indole-3-acetic acid (IAA), gibberellins (GA), cytokinins (ZR) and abscisic acid (ABA) in seeds were determined from 4 to 8 weeks after flowering. K fertilization increased the contents of IAA, GA, ZR, soluble sugar, sucrose and fresh pod yield, but reduced ABA content consistently. When the contents of soluble sugar and sucrose reached the highest level at 7 weeks after flowering for the 2 cultivars, the contents of IAA、GA、ZR all reached the lowest level in general. The content of ABA in seed was negatively correlated with the sucrose content (P abscisic acid content plays a critical role in enhancing sucrose content, which might be a partial mechanism involved in K nutrition to improve the quality of vegetable soybean.

  7. Maternal Pre-Gravid Obesity Changes Gene Expression Profiles Towards Greater Inflammation and Reduced Insulin Sensitivity in Umbilical Cord

    Science.gov (United States)

    Thakali, Keshari M.; Saben, Jessica; Faske, Jennifer B.; Lindsey, Forrest; Gomez-Acevedo, Horacio; Lowery, Curtis L.; Badger, Thomas M.; Andres, Aline; Shankar, Kartik

    2014-01-01

    Background Maternal obesity is associated with unfavorable outcomes, which may be reflected in the as yet undiscovered gene expression profiles of the umbilical cord (UC). Methods UCs from 12 lean (pre-gravid BMI obese (OW/OB, pre-gravid BMI ≥25) women without gestational diabetes were collected for gene expression analysis using Human Primeview microarrays (Affymetrix). Metabolic parameters were assayed in mother’s plasma and cord blood. Results Although offspring birth weight and adiposity (at 2-wk) did not differ between groups, expression of 232 transcripts was affected in UC from OW/OB compared to those of lean mothers. GSEA analysis revealed an up-regulation of genes related to metabolism, stimulus and defense response and inhibitory to insulin signaling in the OW/OB group. We confirmed that EGR1, periostin, and FOSB mRNA expression was induced in UCs from OW/OB moms, while endothelin receptor B, KFL10, PEG3 and EGLN3 expression was decreased. Messenger RNA expression of EGR1, FOSB, MEST and SOCS1 were positively correlated (pmaternal obesity and changes in UC gene expression profiles favoring inflammation and insulin resistance, potentially predisposing infants to develop metabolic dysfunction later on in life. PMID:24819376

  8. Insulin use increases risk of asthma but metformin use reduces the risk in patients with diabetes in a Taiwanese population cohort.

    Science.gov (United States)

    Chen, Chiung-Zuei; Hsu, Chih-Hui; Li, Chung-Yi; Hsiue, Tzuen-Ren

    2017-12-01

    Recent reports have suggested that insulin promotes airway smooth muscle contraction and enhances airway hyperresponsiveness, which are cardinal features of asthma. In contrast, metformin can reduce both airway inflammatory and remodeling properties. However, these results are all from in vitro and animal studies. This study investigated whether diabetes and various antidiabetic agents associate with the risk of asthma. We used a retrospective population-based cohort study using Taiwan's National Health Insurance claim database from 2000 to 2010 and a Cox proportional hazards regression model to compare the incidence of asthma between patients with diabetes (n = 19,428) and a matched non-diabetic group (n = 38,856). We also used a case-control study nested from the above cohort including 1,982 incident cases of asthma and 1,982 age- and sex-matched controls. A time density sampling technique was used to assess the effects of various antidiabetic agents on the risk of asthma. The incidence of asthma was significantly higher in the diabetic cohort than that in the non-diabetic cohort after adjustment for age, sex, and obesity, with a hazard ratio of 1.30 (95% confidence interval [CI]: 1.24-1.38). Insulin was found to increase the risk of asthma among diabetic patients (odds ratio [OR] 2.23; 95% CI: 1.52-3.58). In contrast, the use of metformin correlated with a decreased risk of asthma (OR 0.75; 95% CI: 0.60-0.95). Individuals with diabetes are at an increased risk of asthma. Insulin may further increase the risk of asthma, but the risk could possibly be reduced by using metformin.

  9. Gasoline reformulation to reduce exhaust emissions in Finnish conditions. Influence of sulphur and benzene contents of gasoline on exhaust emissions

    International Nuclear Information System (INIS)

    Kytoe, M.; Aakko, P.; Lappi, M.

    1994-01-01

    At earlier stages of the study it was found that the exhaust emissions from cars are reduced when using fuels with no more than 4 wt% of oxygen. At this stage of the study the work focused on impacts of the sulphur and benzene content of gasoline on exhaust emissions in Finland. Sulphur in gasoline retards the operation of the catalyst, and consequently the exhaust emissions of catalyst cars increase if the sulphur content of the fuel increases. In the present study, evaporation during refuelling were measured for fuels with varying vapour pressures and benzene contents of gasoline. The total hydrocarbon evaporation was reduced by 22 % (10 g) when the vapour pressure of gasoline was reduced from 85 kPa to 65 kPa. Correspondingly, benzene evaporation during refuelling was reduced to a third when the benzene content of the fuel was reduced from the level of 3 wt% to 1 wt%. The reduction of the sulphur content of gasoline from 500 ppm to 100 ppm affected regulated exhaust emissions from the catalyst car at +22 deg C as follows: CO emission was reduced on average by 14 % (0.175 g/km), CH emission by 7 % (0.010 g/km) and NO x emission by 9 % (0.011 g/km). At-7 deg C the percentual changes were smaller. When the benzene content of the fuel was reduced from 3 wt% to 1 wt%, the benzene emission from the catalyst cars was reduced by 20-30 % and from the non-catalyst cars on average by 30 % both at +22 deg C and -7 deg C. The benzene emission ranged 3-22 mg/km for the catalyst cars and 40-90 mg/km for the non-catalyst cars at +22 deg C in the FTP test

  10. Contents

    Directory of Open Access Journals (Sweden)

    Editor IJRED

    2012-11-01

    Full Text Available International Journal of Renewable Energy Development www.ijred.com Volume 1             Number 3            October 2012                ISSN 2252- 4940   CONTENTS OF ARTICLES page Design and Economic Analysis of a Photovoltaic System: A Case Study 65-73 C.O.C. Oko , E.O. Diemuodeke, N.F. Omunakwe, and E. Nnamdi     Development of Formaldehyde Adsorption using Modified Activated Carbon – A Review 75-80 W.D.P Rengga , M. Sudibandriyo and M. Nasikin     Process Optimization for Ethyl Ester Production in Fixed Bed Reactor Using Calcium Oxide Impregnated Palm Shell Activated Carbon (CaO/PSAC 81-86 A. Buasri , B. Ksapabutr, M. Panapoy and N. Chaiyut     Wind Resource Assessment in Abadan Airport in Iran 87-97 Mojtaba Nedaei       The Energy Processing by Power Electronics and its Impact on Power Quality 99-105 J. E. Rocha and B. W. D. C. Sanchez       First Aspect of Conventional Power System Assessment for High Wind Power Plants Penetration 107-113 A. Merzic , M. Music, and M. Rascic   Experimental Study on the Production of Karanja Oil Methyl Ester and Its Effect on Diesel Engine 115-122 N. Shrivastava,  , S.N. Varma and M. Pandey  

  11. The T-allele of TCF7L2 rs7903146 associates with a reduced compensation of insulin secretion for insulin resistance induced by 9 days of bed rest

    DEFF Research Database (Denmark)

    Alibegovic, Amra C; Sonne, Mette P; Højbjerre, Lise

    2010-01-01

    of FPIR in response to insulin resistance induced by bed rest was lower in carriers of the T-allele (P hepatic insulin resistance......OBJECTIVE: The aim of this study was to determine whether the type 2 diabetes-associated T-allele of transcription factor 7-like 2 (TCF7L2) rs7903146 associates with impaired insulin secretion to compensate for insulin resistance induced by bed rest. RESEARCH DESIGN AND METHODS: A total of 38....... The genetic analyses were done assuming a dominant model of inheritance. RESULTS: The first-phase insulin response (FPIR) was significantly lower in carriers of the T-allele compared with carriers of the CC genotype before bed rest, with and without correction for insulin resistance. The incremental rise...

  12. Adiponectin concentration is associated with muscle insulin sensitivity, AMPK phosphorylation and ceramide content in skeletal muslce of men, but not women

    DEFF Research Database (Denmark)

    Høeg, Louise Dalgas; Sjøberg, Kim Anker; Lundsgaard, Annemarie

    2013-01-01

    Adiponectin is an adipokine that regulates metabolism and increases insulin sensitivity. Mechanisms behind this insulin sensitizing effect have been investigated in rodents, but little is known in humans especially in skeletal muscle. Women have higher serum concentrations of adiponectin than men...

  13. The consumption of bread enriched with betaglucan reduces LDL-cholesterol and improves insulin resistance in patients with type 2 diabetes.

    Science.gov (United States)

    Liatis, S; Tsapogas, P; Chala, E; Dimosthenopoulos, C; Kyriakopoulos, K; Kapantais, E; Katsilambros, N

    2009-04-01

    Previous studies have shown that the water-soluble dietary fibre betaglucan, a natural component of oats, reduces cholesterol and postprandial hyperglycaemia. The aim of the present study was to investigate the effect of betaglucan-enriched bread consumption on the lipid profile and glucose homoeostasis of patients with type 2 diabetes (T2D). We conducted a randomized, double-blind study in which 46 patients with T2D and LDL-C greater than 3.37 mmol/l (130 mg/dl) were randomized to incorporate into their diet, for 3 weeks, either bread enriched with betaglucan (providing 3g/day of betaglucan) or white bread without betaglucan. The consumption of bread containing betaglucan led to significant reductions (vs the control group) in LDL-C of 0.66 mmol/l (15.79%) versus 0.11 mmol/l (2.71%) (P=0.009), in total cholesterol of 0.80 mmol/l (12.80%) versus 0.12 mmol/l (1.88%) (P=0.006), in Fasting plasma insulin (FPI) of 3.23 microU/ml versus an increase of 3.77 microU/ml (P=0.03) and in Homa-IR (Homoeostasis model assessment-insulin resistance) by 2.08 versus an increase of 1.33 (P=0.04). Betaglucan enriched bread may contribute to the improvement of the lipid profile and insulin resistance in patients with T2D.

  14. Insulin, cognition, and dementia

    Science.gov (United States)

    Cholerton, Brenna; Baker, Laura D.; Craft, Suzanne

    2015-01-01

    Cognitive disorders of aging represent a serious threat to the social and economic welfare of current society. It is now widely recognized that pathology related to such conditions, particularly Alzheimer’s disease, likely begins years or decades prior to the onset of clinical dementia symptoms. This revelation has led researchers to consider candidate mechanisms precipitating the cascade of neuropathological events that eventually lead to clinical Alzheimer’s disease. Insulin, a hormone with potent effects in the brain, has recently received a great deal of attention for its potential beneficial and protective role in cognitive function. Insulin resistance, which refers to the reduced sensitivity of target tissues to the favorable effects of insulin, is related to multiple chronic conditions known to impact cognition and increase dementia risk. With insulin resistance-associated conditions reaching epidemic proportions, the prevalence of Alzheimer’s disease and other cognitive disorders will continue to rise exponentially. Fortunately, these chronic insulin-related conditions are amenable to pharmacological intervention. As a result, novel therapeutic strategies that focus on increasing insulin sensitivity in the brain may be an important target for protecting or treating cognitive decline. The following review will highlight our current understanding of the role of insulin in brain, potential mechanisms underlying the link between insulin resistance and dementia, and current experimental therapeutic strategies aimed at improving cognitive function via modifying the brain’s insulin sensitivity. PMID:24070815

  15. Insulin and IGF-1 improve mitochondrial function in a PI-3K/Akt-dependent manner and reduce mitochondrial generation of reactive oxygen species in Huntington's disease knock-in striatal cells.

    Science.gov (United States)

    Ribeiro, Márcio; Rosenstock, Tatiana R; Oliveira, Ana M; Oliveira, Catarina R; Rego, A Cristina

    2014-09-01

    Oxidative stress and mitochondrial dysfunction have been described in Huntington's disease, a disorder caused by expression of mutant huntingtin (mHtt). IGF-1 was previously shown to protect HD cells, whereas insulin prevented neuronal oxidative stress. In this work we analyzed the role of insulin and IGF-1 in striatal cells derived from HD knock-in mice on mitochondrial production of reactive oxygen species (ROS) and related antioxidant and signaling pathways influencing mitochondrial function. Insulin and IGF-1 decreased mitochondrial ROS induced by mHtt and normalized mitochondrial SOD activity, without affecting intracellular glutathione levels. IGF-1 and insulin promoted Akt phosphorylation without changing the nuclear levels of phosphorylated Nrf2 or Nrf2/ARE activity. Insulin and IGF-1 treatment also decreased mitochondrial Drp1 phosphorylation, suggesting reduced mitochondrial fragmentation, and ameliorated mitochondrial function in HD cells in a PI-3K/Akt-dependent manner. This was accompanied by increased total and phosphorylated Akt, Tfam, and mitochondrial-encoded cytochrome c oxidase II, as well as Tom20 and Tom40 in mitochondria of insulin- and IGF-1-treated mutant striatal cells. Concomitantly, insulin/IGF-1-treated mutant cells showed reduced apoptotic features. Hence, insulin and IGF-1 improve mitochondrial function and reduce mitochondrial ROS caused by mHtt by activating the PI-3K/Akt signaling pathway, in a process independent of Nrf2 transcriptional activity, but involving enhanced mitochondrial levels of Akt and mitochondrial-encoded complex IV subunit. Copyright © 2014 Elsevier Inc. All rights reserved.

  16. Excess of methyl donor in the perinatal period reduces postnatal leptin secretion in rat and interacts with the effect of protein content in diet.

    Directory of Open Access Journals (Sweden)

    Fanny Giudicelli

    Full Text Available Methionine, folic acid, betaine and choline interact in the one-carbon metabolism which provides methyl groups for methylation reactions. An optimal intake of these nutrients during pregnancy is required for successful completion of fetal development and evidence is growing that they could be involved in metabolic long-term programming. However, the biological pathways involved in the action of these nutrients are still poorly known. This study investigated the interaction between methyl donors and protein content in maternal diet during the preconceptual, pregnancy and lactation periods and the consequences on the rat offspring in the short and long term. Methyl donor supplementation reduced leptin secretion in offspring, whereas insulin levels were mostly affected by protein restriction. The joint effect of protein restriction and methyl donor excess strongly impaired postnatal growth in both gender and long term weight gain in male offspring only, without affecting food intake. In addition, rats born from protein restricted and methyl donor supplemented dams gained less weight when fed a hypercaloric diet. Methylation of the leptin gene promoter in adipose tissue was increased in methyl donor supplemented groups but not affected by protein restriction only. These results suggest that maternal methyl donor supplementation may influence energy homeostasis in a gender-dependent manner, without affecting food intake. Moreover, we showed that macronutrients and micronutrients in maternal diet interact to influence the programming of the offspring.

  17. Low energy availability in exercising men is associated with reduced leptin and insulin but not with changes in other metabolic hormones.

    Science.gov (United States)

    Koehler, Karsten; Hoerner, Neele R; Gibbs, Jenna C; Zinner, Christoph; Braun, Hans; De Souza, Mary Jane; Schaenzer, Wilhelm

    2016-10-01

    Low energy availability, defined as low caloric intake relative to exercise energy expenditure, has been linked to endocrine alterations frequently observed in chronically energy-deficient exercising women. Our goal was to determine the endocrine effects of low energy availability in exercising men. Six exercising men (VO2peak: 49.3 ± 2.4 ml · kg(-1) · min(-1)) underwent two conditions of low energy availability (15 kcal · kg(-1) fat-free mass [FFM] · day(-1)) and two energy-balanced conditions (40 kcal · kg(-1) FFM · day(-1)) in randomised order. During one low energy availability and one balanced condition, participants exercised to expend 15 kcal · kg(-1) FFM · day(-1); no exercise was conducted during the other two conditions. Metabolic hormones were assessed before and after each 4-day period. Following both low energy availability conditions, leptin (-53% to -56%) and insulin (-34% to -38%) were reduced (P exercise (P > 0.80). Low energy availability did not significantly impact ghrelin, triiodothyronine, testosterone and IGF-1 (all P > 0.05). The observed reductions in leptin and insulin were in the same magnitude as changes previously reported in sedentary women. Further research is needed to understand why other metabolic hormones are more robust against low energy availability in exercising men than those in sedentary and exercising women.

  18. Does the active use of nutrition labeling reduce the risk of diabetes mellitus? Results of insulin resistance using Korean National Health and Nutrition Examination Survey.

    Science.gov (United States)

    Han, Kyu-Tae; Kim, Seung Ju; Kim, Dong Jun; Kim, Sun Jung

    2018-05-29

    In 1995, nutrition labeling became mandatory in South Korea. These regulations help consumers make reasonable choices when purchasing food based on nutritional value by providing the nutritional properties of processed foods. We investigated the association between perceptions about nutrition labeling and insulin resistance (IR) in people with no diagnosis of diabetes mellitus (DM). This study used data from the sixth Korea National Health and Nutrition Examination Survey (KNHANES VI-3 in 2015, n=2931). We used multiple regression analysis to investigate the relationship between perceptions about nutrition labeling and the homeostatic model assessment for insulin resistance (HOMA-IR). 75.2% of participants were aware of nutrition labeling and 24.8% of participants checked nutrition labeling and actively used the information. "Actively checked and used the nutrition labeling" was inversely associated with HOMA-IR scores (check nutrition facts and make labeling-dependent purchase decisions: β=-0.108, p=0.0164). These associations were more significant in people who were obese or paid more attention to their health. High levels of perceptions about nutrition labeling and active use of such information could have positive effects on reducing IR and preventing DM. Therefore, it is necessary to improve public perception for effective implementation of healthcare programs. Copyright © 2018 Primary Care Diabetes Europe. Published by Elsevier Ltd. All rights reserved.

  19. Evidence-Based Exercise Recommendations to Reduce Hepatic Fat Content in Youth- a Systematic Review and Meta-Analysis.

    Science.gov (United States)

    Medrano, María; Cadenas-Sanchez, Cristina; Álvarez-Bueno, Celia; Cavero-Redondo, Iván; Ruiz, Jonatan R; Ortega, Francisco B; Labayen, Idoia

    2018-02-13

    The main purposes of this study were to elucidate the effects of supervised-exercise training (ET) interventions on hepatic fat content and on non-alcoholic fatty liver disease (NAFLD) prevalence in children and adolescents and to provide information about the optimal ET prescription (type, intensity, volume, and frequency) needed to reduce hepatic fat content in youths. Supervised-ET interventions performed in children and adolescents (6-19 years) that provided results of exercise effects on hepatic fat content or NAFLD prevalence were included. Supervised-exercise significantly reduced hepatic fat content compared to the control groups. Lifestyle interventions that included supervised-ET significantly reduced the prevalence of NAFLD. This systematic review and meta-analysis shows that supervised-ET could be an effective strategy in the management and prevention of NAFLD in children and adolescents. Both aerobic and resistance ET, at vigorous or moderate-to-vigorous intensities, with a volume ≥60 min/session and a frequency ≥3 sessions/week, aiming to improve cardiorespiratory fitness and muscular strength, had benefits on hepatic fat content reduction in youth. These data concur with the international recommendations of physical activity for health promotion in youth and may be useful when designing ET programs to improve and prevent hepatic steatosis in the pediatric population. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. [Aging reduces contents of endogenous CO, cAMP and cGMP in rat penile tissues].

    Science.gov (United States)

    Qin, Wen-Bo; Wang, Shu-Qiu; Li, Ming; Kang, Yu-Ming; Gui, Shi-Liang; Chi, Bao-Jin

    2009-02-01

    To explore the relationship of aging with the changes of endogenous carbon monoxide (CO), cGMP and cAMP contents in the penile tissues of rats. Twenty-four male rats were equally divided into an 8-month, a 16-month and a 24-month group, and their penile erection was detected by injecting apomorphine, their penile cavernous body harvested, and the contents of CO, cAPM and cGMP detected by improved dual wavelength spectrophotometry. The contents of CO, cAPM and cGMP were reduced with the increase of age, with statistically significant differences between the three age groups (P < 0.01). Aging significantly decreased the contents of CO, cAMP and cGMP in the penile tissues of the rats, which suggests that aging might play an important role in erectile dysfunction.

  1. Growth and production kinetics of human x mouse and mouse hybridoma cells at reduced temperature and serum content.

    Science.gov (United States)

    Borth, N; Heider, R; Assadian, A; Katinger, H

    1992-09-01

    The growth and production kinetics of a mouse hybridoma cell line and a human-mouse heterohybridoma were analyzed under conditions of reduced temperature and serum content. The mouse hybridoma P24 had a constant cell specific production rate and RNA content, while the heterohybridoma 3D6-LC4 showed growth associated production kinetics and an increased RNA content at higher growth rates. This behaviour of 3D6-LC4 cells can be explained by the unusual cell cycle kinetics of this line, which can be arrested in any phase under growth limiting conditions, so that a low growth rate does not result in a greater portion of high producing G1-phase cells. Substrate limitation changes the cell cycle distribution of this cell line to a greater extent than low temperature or serum content, which indicates that this stress factor exerts a greater physiological control than assumed.

  2. Characterization of silane reduced CVD tungsten films with respect to silicon content

    International Nuclear Information System (INIS)

    Suzuki, M.; Kobayashi, N.; Makai, K.

    1990-01-01

    Tungsten (W) films grown by LPCVD using WF 6 and SiH 4 are characterized with respect to Si content ([Si]) in the film. The Si content was influenced by the deposition temperature as well as the flow ratio of WF 6 /SiH 4 . The electrical resistance, film stress, and film composition of as-deposited films are categorized by [Si] into three groups: [Si] ≤ 2 atm%, 2 ≤ [Si] 40 atm%. When [Si] ≤ 2 atm%, the electrical resistance is almost proportional to [Si], and it is mainly determined by the impurity scattering of Si. In this [Si] region, W can be selectively deposited on Si. On the other hand, when 2 ≤ [Si] 20-40 atm%, the electrical resistance is only slightly affected by Si content, and its temperature dependence is peculiar to semiconductors. When [Si] > 40 atm%, the microcrystals of WSi 2 begins to form in the film

  3. Improved Sugar Conversion and Ethanol Yield for Forage Sorghum (Sorghum bicolor L. Moench) Lines with Reduced Lignin Contents

    Science.gov (United States)

    Lignin is known to impede conversion of lignocellulose into ethanol. In this study, forage sorghum plants carrying brown midrib (bmr) mutations, which reduce lignin contents, were evaluated as bioenergy feedstocks. The near isogenic lines evaluated were: wild-type, bmr-6, bmr-12, and bmr-6 bmr-12...

  4. Insulin Secretagogues

    Science.gov (United States)

    ... than sulfonylureas. What are the side effects and disadvantages of insulin secretagogues? Both types of insulin-releasing ... help find the cause. Questions to ask your doctor What else can I do to keep my ...

  5. Insulin-like growth factor-I gene therapy reverses morphologic changes and reduces hyperprolactinemia in experimental rat prolactinomas

    Directory of Open Access Journals (Sweden)

    Bracamonte Maria I

    2008-01-01

    Full Text Available Abstract Background The implementation of gene therapy for the treatment of pituitary tumors emerges as a promising complement to surgery and may have distinct advantages over radiotherapy for this type of tumors. Up to now, suicide gene therapy has been the main experimental approach explored to treat experimental pituitary tumors. In the present study we assessed the effectiveness of insulin-like growth factor I (IGF-I gene therapy for the treatment of estrogen-induced prolactinomas in rats. Results Female Sprague Dawley rats were subcutaneously implanted with silastic capsules filled with 17-β estradiol (E2 in order to induce pituitary prolactinomas. Blood samples were taken at regular intervals in order to measure serum prolactin (PRL. As expected, serum PRL increased progressively and 23 days after implanting the E2 capsules (Experimental day 0, circulating PRL had undergone a 3–4 fold increase. On Experimental day 0 part of the E2-implanted animals received a bilateral intrapituitary injection of either an adenoviral vector expressing the gene for rat IGF-I (RAd-IGFI, or a vector (RAd-GFP expressing the gene for green fluorescent protein (GFP. Seven days post vector injection all animals were sacrificed and their pituitaries morphometrically analyzed to evaluate changes in the lactotroph population. RAd-IGFI but not RAd-GFP, induced a significant fall in serum PRL. Furthermore, RAd-IGFI but not RAd-GFP significantly reversed the increase in lactotroph size (CS and volume density (VD induced by E2 treatment. Conclusion We conclude that IGF-I gene therapy constitutes a potentially useful intervention for the treatment of prolactinomas and that bioactive peptide gene delivery may open novel therapeutic avenues for the treatment of pituitary tumors.

  6. Addiction Potential of Cigarettes With Reduced Nicotine Content in Populations With Psychiatric Disorders and Other Vulnerabilities to Tobacco Addiction.

    Science.gov (United States)

    Higgins, Stephen T; Heil, Sarah H; Sigmon, Stacey C; Tidey, Jennifer W; Gaalema, Diann E; Hughes, John R; Stitzer, Maxine L; Durand, Hanna; Bunn, Janice Y; Priest, Jeff S; Arger, Christopher A; Miller, Mollie E; Bergeria, Cecilia L; Davis, Danielle R; Streck, Joanna M; Reed, Derek D; Skelly, Joan M; Tursi, Lauren

    2017-10-01

    A national policy is under consideration to reduce the nicotine content of cigarettes to lower nicotine addiction potential in the United States. To examine how smokers with psychiatric disorders and other vulnerabilities to tobacco addiction respond to cigarettes with reduced nicotine content. A multisite, double-blind, within-participant assessment of acute response to research cigarettes with nicotine content ranging from levels below a hypothesized addiction threshold to those representative of commercial cigarettes (0.4, 2.3, 5.2, and 15.8 mg/g of tobacco) at 3 academic sites included 169 daily smokers from the following 3 vulnerable populations: individuals with affective disorders (n = 56) or opioid dependence (n = 60) and socioeconomically disadvantaged women (n = 53). Data were collected from March 23, 2015, through April 25, 2016. After a brief smoking abstinence, participants were exposed to the cigarettes with varying nicotine doses across fourteen 2- to 4-hour outpatient sessions. Addiction potential of the cigarettes was assessed using concurrent choice testing, the Cigarette Purchase Task (CPT), and validated measures of subjective effects, such as the Minnesota Nicotine Withdrawal Scale. Among the 169 daily smokers included in the analysis (120 women [71.0%] and 49 men [29.0%]; mean [SD] age, 35.6 [11.4] years), reducing the nicotine content of cigarettes decreased the relative reinforcing effects of smoking in all 3 populations. Across populations, the 0.4-mg/g dose was chosen significantly less than the 15.8-mg/g dose in concurrent choice testing (mean [SEM] 30% [0.04%] vs 70% [0.04%]; Cohen d = 0.40; P vulnerable to tobacco addiction. Smokers with psychiatric conditions and socioeconomic disadvantage are more addicted and less likely to quit and experience greater adverse health impacts. Policies to reduce these disparities are needed; reducing the nicotine content in cigarettes should be a policy focus.

  7. Using Content Acquisition Podcasts to Increase Student Knowledge and to Reduce Perceived Cognitive Load

    Science.gov (United States)

    Kennedy, Michael J.; Hirsch, Shanna Eisner; Dillon, Sarah E.; Rabideaux, Lindsey; Alves, Kathryn D.; Driver, Melissa K.

    2016-01-01

    The use of multimedia-driven instruction in college courses is an emerging practice designed to increase students' knowledge. However, limited research has validated the effectiveness of using multimedia to teach students about functional behavioral assessments (FBAs). To test the effectiveness of a multimedia tool called Content Acquisition…

  8. Short communication: Acute but transient increase in serum insulin reduces messenger RNA expression of hepatic enzymes associated with progesterone catabolism in dairy cows.

    Science.gov (United States)

    Vieira, F V R; Cooke, R F; Aboin, A C; Lima, P; Vasconcelos, J L M

    2013-02-01

    The objective of this experiment was to evaluate the effects of glucose infusion on serum concentrations of glucose, insulin, and progesterone (P4), as well as mRNA expression of hepatic CYP2C19 and CYP3A4 in nonlactating, ovariectomized cows in adequate nutritional status. Eight Gir × Holstein cows were maintained on a low-quality Brachiaria brizantha pasture with reduced forage availability, but they individually received, on average, 3 kg/cow daily (as fed) of a corn-based concentrate from d -28 to 0 of the experiment. All cows had an intravaginal P4-releasing device inserted on d -14, which remained in cows until the end of the experiment (d 1). On d 0, cows were randomly assigned to receive, in a crossover design containing 2 periods of 24h each (d 0 and 1), (1) an intravenous glucose infusion (GLUC; 0.5 g of glucose/kg of BW, over a 3-h period) or (2) an intravenous saline infusion (SAL; 0.9%, over a 3-h period). Cows were fasted for 12h before infusions, and they remained fasted during infusion and sample collections. Blood samples were collected at 0, 3, and 6h relative to the beginning of infusions. Liver biopsies were performed concurrently with blood collections at 0 and 3h. After the last blood collection of period 1, cows received concentrate and returned to pasture. Cows gained BW (16.5 ± 3.6 kg) and BCS (0.08 ± 0.06) from d -28 to 0. Cows receiving GLUC had greater serum glucose and insulin concentrations at 3h compared with SAL cohorts. No treatment effects were detected for serum P4 concentrations, although mRNA expression of CYP2C19 and CYP3A4 after the infusion period was reduced for cows in the GLUC treatment compared with their cohorts in the SAL treatment. In conclusion, hepatic CYP3A4 and CYP2C19 mRNA expression can be promptly modulated by glucose infusion followed by acute increases in circulating insulin, which provides novel insight into the physiological mechanisms associating nutrition and reproductive function in dairy cows

  9. High-molecular-weight adiponectin is selectively reduced in women with polycystic ovary syndrome independent of body mass index and severity of insulin resistance.

    LENUS (Irish Health Repository)

    O'Connor, A

    2010-03-01

    Context: High-molecular-weight (HMW) adiponectin contributes to insulin resistance (IR), which is closely associated with the pathophysiology of polycystic ovary syndrome (PCOS). Abnormalities in adipocyte function have been identified in PCOS and potentially contribute to lower adiponectin concentrations. Objective: Our objective was to determine which variables in plasma and adipose tissue influence HMW adiponectin in a well characterized cohort of women with PCOS. Design: This was a cross-sectional study. Settings and Participants: A teaching hospital. Women with PCOS (n = 98) and body mass index (BMI)-matched controls (n = 103) (including 68 age-, BMI-, and IR-matched pairs). Interventions: A standard 75-g oral glucose tolerance test was performed for each participant. Subcutaneous adipose tissue samples were taken by needle biopsy for a subset of PCOS women (n = 9) and controls (n = 8). Main Outcome Measures: Serum levels of HMW adiponectin and their relation to indices of insulin sensitivity, body composition, and circulating androgens as well as adipose tissue expression levels of ADIPOQ, TNFalpha, PPARgamma, and AR were assessed. Results: HMW adiponectin was significantly lower in women with PCOS compared with both BMI- and BMI- and IR-matched controls (P = 0.009 and P = 0.027, respectively). Although BMI and IR were the main predictors of HMW adiponectin, an interaction between waist to hip ratio and plasma testosterone contributed to its variance (P = 0.026). Adipose tissue gene expression analysis demonstrated that AR and TNFalpha (P = 0.008 and P = 0.035, respectively) but not ADIPOQ mRNA levels were increased in PCOS compared with controls. Conclusions: HMW adiponectin is selectively reduced in women with PCOS, independent of BMI and IR. Gene expression analysis suggests that posttranscriptional\\/translational modification contributes to reduced HMW adiponectin in PCOS.

  10. Polyamine and amino acid content, and activity of polyamine-synthesizing decarboxylases, in liver of streptozotocin-induced diabetic and insulin-treated diabetic rats

    OpenAIRE

    Brosnan, Margaret E.; Roebothan, Barbara V.; Hall, Douglas E.

    1980-01-01

    1. Concentrations of polyamines, amino acids, glycogen, nucleic acids and protein, and activities of ornithine decarboxylase and S-adenosylmethionine decarboxylase, were measured in livers from control, streptozotocin-diabetic and insulin-treated diabetic rats. 2. Total DNA per liver and protein per mg of DNA were unaffected by diabetes, whereas RNA per mg of DNA and glycogen per g of liver were decreased. Insulin treatment of diabetic rats induced both hypertrophy and hyperplasia, as indicat...

  11. Reducing 137Cs content of boletes by means available to the wide public

    International Nuclear Information System (INIS)

    Johnova, Kamila

    2014-01-01

    Radioactivity of dried mushrooms (boletes) can be reduced appreciably by leaching in hot water. Leaching of Boletus badius in water at 100 deg C for 20 minutes reduced 137 Cs to 29-54%. Addition of, e.g. salt or vinegar had no appreciable effect. The contribution of 40 K to internal irradiation was also estimated. (P.A.)

  12. Decreased insulin secretion in pregnant rats fed a low protein diet.

    Science.gov (United States)

    Gao, Haijun; Ho, Eric; Balakrishnan, Meena; Yechoor, Vijay; Yallampalli, Chandra

    2017-10-01

    Low protein (LP) diet during pregnancy leads to reduced plasma insulin levels in rodents, but the underlying mechanisms remain unclear. Glucose is the primary insulin secretagogue, and enhanced glucose-stimulated insulin secretion (GSIS) in beta cells contributes to compensation for insulin resistance and maintenance of glucose homeostasis during pregnancy. In this study, we hypothesized that plasma insulin levels in pregnant rats fed LP diet are reduced due to disrupted GSIS of pancreatic islets. We first confirmed reduced plasma insulin levels, then investigated in vivo insulin secretion by glucose tolerance test and ex vivo GSIS of pancreatic islets in the presence of glucose at different doses, and KCl, glibenclamide, and L-arginine. Main findings include (1) plasma insulin levels were unaltered on day 10, but significantly reduced on days 14-22 of pregnancy in rats fed LP diet compared to those of control (CT) rats; (2) insulin sensitivity was unchanged, but glucose intolerance was more severe in pregnant rats fed LP diet; (3) GSIS in pancreatic islets was lower in LP rats compared to CT rats in the presence of glucose, KCl, and glibenclamide, and the response to L-arginine was abolished in LP rats; and (4) the total insulin content in pancreatic islets and expression of Ins2 were reduced in LP rats, but expression of Gcg was unaltered. These studies demonstrate that decreased GSIS in beta cells of LP rats contributes to reduced plasma insulin levels, which may lead to placental and fetal growth restriction and programs hypertension and other metabolic diseases in offspring. © The Authors 2017. Published by Oxford University Press on behalf of Society for the Study of Reproduction. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  13. The ultraviolet sensitivity of Cockayne syndrome cells is not a consequence of reduced cellular NAD content

    International Nuclear Information System (INIS)

    Mayne, L.V.; Broughton, B.C.; Lehmann, A.R.

    1984-01-01

    Cells from individuals with Cockayne syndrome (CS) are hypersensitive to the lethal effects of ultraviolet light (uv) and show a number of abnormal biochemical responses following uv-irradiation. Fujiwara et al. recently reported that the NAD contents of CS fibroblasts were lower than those of normal fibroblasts, and that addition of NAD to the cellular growth medium rectified most of the abnormal responses of CS cells to uv-irradiation. In our experiments, however, the cellular NAD contents of normal and CS fibroblasts were similar, and addition of NAD to the growth medium had no effect on the hypersensitivity of CS cells to uv-irradiation, nor did it restore the inability of CS cells to recover normal rates of DNA or RNA synthesis following uv-irradiation

  14. The dietary inclusion of Portulaca oleracea to the diet of laying hens increases the n-3 fatty acids content and reduces the cholesterol content in the egg yolk

    Directory of Open Access Journals (Sweden)

    Igino Andrighetto

    2010-01-01

    Full Text Available The effect of n-3 polyunsaturated fatty acids (PUFA-enriched diet on yolk fatty acid profile and cholesterol content was evaluated. Dried Poutulaca oleracea (purslane: PO diet was added to a commercial diet (C diet at 20% of inclusion level. The effect of the supplemented diet was compared to that of C diet. Twenty-six laying hens were fed ad libitum for 21 days with the 2 diets, supplemented also with 300 mg α-tocopherol acetate/kg. Eggs were collected and then the fatty acids (FA profile and the cholesterol content were analysed. The PO diet significantly reduced the saturated FA content (P<0.05 and increased that of the polyunsaturated FA (PUFA: 18:2 n-6 (P<0.001, 18:3 n-3 (P<0.001 and 22:6 n-3 (DHA; P<0.01. Both n-6 and n-3 PUFA significantly increased with the PO diet and the n-6/n-3 ratio was improved (10.4 vs 11.3; P<0.05.

  15. The structural requirements of organophosphorus insecticides (OPI) for reducing chicken embryo NAD(+) content in OPI-induced teratogenesis in chickens.

    Science.gov (United States)

    Seifert, Josef

    2016-05-01

    The objective of this study was to determine the structural requirements of organophosphorus insecticides (OPI) for reducing chicken embryo nicotinamide adenine dinucleotide (NAD(+)) content in OPI-induced teratogenesis and compare them with those needed for OPI inhibition of yolk sac membrane kynurenine formamidase (KFase), the proposed primary target for OPI teratogens in chicken embryos. The comparative molecular field analysis (COMFA) of three-dimensional quantitative structure-activity relationship (3D QSAR) revealed the electrostatic and steric fields as good predictors of OPI structural requirements to reduce NAD(+) content in chicken embryos. The dominant electrostatic interactions were localized at nitrogen-1, nitrogen-3, nitrogen of 2-amino substituent of the pyrimidinyl of pyrimidinyl phosphorothioates, and at the oxygen of crotonamide carbonyl in crotonamide phosphates. Bulkiness of the substituents at carbon-6 of the pyrimidinyls and/or N-substituents of crotonamides was the steric structural component that contributed to superiority of those OPI for reducing embryonic NAD(+) levels. Both electrostatic and steric requirements are similar to those defined in our previous study for OPI inhibition of chicken embryo yolk sac membrane KFase. The findings of this study provide another piece of evidence for the cause-and-effect relationship between yolk sac membrane KFase inhibition and reduced embryo NAD(+) content in NAD-associated OPI-induced teratogenesis in chickens. Copyright © 2015 Elsevier Inc. All rights reserved.

  16. Impurity content of reduced-activation ferritic steels and a vanadium alloy

    International Nuclear Information System (INIS)

    Klueh, R.L.; Grossbeck, M.L.; Bloom, E.E.

    1997-01-01

    Inductively coupled plasma mass spectrometry was used to analyze a reduced-activation ferritic/martensitic steel and a vanadium alloy for low-level impurities that would compromise the reduced-activation characteristics of these materials. The ferritic steel was from the 5-ton IEA heat of modified F82H, and the vanadium alloy was from a 500-kg heat of V-4Cr-4Ti. To compare techniques for analysis of low concentrations of impurities, the vanadium alloy was also examined by glow discharge mass spectrometry. Two other reduced-activation steels and two commercial ferritic steels were also analyzed to determine the difference in the level of the detrimental impurities in the IEA heat and steels for which no extra effort was made to restrict some of the tramp impurities. Silver, cobalt, molybdenum, and niobium proved to be the tramp impurities of most importance. The levels observed in these two materials produced with present technology exceeded the limits for low activation for either shallow land burial or recycling. The chemical analyses provide a benchmark for the improvement in production technology required to achieve reduced activation; they also provide a set of concentrations for calculating decay characteristics for reduced-activation materials. The results indicate the progress that has been made and give an indication of what must still be done before the reduced-activation criteria can be achieved

  17. Solar Ultraviolet-B Radiation Increases Phenolic Content and Ferric Reducing Antioxidant Power in Avena sativa

    Directory of Open Access Journals (Sweden)

    Christopher T. Ruhland

    2007-06-01

    Full Text Available We examined the influence of solar ultraviolet-B radiation (UV-B; 280-320 nm on the maximum photochemical efficiency of photosystem II (Fv/Fm, bulk-soluble phenolic concentrations, ferric-reducing antioxidant power (FRAP and growth of Avena sativa. Treatments involved placing filters on frames over potted plants that reduced levels of biologically effective UV-B by either 71% (reduced UV-B or by 19% (near-ambient UV-B over the 52 day experiment (04 July - 25 August 2002. Plants growing under near-ambient UV-B had 38% less total biomass than those under reduced UV-B. The reduction in biomass was mainly the result of a 24% lower leaf elongation rate, resulting in shorter leaves and less total leaf area than plants under reduced UV-B. In addition, plants growing under near-ambient UV-B had up to 17% lower Fv/Fm values early in the experiment, and this effect declined with plant age. Concentrations of bulk-soluble phenolics and FRAP values were 17 and 24% higher under near-ambient UV-B than under reduced UV-B, respectively. There was a positive relationship between bulk-soluble phenolic concentrations and FRAP values. There were no UV-B effects on concentrations of carotenoids (carotenes + xanthophylls.

  18. Effect of fitness on glucose, insulin and cortisol responses to diets varying in starch and fat content in Thoroughbred horses with recurrent exertional rhabdomyolysis.

    Science.gov (United States)

    Finno, C J; McKenzie, E; Valberg, S J; Pagan, J

    2010-11-01

    Recurrent exertional rhabdomyolysis (RER) occurs in fit, nervous Thoroughbreds fed high nonstructural carbohydrate (NSC) diets. Clinical signs are diminished by feeding low NSC, high fat diets; however, the mechanism is unclear. To determine if the glucose, insulin and cortisol response to isocaloric diets varying in fat and NSC availability differ in fit vs. unfit Thoroughbreds with RER. Four fit (10 weeks treadmill training) RER Thoroughbred mares were exercised and fed 3 isocaloric (121 MJ/day) diets in a 5 day/diet block design. Two high NSC concentrates, sweet feed (SF) and a processed pelleted feed (PL) and a low starch high fat feed (FAT) were used. After 24 h of rest and a 12 h fast, horses ate half their daily concentrate. Blood sampled for [glucose], [insulin] and [cortisol] was obtained before, immediately after and at 30-60 min intervals for 420 min. After 3-6 months detraining period, the block design was repeated. Results for SF and PL were similar. Regardless of diet, cortisol was higher in fit vs. unfit horses. Fit horses on SF/PL had higher post prandial [insulin] and insulin:glucose ratio than unfit horses. FAT resulted in lower post prandial [glucose] and [insulin] vs. SF/PL. Higher [insulin] in fit vs. unfit horses was not seen on the FAT diet. Increased post prandial [glucose], [insulin] and [cortisol] induced by high NSC, but not high fat, feeds are enhanced by fitness in RER horses. This combination may trigger rhabdomyolysis through increased excitability in RER Thoroughbreds. © 2010 EVJ Ltd.

  19. Reduced expression of nuclear-encoded genes involved in mitochondrial oxidative metabolism in skeletal muscle of insulin-resistant women with polycystic ovary syndrome

    DEFF Research Database (Denmark)

    Skov, Vibe; Glintborg, Dorte; Knudsen, Steen

    2007-01-01

    Insulin resistance in skeletal muscle is a major risk factor for the development of type 2 diabetes in women with polycystic ovary syndrome (PCOS). In patients with type 2 diabetes, insulin resistance in skeletal muscle is associated with abnormalities in insulin signaling, fatty acid metabolism......, and mitochondrial oxidative phosphorylation (OXPHOS). In PCOS patients, the molecular mechanisms of insulin resistance are, however, less well characterized. To identify biological pathways of importance for the pathogenesis of insulin resistance in PCOS, we compared gene expression in skeletal muscle...... of metabolically characterized PCOS patients (n = 16) and healthy control subjects (n = 13) using two different approaches for global pathway analysis: gene set enrichment analysis (GSEA 1.0) and gene map annotator and pathway profiler (GenMAPP 2.0). We demonstrate that impaired insulin-stimulated total, oxidative...

  20. Hepatitis C virus eradication by direct antiviral agents improves glucose tolerance and reduces post-load insulin resistance in nondiabetic patients with genotype 1.

    Science.gov (United States)

    Salomone, Federico; Catania, Maurizio; Montineri, Arturo; Bertino, Gaetano; Godos, Justyna; Rizzo, Leonardo; Magrì, Giovanni; Li Volti, Giovanni

    2017-12-19

    Genotype 1 chronic hepatitis C is associated with an impairment of glucose homoeostasis, especially in the advanced stages of the disease. Glucose tolerance is an independent predictor of liver-related mortality in patients with cirrhosis because of chronic hepatitis C. However, no study has demonstrated so far weather hepatitis C virus clearance affects glucose tolerance. To this aim, we performed a prospective study assessing the effects of direct antiviral agents treatment in nondiabetic cirrhotic patients with genotypes 1a/1b and impaired glucose tolerance based on a 75-g oral glucose tolerance test. Impaired glucose tolerance was diagnosed by a 2-hour plasma glucose between 140 and 199 mg/dL. Insulin resistance was estimated by the oral glucose insulin sensitivity index, an oral glucose tolerance test-derived measure. After meeting the inclusion criteria, the study population included 32 outpatients (26/6 genotypes 1b/1a; age 62 ± 7.4 years; 18 males) with compensated Child-A cirrhosis. All patients achieved a sustained virological response following direct antiviral agents treatment. After viral eradication, we did not observe change in fasting plasma glucose (103.5 ± 7.1 vs 102.8 ± 7.2 mg/dL, P = .15) but 2-hour plasma glucose was reduced (165.2 ± 22.7 vs 138.5 ± 21.3 mg/dL, P Hepatitis C virus eradication led also to a significant reduction in HbA1c (6.1 ± 0.2% vs 5.7 ± 0.3%, P resistance as assessed by the oral glucose insulin sensitivity index (6.92 ± 1.56 vs 9.52 ± 1.39 mg/kg/min, P  .5). Our results indicate that hepatitis C virus eradication may early improve glucose tolerance in patients with hepatitis C virus-related cirrhosis. © 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  1. Insulin Resistance in Alzheimer's Disease

    Science.gov (United States)

    Dineley, Kelly T; Jahrling, Jordan B; Denner, Larry

    2014-01-01

    Insulin is a key hormone regulating metabolism. Insulin binding to cell surface insulin receptors engages many signaling intermediates operating in parallel and in series to control glucose, energy, and lipids while also regulating mitogenesis and development. Perturbations in the function of any of these intermediates, which occur in a variety of diseases, cause reduced sensitivity to insulin and insulin resistance with consequent metabolic dysfunction. Chronic inflammation ensues which exacerbates compromised metabolic homeostasis. Since insulin has a key role in learning and memory as well as directly regulating ERK, a kinase required for the type of learning and memory compromised in early Alzheimer's disease (AD), insulin resistance has been identified as a major risk factor for the onset of AD. Animal models of AD or insulin resistance or both demonstrate that AD pathology and impaired insulin signaling form a reciprocal relationship. Of note are human and animal model studies geared toward improving insulin resistance that have led to the identification of the nuclear receptor and transcription factor, peroxisome proliferator-activated receptor gamma (PPARγ) as an intervention tool for early AD. Strategic targeting of alternate nodes within the insulin signaling network has revealed disease-stage therapeutic windows in animal models that coalesce with previous and ongoing clinical trial approaches. Thus, exploiting the connection between insulin resistance and AD provides powerful opportunities to delineate therapeutic interventions that slow or block the pathogenesis of AD. PMID:25237037

  2. Cryptochrome and Phytochrome Cooperatively but Independently Reduce Active Gibberellin Content in Rice Seedlings under Light Irradiation

    OpenAIRE

    Hirose, Fumiaki; Inagaki, Noritoshi; Hanada, Atsushi; Yamaguchi, Shinjiro; Kamiya, Yuji; Miyao, Akio; Hirochika, Hirohiko; Takano, Makoto

    2012-01-01

    In contrast to a wealth of knowledge about the photoregulation of gibberellin metabolism in dicots, that in monocots remains largely unclear. In this study, we found that a blue light signal triggers reduction of active gibberellin content in rice seedlings with simultaneous repression of two gibberellin 20-oxidase genes (OsGA20ox2 and OsGA20ox4) and acute induction of four gibberellin 2-oxidase genes (OsGA2ox4–OsGA2ox7). For further examination of the regulation of these genes, we establishe...

  3. Chinese medicine Jinlida (JLD) ameliorates high-fat-diet induced insulin resistance in rats by reducing lipid accumulation in skeletal muscle

    OpenAIRE

    Zang, Sha-Sha; Song, An; Liu, Yi-Xuan; Wang, Chao; Song, Guang-Yao; Li, Xiao-Ling; Zhu, Ya-Jun; Yu, Xian; Li, Ling; Liu, Chen-Xi; Kang, Jun-Cong; Ren, Lu-Ping

    2015-01-01

    The present paper reports the effects of Jinlida (JLD), a traditional Chinese medicine which has been given as a treatment for high-fat-diet (HFD)-induced insulin resistance. A randomized controlled experiment was conducted to provide evidence in support of the affects of JLD on insulin resistance induced by HFD. The affect of JLD on blood glucose, lipid, insulin, adiponectin, alanine aminotransferase (ALT), aspartate aminotransferase (AST) and total bilirubin (TBIL) in serum and lipid conten...

  4. The T allele of rs7903146 TCF7L2 is associated with impaired insulinotropic action of incretin hormones, reduced 24 h profiles of plasma insulin and glucagon, and increased hepatic glucose production in young healthy men

    DEFF Research Database (Denmark)

    Pilgaard, K; Jensen, C; Schou, J

    2009-01-01

    h glucose, insulin and glucagon profiles; OGTT; mixed meal test; IVGTT; hyperglycaemic clamp with co-infusion of glucagon-like peptide (GLP)-1 or glucose-dependent insulinotropic polypeptide (GIP); and a euglycaemic-hyperinsulinaemic clamp combined with glucose tracer infusion to study hepatic...... and peripheral insulin action. RESULTS: Carriers of the T allele were characterised by reduced 24 h insulin concentrations (p ...-phase insulinotropic action of GLP-1 (p = 0.03) and GIP (p = 0.07) during a 7 mmol/l hyperglycaemic clamp. Secretion of GLP-1 and GIP during the mixed meal test was normal. Despite elevated hepatic glucose production, carriers of the T allele had significantly reduced 24 h glucagon concentrations (p

  5. Balanced high fat diet reduces cardiovascular risk in obese women although changes in adipose tissue, lipoproteins, and insulin resistance differ by race.

    Science.gov (United States)

    Niswender, Kevin D; Fazio, Sergio; Gower, Barbara A; Silver, Heidi J

    2018-05-01

    We previously reported that consuming a balanced high fat diet (BHFD) wherein total saturated fat was reduced and total unsaturated fat increased by proportionately balancing the type of fat (1/3 saturated, 1/3 monounsaturated, 1/3 polyunsaturated) led to significant improvements in inflammatory burden, blood pressure, and vascular function in obese premenopausal European American (EA) and African American (AA) women. Here we compared changes in adipose tissue, lipoproteins, insulin resistance, and cardiovascular risk between EA and AA women. Dietary intakes, plasma fatty acids, lipids, apolipoproteins, lipoproteins, HOMA-IR and ASCVD risk was measured in 144 women who consumed BHFD for 16 weeks. Generalized linear modeling was performed while controlling for change in body weight. EA women had greater reductions in visceral adipose tissue. Only EA women had significant reductions in fasting insulin levels (↓24.8%) and HOMA-IR (↓29%) scores. In EA women, the most significant improvements occurred in VLDL particle size (↑), apolipoprotein B levels (↑), serum TG (↓), number of plasma LDL particles (↓), and serum LDL-cholesterol (↓). In AA women, significant improvements occurred in HDL particle size (↑), number of large HDL particles (↑), and apolipoprotein AI levels (↑). Consequently, both groups had improved ASCVD risk scores (↓5.5%). Consuming the balanced high fat diet led to significant reduction in cardiovascular risk factors in both groups. However, the pattern of response to BHFD differed with EA women responding more in components of the apolipoprotein B pathway versus AA women responding more in components of the apolipoprotein AI pathway. Published by Elsevier Inc.

  6. GLUT4 expression in human muscle fibres is not correlated with intracellular triglyceride (TG) content. Is TG a maker or a marker of insulin resistance?

    DEFF Research Database (Denmark)

    Gaster, M; Ottosen, P D; Vach, W

    2003-01-01

    diabetic subjects, and young lean controls. TG density was significantly higher in slow compared to fast fibres in all studied subjects (pslow twitch fibres of obese diabetic subjects compared to obese (p...We have recently reported a progressive decline in the expression of glucose transporter isoform 4 (GLUT4) from control subjects through obese non-diabetics to obese type 2 diabetic subjects, indicating that the reduced GLUT4 in slow twitch fibres could be secondary to obesity. In this study we...... densities in slow and fast fibres did not correlate with the corresponding GLUT4 density in the same fibres in our study groups (p>0.05). Plasma TG and FFA did not correlate with GLUT4 expression in slow or fast fibres (p>0.05). In conclusion, TG content was increased in diabetic slow fibres with a reduced...

  7. The low-aluminium cast iron of reduced silicon content treated with cerium mischmetal

    Directory of Open Access Journals (Sweden)

    M. S. Soiński

    2008-07-01

    Full Text Available The work presents the effect of cerium mischmetal used in quantities of 0.1 and 0.2 wt-% and ferrosilicon used in quantities from 0.5% to 1.5% on the alloy matrix and the shape of graphite precipitates in the low-aluminium cast iron from seven heats, basing on the examination of its structure. The hypereutectic cast iron of the relatively high carbon content (4.0÷4.2% at the prior-to-treatment silicon and manganese content equal to ca. 0.6% and ca. 0.04%, respectively, has been examined.It has been found that the performed treatment leads to the change in the alloy matrix from the nearly almost pearlitic to the ferritic-pearlitic one accompanied by changes in the shape of graphite precipitates. Due to applying both of the mentioned substances in the above stated amounts the graphite precipitates in cast iron have taken the shape of nodular and vermicular ones, and no presence of flake graphite has been revealed. A quantitative analysis of the performed treatment i.e. determining the fractions of graphite precipitates of different shapes has been possible by means of a computer image analyser.

  8. Despite higher body fat content, Ecuadorian subjects with Laron syndrome have less insulin resistance and lower incidence of diabetes than their relatives.

    Science.gov (United States)

    Guevara-Aguirre, Jaime; Procel, Patricio; Guevara, Carolina; Guevara-Aguirre, Marco; Rosado, Verónica; Teran, Enrique

    2016-06-01

    In the present pandemics of obesity and insulin resistant diabetes mellitus (DM), the specific contribution of etiological factors such as shifts in nutritional and exercise patterns, genetic and hormonal, is subject of ongoing research. Among the hormonal factors implicated, we selected obesity-driven insulin resistance for further evaluation. It is known that growth hormone (GH) has profound effects on carbohydrate metabolism. In consequence, we compared the effects of the lack of the counter-regulatory effects of GH, in a group of subjects with GH receptor deficiency (GHRD) due to a mutated GH receptor vs. that of their normal relatives. It was found that, despite their obesity, subjects with GHRD, have diminished incidence of diabetes, lower glucose and insulin concentrations, and lower values of indexes indicative of insulin resistance such as HOMA-IR. The GHRD subjects were also capable of appropriately handling glucose or mixed meal loads despite diminished insulin secretion. These observations allow us to suggest that the association of obesity with increased risk for diabetes appears to be dependent on intact growth hormone signaling. Copyright © 2015 Elsevier Ltd. All rights reserved.

  9. Identifying the contents of a type 1 diabetes outpatient care program based on the self-adjustment of insulin using the Delphi method.

    Science.gov (United States)

    Kubota, Mutsuko; Shindo, Yukari; Kawaharada, Mariko

    2014-10-01

    The objective of this study is to identify the items necessary for an outpatient care program based on the self-adjustment of insulin for type 1 diabetes patients. Two surveys based on the Delphi method were conducted. The survey participants were 41 certified diabetes nurses in Japan. An outpatient care program based on the self-adjustment of insulin was developed based on pertinent published work and expert opinions. There were a total of 87 survey items in the questionnaire, which was developed based on the care program mentioned earlier, covering matters such as the establishment of prerequisites and a cooperative relationship, the basics of blood glucose pattern management, learning and practice sessions for the self-adjustment of insulin, the implementation of the self-adjustment of insulin, and feedback. The participants' approval on items in the questionnaires was defined at 70%. Participants agreed on all of the items in the first survey. Four new parameters were added to make a total of 91 items for the second survey and participants agreed on the inclusion of 84 of them. Items necessary for a type 1 diabetes outpatient care program based on self-adjustment of insulin were subsequently selected. It is believed that this care program received a fairly strong approval from certified diabetes nurses; however, it will be necessary to have the program further evaluated in conjunction with intervention studies in the future. © 2014 The Authors. Japan Journal of Nursing Science © 2014 Japan Academy of Nursing Science.

  10. Bed rest reduces metabolic protein content and abolishes exercise-induced mRNA responses in human skeletal muscle

    DEFF Research Database (Denmark)

    Jørgensen, Stine Ringholm; Biensø, Rasmus S; Kiilerich, Kristian

    2011-01-01

    Background: The aim was to test the hypothesis that one week of bed rest will reduce mitochondrial number and expression and activity of oxidative proteins in human skeletal muscle, but that exercise-induced intracellular signaling as well as mRNA and microRNA (miR) responses are maintained after......-legged knee extensor exercise performed before and after bed rest. Results: Maximal oxygen uptake decreased 5% and exercise endurance decreased non-significantly 25% by bed rest. Bed rest reduced skeletal muscle mitochondrial DNA/nuclear DNA content 15%, hexokinase II and sirtuin 1 protein content ~45%, 3...... bed rest. Research Design and Methods: Twelve young, healthy, male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies taken before and after bed rest. In addition, muscle biopsies were obtained from 6 of the subjects prior to, immediately after and 3h after 45 min one...

  11. A low-carbohydrate/high-fat diet reduces blood pressure in spontaneously hypertensive rats without deleterious changes in insulin resistance

    OpenAIRE

    Bosse, John D.; Lin, Han Yi; Sloan, Crystal; Zhang, Quan-Jiang; Abel, E. Dale; Pereira, Troy J.; Dolinsky, Vernon W.; Symons, J. David; Jalili, Thunder

    2013-01-01

    Previous studies reported that diets high in simple carbohydrates could increase blood pressure in rodents. We hypothesized that the converse, a low-carbohydrate/high-fat diet, might reduce blood pressure. Six-week-old spontaneously hypertensive rats (SHR; n = 54) and Wistar-Kyoto rats (WKY; n = 53, normotensive control) were fed either a control diet (C; 10% fat, 70% carbohydrate, 20% protein) or a low-carbohydrate/high-fat diet (HF; 20% carbohydrate, 60% fat, 20% protein). After 10 wk, SHR-...

  12. Nitrogen deposition alters nitrogen cycling and reduces soil carbon content in low-productivity semiarid Mediterranean ecosystems

    International Nuclear Information System (INIS)

    Ochoa-Hueso, Raúl; Maestre, Fernando T.; Ríos, Asunción de los; Valea, Sergio; Theobald, Mark R.; Vivanco, Marta G.; Manrique, Esteban; Bowker, Mathew A.

    2013-01-01

    Anthropogenic N deposition poses a threat to European Mediterranean ecosystems. We combined data from an extant N deposition gradient (4.3–7.3 kg N ha −1 yr −1 ) from semiarid areas of Spain and a field experiment in central Spain to evaluate N deposition effects on soil fertility, function and cyanobacteria community. Soil organic N did not increase along the extant gradient. Nitrogen fixation decreased along existing and experimental N deposition gradients, a result possibly related to compositional shifts in soil cyanobacteria community. Net ammonification and nitrification (which dominated N-mineralization) were reduced and increased, respectively, by N fertilization, suggesting alterations in the N cycle. Soil organic C content, C:N ratios and the activity of β-glucosidase decreased along the extant gradient in most locations. Our results suggest that semiarid soils in low-productivity sites are unable to store additional N inputs, and that are also unable to mitigate increasing C emissions when experiencing increased N deposition. -- Highlights: •Soil organic N does not increase along the extant N deposition gradient. •Reduced N fixation is related to compositional shifts in soil cyanobacteria community. •Nitrogen cycling is altered by simulated N deposition. •Soil organic C content decrease along the extant N deposition gradient. •Semiarid soils are unable to mitigate CO 2 emissions after increased N deposition. -- N deposition alters N cycling and reduces soil C content in semiarid Mediterranean ecosystems

  13. Rare Coumarins Induce Apoptosis, G1 Cell Block and Reduce RNA Content in HL60 Cells

    Directory of Open Access Journals (Sweden)

    Widelski Jarosław

    2017-02-01

    Full Text Available The rare coumarins stenocarpin, stenocarpin isobutyrate, oficinalin, oficinalin isobutyrate, 8-methoxypeucedanin and the known xanthotoxin, isoimperatorin, bergapten, peucedanin and 8–methoxyisoimperatorin were isolated from Peucedanum luxurians Tamamsch. (Apiaceae and identified by means of spectral data (1D and 2D NMR. Their immunomodulating activity was evaluated by flow cytometry and their influence on HL60 cells as well as on PHA-stimulated PBLs was tested. All tested coumarins induce apoptosis (maximal in the 48 h culture and decrease cell proliferation in a time- and dose-dependent manner, especially in HL60 cells. They also induce partial G1 block, but only in HL60 cells (at 100 µM concentrations. Dose-dependent reduction of RNA content was also found in G1 cells treated by the coumarins. All of the tested coumarins also possessed immunomodulatory activities. Bergapten and xanthotoxin were found to be the best candidates for further evaluation as anti-cancer drugs.

  14. Insulin resistance and chronic inflammation

    Directory of Open Access Journals (Sweden)

    Natalia Matulewicz

    2016-12-01

    Full Text Available Insulin resistance is a condition of reduced biological response to insulin. Growing evidence indicates the role of the chronic low-grade inflammatory response in the pathogenesis of insulin resistance. Adipose tissue in obesity is characterized by increased lipolysis with the excessive release of free fatty acids, and is also a source of proinflammatory cytokines. Both these factors may inhibit insulin action. Proinflammatory cytokines exert their effect by stimulating major inflammatory NFκB and JNK pathways within the cells. Inflammatory processes in other insulin responsive tissues may also play a role in inducing insulin resistance. This paper is an overview of the chronic low-grade inflammation in adipose tissue, skeletal muscle, liver and endothelial cells during the development of insulin resistance.

  15. Control of discharge conditions to reduce hydrogen content in low Z films produced with DC glow

    International Nuclear Information System (INIS)

    Natsir, M.; Sagara, A.; Tsuzuki, K.; Tsuchiya, B.; Hasegawa, Y.; Motojima, O.

    1995-09-01

    Boronization at near room temperature has been performed in plasma processing teststand (PPT) by using a 5 % diborane gases B 2 H 6 in He on electrically floating or unfloating Al samples under various conditions on DC glow discharge power or total gas pressure. The hydrogen concentration was analyzed by using elastic recoil detection method (ERD) and a new modified normalizing technique with Rutherford back scattering (RBS). Results showed that a high growth rate of film formation and floating surface were effective in reducing hydrogen concentration in B films. This result was in good agreement with earlier measurements of H with flash filament (FF) desorption method. In particular the H/B ratio was reduced by decreasing ions but increasing radicals for B film formation. (author)

  16. Exercise, pregnancy, and insulin sensitivity--what is new?

    DEFF Research Database (Denmark)

    Damm, Peter; Breitowicz, Bettina; Hegaard, Hanne

    2007-01-01

    Pregnancy is characterized by a marked physiological insulin resistance. Overweight and obesity or lack of physical activity can aggravate this reduced insulin sensitivity further. Increased insulin resistance has been associated with serious pregnancy complications, such as gestational diabetes...

  17. Lifelong exercise and locally produced insulin-like growth factor-1 (IGF-1) have a modest influence on reducing age-related muscle wasting in mice.

    Science.gov (United States)

    McMahon, C D; Chai, R; Radley-Crabb, H G; Watson, T; Matthews, K G; Sheard, P W; Soffe, Z; Grounds, M D; Shavlakadze, T

    2014-12-01

    The age-related loss of skeletal muscle mass and function is termed sarcopenia and has been attributed to a decline in concentrations of insulin-like growth factor-1 (IGF-1). We hypothesized that constitutively expressed IGF-1 within skeletal muscles with or without exercise would prevent sarcopenia. Male transgenic mice that overexpress IGF-1 Ea in skeletal muscles were compared with wild-type littermates. Four-month-old mice were assigned to be sedentary, or had access to free-running wheels, until 18 or 28 months of age. In wild-type mice, the mass of the quadriceps muscles was reduced at 28 months and exercise prevented such loss, without affecting the diameter of myofibers. Conversely, increased IGF-1 alone was ineffective, whereas the combination of exercise and IGF-1 was additive in maintaining the diameter of myofibers in the quadriceps muscles. For other muscles, the combination of IGF-1 and exercise was variable and either increased or decreased the mass at 18 months of age, but was ineffective thereafter. Despite an increase in the diameter of myofibers, grip strength was not improved. In conclusion, our data show that exercise and IGF-1 have a modest effect on reducing aged-related wasting of skeletal muscle, but that there is no improvement in muscle function when assessed by grip strength. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

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

    NARCIS (Netherlands)

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

    2001-01-01

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

  19. Mendelian randomization studies do not support a causal role for reduced circulating adiponectin levels in insulin resistance and type 2 diabetes

    NARCIS (Netherlands)

    H. Yaghootkar (Hanieh); C. Lamina (Claudia); R.A. Scott (Robert); Z. Dastani (Zari); M.-F. Hivert (Marie-France); L.L. Warren (Liling); A. Stancáková (Alena); S.G. Buxbaum (Sarah); L.-P. Lyytikäinen (Leo-Pekka); P. Henneman (Peter); Y. Wu (Ying); C.Y.Y. Cheung (Chloe); J.S. Pankow (James); A.U. Jackson (Anne); S. Gustafsson (Stefan); J.H. Zhao (Jing Hua); C. Ballantyne (Christie); W. Xie (Weijia); R.N. Bergman (Richard); M. Boehnke (Michael); F. El Bouazzaoui (Fatiha); F.S. Collins (Francis); S.H. Dunn (Sandra); J. Dupuis (Josée); N.G. Forouhi (Nita); C.J. Gillson (Christopher); A.T. Hattersley (Andrew); J. Hong (Jaeyoung); M. Kähönen (Mika); J. Kuusisto (Johanna); L. Kedenko (Lyudmyla); F. Kronenberg (Florian); A. Doria (Andrea); T.L. Assimes (Themistocles); E. Ferrannini (Ele); T. Hansen (Torben); K. Hao (Ke); H. Häring (Hans); J.W. Knowles (Joshua); C.M. Lindgren (Cecilia); J.J. Nolan (John); J. Paananen (Jussi); O. Pedersen (Oluf); T. Quertermous (Thomas); U. Smith (Ulf); T. Lehtimäki (Terho); C.-T. Liu (Ching-Ti); R.J.F. Loos (Ruth); M.I. McCarthy (Mark); A.D. Morris (Andrew); R.S. Vasan (Ramachandran Srini); T.D. Spector (Timothy); T.M. Teslovich (Tanya); J. Tuomilehto (Jaakko); J.A.P. Willems van Dijk (Ko); J. Viikari (Jorma); N. Zhu (Na); C. Langenberg (Claudia); E. Ingelsson (Erik); R.K. Semple (Robert); A. Sinaiko (Alan); C.N.A. Palmer (Colin); M. Walker (Mark); K.S.L. Lam (Karen); B. Paulweber (Bernhard); K.L. Mohlke (Karen); C.M. van Duijn (Cornelia); O. Raitakari (Olli); A. Bidulescu (Aurelian); N.J. Wareham (Nick); M. Laakso (Markku); D. Waterworth (Dawn); D.A. Lawlor (Debbie); J.B. Meigs (James); J.B. Richards (Brent); T.M. Frayling (Timothy)

    2013-01-01

    textabstractAdiponectin is strongly inversely associated with insulin resistance and type 2 diabetes, but its causal role remains controversial. We used a Mendelian randomization approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used

  20. Mendelian Randomisation Studies Do Not Support a Causal Role for Reduced Circulating Adiponectin Levels in Insulin Resistance and Type 2 Diabetes

    DEFF Research Database (Denmark)

    Yaghootkar, Hanieh; Lamina, Claudia; Scott, Robert A

    2013-01-01

    Adiponectin is strongly inversely associated with insulin resistance and type 2 diabetes but its causal role remains controversial. We used a Mendelian randomisation approach to test the hypothesis that adiponectin causally influences insulin resistance and type 2 diabetes. We used genetic varian...

  1. Lipid and insulin infusion-induced skeletal muscle insulin resistance is likely due to metabolic feedback and not changes in IRS-1, Akt, or AS160 phosphorylation.

    Science.gov (United States)

    Hoy, Andrew J; Brandon, Amanda E; Turner, Nigel; Watt, Matthew J; Bruce, Clinton R; Cooney, Gregory J; Kraegen, Edward W

    2009-07-01

    Type 2 diabetes is characterized by hyperlipidemia, hyperinsulinemia, and insulin resistance. The aim of this study was to investigate whether acute hyperlipidemia-induced insulin resistance in the presence of hyperinsulinemia was due to defective insulin signaling. Hyperinsulinemia (approximately 300 mU/l) with hyperlipidemia or glycerol (control) was produced in cannulated male Wistar rats for 0.5, 1 h, 3 h, or 5 h. The glucose infusion rate required to maintain euglycemia was significantly reduced by 3 h with lipid infusion and was further reduced after 5 h of infusion, with no difference in plasma insulin levels, indicating development of insulin resistance. Consistent with this finding, in vivo skeletal muscle glucose uptake (31%, P muscle diacylglyceride and ceramide content over the same time course. However, there was an increase in cumulative exposure to long-chain acyl-CoA (70%) with lipid infusion. Interestingly, although muscle pyruvate dehydrogenase kinase 4 protein content was decreased in hyperinsulinemic glycerol-infused rats, this decrease was blunted in muscle from hyperinsulinemic lipid-infused rats. Decreased pyruvate dehydrogenase complex activity was also observed in lipid- and insulin-infused animals (43%). Overall, these results suggest that acute reductions in muscle glucose metabolism in rats with hyperlipidemia and hyperinsulinemia are more likely a result of substrate competition than a significant early defect in insulin action or signaling.

  2. Reduced Cerebral Oxygen Content in the DG and SVZ In Situ Promotes Neurogenesis in the Adult Rat Brain In Vivo.

    Directory of Open Access Journals (Sweden)

    Kuan Zhang

    Full Text Available Neurogenesis in the adult brain occurs mainly within two neurogenic structures, the dentate gyrus (DG of the hippocampus and the sub-ventricular zone (SVZ of the forebrain. It has been reported that mild hypoxia promoted the proliferation of Neural Stem Cells (NSCsin vitro. Our previous study further demonstrated that an external hypoxic environment stimulated neurogenesis in the adult rat brain in vivo. However, it remains unknown how external hypoxic environments affect the oxygen content in the brain and result in neurogenesis. Here we use an optical fiber luminescent oxygen sensor to detect the oxygen content in the adult rat brain in situ under normoxia and hypoxia. We found that the distribution of oxygen in cerebral regions is spatiotemporally heterogeneous. The Po2 values in the ventricles (45∼50 Torr and DG (approximately 10 Torr were much higher than those of other parts of the brain, such as the cortex and thalamus (approximately 2 Torr. Interestingly, our in vivo studies showed that an external hypoxic environment could change the intrinsic oxygen content in brain tissues, notably reducing oxygen levels in both the DG and SVZ, the major sites of adult neurogenesis. Furthermore, the hypoxic environment also increased the expression of HIF-1α and VEGF, two factors that have been reported to regulate neurogenesis, within the DG and SVZ. Thus, we have demonstrated that reducing the oxygen content of the external environment decreased Po2 levels in the DG and SVZ. This reduced oxygen level in the DG and SVZ might be the main mechanism triggering neurogenesis in the adult brain. More importantly, we speculate that varying oxygen levels may be the physiological basis of the regionally restricted neurogenesis in the adult brain.

  3. Multidisciplinary care of obese children and adolescents for one year reduces ectopic fat content in liver and skeletal muscle.

    Science.gov (United States)

    Fonvig, Cilius Esmann; Chabanova, Elizaveta; Ohrt, Johanne Dam; Nielsen, Louise Aas; Pedersen, Oluf; Hansen, Torben; Thomsen, Henrik S; Holm, Jens-Christian

    2015-12-30

    Ectopic fat deposition in liver and skeletal muscle tissue is related to cardiovascular disease risk and is a common metabolic complication in obese children. We evaluated the hypotheses of ectopic fat in these organs could be diminished following 1 year of multidisciplinary care specialized in childhood obesity, and whether this reduction would associate with changes in other markers of metabolic function. This observational longitudinal study evaluated 40 overweight children and adolescents enrolled in a multidisciplinary treatment protocol at the Children's Obesity Clinic, Holbæk, Denmark. The participants were assessed by anthropometry, fasting blood samples (HbA1c, glucose, insulin, lipids, and biochemical variables of liver function), and liver and muscle fat content assessed by magnetic resonance spectroscopy at enrollment and following an average of 12.2 months of care. Univariate linear regression models adjusted for age, sex, treatment duration, baseline degree of obesity, and pubertal developmental stage were used for investigating possible associations. The standard deviation score (SDS) of baseline median body mass index (BMI) was 2.80 (range: 1.49-3.85) and the median age was 14 years (10-17). At the end of the observational period, the 40 children and adolescents (21 girls) significantly decreased their BMI SDS, liver fat, muscle fat, and visceral adipose tissue volume. The prevalence of hepatic steatosis changed from 28 to 20 % (p = 0.26) and the prevalence of muscular steatosis decreased from 75 to 45 % (p = 0.007). Changes in liver and muscle fat were independent of changes in BMI SDS, baseline degree of obesity, duration of treatment, age, sex, and pubertal developmental stage. A 1-year multidisciplinary intervention program in the setting of a childhood obesity outpatient clinic confers a biologically important reduction in liver and muscle fat; metabolic improvements that are independent of the magnitude of concurrent weight loss

  4. Adoptable Interventions, Human Health, and Food Safety Considerations for Reducing Sodium Content of Processed Food Products.

    Science.gov (United States)

    Allison, Abimbola; Fouladkhah, Aliyar

    2018-02-01

    Although vital for maintaining health when consumed in moderation, various epidemiological studies in recent years have shown a strong association between excess dietary sodium with an array of health complications. These associations are robust and clinically significant for development of hypertension and prehypertension, two of the leading causes of preventable mortality worldwide, in adults with a high-sodium diet. Data from developed nations and transition economies show worldwide sodium intake of higher than recommended amounts in various nations. While natural foods typically contain a moderate amount of sodium, manufactured food products are the main contributor to dietary sodium intake, up to 75% of sodium in diet of American adults, as an example. Lower cost in formulation, positive effects on organoleptic properties of food products, effects on food quality during shelf-life, and microbiological food safety, make sodium chloride a notable candidate and an indispensable part of formulation of various products. Although low-sodium formulation of each product possesses a unique set of challenges, review of literature shows an abundance of successful experiences for products of many categories. The current study discusses adoptable interventions for product development and reformulation of products to achieve a modest amount of final sodium content while maintaining taste, quality, shelf-stability, and microbiological food safety.

  5. Adoptable Interventions, Human Health, and Food Safety Considerations for Reducing Sodium Content of Processed Food Products

    Science.gov (United States)

    Allison, Abimbola; Fouladkhah, Aliyar

    2018-01-01

    Although vital for maintaining health when consumed in moderation, various epidemiological studies in recent years have shown a strong association between excess dietary sodium with an array of health complications. These associations are robust and clinically significant for development of hypertension and prehypertension, two of the leading causes of preventable mortality worldwide, in adults with a high-sodium diet. Data from developed nations and transition economies show worldwide sodium intake of higher than recommended amounts in various nations. While natural foods typically contain a moderate amount of sodium, manufactured food products are the main contributor to dietary sodium intake, up to 75% of sodium in diet of American adults, as an example. Lower cost in formulation, positive effects on organoleptic properties of food products, effects on food quality during shelf-life, and microbiological food safety, make sodium chloride a notable candidate and an indispensable part of formulation of various products. Although low-sodium formulation of each product possesses a unique set of challenges, review of literature shows an abundance of successful experiences for products of many categories. The current study discusses adoptable interventions for product development and reformulation of products to achieve a modest amount of final sodium content while maintaining taste, quality, shelf-stability, and microbiological food safety. PMID:29389843

  6. Tailoring the Oxygen Content of Graphite and Reduced Graphene Oxide for Specific Applications

    Science.gov (United States)

    Morimoto, Naoki; Kubo, Takuya; Nishina, Yuta

    2016-02-01

    Graphene oxide (GO) is widely recognized as a promising material in a variety of fields, but its structure and composition has yet to be fully controlled. We have developed general strategies to control the oxidation degree of graphene-like materials via two methods: oxidation of graphite by KMnO4 in H2SO4 (oGO), and reduction of highly oxidized GO by hydrazine (rGO). Even though the oxygen content may be the same, oGO and rGO have different properties, for example the adsorption ability, oxidation ability, and electron conductivity. These differences in property arise from the difference in the underlying graphitic structure and the type of defect present. Our results can be used as a guideline for the production of tailor-made graphitic carbons. As an example, we show that rGO with 23.1 wt% oxygen showed the best performance as an electrode of an electric double-layer capacitor.

  7. Tailoring the Oxygen Content of Graphite and Reduced Graphene Oxide for Specific Applications.

    Science.gov (United States)

    Morimoto, Naoki; Kubo, Takuya; Nishina, Yuta

    2016-02-25

    Graphene oxide (GO) is widely recognized as a promising material in a variety of fields, but its structure and composition has yet to be fully controlled. We have developed general strategies to control the oxidation degree of graphene-like materials via two methods: oxidation of graphite by KMnO4 in H2SO4 (oGO), and reduction of highly oxidized GO by hydrazine (rGO). Even though the oxygen content may be the same, oGO and rGO have different properties, for example the adsorption ability, oxidation ability, and electron conductivity. These differences in property arise from the difference in the underlying graphitic structure and the type of defect present. Our results can be used as a guideline for the production of tailor-made graphitic carbons. As an example, we show that rGO with 23.1 wt% oxygen showed the best performance as an electrode of an electric double-layer capacitor.

  8. Reducing beryllium content in mixed bed solid-type breeder blankets

    Energy Technology Data Exchange (ETDEWEB)

    Shimwell, J., E-mail: mail@jshimwell.com [Department of Physics and Astronomy, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH (United Kingdom); Lilley, S.; Morgan, L.; Packer, L.; Kovari, M.; Zheng, S. [Culham Centre for Fusion Energy, Culham Science Centre, Abingdon, Oxfordshire OX14 3DB (United Kingdom); McMillan, J. [Department of Physics and Astronomy, University of Sheffield, Hicks Building, Hounsfield Road, Sheffield S3 7RH (United Kingdom)

    2016-11-01

    Highlights: • The ratio of breeder ceramic to neutron multiplier of breeder blankets was varied linearly with depth. • Blankets with varying composition were found to perform better than uniform composition breeder blankets. • It was also possible to reduce the amount of beryllium required by the blanket. - Abstract: Beryllium (Be) is a precious resource with many high value uses, the low energy threshold (n,2n) reaction makes Be an excellent neutron multiplier for use in fusion breeder blankets. Estimates of Be requirements and available resources suggest that this could represent a major supply difficulty for solid-type blanket concepts. Reducing the quantity of Be required by breeder blankets would help to alleviate the problem to some extent. In addition, it is important that the reduction in the Be quantity does not diminish the blanket's performance in key aspects such as the tritium breeding ratio (TBR), energy multiplication and peak nuclear heating. Mixed pebble bed designs allow for the multiplier fraction to be varied throughout the blanket. This neutronics study used MCNP 6 to investigate linear variations of the multiplier fraction in relation to blanket depth, in order to better utilise the important multiplying Be(n,2n) and breeding reactions. Blankets with a uniform multiplier fraction showed little scope for reduction in Be mass. Blankets with varying multiplier fractions were able to simultaneously use 10% less Be, increase the energy amplification by 1%, reduce the peak heating by 7% and maintaining a sufficient TBR when compared to the performance achievable using a uniform composition.

  9. Preserved glucagon-like peptide-1 responses to oral glucose, but reduced incretin effect, insulin secretion and sensitivity in young Asians with type 2 diabetes mellitus

    DEFF Research Database (Denmark)

    Yeow, Toh Peng; Pacini, Giovanni; Tura, Andrea

    2017-01-01

    are scarce. We examined the insulin resistance, β-cell function (BC), glucagon-like peptide (GLP)-1 hormone and incretin effect in Asian YT2DM. RESEARCH DESIGN AND METHODS: This case-control study recruited 25 Asian YT2DM and 15 healthy controls, matched for gender, ethnicity and body mass index. Serum......OBJECTIVE: Youth onset type 2 diabetes mellitus (YT2DM) is a globally rising phenomenon with substantial Asians representation. The understanding of its pathophysiology is derived largely from studies in the obese African-American and Caucasian populations, while studies on incretin effect...... glucose, insulin, C peptide and GLP-1 were sampled during 2-hour oral glucose tolerance tests (OGTTs) and 1-hour intravenous glucose tolerance tests (IVGTTs). Insulin sensitivity was derived from the Quantitative Insulin Sensitivity Check Index (QUICKI), Oral Glucose Insulin Sensitivity Index (OGIS...

  10. Blood homocysteine and fasting insulin levels are reduced and erythrocyte sedimentation rates increased with a glycophospholipid-vitamin formulation: a retrospective study in older subjects

    Directory of Open Access Journals (Sweden)

    Rita R. Ellithorpe

    2015-04-01

    Full Text Available Background: Elevations in Homocyteine (Hcys levels in the blood have been correlated with increased risk for coronary heart disease and stroke, loss of cognition and memory, and other chronic medical conditions. Objective: A retrospective study was initiated to determine if Hcys levels and other blood markers were altered in subjects taking an oral functional food supplement containing a mixture of phosphoglycolipids (NT Factor® and vitamins. Methods: Thirty-five patients (28 females, 7 males, Av. Age=60.7±9.6 years who had used the functional food Advanced Physician’s FormulaTM with NTFactor® in tablet form each day were enrolled in a retrospective study on blood chemistry. This retrospective study followed a prospective study on the use of the same supplement to reduce fatigue in patients with chronic fatigue. Participants were patients with chronic fatigue syndrome (myalgic encephalomyelitis or other fatiguing illnesses. Subjects had blood drawn over a 6-month period, and routine blood testing was performed. In this laboratory study the results were analyzed for differences, and statistical analyses were performed. Results: All participants responded in the study and showed an average reduction of 31.8% in Hcys levels (from 10.85±0.42 to 7.40±0.42 µmol/L; t-test, p<0.001; Wilcoxon, p<0.001. Women responded better than men: women (from 11.06±0.50 to 8.67±0.82 µmol/L, 34.4% reduction, t-test, p< 0.001; Wilcoxon, p<0.001 versus men (from 10.80±0.51 to 7.01±0.47 µmol/L, 21.6% reduction, t-test, p< 0.0862. Differences were also found in fasting insulin levels (from 12.80±3.11 to 5.30±1.77 µIU/mL, 58.6% reduction, t-test, p<0.005 and erythrocyte sedimentation rate (ESR. ESR increased from 10.5±2.21 to 20.19±3.20 mm/hr (92.2% increase, t-test, p<0.0314; Wilcoxon, p<0.0154. Other tests were not significantly different after 6 months of supplement, there were no side effects from the test supplement, and none of the participants had

  11. Selective Insulin Resistance in Adipocytes*

    Science.gov (United States)

    Tan, Shi-Xiong; Fisher-Wellman, Kelsey H.; Fazakerley, Daniel J.; Ng, Yvonne; Pant, Himani; Li, Jia; Meoli, Christopher C.; Coster, Adelle C. F.; Stöckli, Jacqueline; James, David E.

    2015-01-01

    Aside from glucose metabolism, insulin regulates a variety of pathways in peripheral tissues. Under insulin-resistant conditions, it is well known that insulin-stimulated glucose uptake is impaired, and many studies attribute this to a defect in Akt signaling. Here we make use of several insulin resistance models, including insulin-resistant 3T3-L1 adipocytes and fat explants prepared from high fat-fed C57BL/6J and ob/ob mice, to comprehensively distinguish defective from unaffected aspects of insulin signaling and its downstream consequences in adipocytes. Defective regulation of glucose uptake was observed in all models of insulin resistance, whereas other major actions of insulin such as protein synthesis and anti-lipolysis were normal. This defect corresponded to a reduction in the maximum response to insulin. The pattern of change observed for phosphorylation in the Akt pathway was inconsistent with a simple defect at the level of Akt. The only Akt substrate that showed consistently reduced phosphorylation was the RabGAP AS160 that regulates GLUT4 translocation. We conclude that insulin resistance in adipose tissue is highly selective for glucose metabolism and likely involves a defect in one of the components regulating GLUT4 translocation to the cell surface in response to insulin. PMID:25720492

  12. Growth hormone (GH) treatment increases serum insulin-like growth factor binding protein-3, bone isoenzyme alkaline phosphatase and forearm bone mineral content in young adults with GH deficiency of childhood onset

    DEFF Research Database (Denmark)

    Juul, A; Pedersen, S A; Sørensen, S

    1994-01-01

    Recent studies have demonstrated that growth hormone (GH)-deficient adults have a markedly decreased bone mineral content compared to healthy adults. However, there are conflicting results regarding the effects of GH treatment on bone mineral content in GH-deficient adults. Therefore, we evaluated...... the effect of GH treatment on a marker of bone formation (bone alkaline phosphatase), hepatic excretory function and distal forearm bone mineral content in GH-deficient adults. Growth hormone was administered subcutaneously in 21 adults (13 males and 8 females) with GH deficiency of childhood onset for 4...... months in a double-blind, placebo-controlled GH trial, while 13 of the patients then received further GH for an additional 14 months. Serum insulin-like growth factor I (IGF-I) increased significantly from 100 to 279 micrograms/l and IGF binding protein-3 (IGFBP-3) from 1930 to 3355 micrograms/l after 4...

  13. Intramyocellular lipid content and insulin sensitivity are increased following a short-term low-glycemic index diet and exercise intervention

    DEFF Research Database (Denmark)

    Haus, Jacob M; Solomon, Thomas; Lu, Lan

    2011-01-01

    The relationship between intramyocellular (IMCL) and extramyocellular lipid (EMCL) accumulation and skeletal muscle insulin resistance is complex and dynamic. We examined the effect of a short-term (7-day) low-glycemic index (LGI) diet and aerobic exercise training intervention (EX) on IMCL and i...

  14. Baking reduces prostaglandin, resolvin, and hydroxy-fatty acid content of farm-raised Atlantic salmon (Salmo salar).

    Science.gov (United States)

    Raatz, Susan K; Golovko, Mikhail Y; Brose, Stephen A; Rosenberger, Thad A; Burr, Gary S; Wolters, William R; Picklo, Matthew J

    2011-10-26

    The consumption of seafood enriched in n-3 polyunsaturated fatty acids (PUFA) is associated with a decreased risk of cardiovascular disease. Several n-3 oxidation products from eicosapentaenoic acid (EPA; 20:5n-3) and docosahexaenoic acid (22:6n-3) have known protective effects in the vasculature. It is not known whether the consumption of cooked seafood enriched in n-3 PUFA causes appreciable consumption of lipid oxidation products. We tested the hypothesis that baking Atlantic salmon (Salmo salar) increases the level of n-3 and n-6 PUFA oxidation products over raw salmon. We measured the contents of several monohydroxy-fatty acids (MHFA), prostanoids, and resolvins. Our data demonstrate that baking did not change the overall total levels of MHFA. However, baking resulted in selective regioisomeric loss of hydroxy fatty acids from arachidonic acid (20:4n-6) and EPA, while significantly increasing hydroxyl-linoleic acid levels. The contents of prostanoids and resolvins were reduced several-fold with baking. The inclusion of a coating on the salmon prior to baking reduced the loss of some MHFA but had no effect on prostanoid losses incurred by baking. Baking did not decrease n-3 PUFA contents, indicating that baking of salmon is an acceptable means of preparation that does not alter the potential health benefits of high n-3 seafood consumption. The extent to which the levels of MHFA, prostanoids, and resolvins in the raw or baked fish have physiologic consequence for humans needs to be determined.

  15. Polyoxymethylene passive samplers to assess the effectiveness of biochar by reducing the content of freely dissolved fipronil and ethiprole.

    Science.gov (United States)

    Li, Shasha; Wang, Pingping; Liu, Xingang; Wu, Xiaohu; Dong, Fengshou; Xu, Jun; Zheng, Yongquan

    2018-07-15

    An equilibrium passive sampler based on polyoxymethylene (POM) was used to determine the freely dissolved concentrations (C free ) of fipronil and ethiprole. The sorption equilibrium times of fipronil and ethiprole in POM were 14.2d and 24.0d, respectively. The POM-water partitioning coefficients (logK POM-water ) were 2.6 for fipronil and 1.4 for ethiprole. The method was further used to evaluate the sorption behavior of biochars which produced by pyrolysis of Magnolia wood (Magnolia denudata) at 300°C, 500°C and 700°C. The amounts of target compounds adsorbed increased with increasing pyrolysis temperature of the biochars. Biochars characterized by a low polarity index had better sorption capacity for the target compounds. The additions of biochars to sediment were effective in reducing C free , and the enhancement was found to be more pronounced with high biochar content. C free in sediment with more organic matter was significantly higher after biochar addition. Increasing the sediment-biochar contact time from 7 to 30d resulted in an increase in sorption of the compounds. We conclude that Magnolia wood biochar effectively reduces the content of freely dissolved fipronil and ethiprole content in sediment. Copyright © 2018. Published by Elsevier B.V.

  16. Insulin receptor internalization defect in an insulin-resistant mouse melanoma cell line

    International Nuclear Information System (INIS)

    Androlewicz, M.J.; Straus, D.S.; Brandenburg, D.F.

    1989-01-01

    Previous studies from this laboratory demonstrated that the PG19 mouse melanoma cell line does not exhibit a biological response to insulin, whereas melanoma x mouse embryo fibroblast hybrids do respond to insulin. To investigate the molecular basis of the insulin resistance of the PG19 melanoma cells, insulin receptors from the insulin-resistant melanoma cells and insulin-sensitive fibroblast x melanoma hybrid cells were analyzed by the technique of photoaffinity labeling using the photoprobe 125 I-NAPA-DP-insulin. Photolabeled insulin receptors from the two cell types have identical molecular weights as determined by SDS gel electrophoresis under reducing and nonreducing conditions, indicating that the receptors on the two cell lines are structurally similar. Insulin receptor internalization studies revealed that the hybrid cells internalize receptors to a high degree at 37 degree C, whereas the melanoma cells internalize receptors to a very low degree or not at all. The correlation between ability to internalize insulin receptors and sensitivity to insulin action in this system suggests that uptake of the insulin-receptor complex may be required for insulin action in these cells. Insulin receptors from the two cell lines autophosphorylate in a similar insulin-dependent manner both in vitro and in intact cells, indicating that insulin receptors on the melanoma and hybrid cells have functional tyrosine protein kinase activity. Therefore, the block in insulin action in the PG19 melanoma cells appears to reside at a step beyond insulin-stimulated receptor autophosphorylation

  17. AMPK and insulin action

    DEFF Research Database (Denmark)

    Frøsig, Christian; Jensen, Thomas Elbenhardt; Jeppesen, Jacob

    2013-01-01

    The 5'-AMP-activated protein kinase (AMPK) is considered "a metabolic master-switch" in skeletal muscle reducing ATP- consuming processes whilst stimulating ATP regeneration. Within recent years, AMPK has also been proposed as a potential target to attenuate insulin resistance, although the exact...... role of AMPK is not well understood. Here we hypothesized that mice lacking a2AMPK activity in muscle would be more susceptible to develop insulin resistance associated with ageing alone or in combination with high fat diet. Young (~4 month) or old (~18 month) wild type and muscle specific a2AMPK...... kinase-dead mice on chow diet as well as old mice on 17 weeks of high fat diet were studied for whole body glucose homeostasis (OGTT, ITT and HOMA-IR), insulin signaling and insulin-stimulated glucose uptake in muscle. We demonstrate that high fat diet in old mice results in impaired glucose homeostasis...

  18. Arterial oxygen partial pressures reduce the insulin-dependent induction of the perivenously located glucokinase in rat hepatocyte cultures: mimicry of arterial oxygen pressures by H2O2.

    OpenAIRE

    Kietzmann, T; Roth, U; Freimann, S; Jungermann, K

    1997-01-01

    Liver glucokinase (GK) is localized predominantly in the perivenous zone. GK mRNA was induced by insulin maximally under venous O2 partial pressure (pO2) and only half-maximally under arterial pO2. CoCl2 and desferrioxamine mimicked venous pO2 and enhanced the insulin-dependent induction of GK mRNA under arterial pO2. H2O2 mimicked arterial pO2 and reduced insulin-induced GK mRNA under venous pO2 to the lower arterial levels. Thus the zonal O2 gradient in liver seems to have a key role in the...

  19. Community structure, cellular rRNA content, and activity of sulfate-reducing bacteria in marine Arctic sediments

    DEFF Research Database (Denmark)

    Ravenschlag, K.; Sahm, K.; Knoblauch, C.

    2000-01-01

    The community structure of sulfate-reducing bacteria (SRB) of a marine Arctic sediment (Smeerenburg-fjorden, Svalbard) a-as characterized by both fluorescence in situ hybridization (FISH) and rRNA slot blot hybridization by using group- and genus-specific 16S rRNA-targeted oligonucleotide probes...... that FISH and rRNA slot blot hybridization gave comparable results. Furthermore, a combination of the two methods allowed us to calculate specific cellular rRNA contents with respect to localization in the sediment profile. The rRNA contents of Desulfosarcina-Desulfococcus cells were highest in the first 5...... mm of the sediment (0.9 and 1.4 fg, respectively) and decreased steeply with depth, indicating that maximal metabolic activity occurred close to the surface, Based on SRB cell numbers, cellular sulfate reduction rates were calculated. The rates were highest in the surface layer (0.14 fmol cell(-1...

  20. BDA-410 Treatment Reduces Body Weight and Fat Content by Enhancing Lipolysis in Sedentary Senescent Mice.

    Science.gov (United States)

    Pereyra, Andrea S; Wang, Zhong-Min; Messi, Maria Laura; Zhang, Tan; Wu, Hanzhi; Register, Thomas C; Forbes, Elizabeth; Devarie-Baez, Nelmi O; Files, Daniel Clark; Abba, Martin C; Furdui, Cristina; Delbono, Osvaldo

    2017-08-01

    Loss of muscle mass and force with age leads to fall risk, mobility impairment, and reduced quality of life. This article shows that BDA-410, a calpain inhibitor, induced loss of body weight and fat but not lean mass or skeletal muscle proteins in a cohort of sedentary 23-month-old mice. Food and water intake and locomotor activity were not modified, whereas BDA-410 treatment decreased intramyocellular lipid and perigonadal fat, increased serum nonesterified fatty acids, and upregulated the genes mediating lipolysis and oxidation, lean phenotype, muscle contraction, muscle transcription regulation, and oxidative stress response. This finding is consistent with our recent report that lipid accumulation in skeletal myofibers is significantly correlated with slower fiber-contraction kinetics and diminished power in obese older adult mice. A proteomic analysis and immunoblot showed downregulation of the phosphatase PPP1R12B, which increases phosphorylated myosin half-life and modulates the calcium sensitivity of the contractile apparatus. This study demonstrates that BDA-410 exerts a beneficial effect on skeletal muscle contractility through new, alternative mechanisms, including enhanced lipolysis, upregulation of "lean phenotype-related genes," downregulation of the PP1R12B phosphatase, and enhanced excitation-contraction coupling. This single compound holds promise for treating age-dependent decline in muscle composition and strength. © The Author 2016. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  1. Booster Vaccination: The Role of Reduced Antigen Content Vaccines as a Preschool Booster

    Directory of Open Access Journals (Sweden)

    Giovanni Gabutti

    2014-01-01

    Full Text Available The need for boosters for tetanus, diphtheria, pertussis, and polio, starting from preschool age, is related to the waning immune protection conferred by vaccination, the elimination/reduction of natural boosters due to large-scale immunization programs, and the possibility of reintroduction of wild agents from endemic areas. Taking into account the relevance of safety/tolerability in the compliance with vaccination among the population, it have been assessed whether today enough scientific evidences are available to support the use of dTap-IPV booster in preschool age. The review of the literature was conducted using the PubMed search engine. A total of 41 works has been selected; besides, the documentation produced by the World Health Organization, the European Centre for Disease Control, and the Italian Ministry of Health has been consulted. Many recent papers confirm the opportunity to use a low antigenic dose vaccine starting from 4 to 6 years of age. There is also evidence that 10 years after immunization the rate of seroprotected subjects against diphtheria does not differ significantly between those vaccinated with paediatric dose (DTaP or reduced dose (dTaP or dTap product. The dTpa vaccine is highly immunogenic for diphtheria toxoids regardless of prior vaccination history (2 + 1 and 3 + 1 schedules.

  2. HNF1A variant, energy-reduced diets and insulin resistance improvement during weight loss: The POUNDS Lost trial and DIRECT.

    Science.gov (United States)

    Huang, Tao; Wang, Tiange; Heianza, Yoriko; Sun, Dianjianyi; Ivey, Kerry; Durst, Ronen; Schwarzfuchs, Dan; Stampfer, Meir J; Bray, George A; Sacks, Frank M; Shai, Iris; Qi, Lu

    2018-06-01

    To determine whether weight-loss diets varying in macronutrients modulate the genetic effect of hepatocyte nuclear factor 1α (HNF1A) rs7957197 on weight loss and improvement of insulin resistance. We analysed the interaction between HNF1A rs7957197 and weight-loss diets with regard to weight loss and insulin resistance improvement among 722 overweight/obese adults from a 2-year randomized weight-loss trial, the POUNDS Lost trial. The findings were replicated in another independent 2-year weight-loss trial, the Dietary Intervention Randomized Controlled Trial (DIRECT), in 280 overweight/obese adults. In the POUNDS Lost trial, we found that a high-fat diet significantly modified the genetic effect of HNF1A on weight loss and reduction in waist circumference (P for interaction = .006 and .005, respectively). Borderline significant interactions for fasting insulin and insulin resistance (P for interaction = .07 and .06, respectively) were observed. We replicated the results in DIRECT. Pooled results showed similar significant interactions with weight loss, waist circumference reduction, and improvement in fasting insulin and insulin resistance (P values for interaction = .001, .005, .02 and .03, respectively). Greater decreases in weight, waist circumference, fasting insulin level and insulin resistance were observed in participants with the T allele compared to those without the T allele in the high-fat diet group (P = .04, .03 and .01, respectively). Our replicable findings provide strong evidence that individuals with the HNF1A rs7957197 T allele might obtain more benefits in weight loss and improvement of insulin resistance by choosing a hypocaloric and high-fat diet. © 2018 John Wiley & Sons Ltd.

  3. Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice.

    Directory of Open Access Journals (Sweden)

    Sindhu K Madathil

    Full Text Available Traumatic brain injury (TBI survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1, a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal overexpression of IGF-1 using the controlled cortical impact (CCI injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI.

  4. Astrocyte-Specific Overexpression of Insulin-Like Growth Factor-1 Protects Hippocampal Neurons and Reduces Behavioral Deficits following Traumatic Brain Injury in Mice

    Science.gov (United States)

    Madathil, Sindhu K.; Carlson, Shaun W.; Brelsfoard, Jennifer M.; Ye, Ping; D’Ercole, A. Joseph; Saatman, Kathryn E.

    2013-01-01

    Traumatic brain injury (TBI) survivors often suffer from long-lasting cognitive impairment that stems from hippocampal injury. Systemic administration of insulin-like growth factor-1 (IGF-1), a polypeptide growth factor known to play vital roles in neuronal survival, has been shown to attenuate posttraumatic cognitive and motor dysfunction. However, its neuroprotective effects in TBI have not been examined. To this end, moderate or severe contusion brain injury was induced in mice with conditional (postnatal) overexpression of IGF-1 using the controlled cortical impact (CCI) injury model. CCI brain injury produces robust reactive astrocytosis in regions of neuronal damage such as the hippocampus. We exploited this regional astrocytosis by linking expression of hIGF-1 to the astrocyte-specific glial fibrillary acidic protein (GFAP) promoter, effectively targeting IGF-1 delivery to vulnerable neurons. Following brain injury, IGF-1Tg mice exhibited a progressive increase in hippocampal IGF-1 levels which was coupled with enhanced hippocampal reactive astrocytosis and significantly greater GFAP levels relative to WT mice. IGF-1 overexpression stimulated Akt phosphorylation and reduced acute (1 and 3d) hippocampal neurodegeneration, culminating in greater neuron survival at 10d after CCI injury. Hippocampal neuroprotection achieved by IGF-1 overexpression was accompanied by improved motor and cognitive function in brain-injured mice. These data provide strong support for the therapeutic efficacy of increased brain levels of IGF-1 in the setting of TBI. PMID:23826235

  5. Modern basal insulin analogs: An incomplete story

    OpenAIRE

    Singh, Awadhesh Kumar; Gangopadhyay, Kalyan Kumar

    2014-01-01

    The currently available basal insulin does not completely mimic the endogenous insulin secretion. This has continued to promote the search for ideal basal insulin. The newer basal insulin have primarily focused on increasing the duration of action, reducing variability, and reducing the incidence of hypoglycemia, particularly nocturnal. However, the changing criteria of hypoglycemia within a short span of a few years along with the surprising introduction of major cardiac events as another ou...

  6. Parametric investigation on the effect of nitrogen to reduce SF6 content in spark gap

    Science.gov (United States)

    Raj, Avinash; Khaidir, Nur; Ishak, Sanuri; Ghani, Basri Abdul; Chakrabarty, Chandan; Permal, Navitharshaani; Ahmad, Harizan

    2017-03-01

    Almost all the MV and HV switchgears used by power utilities for interrupting faults are Sulphur Hexaflouride SF6 gas circuit breakers as this gas has the best dielectric properties to quench the onset of an arc in the event of fault. However due to strong dissociating properties of this gas when in contact with air that can release fluorine into the atmosphere, the Kyoto protocol has mandated to reduce the usage of SF6 in the future. SF6 is a greenhouse gas and it's about 3000 more severe than CO2. And that's the reason for replacing this gas. A close match in the quenching properties to SF6 that is now being intensively researched is nitrogen N2. This gas is considered to be an inert gas, and its release into the atmosphere has no harmful effects (except for asphyxiation - which can be easily handled with awareness). As the need for a replacement of SF6 becomes critical in the near future, the urgency to find the right gas is immediate. Hence the proposed work in this paper is to make a comprehensive parametric investigation of N2 gas in vacuum spark-gap. The spark-gap is chosen due to flexibility in changing the gap distance and easily be housed in vacuum. The parameters to be investigated are pure N2 and N2/ SF6 mix. The settling-time of the electrical break-down voltage and current are measured using voltage probe and Pearson probe. This time is paramount as it determines the speed of breaking the circuit. A faster breaking time ensures the safety of other HV equipment in the circuit. A comparative study between the various parameters will be conducted to obtain the best recipe (gas mix and gap distance) that gives the shortest settling time the breakdown using N2/ SF6/Mixture gas was successfully conducted and a Paschen curve has been established.

  7. Curcumin reverses the depressive-like behavior and insulin resistance induced by chronic mild stress.

    Science.gov (United States)

    Shen, Ji-Duo; Wei, Yu; Li, Yu-Jie; Qiao, Jing-Yi; Li, Yu-Cheng

    2017-08-01

    Increasing evidence has demonstrated that patients with depression have a higher risk of developing type 2 diabetes. Insulin resistance has been identified as the key mechanism linking depression and diabetes. The present study established a rat model of depression complicated by insulin resistance using a 12-week exposure to chronic mild stress (CMS) and investigated the therapeutic effects of curcumin. Sucrose intake tests were used to evaluate depressive-like behaviors, and oral glucose tolerance tests (OGTT) and intraperitoneal insulin tolerance tests (IPITT) were performed to evaluate insulin sensitivity. Serum parameters were detected using commercial kits. Real-time quantitative PCR was used to examine mRNA expression. CMS rats exhibited reduced sucrose consumption, increased serum glucose, insulin, triglyceride (TG), low density lipoprotein-cholesterol (LDL-C), non-esterified fatty acid (NEFA), glucagon, leptin, and corticosterone levels, as well as impaired insulin sensitivity. Curcumin upregulated the phosphorylation of insulin receptor substrate (IRS)-1 and protein kinase B (Akt) in the liver, enhanced insulin sensitivity, and reversed the metabolic abnormalities and depressive-like behaviors mentioned above. Moreover, curcumin increased the hepatic glycogen content by inhibiting glycogen synthase kinase (GSK)-3β and prevented gluconeogenesis by inhibiting phosphoenolpyruvate carboxykinase (PEPCK) and glucose 6-phosphatase (G6Pase). These results suggest that curcumin not only exerted antidepressant-like effects, but also reversed the insulin resistance and metabolic abnormalities induced by CMS. These data may provide evidence to support the potential use of curcumin against depression and/or metabolic disorders.

  8. High internal phase agar hydrogel dispersions in cocoa butter and chocolate as a route towards reducing fat content.

    Science.gov (United States)

    Skelhon, Thomas S; Olsson, Patrik K A; Morgan, Adam R; Bon, Stefan A F

    2013-09-01

    Reducing the fat content of chocolate formulations is a major challenge for the confectionery industry. We report the suspension of aqueous microgel agar particles of up to 80% v/v within sunflower oil, cocoa butter, and ultimately chocolate. The optimised emulsification process involves a shear-cooling step. We demonstrate the versatility of our method when applied to white, milk, and dark chocolate formulations, whilst preserving the desired polymorph V of the cocoa butter matrix. In addition, we show that this technology can be used as a strategy to disperse alcoholic beverages into chocolate confectionery.

  9. SOCS-1 deficiency does not prevent diet-induced insulin resistance

    DEFF Research Database (Denmark)

    Emanuelli, Brice; Macotela, Yazmin; Boucher, Jérémie

    2008-01-01

    Obesity is associated with inflammation and increased expression of suppressor of cytokine signaling (SOCS) proteins, which inhibit cytokine and insulin signaling. Thus, reducing SOCS expression could prevent the development of obesity-induced insulin resistance. Using SOCS-1 knockout mice, we...... investigated the contribution of SOCS-1 in the development of insulin resistance induced by a high-fat diet (HFD). SOCS-1 knockout mice on HFD gained 70% more weight, displayed a 2.3-fold increase in epididymal fat pads mass and increased hepatic lipid content. This was accompanied by increased mRNA expression...... of leptin and the macrophage marker CD68 in white adipose tissue and of SREBP1c and FAS in liver. HFD also induced hyperglycemia in SOCS-1 deficient mice with impairment of glucose and insulin tolerance tests. Thus, despite the role of SOCS proteins in obesity-related insulin resistance, SOCS-1 deficiency...

  10. The potential of phototherapy to reduce body fat, insulin resistance and "metabolic inflexibility" related to obesity in women undergoing weight loss treatment.

    Science.gov (United States)

    Sene-Fiorese, Marcela; Duarte, Fernanda Oliveira; de Aquino Junior, Antonio Eduardo; Campos, Raquel Munhoz da Silveira; Masquio, Deborah Cristina Landi; Tock, Lian; de Oliveira Duarte, Ana Claudia Garcia; Dâmaso, Ana Raimunda; Parizotto, Nivaldo Antonio; Bagnato, Vanderlei Salvador

    2015-10-01

    The metabolic flexibility is often impaired in diseases associated with obesity, and many studies are based on the hypothesis that dysfunction in peripheral tissues such as skeletal muscle, liver and adipose tissue represent the etiology of development of metabolic inflexibility. Experimental evidence shows that the use of phototherapy combined with exercise was effective in controlling the lipid profile, reducing the mass of adipose tissue, suggesting increased metabolic activity and changes in lipid metabolism. However, we found few data in the literature involving the use of phototherapy in association to physical training in the obese population. Thus, our objective was to evaluate the effects of exercise training (aerobic plus resistance exercises) plus phototherapy (laser, 808 nm) on metabolic profile and adiponectinemia in obese women. Sixty-four obese women (BMI 30-40 kg/m2 , age between 20 and 40 years old) were randomly assigned in two groups: Exercise Training plus SHAM group (ET-SHAM, n = 32) and Exercise Training plus Phototherapy group (ET-PHOTO, n = 32). The treatment consisted in physical exercise intervention and the individual application of phototherapy immediately after the end of the training session. However, in the ET-SHAM group the device was turned off simulating the phototherapy application (placebo effect). The study protocol lasted for 20 weeks and comprised of three weekly sessions of aerobic plus resistance training and application of phototherapy (when applicable). The body composition and metabolic parameters were assessed (HOMA, adiponectin, insulin, glucose). Comparing the magnitude of effects between groups (ET-PHOTO vs. ET-SHAM), we observed that physical training plus phototherapy was more effective than physical training in reducing the delta of percentage of fat mass (%; -5.60 ± 1.59 vs. -4.33 ± 1.5; P obese women undergoing weight loss treatment promoting significant changes in inflexibility metabolic

  11. Aging and oxidative stress reduce the response of human articular chondrocytes to insulin-like growth factor 1 and osteogenic protein 1.

    Science.gov (United States)

    Loeser, Richard F; Gandhi, Uma; Long, David L; Yin, Weihong; Chubinskaya, Susan

    2014-08-01

    To determine the effects of aging and oxidative stress on the response of human articular chondrocytes to insulin-like growth factor 1 (IGF-1) and osteogenic protein 1 (OP-1). Chondrocytes isolated from normal articular cartilage obtained from tissue donors were cultured in alginate beads or monolayer. Cells were stimulated with 50-100 ng/ml of IGF-1, OP-1, or both. Oxidative stress was induced using tert-butyl hydroperoxide. Sulfate incorporation was used to measure proteoglycan synthesis, and immunoblotting of cell lysates was performed to analyze cell signaling. Confocal microscopy was performed to measure nuclear translocation of Smad4. Chondrocytes isolated from the articular cartilage of tissue donors ranging in age from 24 years to 81 years demonstrated an age-related decline in proteoglycan synthesis stimulated by IGF-1 and IGF-1 plus OP-1. Induction of oxidative stress inhibited both IGF-1- and OP-1-stimulated proteoglycan synthesis. Signaling studies showed that oxidative stress inhibited IGF-1-stimulated Akt phosphorylation while increasing phosphorylation of ERK, and that these effects were greater in cells from older donors. Oxidative stress also increased p38 phosphorylation, which resulted in phosphorylation of Smad1 at the Ser(206) inhibitory site and reduced nuclear accumulation of Smad1. Oxidative stress also modestly reduced OP-1-stimulated nuclear translocation of Smad4. These results demonstrate an age-related reduction in the response of human chondrocytes to IGF-1 and OP-1, which are 2 important anabolic factors in cartilage, and suggest that oxidative stress may be a contributing factor by altering IGF-1 and OP-1 signaling. Copyright © 2014 by the American College of Rheumatology.

  12. Zero added oxygen for high quality sputtered ITO: A data science investigation of reduced Sn-content and added Zr

    International Nuclear Information System (INIS)

    Peshek, Timothy J.; Burst, James M.; Coutts, Timothy J.; Gessert, Timothy A.

    2016-01-01

    The authors demonstrate mobilities of >45 cm 2 /V s for sputtered tin-doped indium oxide (ITO) films at zero added oxygen. All films were deposited with 5 wt. % SnO 2 , instead of the more conventional 8–10 wt. %, and had varying ZrO 2 content from 0 to 3 wt. %, with a subsequent reduction in In 2 O 3 content. These films were deposited by radio-frequency magnetron sputtering from nominally stoichiometric targets with varying oxygen partial pressure in the sputter ambient. Anomalous behavior was discovered for films with no Zr-added, where a bimodality of high and low mobilities was discovered for nominally similar growth conditions. However, all films showed the lowest resistivity and highest mobilities when the oxygen partial pressure in the sputter ambient was zero. This result is contrasted with several other reports of ITO transport performance having a maximum for small but nonzero oxygen partial pressure. This result is attributed to the reduced concentration of SnO 2 . The addition of ZrO 2 yielded the highest mobilities at >55 cm 2 /V s and the films showed a modest increase in optical transmission with increasing Zr-content

  13. Examination of food industry progress in reducing the sodium content of packaged foods in Canada: 2010 to 2013.

    Science.gov (United States)

    Arcand, JoAnne; Jefferson, Katherine; Schermel, Alyssa; Shah, Ferdeela; Trang, Susan; Kutlesa, Daniela; Lou, Wendy; L'Abbe, Mary R

    2016-06-01

    In 2010, as part of a national sodium reduction strategy, Canada published sodium reduction benchmark targets for packaged foods; however, no evaluation of this policy has occurred. The objective was to evaluate changes in the sodium content of packaged foods, identify categories reduced in sodium, and determine the proportion meeting Health Canada's sodium reduction benchmarks. This was a cross-sectional analysis of Canadian packaged foods in 2010 and 2013 (n = 10 487 and n = 15 394, respectively). Sodium content was obtained from the Nutrition Facts table. Overall, 16.2% of food categories had significantly reduced sodium levels. The greatest shifts in the distribution of sodium within food categories occurred in imitation seafood (mean ± SD, mg/100 g; 602 ± 50 to 444 ± 81, 26.2%, p = 0.002), condiments (1309 ± 790 to 1048 ± 620, 19.9%, p = 0.005), breakfast cereals (375 ± 26 to 301 ± 242, 19.7%, p = 0.001), canned vegetables/legumes (269 ± 156 to 217 ± 180, 19.3%, p foods meeting at least 1 of the 3 phases of the sodium reduction benchmark targets slightly increased (51.4% to 58.2%) and the proportion exceeding maximum benchmark levels decreased (25.2% to 20.8%). These data provide a critical evaluation of changes in sodium levels in the Canadian food supply. Although progress in reducing sodium in packaged foods is evident, the food industry needs to continue efforts in reducing the sodium in the foods they produce.

  14. Formulation of yeast-leavened bread with reduced salt content by using a Lactobacillus plantarum fermentation product.

    Science.gov (United States)

    Valerio, Francesca; Conte, Amalia; Di Biase, Mariaelena; Lattanzio, Veronica M T; Lonigro, S Lisa; Padalino, Lucia; Pontonio, Erica; Lavermicocca, Paola

    2017-04-15

    A Lactobacillus plantarum fermentation product (Bio21B), obtained after strain growth (14h) in a wheat flour-based medium, was applied in the bread-making process as taste enhancer, in order to obtain a yeast-leavened bread with reduced salt content (20% and 50%) with respect to a reference bread (REF) not containing the fermentation product. Sensory analysis indicated that the Bio21B bread with salt reduced by 50% had a pleasant taste similar to the salt-containing bread (REF). l-Glutamate and total free amino acid content did not differ between REF and Bio21B breads, while the acids lactic, acetic, phenyllactic, 4-OH-phenyllactic and indole-3-lactic were present only in Bio21B breads. Moreover, the presence of several umami (uridine monophosphate, inosine monophosphate, adenosine, and guanosine) and kokumi (γ-l-glutamyl-l-valine) taste-related molecules was ascertained both in REF and in Bio21B breads. Therefore, a possible role of the acidic molecules in compensating the negative perception of salt reduction can be hypothesized. Copyright © 2016 Elsevier Ltd. All rights reserved.

  15. Effect of resistance exercise under conditions of reduced blood insulin on AMPKα Ser485/491 inhibitory phosphorylation and AMPK pathway activation.

    Science.gov (United States)

    Kido, Kohei; Yokokawa, Takumi; Ato, Satoru; Sato, Koji; Fujita, Satoshi

    2017-08-01

    Insulin stimulates skeletal muscle glucose uptake via activation of the protein kinase B/Akt (Akt) pathway. Recent studies suggest that insulin downregulates AMP-activated protein kinase (AMPK) activity via Ser485/491 phosphorylation of the AMPK α-subunit. Thus lower blood insulin concentrations may induce AMPK signal activation. Acute exercise is one method to stimulate AMPK activation; however, no study has examined the relationship between blood insulin levels and acute resistance exercise-induced AMPK pathway activation. Based on previous findings, we hypothesized that the acute resistance exercise-induced AMPK pathway activation would be augmented by disruptions in insulin secretion through a decrease in AMPKα Ser485/491 inhibitory phosphorylation. To test the hypothesis, 10-wk-old male Sprague-Dawley rats were administered the toxin streptozotocin (STZ; 55 mg/kg) to destroy the insulin secreting β-cells. Three days postinjection, the right gastrocnemius muscle from STZ and control rats was subjected to resistance exercise by percutaneous electrical stimulation. Animals were killed 0, 1, or 3 h later; activation of the Akt/AMPK and downstream pathways in the muscle tissue was analyzed by Western blotting and real-time PCR. Notably, STZ rats showed a significant decrease in basal Akt and AMPKα Ser485/491 phosphorylation, but substantial exercise-induced increases in both AMPKα Thr172 and acetyl-CoA carboxylase (ACC) Ser79 phosphorylation were observed. Although no significant impact on resistance exercise-induced Akt pathway activation or glucose uptake was found, resistance exercise-induced peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1 α (PGC-1α) gene expression was augmented by STZ treatment. Collectively, these data suggest that circulating insulin levels may regulate acute resistance exercise-induced AMPK pathway activation and AMPK-dependent gene expression relating to basal AMPKα Ser485/491 phosphorylation. Copyright © 2017

  16. Insulin-regulated aminopeptidase immunoreactivity is abundantly present in human hypothalamus and posterior pituitary gland, with reduced expression in paraventricular and suprachiasmatic neurons in chronic schizophrenia.

    Science.gov (United States)

    Bernstein, Hans-Gert; Müller, Susan; Dobrowolny, Hendrik; Wolke, Carmen; Lendeckel, Uwe; Bukowska, Alicja; Keilhoff, Gerburg; Becker, Axel; Trübner, Kurt; Steiner, Johann; Bogerts, Bernhard

    2017-08-01

    The vasopressin- and oxytocin-degrading enzyme insulin-regulated aminopeptidase (IRAP) is expressed in various organs including the brain. However, knowledge about its presence in human hypothalamus is fragmentary. Functionally, for a number of reasons (genetic linkage, hydrolysis of oxytocin and vasopressin, its role as angiotensin IV receptor in learning and memory and others) IRAP might play a role in schizophrenia. We studied the regional and cellular localization of IRAP in normal human brain with special emphasis on the hypothalamus and determined numerical densities of IRAP-expressing cells in the paraventricular, supraoptic and suprachiasmatic nuclei in schizophrenia patients and controls. By using immunohistochemistry and Western blot analysis, IRAP was immunolocalized in postmortem human brains. Cell countings were performed to estimate numbers and numerical densities of IRAP immunoreactive hypothalamic neurons in schizophrenia patients and control cases. Shape, size and regional distribution of IRAP-expressing cells, as well the lack of co-localization with the glia marker glutamine synthetase, show that IRAP is expressed in neurons. IRAP immunoreactive cells were observed in the hippocampal formation, cerebral cortex, thalamus, amygdala and, abundantly, hypothalamus. Double labeling experiments (IRAP and oxytocin/neurophysin 1, IRAP with vasopressin/neurophysin 2) revealed that IRAP is present in oxytocinergic and in vasopressinergic neurons. In schizophrenia patients, the numerical density of IRAP-expressing neurons in the paraventricular and the suprachiasmatic nuclei is significantly reduced, which might be associated with the reduction in neurophysin-containing neurons in these nuclei in schizophrenia. The pathophysiological role of lowered hypothalamic IRAP expression in schizophrenia remains to be established.

  17. Reduced risk for metabolic syndrome and insulin resistance associated with ovo-lacto-vegetarian behavior in female Buddhists: a case-control study.

    Science.gov (United States)

    Chiang, Jui-Kun; Lin, Ying-Lung; Chen, Chi-Ling; Ouyang, Chung-Mei; Wu, Ying-Tai; Chi, Yu-Chiao; Huang, Kuo-Chin; Yang, Wei-Shiung

    2013-01-01

    The association of vegetarian status with the risk of metabolic syndrome (MetS) is not clear. In Asia, Buddhists often have vegetarian behavior for religious rather than for health reasons. We hypothesize that the vegetarian in Buddhism is associated with better metabolic profiles, lower risk for the MetS and insulin resistance (IR). We enrolled 391 female vegetarians (~80% lacto-ovo-vegetarians) and 315 non-vegetarians from health-checkup clinics at a Buddhist hospital in Taiwan. The vegetarian status was associated with lower body mass index, smaller waist circumference, lower total cholesterol, lower low density lipoprotein-cholesterol (LDL-C), and lower HDL-C in multivariate linear regression analyses. Despite having lower HDL-C level, the vegetarians had significantly lower total cholesterol/HDL-C and LDL-C/HDL-C ratios. After adjusting the other covariates, the risks for the MetS were lower for ovo-lacto-vegetarians of 1-11 years and >11 years respectively by 54% (odds ratio [OR] =0.46, 95%C.I.:0.26-0.79) and 57% (OR=0.43, 95%C.I.:0.23-0.76) compared to non-vegetarians by the IDF criteria. Likewise, they were lower respectively by 45% (OR=0.55, 95%C.I.:0.32-0.92) and 42% (OR=0.58, 95%C.I.:0.33-0.997), for the MetS by the modified NCEP criteria. In the subgroup of non-diabetic subjects, the vegetarians also had lower risk for IR by HOMA compared to the non-vegetarians (OR=0.71, 95%C.I.:0.48-1.06). The vegetarian behavior, mainly lacto-ovo-vegetarian, related to Buddhism, although not meant for its health effects, is associated with reduced risk for the MetS and IR and may potentially provide metabolic and cardiovascular protective effects in women.

  18. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance

    DEFF Research Database (Denmark)

    Højlund, Kurt

    2014-01-01

    . These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes...... described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance....... Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin...

  19. Influence of Plum Rootstocks on the Content of Reducing Sugars in the Annual Shoots of Cultivar ‘Kubanskaya Kometa’

    Directory of Open Access Journals (Sweden)

    Dēķena Dzintra

    2014-12-01

    Full Text Available The lack of suitable plum rootstocks for Baltic conditions has become a problem during recent years due to changing climatic conditions. Rapid temperature fluctuations between freezing and thawing are occurring more frequently. The winter-hardiness of rootstocks is essential for overwintering of trees in such conditions. The content of accumulated reducing sugars is an important physiological factor influencing wintering ability of trees. The dynamics of reducing sugars was investigated during two winter seasons (2010/2011 and 2011/2012 in one-year-old ‘Kubanskaya Kometa’ (Prunus x rossica Erem. hybrid plum shoots from two orchards planted in 2001 at Pūre Horticultural Research Centre (Latvia and Polli Horticultural Research Centre (Estonia. Cultivar ‘Kubanskaya Kometa’ was grafted on eight clonal rootstocks: ‘St. Julien A’, ‘Brompton’ cuttings, ‘Ackermann’, ‘Pixy’, GF8/1, G5/22, GF655/2, ‘Hamyra’ and eight seedling rootstocks: ‘St. Julien INRA 2’, ‘St. Julien d’Orleans’, ‘St. Julien Noir’, ‘Brompton’ seedlings, ‘Wangenheims Zwetsche’, ‘St. Julien Wädenswill’, ‘Myrobаlan’ and Prunus cerasifera var. divaricata. Trees were planted at 5×3 m spacing in four replications per rootstock with three trees per plot. Shoot samples were harvested five times during the winter period. The concentration of reducing sugars (mg g-1 dry weight was determined with Bertran’s method. Significant differences in concentration of reducing sugar were found between samples coming from different locations and in two seasons. The maximum concentration of reducing sugar was found in December or January depending on growing location and meteorological conditions

  20. Blood pressure is reduced and insulin sensitivity increased in glucose-intolerant, hypertensive subjects after 15 days of consuming high-polyphenol dark chocolate.

    Science.gov (United States)

    Grassi, Davide; Desideri, Giovambattista; Necozione, Stefano; Lippi, Cristina; Casale, Raffaele; Properzi, Giuliana; Blumberg, Jeffrey B; Ferri, Claudio

    2008-09-01

    Flavanols from chocolate appear to increase nitric oxide bioavailability, protect vascular endothelium, and decrease cardiovascular disease (CVD) risk factors. We sought to test the effect of flavanol-rich dark chocolate (FRDC) on endothelial function, insulin sensitivity, beta-cell function, and blood pressure (BP) in hypertensive patients with impaired glucose tolerance (IGT). After a run-in phase, 19 hypertensives with IGT (11 males, 8 females; 44.8 +/- 8.0 y) were randomized to receive isocalorically either FRDC or flavanol-free white chocolate (FFWC) at 100 g/d for 15 d. After a wash-out period, patients were switched to the other treatment. Clinical and 24-h ambulatory BP was determined by sphygmometry and oscillometry, respectively, flow-mediated dilation (FMD), oral glucose tolerance test, serum cholesterol and C-reactive protein, and plasma homocysteine were evaluated after each treatment phase. FRDC but not FFWC ingestion decreased insulin resistance (homeostasis model assessment of insulin resistance; P < 0.0001) and increased insulin sensitivity (quantitative insulin sensitivity check index, insulin sensitivity index (ISI), ISI(0); P < 0.05) and beta-cell function (corrected insulin response CIR(120); P = 0.035). Systolic (S) and diastolic (D) BP decreased (P < 0.0001) after FRDC (SBP, -3.82 +/- 2.40 mm Hg; DBP, -3.92 +/- 1.98 mm Hg; 24-h SBP, -4.52 +/- 3.94 mm Hg; 24-h DBP, -4.17 +/- 3.29 mm Hg) but not after FFWC. Further, FRDC increased FMD (P < 0.0001) and decreased total cholesterol (-6.5%; P < 0.0001), and LDL cholesterol (-7.5%; P < 0.0001). Changes in insulin sensitivity (Delta ISI - Delta FMD: r = 0.510, P = 0.001; Delta QUICKI - Delta FMD: r = 0.502, P = 0.001) and beta-cell function (Delta CIR(120) - Delta FMD: r = 0.400, P = 0.012) were directly correlated with increases in FMD and inversely correlated with decreases in BP (Delta ISI - Delta 24-h SBP: r = -0.368, P = 0.022; Delta ISI - Delta 24-h DBP r = -0.384, P = 0.017). Thus, FRDC

  1. On the detection and monitoring of reduced water content in plants using spectral responses in the visible domain

    Science.gov (United States)

    Baranoski, Gladimir V. G.; Van Leeuwen, Spencer; Chen, Tenn F.

    2016-05-01

    The water status of cultivated plants can have a significant impact not only on food production, but also on the appropriate usage of increasingly scarce freshwater supplies. Accordingly, the cost-effective detection and monitoring of changes in their water content are longstanding remote sensing goals. Existing procedures employed to achieve these goals are largely based on the spectral responses of plant leaves in the infrared domain where the light absorption within the foliar tissues is dominated by water. Recently, it has been suggested that such procedures could be implemented using spectral responses, more specifically spectral subsurface reflectance to transmittance ratios, obtained in the visible domain. The basis for this proposition resides on the premise that a reduced water content (RWC) can result in histological changes whose effects on the foliar optical properties may not be limited to the infrared domain. However, the experiments leading to this proposition were performed on detached leaves, which were not influenced by the whole plant's adaptation mechanisms to water stress. In this work, we investigate whether the spectral responses of living plant leaves in the visible domain can lead to reliable RWC estimations. We employ measured biophysical data and predictive light transport simulations in order to extend qualitatively and quantitatively the scope of previous studies in this area. Our findings indicate that the living specimens' physiological responses to water stress should be taken into account in the design of new procedures for the cost-effective RWC estimation using visible subsurface reflectance to transmittance ratios.

  2. Chromium content in human skin after in vitro application of ordinary cement and ferrous-sulphate-reduced cement

    DEFF Research Database (Denmark)

    Fullerton, A; Gammelgaard, Bente; Avnstorp, C

    1993-01-01

    The amount of chromium found in human skin after in vitro application of cement suspensions on full-thickness human skin in diffusion cells was investigated. Cement suspensions made from ordinary Portland cement or Portland cement with the chromate reduced with added ferrous sulphate were used....... The cement suspensions were either applied on the skin surface under occlusion for 48 h or applied repeatedly every 24 h for 96 h. No statistically significant difference in chromium content of skin layers between skin exposed to ordinary Portland cement, skin exposed to cement with added ferrous sulphate...... and unexposed skin was observed, despite a more permeable skin barrier at the alkaline pH of the cement suspensions, i.e., pH 12.5. Increased chromium levels in epidermis and dermis were seen when ordinary Portland cement was applied as a suspension with added sodium sulphate (20%) on the skin surface for 96 h...

  3. Consumer attitude towards sodium reduction in meat products and acceptability of fermented sausages with reduced sodium content.

    Science.gov (United States)

    Guàrdia, M D; Guerrero, L; Gelabert, J; Gou, P; Arnau, J

    2006-07-01

    Lowering salt content in meat products is possible from a technological and sensorial point of view, although little information is available about the consumers' attitude and acceptance of these products. Attitude towards low salt meat products, following the Theory of Planned Behaviour (TPB) proposed by Ajzen, was evaluated by 392 consumers. Acceptability of small calibre fermented sausages with 50% molar substitution of NaCl by six different mixtures of KCl (0-50%) and K-lactate (0-50%) and the control (22g NaCl/kg) was determined by 98 consumers. The preference of the previous best two treatments was compared to the batch control by 279 consumers. In general consumers had a positive attitude towards low salt meat products, being higher for women than for men. Women showed stronger ideas and higher Perceived Control on the Behaviour towards reduced sodium meat products than men. Smokers showed lower intense beliefs than non-smokers. Consumers with a basic level of education were more affected by what other people important for them thought they should do. The final model obtained using the Theory of Planned Behaviour showed a good predictive capacity (R(2)=0.60) and a good internal consistency. Regarding the acceptability study, batches with substitution levels of 50% and 40% by K-lactate, showed lower overall acceptance than the control batch. Significant differences in acceptability were found regarding the gender and place of residence of the consumers. The preference study showed no differences between the batch control and batches with 50% KCl and 40% KCl + 10% of K-lactate substitution levels. According to these results and from a sensorial point of view, it is possible to reduce NaCl content in small calibre fermented sausages by 50% and obtain a product acceptable for consumers.

  4. Deficiency of insulin-like growth factor 1 reduces vulnerability to chronic alcohol intake-induced cardiomyocyte mechanical dysfunction: role of AMPK.

    Science.gov (United States)

    Ge, Wei; Li, Qun; Turdi, Subat; Wang, Xiao-Ming; Ren, Jun

    2011-08-01

    Circulating insulin-like growth factor I (IGF-1) levels are closely associated with cardiac performance although the role of IGF-1 in alcoholic cardiac dysfunction is unknown. This study was designed to evaluate the impact of severe liver IGF-1 deficiency (LID) on chronic alcohol-induced cardiomyocyte contractile and intracellular Ca(2+) dysfunction. Adult male C57 and LID mice were placed on a 4% alcohol diet for 15 weeks. Cardiomyocyte contractile and intracellular Ca(2+) properties were evaluated including peak shortening (PS), maximal velocity of shortening/relengthening (±dL/dt), time-to-relengthening (TR(90) ), change in fura-fluorescence intensity (ΔFFI) and intracellular Ca(2+) decay. Levels of apoptotic regulators caspase-3, Bcl-2 and c-Jun NH2-terminal kinase (JNK), the ethanol metabolizing enzyme mitochondrial aldehyde dehydrogenase (ALDH2), as well as the cellular fuel gauge AMP-activated protein kinase (AMPK) were evaluated. Chronic alcohol intake enlarged myocyte cross-sectional area, reduced PS, ± dL/dt and ΔFFI as well as prolonged TR(90) and intracellular Ca(2+) decay, the effect of which was greatly attenuated by IGF-1 deficiency. The beneficial effect of LID against alcoholic cardiac mechanical defect was ablated by IGF-1 replenishment. Alcohol intake increased caspase-3 activity/expression although it down-regulated Bcl-2, ALDH2 and pAMPK without affecting JNK and AMPK. IGF-1 deficiency attenuated alcoholism-induced responses in all these proteins with the exception of Bcl-2. In addition, the AMPK agonist 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside abrogated short-term ethanol incubation-elicited cardiac mechanical dysfunction. Taken together, these data suggested that IGF-1 deficiency may reduce the sensitivity to ethanol-induced myocardial mechanical dysfunction. Our data further depicted a likely role of Caspase-3, ALDH2 and AMPK activation in IGF-1 deficiency induced 'desensitization' of alcoholic cardiomyopathy. © 2011 The

  5. GLUT4 and glycogen synthase are key players in bed rest-induced insulin resistance

    DEFF Research Database (Denmark)

    Biensø, Rasmus Sjørup; Jørgensen, Stine Ringholm; Kiilerich, Kristian

    2012-01-01

    To elucidate the molecular mechanisms behind physical inactivity-induced insulin resistance in skeletal muscle, 12 young, healthy male subjects completed 7 days of bed rest with vastus lateralis muscle biopsies obtained before and after. In six of the subjects, muscle biopsies were taken from both...... than before bed rest. This bed rest-induced insulin resistance occurred together with reduced muscle GLUT4, hexokinase II, protein kinase B/Akt1, and Akt2 protein level, and a tendency for reduced 3-hydroxyacyl-CoA dehydrogenase activity. The ability of insulin to phosphorylate Akt and activate....... The present findings demonstrate that physical inactivity-induced insulin resistance in muscle is associated with lower content/activity of key proteins in glucose transport/phosphorylation and storage....

  6. Insulin Resistance and Mitochondrial Dysfunction.

    Science.gov (United States)

    Gonzalez-Franquesa, Alba; Patti, Mary-Elizabeth

    2017-01-01

    Insulin resistance precedes and predicts the onset of type 2 diabetes (T2D) in susceptible humans, underscoring its important role in the complex pathogenesis of this disease. Insulin resistance contributes to multiple tissue defects characteristic of T2D, including reduced insulin-stimulated glucose uptake in insulin-sensitive tissues, increased hepatic glucose production, increased lipolysis in adipose tissue, and altered insulin secretion. Studies of individuals with insulin resistance, both with established T2D and high-risk individuals, have consistently demonstrated a diverse array of defects in mitochondrial function (i.e., bioenergetics, biogenesis and dynamics). However, it remains uncertain whether mitochondrial dysfunction is primary (critical initiating defect) or secondary to the subtle derangements in glucose metabolism, insulin resistance, and defective insulin secretion present early in the course of disease development. In this chapter, we will present the evidence linking mitochondrial dysfunction and insulin resistance, and review the potential for mitochondrial targets as a therapeutic approach for T2D.

  7. Streptozotocin Aggravated Osteopathology and Insulin Induced Osteogenesis Through Co-treatment with Fluoride.

    Science.gov (United States)

    Yang, Chen; Zhang, Mengmeng; Li, Yagang; Wang, Yan; Mao, Weixian; Gao, Yuan; Xu, Hui

    2015-12-01

    The role of insulin in the mechanism underlying the excessive fluoride that causes skeletal lesion was studied. The in vitro bone marrow stem cells (BMSC) collected from Kunming mice were exposed to varying concentrations of fluoride with or without insulin. The cell viability and early differentiation of BMSC co-treated with fluoride and insulin were measured by using cell counting kit-8 and Gomori modified calcium-cobalt method, respectively. We further investigated the in vivo effects of varying dose of fluoride on rats co-treated with streptozotocin (STZ). Wistar rats were divided into six groups which included normal control, 10 mg fluoride/kg day group, 20 mg fluoride/kg day group, STZ control, STZ+10 mg fluoride/kg day group, and STZ+20 mg fluoride/kg day group. The rats were administered with sodium fluoride (NaF) by gavage with water at doses 10 and 20 mg fluoride/kg day for 2 months. In a period of one month, half of rats in every group were treated with streptozotocin (STZ) once through intraperitoneal injection at 52 mg/kg body weight. The serum glucose, HbA1c, and insulin were determined. Bone mineral content and insulin release were assessed. The results showed insulin combined with fluoride stimulated BMSC cell viability in vitro. The bone mineral content reduced in rats treated with higher dose of fluoride and decreased immensely in rat co-treated with fluoride and STZ. Similarly, a combination treatment of a high dose of fluoride and STZ decreased insulin sensitivity and activity. To sum up, these data indicated fluoride influenced insulin release, activity, and sensitivity. Furthermore, the insulin state in vivo interfered in the osteogenesis in turn and implied there was a close relation between insulin and bone pathogenesis in the mechanism of fluoride toxicity.

  8. Improved Brain Insulin/IGF Signaling and Reduced Neuroinflammation with T3D-959 in an Experimental Model of Sporadic Alzheimer's Disease.

    Science.gov (United States)

    de la Monte, Suzanne M; Tong, Ming; Schiano, Irio; Didsbury, John

    2017-01-01

    Alzheimer's disease (AD) is associated with progressive impairments in brain insulin, insulin-like growth factor (IGF), and insulin receptor substrate (IRS) signaling through Akt pathways that regulate neuronal growth, survival, metabolism, and plasticity. The intracerebral streptozotocin (i.c. STZ) model replicates the full range of abnormalities in sporadic AD. T3D-959, an orally active PPAR-delta/gamma agonist remediates neurocognitive deficits and AD neuropathology in the i.c. STZ model. This study characterizes the effects of T3D-959 on AD biomarkers, insulin/IGF/IRS signaling through Akt pathways, and neuroinflammation in an i.c. STZ model. Long Evans rats were treated with i.c. STZ or saline, followed by daily oral doses of T3D-959 (1 mg/kg) or saline initiated 1 day (T3D-959-E) or 7 days (T3D-959-L) later through Experimental Day 28. Protein and phospho-protein expression and pro-inflammatory cytokine activation were measured in temporal lobe homogenates by duplex or multiplex bead-based ELISAs. i.c. STZ treatments caused neurodegeneration with increased pTau, AβPP, Aβ42, ubiquitin, and SNAP-25, and reduced levels of synaptophysin, IGF-1 receptor (R), IRS-1, Akt, p70S6K, mTOR, and S9-GSK-3β. i.c. STZ also broadly increased neuroinflammation. T3D-959 abrogated or reduced most of the AD neuropathological and biomarker abnormalities, increased/normalized IGF-1R, IRS-1, Akt, p70S6K, and S9-GSK-3β, and decreased expression of multiple pro-inflammatory cytokines. T3D-959-E or -L effectively restored insulin/IGF signaling, whereas T3D-959-L more broadly resolved neuroinflammation. AD remediating effects of T3D-959 are potentially due to enhanced expression of key insulin/IGF signaling proteins and inhibition of GSK-3β and neuroinflammation. These effects lead to reduced neurodegeneration, cognitive impairment, and AD biomarker levels in the brain.

  9. Central Nervous Insulin Signaling in Sleep-Associated Memory Formation and Neuroendocrine Regulation.

    Science.gov (United States)

    Feld, Gordon B; Wilhem, Ines; Benedict, Christian; Rüdel, Benjamin; Klameth, Corinna; Born, Jan; Hallschmid, Manfred

    2016-05-01

    The neurochemical underpinnings of sleep's contribution to the establishment and maintenance of memory traces are largely unexplored. Considering that intranasal insulin administration to the CNS improves memory functions in healthy and memory-impaired humans, we tested whether brain insulin signaling and sleep interact to enhance memory consolidation in healthy participants. We investigated the effect of intranasal insulin on sleep-associated neurophysiological and neuroendocrine parameters and memory consolidation in 16 men and 16 women (aged 18-30 years), who learned a declarative word-pair task and a procedural finger sequence tapping task in the evening before intranasal insulin (160 IU) or placebo administration and 8 h of nocturnal sleep. On the subsequent evening, they learned interfering word-pairs and a new finger sequence before retrieving the original memories. Insulin increased growth hormone concentrations in the first night-half and EEG delta power during the second 90 min of non-rapid-eye-movement sleep. Insulin treatment impaired the acquisition of new contents in both the declarative and procedural memory systems on the next day, whereas retrieval of original memories was unchanged. Results indicate that sleep-associated memory consolidation is not a primary mediator of insulin's acute memory-improving effect, but that the peptide acts on mechanisms that diminish the subsequent encoding of novel information. Thus, by inhibiting processes of active forgetting during sleep, central nervous insulin might reduce the interfering influence of encoding new information.

  10. Effect of a sustained reduction in plasma free fatty acid concentration on insulin signalling and inflammation in skeletal muscle from human subjects.

    Science.gov (United States)

    Liang, Hanyu; Tantiwong, Puntip; Sriwijitkamol, Apiradee; Shanmugasundaram, Karthigayan; Mohan, Sumathy; Espinoza, Sara; Defronzo, Ralph A; Dubé, John J; Musi, Nicolas

    2013-06-01

    Free fatty acids (FFAs) have been implicated in the pathogenesis of insulin resistance. Reducing plasma FFA concentration in obese and type 2 diabetic (T2DM) subjects improves insulin sensitivity. However, the molecular mechanism by which FFA reduction improves insulin sensitivity in human subjects is not fully understood. In the present study, we tested the hypothesis that pharmacological FFA reduction enhances insulin action by reducing local (muscle) inflammation, leading to improved insulin signalling. Insulin-stimulated total glucose disposal (TGD), plasma FFA species, muscle insulin signalling, IBα protein, c-Jun phosphorylation, inflammatory gene (toll-like receptor 4 and monocyte chemotactic protein 1) expression, and ceramide and diacylglycerol (DAG) content were measured in muscle from a group of obese and T2DM subjects before and after administration of the antilipolytic drug acipimox for 7 days, and the results were compared to lean individuals. We found that obese and T2DM subjects had elevated saturated and unsaturated FFAs in plasma, and acipimox reduced all FFA species. Acipimox-induced reductions in plasma FFAs improved TGD and insulin signalling in obese and T2DM subjects. Acipimox increased IBα protein (an indication of decreased IB kinase-nuclear factor B signalling) in both obese and T2DM subjects, but did not affect c-Jun phosphorylation in any group. Acipimox also decreased inflammatory gene expression, although this reduction only occurred in T2DM subjects. Ceramide and DAG content did not change. To summarize, pharmacological FFA reduction improves insulin signalling in muscle from insulin-resistant subjects. This beneficial effect on insulin action could be related to a decrease in local inflammation. Notably, the improvements in insulin action were more pronounced in T2DM, indicating that these subjects are more susceptible to the toxic effect of FFAs.

  11. Pectin methyl esterase treatment on high-methoxy pectin for making fruit jam with reduced sugar content.

    Science.gov (United States)

    Wang, Yuh-Tai; Lien, Ling-Lan; Chang, Ya-Chu; Wu, James Swi-Bea

    2013-01-01

    Pectin methyl esterase (PME) has been postulated to catalyse the transacylation reaction between pectin molecules. The present study aimed to prove the occurrence of this reaction. The feasibility of applying PME-catalysed transacylation between high-methoxy pectin molecules in making fruit jam with reduced sugar content was also investigated. PME treatment increased the turbidity and particle size in pectin solution and the molecular weight of pectin, while it decreased the number of methoxy ester linkages and the intensity of the CH₃ absorption peak in the Fourier transform infrared spectrum without changes in the number of total ester linkages in pectin molecules. These findings support the occurrence of PME-catalysed transacylation between pectin molecules. Higher values of hardness, gumminess and chewiness were found in a jam containing PME-treated citrus pectin (10 g L⁻¹) and sugar (350 g L⁻¹) as compared with either a jam containing untreated citrus pectin (10 g L⁻¹) and sugar (350 g L⁻¹) or strawberry jam containing pectin (10 g L⁻¹) from the fruit and sugar (650 g L⁻¹). The demand for sugar in jam making can be greatly reduced by the use of PME-treated high-methoxy pectin. Copyright © 2012 Society of Chemical Industry.

  12. The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1

    International Nuclear Information System (INIS)

    Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

    2016-01-01

    Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. - Highlights: • A novel model of liver-specific Prep1 knockout is established. • Ablation of Prep1 in hepatocytes increases insulin sensitivity. • Prep1 controls hepatic insulin sensitivity by regulating localization of FOXO1. • Prep1 regulates

  13. Osteocalcin improves insulin resistance and inflammation in obese mice: Participation of white adipose tissue and bone.

    Science.gov (United States)

    Guedes, J A C; Esteves, J V; Morais, M R; Zorn, T M; Furuya, D T

    2017-11-26

    The discovery of osteocalcin, a protein synthetized by osteoblasts, as a hormone that has positive effects on insulin resistance, contributed to support the concept of bone as an endocrine organ. However, very little is known about the molecular pathways involved in osteocalcin improved-insulin resistance. The present study aimed to investigate the mechanisms of action of osteocalcin on insulin resistance and inflammation in obese mice and 3T3-L1 adipocytes. Lean control, saline-treated obese and uncarboxylated osteocalcin (uOC)-treated obese mice were subjected to insulin tolerance test in vivo. Blood was collect for biochemical/metabolic profile analysis; and, skeletal muscle, white adipose tissue (WAT) and bone were collected for protein (Western blotting) and mRNA (RT-qPCR) analysis. uOC effects on insulin resistance and inflammation were also investigated in 3T3-L1 adipocytes challenged with tumor necrosis factor. Osteocalcin treatment improved in vivo insulin resistance in obese mice. In WAT, osteocalcin had positive effects such as (1) WAT weight reduction; (2) upregulation of glucose transporter (GLUT) 4 protein and its mRNA (Slc2a4); (3) improved insulin-induced AKT phosphorylation; (4) downregulation of several genes involved in inflammation and inflammassome transcriptional machinery, and (5) reduction of the density of macrophage in crown-like structures (histomorphometrical analysis). Notably, in 3T3-L1 adipocytes, osteocalcin restored Slc2a4/GLUT4 content and reduced the expression of inflammatory genes after TNF-a challenge; moreover, osteocalcin treatment increased AKT phosphorylation induced by insulin. Finally, it was observed that in bone, osteocalcin improves insulin resistance by increasing insulin-induced AKT phosphorylation and reducing the expression of genes involved in bone insulin resistance, resulting in increased secretion of uncarboxylated osteocalcin in circulation. We provided some mechanisms of action for osteocalcin in the

  14. Bone morphogenetic protein 4 inhibits insulin secretion from rodent beta cells through regulation of calbindin1 expression and reduced voltage-dependent calcium currents

    DEFF Research Database (Denmark)

    Christensen, Gitte L.; Jacobsen, Maria L. B.; Wendt, Anna

    2015-01-01

    AIMS/HYPOTHESIS: Type 2 diabetes is characterised by progressive loss of pancreatic beta cell mass and function. Therefore, it is of therapeutic interest to identify factors with the potential to improve beta cell proliferation and insulin secretion. Bone morphogenetic protein 4 (BMP4) expression...

  15. Orosomucoid binds insulin and IGF1 and reduces hormone stimulated protein synthesis and glucose metabolism in C2C12 myotubes

    Science.gov (United States)

    Previous research has indicated that orosomuciod (ORM1) may enhance insulin response in 3T3-L1 adipocytes. The present study was undertaken to determine if ORM1 can modify muscle metabolism by examining glucose oxidation and protein synthesis in the C2C12 muscle cell line. Cells were used for expe...

  16. HPMC supplementation reduces fatty liver, intestinal permeability, and insulin resistance with altered hepatic gene expression in diet-induced obese mice

    Science.gov (United States)

    The effects of hydroxypropyl methylcellulose (HPMC), a highly viscous nonfermentable soluble dietary fiber, were evaluated on global hepatic gene profiles, steatosis and insulin resistance in high-fat (HF) diet-induced obese (DIO) mice. DIO C57BL/6J mice were fed a HF diet supplemented with either ...

  17. Decreased hepatic RBP4 secretion is correlated with reduced hepatic glucose production but is not associated with insulin resistance in patients with liver cirrhosis

    NARCIS (Netherlands)

    Bahr, Matthias J.; Boeker, Klaus H. W.; Manns, Michael P.; Tietge, Uwe J. F.

    Patients with liver cirrhosis have a high incidence of insulin resistance and diabetes. This study was designed to determine circulating levels and hepatic production of retinol-binding protein 4 (RBP4) in relation to parameters of hepatic and systemic metabolism in patients with liver cirrhosis.

  18. Insulin analogues with improved absorption characteristics.

    Science.gov (United States)

    Brange, J; Hansen, J F; Langkjaer, L; Markussen, J; Ribel, U; Sørensen, A R

    1992-01-01

    The insulin preparations available today are not ideal for therapy as s.c. injection does not provide a physiological insulin profile. With the aim to improve the absorption properties recombinant DNA technology has been utilized to design novel insulin molecules with changed physico-chemical characteristics and hence altered subcutaneous absorption kinetics. Soluble, long-acting human insulin analogues in which the isoelectric point has been increased from 5.4 to approx. 7 are absorbed very slowly, providing a more constant basal insulin delivery with lower day-to-day variation than present protracted preparations. In addition they have better storage stability. Rapid-acting human insulin analogues with largely reduced self-association are absorbed substantially faster from subcutaneous tissue than current regular insulin and thus are better suited for bolus injection. The absorption kinetics of these analogues have been able to explain the mechanism behind the dose effect on insulin absorption rate.

  19. Insulin Resistance

    DEFF Research Database (Denmark)

    Jensen, Benjamin Anderschou Holbech

    Insulin resistance (IR) is escalating with alarming pace and is no longer restricted to westernized countries. As a forerunner for some of the most serious threats to human health including metabolic syndrome, cardiovascular diseases, and type 2-diabetes, the need for new treatment modalities...... interventions. We further show that improving the inflammatory toning, using fish oil as fat source, protects mice against diet induced obesity and -inflammation while preserving insulin sensitivity, even in the absence of free fatty acid receptor 4. Conversely, HFD-induced intestinal dysbiosis is associated...

  20. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Yokokawa, Takumi; Endo, Yuriko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Iwanaka, Nobumasa [Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Higashida, Kazuhiko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Faculty of Sport Science, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192 (Japan); Taguchi, Sadayoshi [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan)

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  1. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    International Nuclear Information System (INIS)

    Hashimoto, Takeshi; Yokokawa, Takumi; Endo, Yuriko; Iwanaka, Nobumasa; Higashida, Kazuhiko; Taguchi, Sadayoshi

    2013-01-01

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O 2 for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  2. Exogenous insulin antibody syndrome (EIAS): a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients.

    Science.gov (United States)

    Hu, Xiaolei; Chen, Fengling

    2018-01-01

    Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs). IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS). The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS. © 2018 The authors.

  3. Rosiglitazone treatment of patients with extreme insulin resistance and diabetes mellitus due to insulin receptor mutations has no effects on glucose and lipid metabolism

    DEFF Research Database (Denmark)

    Vestergaard, H; Lund, S; Pedersen, O

    2001-01-01

    Rosiglitazone, a thiazolidinedione (TZD), increases insulin sensitivity by reducing levels of plasma NEFA, triglycerides (TG), glucose and serum insulin. Rosiglitazone treatment decreases insulin resistance in type 2 diabetic patients, but no data exist concerning rosiglitazone treatment...

  4. Ligation-mediated PCR with a back-to-back adapter reduces amplification bias resulting from variations in GC content.

    Science.gov (United States)

    Ishihara, Satoru; Kotomura, Naoe; Yamamoto, Naoki; Ochiai, Hiroshi

    2017-08-15

    Ligation-mediated polymerase chain reaction (LM-PCR) is a common technique for amplification of a pool of DNA fragments. Here, a double-stranded oligonucleotide consisting of two primer sequences in back-to-back orientation was designed as an adapter for LM-PCR. When DNA fragments were ligated with this adapter, the fragments were sandwiched between two adapters in random orientations. In the ensuing PCR, ligation products linked at each end to an opposite side of the adapter, i.e. to a distinct primer sequence, were preferentially amplified compared with products linked at each end to an identical primer sequence. The use of this adapter in LM-PCR reduced the impairment of PCR by substrate DNA with a high GC content, compared with the use of traditional LM-PCR adapters. This result suggested that our method has the potential to contribute to reduction of the amplification bias that is caused by an intrinsic property of the sequence context in substrate DNA. A DNA preparation obtained from a chromatin immunoprecipitation assay using pulldown of a specific form of histone H3 was successfully amplified using the modified LM-PCR, and the amplified products could be used as probes in a fluorescence in situ hybridization analysis. Copyright © 2017 Elsevier Inc. All rights reserved.

  5. Enhancing the use of waste activated sludge as bio-fuel through selectively reducing its heavy metal content.

    Science.gov (United States)

    Dewil, Raf; Baeyens, Jan; Appels, Lise

    2007-06-18

    Power plant or cement kiln co-incineration are important disposal routes for the large amounts of waste activated sludge (WAS) which are generated annually. The presence of significant amounts of heavy metals in the sludge however poses serious problems since they are partly emitted with the flue gases (and collected in the flue gas dedusting) and partly incorporated in the ashes of the incinerator: in both cases, the disposal or reuse of the fly ash and bottom ashes can be jeopardized since subsequent leaching in landfill disposal can occur, or their "pozzolanic" incorporation in cement cannot be applied. The present paper studies some physicochemical methods for reducing the heavy metal content of WAS. The used techniques include acid and alkaline thermal hydrolysis and Fenton's peroxidation. By degrading the extracellular polymeric substances, binding sites for a large amount of heavy metals, the latter are released into the sludge water. The behaviour of several heavy metals (Cd, Cr, Cu, Hg, Pb, Ni, Zn) was assessed in laboratory tests. Results of these show a significant reduction of most heavy metals.

  6. GLP-1-(9-36) amide reduces blood glucose in anesthetized pigs by a mechanism that does not involve insulin secretion

    DEFF Research Database (Denmark)

    Deacon, Carolyn F; Plamboeck, Astrid; Møller, Søren

    2002-01-01

    impossible to assess its true efficacy in vivo. In chloralose-anesthetized pigs given valine-pyrrolidide (to block endogenous DPP IV activity), the independent effects of GLP-1-(7-36) amide on glucose and insulin responses to intravenous glucose were assessed, and the metabolite generated by DPP IV, GLP-1......-(9-36) amide, was investigated for any ability to influence these responses. GLP-1-(7-36) amide enhanced insulin secretion (P amide was without effect, either alone or when coinfused with GLP-1-(7-36) amide. In contrast, GLP-1-(9-36) amide did affect glucose responses (P...... amide (73 +/- 19 mmol x l(-1) x min; P amide (62 +/- 13 mmol x l(-1) x min; P amide + GLP-1-(9-36) amide (50 +/-13 mmol x l(-1) x min; P

  7. Evidence for altered transport of insulin across the blood-brain barrier in insulin-resistant humans.

    Science.gov (United States)

    Heni, Martin; Schöpfer, Patricia; Peter, Andreas; Sartorius, Tina; Fritsche, Andreas; Synofzik, Matthis; Häring, Hans-Ulrich; Maetzler, Walter; Hennige, Anita M

    2014-08-01

    Eating behavior, body weight regulation, peripheral glucose metabolism, and cognitive function depend on adequate insulin action in the brain, and recent studies in humans suggested that impaired insulin action in the brain emerges upon fat intake, obesity, and genetic variants. As insulin enters into the brain in a receptor-mediated fashion, we hypothesized that whole-body insulin sensitivity might affect the transport of insulin into the brain and contribute to the aversive effect of insulin resistance in the central nervous system. In this study, we aimed to determine the ratio of insulin in the cerebrospinal fluid and serum to whole-body insulin sensitivity. Healthy human subjects participated in an oral glucose tolerance test to determine whole-body insulin sensitivity and underwent lumbar puncture. Blood and CSF concentrations of insulin were significantly correlated. The CSF/serum ratio for insulin was significantly associated with whole body insulin sensitivity with reduced insulin transported into the CSF in insulin-resistant subjects. Together, our data suggest that transport of insulin into the CSF relates to peripheral insulin sensitivity and impairs insulin action in the brain. This underlines the need for sensitizing measures in insulin-resistant subjects.

  8. Anti-insulin antibody test

    Science.gov (United States)

    Insulin antibodies - serum; Insulin Ab test; Insulin resistance - insulin antibodies; Diabetes - insulin antibodies ... Normally, there are no antibodies against insulin in your blood. ... different laboratories. Some labs use different measurements or ...

  9. Stimulation of protein synthesis by internalized insulin

    International Nuclear Information System (INIS)

    Miller, D.S.; Sykes, D.B.

    1991-01-01

    Previous studies showed that microinjected insulin stimulates transcription and translation in Stage 4 Xenopus oocytes by acting at nuclear and cytoplasmic sites. The present report is concerned with the question of whether hormone, internalized from an external medium, can act on those sites to alter cell function. Both intracellular accumulation of undegraded 125I-insulin and insulin-stimulated 35S-methionine incorporation into oocyte protein were measured. Anti-insulin antiserum and purified anti-insulin antibody were microinjected into the cytoplasm of insulin-exposed cells to determine if insulin derived from the medium acted through internal sites. In cells exposed for 2 h to 7 or 70 nM external insulin, methionine incorporation was stimulated, but intracellular hormone accumulation was minimal and microinjected antibody was without effect. In cells exposed for 24 h, methionine incorporation again increased, but now accumulation of undegraded, intracellular hormone was substantial (2.6 and 25.3 fmol with 7 and 70 nM, respectively), and microinjected anti-insulin antibody significantly reduced the insulin-stimulated component of incorporation; basal incorporation was not affected. For cells exposed to 70 nM insulin for 24 h, inhibition of the insulin-stimulated component was maximal at 39%. Thus under those conditions, about 40% of insulin's effects were mediated by the internal sites. Together, the data show that inhibition of insulin-stimulated protein synthesis by microinjected antibody was associated with the intracellular accumulation of insulin. They indicate that when oocytes are exposed to external insulin, hormone eventually gains access to intracellular sites of action and through these stimulates translation. Control of translation appears to be shared between the internal sites and the surface receptor

  10. Replacement of glycaemic carbohydrates by inulin-type fructans from chicory (oligofructose, inulin) reduces the postprandial blood glucose and insulin response to foods: report of two double-blind, randomized, controlled trials.

    Science.gov (United States)

    Lightowler, Helen; Thondre, Sangeetha; Holz, Anja; Theis, Stephan

    2018-04-01

    Inulin-type fructans are recognized as prebiotic dietary fibres and classified as non-digestible carbohydrates that do not contribute to glycaemia. The aim of the present studies was to investigate the glycaemic response (GR) and insulinaemic response (IR) to foods in which sucrose was partially replaced by inulin or oligofructose from chicory. In a double-blind, randomized, controlled cross-over design, 40-42 healthy adults consumed a yogurt drink containing oligofructose or fruit jelly containing inulin and the respective full-sugar variants. Capillary blood glucose and insulin were measured in fasted participants and at 15, 30, 45, 60, 90, and 120 min after starting to drink/eat. For each test food, the incremental area under the curve (iAUC) for glucose and insulin was calculated and the GR and IR determined. Consumption of a yogurt drink with oligofructose which was 20% reduced in sugars significantly lowered the glycaemic response compared to the full-sugar reference (iAUC 120min 31.9 and 37.3 mmol/L/min, respectively; p inulin and containing 30% less sugars than the full-sugar variant likewise resulted in a significantly reduced blood glucose response (iAUC 120min 53.7 and 63.7 mmol/L/min, respectively; p inulin-type fructans (p inulin or oligofructose from chicory may be an effective strategy to reduce the postprandial blood glucose response to foods.

  11. Pathogenesis of Insulin Resistance in Skeletal Muscle

    Directory of Open Access Journals (Sweden)

    Muhammad A. Abdul-Ghani

    2010-01-01

    Full Text Available Insulin resistance in skeletal muscle is manifested by decreased insulin-stimulated glucose uptake and results from impaired insulin signaling and multiple post-receptor intracellular defects including impaired glucose transport, glucose phosphorylation, and reduced glucose oxidation and glycogen synthesis. Insulin resistance is a core defect in type 2 diabetes, it is also associated with obesity and the metabolic syndrome. Dysregulation of fatty acid metabolism plays a pivotal role in the pathogenesis of insulin resistance in skeletal muscle. Recent studies have reported a mitochondrial defect in oxidative phosphorylation in skeletal muscle in variety of insulin resistant states. In this review, we summarize the cellular and molecular defects that contribute to the development of insulin resistance in skeletal muscle.

  12. Impact of smoking reduced nicotine content cigarettes on sensitivity to cigarette price: further results from a multi-site clinical trial.

    Science.gov (United States)

    Smith, Tracy T; Cassidy, Rachel N; Tidey, Jennifer W; Luo, Xianghua; Le, Chap T; Hatsukami, Dorothy K; Donny, Eric C

    2017-02-01

    To assess the impact of a reduction in the nicotine content of cigarettes on estimated consumption of reduced nicotine cigarettes and usual brand cigarettes at a variety of hypothetical prices. Double-blind study with participants assigned randomly to receive cigarettes for 6 weeks that were either usual brand or an investigational cigarette with one of five nicotine contents. Ten sites across the United States. A total of 839 eligible adult smokers randomized from 2013 to 2014. Participants received their usual brand or an investigational cigarette with one of five nicotine contents: 15.8 (primary control), 5.2, 2.4, 1.3, or 0.4 mg/g. The Cigarette Purchase Task was completed at baseline and at the week 6 post-randomization visit. Compared with normal nicotine content controls, the lowest nicotine content (0.4 mg/g) reduced the number of study cigarettes participants estimated they would smoke at a range of prices [mean reduction relative to 15.8 mg/g at a price of $4.00/pack: 9.50, 95% confidence interval (CI) = 6.81,12.19]. The lowest nicotine content also reduced the maximum amount of money allocated to study cigarettes and the price at which participants reported they would stop buying study cigarettes [median reduction relative to 15.8 mg/g, 95% CI = $8.21 (4.27,12.15) per day and $0.44 (0.17,0.71) per cigarette, respectively]. A reduction in nicotine content to the lowest level also reduced the maximum amount of money allocated to usual brand cigarettes (median reduction relative to 15.8 mg/g: $4.39 per day, 95% CI = 1.88,6.90). In current smokers, a reduction in nicotine content may reduce cigarette consumption, reduce the reinforcement value of cigarettes and increase cessation if reduced nicotine content cigarettes were the only cigarette available for purchase. © 2016 Society for the Study of Addiction.

  13. Experiments on the inclusion of insulin in lecithin microvesicles using 125I insulin and 131I lecithin as indicators

    International Nuclear Information System (INIS)

    Sarrach, D.; Lachmann, U.; Zipper, J.; Axt, J.; Akademie der Wissenschaften der DDR, Berlin. Inst. fuer Wirkstofforschung)

    1980-01-01

    Egg lecithin was labelled with 131 ICl and used together with 125 I insulin for studying the insulin inclusion in lecithin monolayer liposomes. The application of ultrasonics led to the formation of insulin-containing microvesicles which were characterized by electron microscopy and gel chromatography. With growing insulin concentration the yield of bound insulin increased to a value comparable to the included water volume. In the presence of lecithin insulin disintegration by ultrasonics was strongly reduced The bound insulin proved to be in good immunological state. (author)

  14. Chitosan nanofibers for transbuccal insulin delivery.

    Science.gov (United States)

    Lancina, Michael G; Shankar, Roopa Kanakatti; Yang, Hu

    2017-05-01

    In this work, they aimed at producing chitosan based nanofiber mats capable of delivering insulin via the buccal mucosa. Chitosan was electrospun into nanofibers using poly(ethylene oxide) (PEO) as a carrier molecule in various feed ratios. The mechanical properties and degradation kinetics of the fibers were measured. Insulin release rates were determined in vitro using an ELISA assay. The bioactivity of released insulin was measured in terms of Akt activation in pre-adipocytes. Insulin permeation across the buccal mucosa was measured in an ex-vivo porcine transbuccal model. Fiber morphology, mechanical properties, and in vitro stability were dependent on PEO feed ratio. Lower PEO content blends produced smaller diameter fibers with significantly faster insulin release kinetics. Insulin showed no reduction in bioactivity due to electrospinning. Buccal permeation of insulin facilitated by high chitosan content blends was significantly higher than that of free insulin. Taken together, the work demonstrates that chitosan-based nanofibers have the potential to serve as a transbuccal insulin delivery vehicle. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1252-1259, 2017. © 2017 Wiley Periodicals, Inc.

  15. Reduced transcapillary escape of albumin during acute blood pressure-lowering in type 1 (insulin-dependent) diabetic patients with nephropathy

    DEFF Research Database (Denmark)

    Parving, H H; Kastrup, J; Smidt, U M

    1985-01-01

    The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance....... This may be due to elevated hydrostatic pressure in the microcirculation.......The effect of acute arterial blood pressure lowering upon albumin extravasation was studied in 10 patients with nephropathy and retinopathy due to long-standing Type 1 (insulin-dependent) diabetes. The following variables were measured: transcapillary escape rate of albumin (initial disappearance...... induced the following changes: arterial blood pressure decreased from 134/87 to 107/73 mmHg (p less than 0.01), transcapillary escape rate of albumin declined from 8.1 to 6.7% of the intravascular mass of albumin/h (p less than 0.01), albuminuria diminished from 1434 to 815 micrograms/min (p less than 0...

  16. Lipid-induced insulin resistance does not impair insulin access to skeletal muscle

    Science.gov (United States)

    Richey, Joyce M.; Castro, Ana Valeria B.; Broussard, Josiane L.; Ionut, Viorica; Bergman, Richard N.

    2015-01-01

    Elevated plasma free fatty acids (FFA) induce insulin resistance in skeletal muscle. Previously, we have shown that experimental insulin resistance induced by lipid infusion prevents the dispersion of insulin through the muscle, and we hypothesized that this would lead to an impairment of insulin moving from the plasma to the muscle interstitium. Thus, we infused lipid into our anesthetized canine model and measured the appearance of insulin in the lymph as a means to sample muscle interstitium under hyperinsulinemic euglycemic clamp conditions. Although lipid infusion lowered the glucose infusion rate and induced both peripheral and hepatic insulin resistance, we were unable to detect an impairment of insulin access to the lymph. Interestingly, despite a significant, 10-fold increase in plasma FFA, we detected little to no increase in free fatty acids or triglycerides in the lymph after lipid infusion. Thus, we conclude that experimental insulin resistance induced by lipid infusion does not reduce insulin access to skeletal muscle under clamp conditions. This would suggest that the peripheral insulin resistance is likely due to reduced cellular sensitivity to insulin in this model, and yet we did not detect a change in the tissue microenvironment that could contribute to cellular insulin resistance. PMID:25852002

  17. Skeletal Muscle Fibre-Specific Knockout of p53 Does Not Reduce Mitochondrial Content or Enzyme Activity

    Directory of Open Access Journals (Sweden)

    Ben Stocks

    2017-12-01

    Full Text Available Tumour protein 53 (p53 has been implicated in the regulation of mitochondrial biogenesis in skeletal muscle, with whole-body p53 knockout mice displaying impairments in basal mitochondrial content, respiratory capacity, and enzyme activity. This study aimed to determine the effect of skeletal muscle-specific loss of p53 on mitochondrial content and enzyme activity. Mitochondrial protein content, enzyme activity and mRNA profiles were assessed in skeletal muscle of 8-week-old male muscle fibre-specific p53 knockout mice (p53 mKO and floxed littermate controls (WT under basal conditions. p53 mKO and WT mice displayed similar content of electron transport chain proteins I-V and citrate synthase enzyme activity in skeletal muscle. In addition, the content of proteins regulating mitochondrial morphology (MFN2, mitofillin, OPA1, DRP1, FIS1, fatty acid metabolism (β-HAD, ACADM, ACADL, ACADVL, carbohydrate metabolism (HKII, PDH, energy sensing (AMPKα2, AMPKβ2, and gene transcription (NRF1, PGC-1α, and TFAM were comparable in p53 mKO and WT mice (p > 0.05. Furthermore, p53 mKO mice exhibited normal mRNA profiles of targeted mitochondrial, metabolic and transcriptional proteins (p > 0.05. Thus, it appears that p53 expression in skeletal muscle fibres is not required to develop or maintain mitochondrial protein content or enzyme function in skeletal muscle under basal conditions.

  18. Serum Insulin, Glucose, Indices of Insulin Resistance, and Risk of Lung Cancer.

    Science.gov (United States)

    Argirion, Ilona; Weinstein, Stephanie J; Männistö, Satu; Albanes, Demetrius; Mondul, Alison M

    2017-10-01

    Background: Although insulin may increase the risk of some cancers, few studies have examined fasting serum insulin and lung cancer risk. Methods: We examined serum insulin, glucose, and indices of insulin resistance [insulin:glucose molar ratio and homeostasis model assessment of insulin resistance (HOMA-IR)] and lung cancer risk using a case-cohort study within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study of Finnish men. A total of 196 cases and 395 subcohort members were included. Insulin and glucose were measured in fasting serum collected 5 to 12 years before diagnosis. Cox proportional hazards models were utilized to estimate the relative risk of lung cancer. Results: The average time between blood collection and lung cancer was 9.6 years. Fasting serum insulin levels were 8.7% higher in subcohort members than cases. After multivariable adjustment, men in the fourth quartile of insulin had a significantly higher risk of lung cancer than those in the first quartile [HR = 2.10; 95% confidence interval (CI), 1.12-3.94]. A similar relationship was seen with HOMA-IR (HR = 1.83; 95% CI, 0.99-3.38). Risk was not strongly associated with glucose or the insulin:glucose molar ratio ( P trend = 0.55 and P trend = 0.27, respectively). Conclusions: Higher fasting serum insulin concentrations, as well as the presence of insulin resistance, appear to be associated with an elevated risk of lung cancer development. Impact: Although insulin is hypothesized to increase risk of some cancers, insulin and lung cancer remain understudied. Higher insulin levels and insulin resistance were associated with increased lung cancer risk. Although smoking cessation is the best method of lung cancer prevention, other lifestyle changes that affect insulin concentrations and sensitivity may reduce lung cancer risk. Cancer Epidemiol Biomarkers Prev; 26(10); 1519-24. ©2017 AACR . ©2017 American Association for Cancer Research.

  19. Mechanisms of insulin resistance in obesity

    Science.gov (United States)

    Ye, Jianping

    2014-01-01

    Obesity increases the risk for type 2 diabetes through induction of insulin resistance. Treatment of type 2 diabetes has been limited by little translational knowledge of insulin resistance although there have been several well-documented hypotheses for insulin resistance. In those hypotheses, inflammation, mitochondrial dysfunction, hyperinsulinemia and lipotoxicity have been the major concepts and have received a lot of attention. Oxidative stress, endoplasmic reticulum (ER) stress, genetic background, aging, fatty liver, hypoxia and lipodystrophy are active subjects in the study of these concepts. However, none of those concepts or views has led to an effective therapy for type 2 diabetes. The reason is that there has been no consensus for a unifying mechanism of insulin resistance. In this review article, literature is critically analyzed and reinterpreted for a new energy-based concept of insulin resistance, in which insulin resistance is a result of energy surplus in cells. The energy surplus signal is mediated by ATP and sensed by adenosine monophosphate-activated protein kinase (AMPK) signaling pathway. Decreasing ATP level by suppression of production or stimulation of utilization is a promising approach in the treatment of insulin resistance. In support, many of existing insulin sensitizing medicines inhibit ATP production in mitochondria. The effective therapies such as weight loss, exercise, and caloric restriction all reduce ATP in insulin sensitive cells. This new concept provides a unifying cellular and molecular mechanism of insulin resistance in obesity, which may apply to insulin resistance in aging and lipodystrophy. PMID:23471659

  20. High intensity interval training improves liver and adipose tissue insulin sensitivity

    Science.gov (United States)

    Marcinko, Katarina; Sikkema, Sarah R.; Samaan, M. Constantine; Kemp, Bruce E.; Fullerton, Morgan D.; Steinberg, Gregory R.

    2015-01-01

    Objective Endurance exercise training reduces insulin resistance, adipose tissue inflammation and non-alcoholic fatty liver disease (NAFLD), an effect often associated with modest weight loss. Recent studies have indicated that high-intensity interval training (HIIT) lowers blood glucose in individuals with type 2 diabetes independently of weight loss; however, the organs affected and mechanisms mediating the glucose lowering effects are not known. Intense exercise increases phosphorylation and inhibition of acetyl-CoA carboxylase (ACC) by AMP-activated protein kinase (AMPK) in muscle, adipose tissue and liver. AMPK and ACC are key enzymes regulating fatty acid metabolism, liver fat content, adipose tissue inflammation and insulin sensitivity but the importance of this pathway in regulating insulin sensitivity with HIIT is unknown. Methods In the current study, the effects of 6 weeks of HIIT were examined using obese mice with serine–alanine knock-in mutations on the AMPK phosphorylation sites of ACC1 and ACC2 (AccDKI) or wild-type (WT) controls. Results HIIT lowered blood glucose and increased exercise capacity, food intake, basal activity levels, carbohydrate oxidation and liver and adipose tissue insulin sensitivity in HFD-fed WT and AccDKI mice. These changes occurred independently of weight loss or reductions in adiposity, inflammation and liver lipid content. Conclusions These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC. PMID:26909307

  1. Intranasal Insulin Restores Metabolic Parameters and Insulin Sensitivity in Rats with Metabolic Syndrome.

    Science.gov (United States)

    Derkach, K V; Ivantsov, A O; Chistyakova, O V; Sukhov, I B; Buzanakov, D M; Kulikova, A A; Shpakov, A O

    2017-06-01

    We studied the effect of 10-week treatment with intranasal insulin (0.5 IU/day) on glucose tolerance, glucose utilization, lipid metabolism, functions of pancreatic β cells, and insulin system in the liver of rats with cafeteria diet-induced metabolic syndrome. The therapy reduced body weight and blood levels of insulin, triglycerides, and atherogenic cholesterol that are typically increased in metabolic syndrome, normalized glucose tolerance and its utilization, and increased activity of insulin signaling system in the liver, thus reducing insulin resistance. The therapy did not affect the number of pancreatic islets and β cells. The study demonstrates prospects of using intranasal insulin for correction of metabolic parameters and reduction of insulin resistance in metabolic syndrome.

  2. The transcription factor Prep1 controls hepatic insulin sensitivity and gluconeogenesis by targeting nuclear localization of FOXO1.

    Science.gov (United States)

    Kulebyakin, Konstantin; Penkov, Dmitry; Blasi, Francesco; Akopyan, Zhanna; Tkachuk, Vsevolod

    2016-12-02

    Liver plays a key role in controlling body carbohydrate homeostasis by switching between accumulation and production of glucose and this way maintaining constant level of glucose in blood. Increased blood glucose level triggers release of insulin from pancreatic β-cells. Insulin represses hepatic glucose production and increases glucose accumulation. Insulin resistance is the main cause of type 2 diabetes and hyperglycemia. Currently thiazolidinediones (TZDs) targeting transcriptional factor PPARγ are used as insulin sensitizers for treating patients with type 2 diabetes. However, TZDs are reported to be associated with cardiovascular and liver problems and stimulate obesity. Thus, it is necessary to search new approaches to improve insulin sensitivity. A promising candidate is transcriptional factor Prep1, as it was shown earlier it could affect insulin sensitivity in variety of insulin-sensitive tissues. The aim of the present study was to evaluate a possible involvement of transcriptional factor Prep1 in control of hepatic glucose accumulation and production. We created mice with liver-specific Prep1 knockout and discovered that hepatocytes derived from these mice are much more sensitive to insulin, comparing to their WT littermates. Incubation of these cells with 100 nM insulin results in almost complete inhibition of gluconeogenesis, while in WT cells this repression is only partial. However, Prep1 doesn't affect gluconeogenesis in the absence of insulin. Also, we observed that nuclear content of gluconeogenic transcription factor FOXO1 was greatly reduced in Prep1 knockout hepatocytes. These findings suggest that Prep1 may control hepatic insulin sensitivity by targeting FOXO1 nuclear stability. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. Advanced Glycation End-Products affect transcription factors regulating insulin gene expression

    International Nuclear Information System (INIS)

    Puddu, A.; Storace, D.; Odetti, P.; Viviani, G.L.

    2010-01-01

    Advanced Glycation End-Products (AGEs) are generated by the covalent interaction of reducing sugars with proteins, lipids or nucleic acids. AGEs are implicated in diabetic complications and pancreatic β-cell dysfunction. We previously demonstrated that exposure of the pancreatic islet cell line HIT-T15 to high concentrations of AGEs leads to a significant decrease of insulin secretion and content. Insulin gene transcription is positively regulated by the beta cell specific transcription factor PDX-1 (Pancreatic and Duodenal Homeobox-1). On the contrary, the forkhead transcription factor FoxO1 inhibits PDX-1 gene transcription. Activity of FoxO1 is regulated by post-translational modifications: phosphorylation deactivates FoxO1, and acetylation prevents FoxO1 ubiquitination. In this work we investigated whether AGEs affect expression and subcellular localization of PDX-1 and FoxO1. HIT-T15 cells were cultured for 5 days in presence of AGEs. Cells were then lysed and processed for subcellular fractionation. We determined intracellular insulin content, then we assessed the expression and subcellular localization of PDX-1, FoxO1, phosphoFoxO1 and acetylFoxO1. As expected intracellular insulin content was lower in HIT-T15 cells cultured with AGEs. The results showed that AGEs decreased expression and nuclear localization of PDX-1, reduced phosphorylation of FoxO1, and increased expression and acetylation of FoxO1. These results suggest that AGEs decrease insulin content unbalancing transcription factors regulating insulin gene expression.

  4. Acrylamide formation in plantain (Musa paradisiaca) chips influenced by different ripening stages: A correlation study with respect to reducing sugars, amino acids and phenolic content.

    Science.gov (United States)

    Shamla, L; Nisha, P

    2017-05-01

    The effect of ripening on the formation of acrylamide in deep fried plantain chips made from Nendran variety (Musa paradisiaca) was investigated. The precursors of acrylamide formation, reducing sugars (glucose and fructose) and ten major amino acids, were quantified during different stages of ripening using HPLC and correlated with acrylamide formation. The total phenolic content and total flavonoid content were also estimated and correlated with acrylamide formation. Both glucose and fructose increased during ripening and demonstrated a positive correlation on formation of acrylamide (correlation coefficient of r=0.95 and 0.94 respectively (p0.05). The decreased levels of phenolic content during ripening of plantain were negatively correlated with acrylamide formation in the deep fried chips prepared. Thus the selection of proper ripening stage renders reduced formation of acrylamide in plantain chips to a reasonable extend. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. Reduced intracellular c-di-GMP content increases expression of quorum sensing-regulated genes in Pseudomonas aeruginosa

    DEFF Research Database (Denmark)

    Chua, Song Lin; Liu, Yang; Li, Yingying

    2017-01-01

    Cyclic-di-GMP (c-di-GMP) is an intracellular secondary messenger which controls the biofilm life cycle in many bacterial species. High intracellular c-di-GMP content enhances biofilm formation via the reduction of motility and production of biofilm matrix, while low c-di-GMP content in biofilm...... cells leads to increased motility and biofilm dispersal. While the effect of high c-di-GMP levels on bacterial lifestyles is well studied, the physiology of cells at low c-di-GMP levels remains unclear. Here, we showed that Pseudomonas aeruginosa cells with high and low intracellular c-di-GMP contents...... possessed distinct transcriptome profiles. There were 535 genes being upregulated and 432 genes downregulated in cells with low c-di-GMP, as compared to cells with high c-di-GMP. Interestingly, both rhl and pqs quorum-sensing (QS) operons were expressed at higher levels in cells with low intracellular c-di-GMP...

  6. The effect of reduced oxygen content powder on the impact toughness of 316 steel powder joined to 316 steel by low temperature HIP

    International Nuclear Information System (INIS)

    Lind, Anders; Sundstroem, Johan; Peacock, Alan

    2005-01-01

    During the manufacture of the blanket modules, 316L steel powder is simultaneously consolidated and joined to tubes and blocks of 316L materials by hot isostatic pressing (HIP). The high processing temperature can detrimentally increase the grain size of the water-cooling tubes in the structure and the blocks reducing their strength. It is well known [L. Arnberg, A. Karlsson, Influence of powder surface oxidation on some properties of a HIPed martensitic chromium steel, Int. J. Powder Metall. 24 (2) (1988) 107-112] that surface oxides on the powder particles negatively influence the impact toughness of material and joints consolidated in this way. At a high HIP temperature, the oxides are at least partly transformed, thereby improving the impact toughness [L. Nyborg, I. Olefjord, Surface analysis of PM martensitic steel before and after consolidation. Part 2. Surface analysis of compacted material, Powder Metall. 31 (1) (1988) 40-44]. In order to get acceptable mechanical properties of materials produced at a low HIP temperature, the oxygen content on the powder surfaces needs to be reduced. In order to study the effect of reducing the powder oxygen content, it was reduced and the results were compared to those of specimens with ordinary oxygen content. The effect on the impact toughness and the tensile strength of low temperature (1020 and 1060 deg. C) HIP joints between steel blocks and powder consolidated material with low and ordinary oxygen content was measured

  7. Primary vaccination of adults with reduced antigen-content diphtheria-tetanus-acellular pertussis or dTpa-inactivated poliovirus vaccines compared to diphtheria-tetanus-toxoid vaccines.

    NARCIS (Netherlands)

    Theeten, H.; Rumke, H.C.; Hoppener, F.J.; Vilatimo, R.; Narejos, S.; Damme, P. van; Hoet, B.

    2007-01-01

    OBJECTIVE: To evaluate immunogenicity and reactogenicity of primary vaccination with reduced-antigen-content diphtheria-tetanus-acellular pertussis (dTpa) or dTpa-inactivated poliovirus (dTpa-IPV) vaccine compared to diphtheria-tetanus-toxoid vaccines (Td) in adults > or = 40 years of age without

  8. Interactive effect of reduced pollen availability and Varroa destructor infestation limits growth and protein content of young honey bees

    NARCIS (Netherlands)

    Dooremalen, van C.; Stam, E.; Gerritsen, L.J.M.; Cornelissen, B.; Steen, van der J.J.M.; Langevelde, van F.; Blacquiere, T.

    2013-01-01

    Varroa destructor in combination with one or more stressors, such as low food availability or chemical exposure, is considered to be one of the main causes for honey bee colony losses. We examined the inter-active effect of pollen availability on the protein content and body weight of young bees

  9. The effect of reduced oxygen content powder on the impact toughness of 316 steel powder joined to 316 steel by low temperature HIP

    International Nuclear Information System (INIS)

    Lind, Anders; Sundstroem, Johan

    2004-11-01

    During the manufacture of the blanket modules, 316L steel powder is simultaneously consolidated and joined to tubes and blocks of 316L materials by Hot Isostatic Pressing (HIP). The high processing temperature can detrimentally increase the grain size of the water cooling tubes in the structure and the blocks reducing their strength. It is well known that surface oxides on the powder particles negatively influence the impact toughness of material and joints consolidated in this way. By increasing the consolidation temperature the metallurgical bonding is improved, due to a redistribution of oxygen within the oxide layer towards more discrete oxide particles. In order to get acceptable mechanical properties of materials produced at a low HIP temperature the oxygen content on the powder surfaces needs to be reduced. The aim of this new techniques to reduce the oxygen content of the metal powder. The influence on Charpy impact energy and tensile strength were demonstrated

  10. Degludec insulin: A novel basal insulin

    OpenAIRE

    Kalra, Sanjay; Unnikrishnan, Ambika Gopalakrishnan; Baruah, Manash; Kalra, Bharti

    2011-01-01

    This paper reviews a novel insulin analogue, degludec, which has the potential to emerge as an ideal basal insulin. It reviews the limitations of existing basal insulin and analogues, and highlights the need for a newer molecule. The paper discusses the potential advantages of degludec, while reviewing its pharmacologic and clinical studies done so far. The paper assesses the potential role of insulin degludec and degludec plus in clinical diabetes practice.

  11. A Lower-Carbohydrate, Higher-Fat Diet Reduces Abdominal and Intermuscular Fat and Increases Insulin Sensitivity in Adults at Risk of Type 2 Diabetes123

    Science.gov (United States)

    Gower, Barbara A; Goss, Amy M

    2015-01-01

    Background: Obesity, particularly visceral and ectopic adiposity, increases the risk of type 2 diabetes. Objective: The aim of this study was to determine if restriction of dietary carbohydrate is beneficial for body composition and metabolic health. Methods: Two studies were conducted. In the first, 69 overweight/obese men and women, 53% of whom were European American (EA) and 47% of whom were African American (AA), were provided with 1 of 2 diets (lower-fat diet: 55%, 18%, and 27% of energy from carbohydrate, protein, and fat, respectively; lower-carbohydrate diet: 43%, 18%, and 39%, respectively) for 8 wk at a eucaloric level and 8 wk at a hypocaloric level. In the second study, 30 women with polycystic ovary syndrome (PCOS) were provided with 2 diets (lower-fat diet: 55%, 18%, and 27% of energy from carbohydrate, protein, and fat, respectively; lower-carbohydrate diet: 41%, 19%, and 40%, respectively) at a eucaloric level for 8 wk in a random-order crossover design. Results: As previously reported, among overweight/obese adults, after the eucaloric phase, participants who consumed the lower-carbohydrate vs. the lower-fat diet lost more intra-abdominal adipose tissue (IAAT) (11 ± 3% vs. 1 ± 3%; P diet had 4.4% less total fat mass. Original to this report, across the entire 16-wk study, AAs lost more fat mass with a lower-carbohydrate diet (6.2 vs. 2.9 kg; P diets. As previously reported, among women with PCOS, the lower-carbohydrate arm showed decreased fasting insulin (−2.8 μIU/mL; P < 0.001) and fasting glucose (−4.7 mg/dL; P < 0.01) and increased insulin sensitivity (1.06 arbitrary units; P < 0.05) and “dynamic” β-cell response (96.1 · 109; P < 0.001). In the lower-carbohydrate arm, women lost both IAAT (−4.8 cm2; P < 0.01) and intermuscular fat (−1.2 cm2; P < 0.01). In the lower-fat arm, women lost lean mass (−0.6 kg; P < 0.05). Original to this report, after the lower-carbohydrate arm, the change in IAAT was positively associated with the

  12. Metabolism and insulin signaling in common metabolic disorders and inherited insulin resistance.

    Science.gov (United States)

    Højlund, Kurt

    2014-07-01

    Type 2 diabetes, obesity and polycystic ovary syndrome (PCOS) are common metabolic disorders which are observed with increasing prevalences, and which are caused by a complex interplay between genetic and environmental factors, including increased calorie intake and physical inactivity. These metabolic disorders are all characterized by reduced plasma adiponectin and insulin resistance in peripheral tissues. Quantitatively skeletal muscle is the major site of insulin resistance. Both low plasma adiponectin and insulin resistance contribute to an increased risk of type 2 diabetes and cardiovascular disease. In several studies, we have investigated insulin action on glucose and lipid metabolism, and at the molecular level, insulin signaling to glucose transport and glycogen synthesis in skeletal muscle from healthy individuals and in obesity, PCOS and type 2 diabetes. Moreover, we have described a novel syndrome characterized by postprandial hyperinsulinemic hypoglycemia and insulin resistance. This syndrome is caused by a mutation in the tyrosine kinase domain of the insulin receptor gene (INSR). We have studied individuals with this mutation as a model of inherited insulin resistance. Type 2 diabetes, obesity and PCOS are characterized by pronounced defects in the insulin-stimulated glucose uptake, in particular glycogen synthesis and to a lesser extent glucose oxidation, and the ability of insulin to suppress lipid oxidation. In inherited insulin resistance, however, only insulin action on glucose uptake and glycogen synthesis is impaired. This suggests that the defects in glucose and lipid oxidation in the common metabolic disorders are secondary to other factors. In young women with PCOS, the degree of insulin resistance was similar to that seen in middle-aged patients with type 2 diabetes. This supports the hypothesis of an unique pathogenesis of insulin resistance in PCOS. Insulin in physiological concentrations stimulates glucose uptake in human skeletal

  13. Exposure of Pregnant Mice to Triclosan Causes Insulin Resistance via Thyroxine Reduction.

    Science.gov (United States)

    Hua, Xu; Cao, Xin-Yuan; Wang, Xiao-Li; Sun, Peng; Chen, Ling

    2017-11-01

    Exposure to triclosan (TCS), an antibacterial agent, during pregnancy is associated with hypothyroxinemia and decreases in placental glucose transporter expression and activity. The objective of this study was to investigate the influence of TCS on glucose homeostasis and insulin sensitivity in gestational mice (G-mice) and nongestational female mice (Ng-mice) as a control. Herein, we show that the exposure of G-mice to TCS (8 mg/kg) from gestational day (GD) 5 to GD17 significantly increased their levels of fasting plasma glucose and serum insulin, and insulin content in pancreatic β-cells with reduced homeostasis model assessment (HOMA)-β index and increased HOMA-IR index. Area under curve (AUC) of glucose and insulin tolerance tests in TCS (8 mg/kg)-treated G-mice were markedly larger than controls. When compared with controls, TCS (8 mg/kg)-treated G-mice showed a significant decrease in the levels of thyroxine and triiodothyroninelevels, PPARγ and glucose transporter 4 (GLUT4) expression, and Akt phosphorylation in adipose tissue and muscle. Replacement of L-thyroxine in TCS (8 mg/kg)-treated G-mice corrected their insulin resistance and recovered the levels of insulin, PPARγ and GLUT4 expression, and Akt phosphorylation. Activation of PPARγ by administration of rosiglitazone recovered the decrease in Akt phosphorylation, but not GLUT4 expression. Although exposure to TCS (8 mg/kg) in Ng-mice reduced thyroid hormones levels, it did not cause the insulin resistance or affect PPARγ and GLUT4 expression, and Akt phosphorylation. The findings indicate that the exposure of gestational mice to TCS (≥8 mg/kg) results in insulin resistance via thyroid hormones reduction. © The Author 2017. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  14. Hydrogen peroxide production regulates the mitochondrial function in insulin resistant muscle cells: effect of catalase overexpression.

    Science.gov (United States)

    Barbosa, Marina R; Sampaio, Igor H; Teodoro, Bruno G; Sousa, Thais A; Zoppi, Claudio C; Queiroz, André L; Passos, Madla A; Alberici, Luciane C; Teixeira, Felipe R; Manfiolli, Adriana O; Batista, Thiago M; Cappelli, Ana Paula Gameiro; Reis, Rosana I; Frasson, Danúbia; Kettelhut, Isis C; Parreiras-e-Silva, Lucas T; Costa-Neto, Claudio M; Carneiro, Everardo M; Curi, Rui; Silveira, Leonardo R

    2013-10-01

    The mitochondrial redox state plays a central role in the link between mitochondrial overloading and insulin resistance. However, the mechanism by which the ROS induce insulin resistance in skeletal muscle cells is not completely understood. We examined the association between mitochondrial function and H2O2 production in insulin resistant cells. Our hypothesis is that the low mitochondrial oxygen consumption leads to elevated ROS production by a mechanism associated with reduced PGC1α transcription and low content of phosphorylated CREB. The cells were transfected with either the encoded sequence for catalase overexpression or the specific siRNA for catalase inhibition. After transfection, myotubes were incubated with palmitic acid (500μM) and the insulin response, as well as mitochondrial function and fatty acid metabolism, was determined. The low mitochondrial oxygen consumption led to elevated ROS production by a mechanism associated with β-oxidation of fatty acids. Rotenone was observed to reduce the ratio of ROS production. The elevated H2O2 production markedly decreased the PGC1α transcription, an effect that was accompanied by a reduced phosphorylation of Akt and CREB. The catalase transfection prevented the reduction in the phosphorylated level of Akt and upregulated the levels of phosphorylated CREB. The mitochondrial function was elevated and H2O2 production reduced, thus increasing the insulin sensitivity. The catalase overexpression improved mitochondrial respiration protecting the cells from fatty acid-induced, insulin resistance. This effect indicates that control of hydrogen peroxide production regulates the mitochondrial respiration preventing the insulin resistance in skeletal muscle cells by a mechanism associated with CREB phosphorylation and β-oxidation of fatty acids. Copyright © 2013 Elsevier B.V. All rights reserved.

  15. Insulin analogs with improved pharmacokinetic profiles.

    Science.gov (United States)

    Brange; Vølund

    1999-02-01

    The aim of insulin replacement therapy is to normalize blood glucose in order to reduce the complications of diabetes. The pharmacokinetics of the traditional insulin preparations, however, do not match the profiles of physiological insulin secretion. The introduction of the rDNA technology 20 years ago opened new ways to create insulin analogs with altered properties. Fast-acting analogs are based on the idea that an insulin with less tendency to self-association than human insulin would be more readily absorbed into the systemic circulation. Protracted-acting analogs have been created to mimic the slow, steady rate of insulin secretion in the fasting state. The present paper provides a historical review of the efforts to change the physicochemical and pharmacological properties of insulin in order to improve insulin therapy. The available clinical studies of the new insulins are surveyed and show, together with modeling results, that new strategies for optimal basal-bolus treatment are required for utilization of the new fast-acting analogs.

  16. Silica-Coated Liposomes for Insulin Delivery

    Directory of Open Access Journals (Sweden)

    Neelam Dwivedi

    2010-01-01

    Full Text Available Liposomes coated with silica were explored as protein delivery vehicles for their enhanced stability and improved encapsulation efficiency. Insulin was encapsulated within the fluidic phosphatidylcholine lipid vesicles by thin film hydration at pH 2.5, and layer of silica was formed above lipid bilayer by acid catalysis. The presence of silica coating and encapsulated insulin was identified using confocal and electron microscopy. The native state of insulin present in the formulation was evident from Confocal Micro-Raman spectroscopy. Silica coat enhances the stability of insulin-loaded delivery vehicles. In vivo study shows that these silica coated formulations were biologically active in reducing glucose levels.

  17. Enhanced hepatic insulin signaling in the livers of high altitude native rats under basal conditions and in the livers of low altitude native rats under insulin stimulation: a mechanistic study.

    Science.gov (United States)

    Al Dera, Hussain; Eleawa, Samy M; Al-Hashem, Fahaid H; Mahzari, Moeber M; Hoja, Ibrahim; Al Khateeb, Mahmoud

    2017-07-01

    This study was designed to investigate the role of the liver in lowering fasting blood glucose levels (FBG) in rats native to high (HA) and low altitude (LA) areas. As compared with LA natives, besides the improved insulin and glucose tolerance, HA native rats had lower FBG, at least mediated by inhibition of hepatic gluconeogenesis and activation of glycogen synthesis. An effect that is mediated by the enhancement of hepatic insulin signaling mediated by the decreased phosphorylation of TSC induced inhibition of mTOR function. Such effect was independent of activation of AMPK nor stabilization of HIF1α, but most probably due to oxidative stress induced REDD1 expression. However, under insulin stimulation, and in spite of the less activated mTOR function in HA native rats, LA native rats had higher glycogen content and reduced levels of gluconeogenic enzymes with a more enhanced insulin signaling, mainly due to higher levels of p-IRS1 (tyr612).

  18. The glucagon-like peptide-1 metabolite GLP-1-(9-36) amide reduces postprandial glycemia independently of gastric emptying and insulin secretion in humans

    DEFF Research Database (Denmark)

    Meier, Juris J; Gethmann, Arnica; Nauck, Michael A

    2006-01-01

    Glucagon-like peptide 1 (GLP-1) lowers glycemia by modulating gastric emptying and endocrine pancreatic secretion. Rapidly after its secretion, GLP-1-(7-36) amide is degraded to the metabolite GLP-1-(9-36) amide. The effects of GLP-1-(9-36) amide in humans are less well characterized. Fourteen...... healthy volunteers were studied with intravenous infusion of GLP-1-(7-36) amide, GLP-1-(9-36) amide, or placebo over 390 min. After 30 min, a solid test meal was served, and gastric emptying was assessed. Blood was drawn for GLP-1 (total and intact), glucose, insulin, C-peptide, and glucagon measurements....... Administration of GLP-1-(7-36) amide and GLP-1-(9-36) amide significantly raised total GLP-1 plasma levels. Plasma concentrations of intact GLP-1 increased to 21 +/- 5 pmol/l during the infusion of GLP-1-(7-36) amide but remained unchanged during GLP-1-(9-36) amide infusion [5 +/- 3 pmol/l; P

  19. Effects of long-time elevated temperature exposures on hot-isostatically-pressed power-metallurgy Udimet 700 alloys with reduced cobalt contents

    Science.gov (United States)

    Hart, F. H.

    1984-01-01

    Because almost the entire U.S. consumption of cobalt depends on imports, this metal has been designated "strategic'. The role and effectiveness of cobalt is being evaluated in commercial nickel-base superalloys. Udiment 700 type alloys in which the cobalt content was reduced from the normal 17% down to 12.7%, 8.5%, 4.3%, and 0% were prepared by standard powder metallurgy techniques and hot isostatically pressed into billets. Mechanical testing and microstructural investigations were performed. The mechanical properties of alloys with reduced cobalt contents which were heat-treated identically were equal or better than those of the standard alloy, except that creep rates tended to increase as cobalt was reduced. The effects of long time exposures at 760 C on mechanical properties and at 760 C and 845 C on microstructures were determined. Decreased tensile properties and shorter rupture lives with increased creep rates were observed in alloy modifications. The exposures caused gamma prime particle coarsening and formation of sigma phase in the alloys with higher cobalt contents. Exposure at 845 C also reduced the amount of MC carbides.

  20. Identification of four amino acid substitutions in hexokinase II and studies of relationships to NIDDM, glucose effectiveness, and insulin sensitivity

    DEFF Research Database (Denmark)

    Echwald, Søren Morgenthaler; Bjørbaek, C; Hansen, Torben

    1995-01-01

    not predict any change in amino acid composition of the protein. One homozygous and nine heterozygous carriers of the codon 142 mutation were found among the NIDDM patients. The mutations at codons 148, 497, and 844 were each found in one diabetic subject and only on one allele. There were no carriers......Human hexokinase (HK) II, a glucose phosphorylating enzyme in muscle tissue, plays a central role in glucose metabolism. Since reduced insulin-stimulated glucose uptake and reduced glucose-6-phosphate content in muscle have been demonstrated in pre-non-insulin-dependent diabetes mellitus (pre...

  1. Reduced insulin-like growth factor-I serum levels in formerly obese women subjected to laparoscopic-adjustable gastric banding or diet-induced long-term caloric restriction.

    Science.gov (United States)

    Mitterberger, Maria C; Mattesich, Monika; Klaver, Elise; Piza-Katzer, Hildegunde; Zwerschke, Werner

    2011-11-01

    Life-span extension in laboratory rodents induced by long-term caloric restriction correlates with decreased serum insulin-like growth factor-I (IGF-I) levels. Reduced activity of the growth hormone/IGF-I signaling system slows aging and increases longevity in mutant mouse models. In the present study, we show that long-term caloric restriction achieved by two different interventions for 4 years, either laparoscopic-adjustable gastric banding or reducing diet, leads to reduced IGF-I serum levels in formerly obese women relative to normal-weight women eating ad libitum. Moreover, we present evidence that the long-term caloric restriction interventions reduce fasting growth hormone serum levels. The present study indicates that the activity of the growth hormone/IGF-I axis is reduced in long-term calorically restricted formerly obese humans. Furthermore, our findings suggest that the duration and severity of the caloric restriction intervention are important for the outcome on the growth hormone/IGF-I axis in humans.

  2. An 11-bp insertion in Zea mays fatb reduces the palmitic acid content of fatty acids in maize grain.

    Directory of Open Access Journals (Sweden)

    Lin Li

    Full Text Available The ratio of saturated to unsaturated fatty acids in maize kernels strongly impacts human and livestock health, but is a complex trait that is difficult to select based on phenotype. Map-based cloning of quantitative trait loci (QTL is a powerful but time-consuming method for the dissection of complex traits. Here, we combine linkage and association analyses to fine map QTL-Pal9, a QTL influencing levels of palmitic acid, an important class of saturated fatty acid. QTL-Pal9 was mapped to a 90-kb region, in which we identified a candidate gene, Zea mays fatb (Zmfatb, which encodes acyl-ACP thioesterase. An 11-bp insertion in the last exon of Zmfatb decreases palmitic acid content and concentration, leading to an optimization of the ratio of saturated to unsaturated fatty acids while having no effect on total oil content. We used three-dimensional structure analysis to explain the functional mechanism of the ZmFATB protein and confirmed the proposed model in vitro and in vivo. We measured the genetic effect of the functional site in 15 different genetic backgrounds and found a maximum change of 4.57 mg/g palmitic acid content, which accounts for ∼20-60% of the variation in the ratio of saturated to unsaturated fatty acids. A PCR-based marker for QTL-Pal9 was developed for marker-assisted selection of nutritionally healthier maize lines. The method presented here provides a new, efficient way to clone QTL, and the cloned palmitic acid QTL sheds lights on the genetic mechanism of oil biosynthesis and targeted maize molecular breeding.

  3. An 11-bp Insertion in Zea mays fatb Reduces the Palmitic Acid Content of Fatty Acids in Maize Grain

    Science.gov (United States)

    Li, Qing; Yang, Xiaohong; Zheng, Debo; Warburton, Marilyn; Chai, Yuchao; Zhang, Pan; Guo, Yuqiu; Yan, Jianbing; Li, Jiansheng

    2011-01-01

    The ratio of saturated to unsaturated fatty acids in maize kernels strongly impacts human and livestock health, but is a complex trait that is difficult to select based on phenotype. Map-based cloning of quantitative trait loci (QTL) is a powerful but time-consuming method for the dissection of complex traits. Here, we combine linkage and association analyses to fine map QTL-Pal9, a QTL influencing levels of palmitic acid, an important class of saturated fatty acid. QTL-Pal9 was mapped to a 90-kb region, in which we identified a candidate gene, Zea mays fatb (Zmfatb), which encodes acyl-ACP thioesterase. An 11-bp insertion in the last exon of Zmfatb decreases palmitic acid content and concentration, leading to an optimization of the ratio of saturated to unsaturated fatty acids while having no effect on total oil content. We used three-dimensional structure analysis to explain the functional mechanism of the ZmFATB protein and confirmed the proposed model in vitro and in vivo. We measured the genetic effect of the functional site in 15 different genetic backgrounds and found a maximum change of 4.57 mg/g palmitic acid content, which accounts for ∼20–60% of the variation in the ratio of saturated to unsaturated fatty acids. A PCR-based marker for QTL-Pal9 was developed for marker-assisted selection of nutritionally healthier maize lines. The method presented here provides a new, efficient way to clone QTL, and the cloned palmitic acid QTL sheds lights on the genetic mechanism of oil biosynthesis and targeted maize molecular breeding. PMID:21931818

  4. New ways of insulin delivery.

    Science.gov (United States)

    Heinemann, L

    2011-02-01

    mean that more patients are willing to start insulin therapy earlier than with conventional SC insulin therapy? With TI we have a product that has improved pharmacological properties (also in comparison to Exubera) for coverage of prandial insulin requirements. Subsequently, in the clinical trials performed, postprandial glycaemic excursions were lower than with SC injection of RHI or rapid-acting insulin analogues. This only in part (if at all) results in an improved metabolic control in general (= lower HbA1c) (see below). The outlook for 2011 is that there are chances that we shall have an inhaled insulin product on the market. Probably also the first OI will be submitted to the regulatory authorities for market approval or will even be available in less regulated markets. In order to select all relevant publications about new ways of insulin delivery I performed a PUBMED search and also checked the table of contents of a number of journals that publish heavily in this area of research as well references in the publications I found for additional references. Selection of the manuscripts from all publications was predominately based on the fact whether they presented data from clinical studies or not. The selected studies were critically reviewed for novelty and appropriate study design etc. In some cases also reviews about a given topic were selected if they provide relevant novel insights. © 2011 Blackwell Publishing Ltd.

  5. Interactive effects of UV radiation and reduced precipitation on the seasonal leaf phenolic content/composition and the antioxidant activity of naturally growing Arbutus unedo plants.

    Science.gov (United States)

    Nenadis, Nikolaos; Llorens, Laura; Koufogianni, Agathi; Díaz, Laura; Font, Joan; Gonzalez, Josep Abel; Verdaguer, Dolors

    2015-12-01

    The effects of UV radiation and rainfall reduction on the seasonal leaf phenolic content/composition and antioxidant activity of the Mediterranean shrub Arbutus unedo were studied. Naturally growing plants of A. unedo were submitted to 97% UV-B reduction (UVA), 95% UV-A+UV-B reduction (UV0) or near-ambient UV levels (UVBA) under two precipitation regimes (natural rainfall or 10-30% rainfall reduction). Total phenol, flavonol and flavanol contents, levels of eight phenols and antioxidant activity [DPPH(●) radical scavenging and Cu (II) reducing capacity] were measured in sun-exposed leaves at the end of four consecutive seasons. Results showed a significant seasonal variation in the leaf content of phenols of A. unedo, with the lowest values found in spring and the highest in autumn and/or winter. Leaf ontogenetic development and/or a possible effect of low temperatures in autumn/winter may account for such findings. Regardless of the watering regime and the sampling date, plant exposure to UV-B radiation decreased the total flavanol content of leaves, while it increased the leaf content in quercitrin (the most abundant quercetin derivative identified). By contrast, UV-A radiation increased the leaf content of theogallin, a gallic acid derivative. Other phenolic compounds (two quercetin derivatives, one of them being avicularin, and one kaempferol derivative, juglanin), as well as the antioxidant activity of the leaves, showed different responses to UV radiation depending on the precipitation regime. Surprisingly, reduced rainfall significantly decreased the total amount of quantified quercetin derivatives as well as the DPPH scavenging activity in A. unedo leaves. To conclude, present findings indicate that leaves of A. unedo can be a good source of antioxidants throughout the year, but especially in autumn and winter. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Fourier transform infrared imaging showing reduced unsaturated lipid content in the hippocampus of a mouse model of Alzheimer's disease.

    Science.gov (United States)

    Leskovjan, Andreana C; Kretlow, Ariane; Miller, Lisa M

    2010-04-01

    Polyunsaturated fatty acids are essential to brain functions such as membrane fluidity, signal transduction, and cell survival. It is also thought that low levels of unsaturated lipid in the brain may contribute to Alzheimer's disease (AD) risk or severity. However, it is not known how accumulation of unsaturated lipids is affected in different regions of the hippocampus, which is a central target of AD plaque pathology, during aging. In this study, we used Fourier transform infrared imaging (FTIRI) to visualize the unsaturated lipid content in specific regions of the hippocampus in the PSAPP mouse model of AD as a function of plaque formation. Specifically, the unsaturated lipid content was imaged using the olefinic =CH stretching mode at 3012 cm(-1). The axonal, dendritic, and somatic layers of the hippocampus were examined in the mice at 13, 24, 40, and 56 weeks old. Results showed that lipid unsaturation in the axonal layer was significantly increased with normal aging in control (CNT) mice (p avoiding progression of the disease.

  7. [Effect of Jinlida on DGAT1 in Skeletal Muscle in Fat-Induced Insulin Resistance ApoE -/- Mice].

    Science.gov (United States)

    Jin, Xin; Zhang, Hui-xin; Cui, Wen-wen

    2015-06-01

    To investigate the effect of Jinlida on DGAT1 in skeletal muscle in fat-induced insulin resistance ApoE-/- mice. Eight male C57BL/6J mice were used as normal group. 40 male ApoE -/- mice were fed high-fat diet for 16 weeks and divided into five groups: control group, rosiglitazone group, and Jinlida low, middle and high dose groups. Then corresponding drugs were administrated intragastrically for eight weeks. TG content in skeletal muscle was measured by enzymic enzymatic, Glucose tolerance test (OGTT) was used to evaluate the degree of insulin resistance in mice. The mRNA and protein expression of insulin receptor substrate (IRS-1) and diacylglycerol acyltransferase 1 (DGAT1) in skeletal muscle were measured by real-time quantitative reverse transcription PCR (RT-PCR)and Western blot. Jinlida particles reduced fasting blood glucose (FBG) cholesterol (TC), triglyceride (TG), free fatty acid (FFA)and fasting insulin (FIns) levels, raised insulin sensitive index (ISI), improved glucose tolerance, and reduced skeletal muscle lipid deposition in ApoE -/- mice significantly. Jinlida particles increased the expression of IRS-1 mRNA and protein, and reduced DGAT1. Jinlida can alleviate the expression of DGAT in skeletal muscle in fat-induced insulin resistance ApoE-/- mice.

  8. Hormone-sensitive lipase null mice exhibit signs of impaired insulin sensitivity whereas insulin secretion is intact

    DEFF Research Database (Denmark)

    Mulder, Hindrik; Sörhede-Winzell, Maria; Contreras, Juan Antonio

    2003-01-01

    of increased amounts of insulin. Impaired insulin sensitivity was further indicated by retarded glucose disposal during an insulin tolerance test. A euglycemic hyperinsulinemic clamp revealed that hepatic glucose production was insufficiently blocked by insulin in HSL null mice. In vitro, insulin......-stimulated glucose uptake into soleus muscle, and lipogenesis in adipocytes were moderately reduced, suggesting additional sites of insulin resistance. Morphometric analysis of pancreatic islets revealed a doubling of beta-cell mass in HSL null mice, which is consistent with an adaptation to insulin resistance....... Insulin secretion in vitro, examined by perifusion of isolated islets, was not impacted by HSL deficiency. Thus, HSL deficiency results in a moderate impairment of insulin sensitivity in multiple target tissues of the hormone but is compensated by hyperinsulinemia....

  9. Lipid metabolism disturbances contribute to insulin resistance and decrease insulin sensitivity by malathion exposure in Wistar rat.

    Science.gov (United States)

    Lasram, Mohamed Montassar; Bouzid, Kahena; Douib, Ines Bini; Annabi, Alya; El Elj, Naziha; El Fazaa, Saloua; Abdelmoula, Jaouida; Gharbi, Najoua

    2015-04-01

    Several studies showed that organophosphorus pesticides disturb glucose homeostasis and can increase incidence of metabolic disorders and diabetes via insulin resistance. The current study investigates the influence of malathion on glucose metabolism regulation, in vivo, during subchronic exposure. Malathion was administered orally (200 mg/kg), once a day for 28 consecutive days. Plasma glucose, insulin and Glycated hemoglobin levels were significantly increased while hepatic glycogen content was decreased in intoxicated animals compared with the control group. Furthermore, there was a significant disturbance of lipid content in subchronic treated and post-treated rats deprived of malathion for one month. In addition, we used the homeostasis model assessment (HOMA) to assess insulin resistance (HOMA-IR) and pancreatic β-cell function (HOMA-β). Our results show that malathion increases insulin resistance biomarkers and decreases insulin sensitivity indices. Statistical analysis demonstrates that there was a positive and strong significant correlation between insulin level and insulin resistance indices, HOMA-IR, HOMA-β. Similarly, a negative and significant correlation was also found between insulin level and insulin sensitivity indices. For the first time, we demonstrate that malathion induces insulin resistance in vivo using homeostasis model assessment and these changes were detectable one month after the end of exposure. To explain insulin resistance induced by malathion we focus on lipid metabolism disturbances and their interaction with many proteins involved in insulin signaling pathways.

  10. Insulin-loaded poly(epsilon-caprolactone) nanoparticles: efficient, sustained and safe insulin delivery system.

    Science.gov (United States)

    de Araújo, Thiago M; Teixeira, Zaine; Barbosa-Sampaio, Helena C; Rezende, Luiz F; Boschero, Antonio C; Durán, Nelson; Höehr, Nelci F

    2013-06-01

    The aim of this work was to develop an efficient, biodegradable, biocompatible and safe controlled release system using insulin-loaded poly(epsilon-caprolactone) (PCL) nanoparticles. The insulin-loaded PCL nanoparticles were prepared by double emulsion method (water-in-oil-in-water) using Pluronic F68 as emulsifier. Using the double emulsion method a high insulin encapsulation efficiency (90.6 +/-1.6%) with a zeta potential of -29 +/-2.7 mV and average particle size of 796 +/-10.5 nm was obtained. Insulin-loaded PCL nanoparticles showed no toxicity to MIN6 cells. Insulin nanoparticles administered subcutaneously and intraperitoneally in rats reduced glycaemia of basal levels after 15 minutes, and presented a sustainable hypoglycemic effect on insulin-dependent type 1 diabetic rats, showing to be more efficient than unencapsulated insulin. Furthermore, these nanoparticles were not hepatotoxic, as evaluated by the effect over liver cell-death and oxidative stress scavenger system in rats. These results suggest that insulin-loaded PCL nanoparticles prepared by water-in-oil-in-water emulsion method are biocompatible, efficient and safe insulin-delivering system with controlled insulin release, which indicates that it may be a powerful tool for insulin-dependent patients care.

  11. Insulin and the Brain

    Directory of Open Access Journals (Sweden)

    Grosu Cristina

    2017-12-01

    Full Text Available The brain represents an important site for the action of insulin. Besides the traditionally known importance in glucoregulation, insulin has significant neurotrophic properties and influences the brain activity: insulin influences eating behavior, regulates the storage of energy and several aspects concerning memory and knowledge. Insulin resistance and hyperinsulinism could be associated with brain aging, vascular and metabolic pathologies. Elucidating the pathways and metabolism of brain insulin could have a major impact on future targeted therapies.

  12. Exercise training performed simultaneously to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in mice

    Directory of Open Access Journals (Sweden)

    Farias JM

    2012-10-01

    Full Text Available Abstract Background The aim of the present study was to evaluate the protective effect of concurrent exercise in the degree of the insulin resistance in mice fed with a high-fat diet, and assess adiponectin receptors (ADIPOR1 and ADIPOR2 and endosomal adaptor protein APPL1 in different tissues. Methods Twenty-four mice were randomized into four groups (n = 6: chow standard diet and sedentary (C; chow standard diet and simultaneous exercise training (C-T; fed on a high-fat diet and sedentary (DIO; and fed on a high-fat diet and simultaneous exercise training (DIO-T. Simultaneously to starting high-fat diet feeding, the mice were submitted to a swimming exercise training protocol (2 x 30 minutes, with 5 minutes of interval/day, five days per week, for twelve weeks (90 days. Animals were then euthanized 48 hours after the last exercise training session, and adipose, liver, and skeletal muscle tissue were extracted for an immunoblotting analysis. Results IR, IRs, and Akt phosphorylation decreased in the DIO group in the three analyzed tissues. In addition, the DIO group exhibited ADIPOR1 (skeletal muscle and adipose tissue, ADIPOR2 (liver, and APPL1 reduced when compared with the C group. However, it was reverted when exercise training was simultaneously performed. In parallel, ADIPOR1 and 2 and APPL1 protein levels significantly increase in exercised mice. Conclusions Our findings demonstrate that exercise training performed concomitantly to a high-fat diet reduces the degree of insulin resistance and improves adipoR1-2/APPL1 protein levels in the hepatic, adipose, and skeletal muscle tissue.

  13. Effects of insulin detemir and NPH insulin on renal handling of sodium, fluid retention and weight in type 2 diabetic patients

    DEFF Research Database (Denmark)

    Hendriksen, K V; Jensen, Tonny Joran; Oturai, P

    2012-01-01

    In type 2 diabetic patients, insulin detemir (B29Lys(ε-tetradecanoyl),desB30 human insulin) induces less weight gain than NPH insulin. Due to the proposed reduction of tubular action by insulin detemir, type 2 diabetic patients should have increased urinary sodium excretion, thereby reducing extr...

  14. Investigations on the role of insulin and scorpion antivenom in scorpion envenoming syndrome

    Directory of Open Access Journals (Sweden)

    K. Radha Krishna Murthy

    2003-01-01

    Full Text Available Acute myocardiopathy in alloxan treated experimental dogs and rabbits was induced by subcutaneous (SQ injection of scorpion venom from Mesobuthus tamulus concanesis, Pocock. Envenoming resulted in an initial transient hypertension (180-320 mm Hg. followed by hypotension. Simultaneous administration of venom and species-specific scorpion antivenom (SAV prevented hypertension and hypotension. Hypotension did not occur when SAV was given 60 min after envenoming. Blood glucose, triglycerides, cholesterol, amylase, insulin, glucagon, cortisol, hematocrit, mean corpuscular volume (MCV, mean corpuscular hemoglobin (MCH, mean corpuscular hemoglobin concentration (MCHC, platelet count, red blood cell (RBC count, hemoglobin (Hb, 2,3-diphosphoglycerate (2,3-DPG, and glutathione levels were increased 60 and 90 min after envenoming. Total white blood cell (WBC count was reduced 60 min and increased 90 min after envenoming. Simultaneous administration of venom and SAV did not alter Hb, MCHC, and packed cell volume (PCV levels, or ECG, and cardiovascular, biochemical, metabolic, and hormonal changes. Hematological parameters were reversed when SAV was given 30 and 60 min after envenoming. PCV, Hb, and MCHC values returned to normal 120 min after SAV. Alloxan-treated dogs showed increased blood glucose, cholesterol, glucagon, cortisol levels; reduced glycogen content of liver, cardiac and skeletal muscles; and reduced insulin levels and insulin/ glucagon ratio (I/G ratio. Envenoming in the alloxan pre-treated dogs further increased these levels and reduced tissue glycogen content, insulin levels, and I/G ratio. Administration of 4 U of insulin to alloxan pre-treated envenomed rabbits caused a biochemical and clinical improvement and increased glycogen content of all tissues in comparison with the values from those administered with SAV to alloxan pre-treated envenomed animals. SAV administration to envenomed alloxan pre-treated rabbits did not cause clinical or

  15. Regulation of autophagy in human skeletal muscle: effects of exercise, exercise training and insulin stimulation

    Science.gov (United States)

    Fritzen, Andreas M.; Madsen, Agnete B.; Kleinert, Maximilian; Treebak, Jonas T.; Lundsgaard, Anne‐Marie; Jensen, Thomas E.; Richter, Erik A.; Wojtaszewski, Jørgen; Kiens, Bente

    2016-01-01

    Key points Regulation of autophagy in human muscle in many aspects differs from the majority of previous reports based on studies in cell systems and rodent muscle.An acute bout of exercise and insulin stimulation reduce human muscle autophagosome content.An acute bout of exercise regulates autophagy by a local contraction‐induced mechanism.Exercise training increases the capacity for formation of autophagosomes in human muscle.AMPK activation during exercise seems insufficient to regulate autophagosome content in muscle, while mTORC1 signalling via ULK1 probably mediates the autophagy‐inhibiting effect of insulin. Abstract Studies in rodent muscle suggest that autophagy is regulated by acute exercise, exercise training and insulin stimulation. However, little is known about the regulation of autophagy in human skeletal muscle. Here we investigate the autophagic response to acute one‐legged exercise, one‐legged exercise training and subsequent insulin stimulation in exercised and non‐exercised human muscle. Acute one‐legged exercise decreased (Pexercise in human muscle. The decrease in LC3‐II/LC3‐I ratio did not correlate with activation of 5′AMP activated protein kinase (AMPK) trimer complexes in human muscle. Consistently, pharmacological AMPK activation with 5‐aminoimidazole‐4‐carboxamide riboside (AICAR) in mouse muscle did not affect the LC3‐II/LC3‐I ratio. Four hours after exercise, insulin further reduced (Pexercised and non‐exercised leg in humans. This coincided with increased Ser‐757 phosphorylation of Unc51 like kinase 1 (ULK1), which is suggested as a mammalian target of rapamycin complex 1 (mTORC1) target. Accordingly, inhibition of mTOR signalling in mouse muscle prevented the ability of insulin to reduce the LC3‐II/LC3‐I ratio. In response to 3 weeks of one‐legged exercise training, the LC3‐II/LC3‐I ratio decreased (Pexercise and insulin stimulation reduce muscle autophagosome content, while exercise

  16. Low-activation Mn-Cr austenitic stainless steel with further reduced content of long-lived radioactive elements

    Energy Technology Data Exchange (ETDEWEB)

    Onozuka, M.; Saida, T.; Hirai, S. [Mitsubishi Heavy Ind. Ltd., Yokohama (Japan); Kusuhashi, M.; Sato, I.; Hatakeyama, T. [The Japan Steel Works Ltd., Chatsu-machi 4, Muroran 051-8505 (Japan)

    1998-06-01

    Low-activation austenitic stainless steel based on Mn-Cr non-magnetic steels has been developed. The alloying elements of long-life activation, such as Ni, Mo and Co, were eliminated and substituted with Mn along with an addition of N. A Mn-Cr austenitic stainless steel, 24.5Mn-13.5Cr-0.02C-0.2N, has been developed successfully. Examined material properties, including mechanical, thermal and magnetic properties, as well as weldability and characteristics of corrosion resistance, are presented. It was found that the alloy has excellent material properties virtually equivalent to those of 316SS. In this study, the applicability of the Schaeffler, DeLong and Hull constitution diagrams for the stainless steels with low Ni and high Mn contents was also examined. The boundary conditions distinguishing the single austenite phase from the others have been identified for the Mn-Cr steels. (orig.) 22 refs.

  17. Low-activation Mn Cr austenitic stainless steel with further reduced content of long-lived radioactive elements

    Science.gov (United States)

    Onozuka, Masanori; Saida, Tomikane; Hirai, Shouzou; Kusuhashi, Mikio; Sato, Ikuo; Hatakeyama, Tsuyoshi

    1998-06-01

    Low-activation austenitic stainless steel based on Mn-Cr non-magnetic steels has been developed. The alloying elements of long-life activation, such as Ni, Mo and Co, were eliminated and substituted with Mn along with an addition of N. A Mn-Cr austenitic stainless steel, 24.5Mn-13.5Cr-0.02C-0.2N, has been developed successfully. Examined material properties, including mechanical, thermal and magnetic properties, as well as weldability and characteristics of corrosion resistance, are presented. It was found that the alloy has excellent material properties virtually equivalent to those of 316SS. In this study, the applicability of the Schaeffler, DeLong and Hull constitution diagrams for the stainless steels with low Ni and high Mn contents was also examined. The boundary conditions distinguishing the single austenite phase from the others have been identified for the Mn-Cr steels.

  18. Feasibility of Reducing the Fiber Content in Ultra-High-Performance Fiber-Reinforced Concrete under Flexure.

    Science.gov (United States)

    Park, Jung-Jun; Yoo, Doo-Yeol; Park, Gi-Joon; Kim, Sung-Wook

    2017-01-28

    In this study, the flexural behavior of ultra-high-performance fiber-reinforced concrete (UHPFRC) is examined as a function of fiber length and volume fraction. Straight steel fiber with three different lengths ( l f ) of 13, 19.5, and 30 mm and four different volume fractions ( v f ) of 0.5%, 1.0%, 1.5%, and 2.0% are considered. Test results show that post-cracking flexural properties of UHPFRC, such as flexural strength, deflection capacity, toughness, and cracking behavior, improve with increasing fiber length and volume fraction, while first-cracking properties are not significantly influenced by fiber length and volume fraction. A 0.5 vol % reduction of steel fiber content relative to commercial UHPFRC can be achieved without deterioration of flexural performance by replacing short fibers ( l f of 13 mm) with longer fibers ( l f of 19.5 mm and 30 mm).

  19. Fibromodulin deficiency reduces collagen structural network but not glycosaminoglycan content in a syngeneic model of colon carcinoma.

    Science.gov (United States)

    Olsson, P Olof; Kalamajski, Sebastian; Maccarana, Marco; Oldberg, Åke; Rubin, Kristofer

    2017-01-01

    Tumor barrier function in carcinoma represents a major challenge to treatment and is therefore an attractive target for increasing drug delivery. Variables related to tumor barrier include aberrant blood vessels, high interstitial fluid pressure, and the composition and structure of the extracellular matrix. One of the proteins associated with dense extracellular matrices is fibromodulin, a collagen fibrillogenesis modulator expressed in tumor stroma but scarce in normal loose connective tissues. Here, we investigated the effects of fibromodulin on stroma ECM in a syngeneic murine colon carcinoma model. We show that fibromodulin deficiency decreased collagen fibril thickness but glycosaminoglycan content and composition were unchanged. Furthermore, vascular density, pericyte coverage and macrophage amount were unaffected. Fibromodulin can therefore be a unique effector of dense collagen matrix assembly in tumor stroma and, without affecting other major matrix components or the cellular composition, can function as a main agent in tumor barrier function.

  20. In vivo response of Mesocestoides vogae to human insulin.

    Science.gov (United States)

    Canclini, L; Esteves, A

    2009-02-01

    Successful host invasion by parasitic helminths involves detection and appropriate response to a range of host-derived signals. Insulin signal response pathways are ancient and highly-conserved throughout the metazoans. However, very little is known about helminth insulin signalling and the potential role it may play in host-parasite interactions. The response of Mesocestoides vogae (Cestoda: Cyclophyllidea) larvae to human insulin was investigated, focusing on tyrosine-phosphorylation status, glucose content, survival and asexual reproduction rate. Parasite larvae were challenged with different levels of insulin for variable periods. The parameters tested were influenced by human insulin, and suggested a host-parasite molecular dialogue.

  1. Quercetin suppresses insulin receptor signaling through inhibition of the insulin ligand–receptor binding and therefore impairs cancer cell proliferation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Feng [Department of Gastroenterology, The Tenth People’s Hospital of Shanghai, Tongji University, Shanghai 200072 (China); Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Yang, Yong, E-mail: yyang@houstonmethodist.org [Department of Nanomedicine, Houston Methodist Research Institute, Houston, TX 77030 (United States); Department of Medicine, Weill Cornell Medical College, New York, NY 10065 (United States)

    2014-10-03

    Graphical abstract: - Highlights: • Quercetin inhibits insulin ligand–receptor interactions. • Quercetin reduces downstream insulin receptor signaling. • Quercetin blocks insulin induced glucose uptake. • Quercetin suppresses insulin stimulated cancer cell proliferation and tumor growth. - Abstract: Although the flavonoid quercetin is known to inhibit activation of insulin receptor signaling, the inhibitory mechanism is largely unknown. In this study, we demonstrate that quercetin suppresses insulin induced dimerization of the insulin receptor (IR) through interfering with ligand–receptor interactions, which reduces the phosphorylation of IR and Akt. This inhibitory effect further inhibits insulin stimulated glucose uptake due to decreased cell membrane translocation of glucose transporter 4 (GLUT4), resulting in impaired cancer cell proliferation. The effect of quercetin in inhibiting tumor growth was also evident in an in vivo model, indicating a potential future application for quercetin in the treatment of cancers.

  2. Quercetin suppresses insulin receptor signaling through inhibition of the insulin ligand–receptor binding and therefore impairs cancer cell proliferation

    International Nuclear Information System (INIS)

    Wang, Feng; Yang, Yong

    2014-01-01

    Graphical abstract: - Highlights: • Quercetin inhibits insulin ligand–receptor interactions. • Quercetin reduces downstream insulin receptor signaling. • Quercetin blocks insulin induced glucose uptake. • Quercetin suppresses insulin stimulated cancer cell proliferation and tumor growth. - Abstract: Although the flavonoid quercetin is known to inhibit activation of insulin receptor signaling, the inhibitory mechanism is largely unknown. In this study, we demonstrate that quercetin suppresses insulin induced dimerization of the insulin receptor (IR) through interfering with ligand–receptor interactions, which reduces the phosphorylation of IR and Akt. This inhibitory effect further inhibits insulin stimulated glucose uptake due to decreased cell membrane translocation of glucose transporter 4 (GLUT4), resulting in impaired cancer cell proliferation. The effect of quercetin in inhibiting tumor growth was also evident in an in vivo model, indicating a potential future application for quercetin in the treatment of cancers

  3. Molecular Mechanisms of Insulin Resistance in Chronic Kidney Disease

    Science.gov (United States)

    Thomas, Sandhya S.; Zhang, Liping; Mitch, William E.

    2015-01-01

    Insulin resistance refers to reduced sensitivity of organs to insulin-initiated biologic processes that result in metabolic defects. Insulin resistance is common in patients with end-stage renal disease but also occurs in patients with chronic kidney disease (CKD), even when the serum creatinine is minimally increased. Following insulin binding to its receptor, auto-phosphorylation of the insulin receptor is followed by kinase reactions that phosphorylate insulin receptor substrate-1 (IRS-1), phosphatidylinositol 3-kinase (PI3K) and Akt. In fact, low levels of Akt phosphorylation (p-Akt) identifies the presence of the insulin resistance that leads to metabolic defects in insulin-initiated metabolism of glucose, lipids and muscle proteins. Besides CKD, other complex conditions (e.g., inflammation, oxidative stress, metabolic acidosis, aging and excess angiotensin II) reduce p-Akt resulting in insulin resistance. Insulin resistance in each of these conditions is due to activation of different, E3 ubiquitin ligases which specifically conjugate ubiquitin to IRS-1 marking it for degradation in the ubiquitin-proteasome system (UPS). Consequently, IRS-1 degradation suppresses insulin-induced intracellular signaling, causing insulin resistance. Understanding mechanisms of insulin resistance could lead to therapeutic strategies that improve the metabolism of patients with CKD. PMID:26444029

  4. MicroRNA-214 Reduces Insulin-like Growth Factor-1 (IGF-1) Receptor Expression and Downstream mTORC1 Signaling in Renal Carcinoma Cells*

    Science.gov (United States)

    Das, Falguni; Dey, Nirmalya; Bera, Amit; Kasinath, Balakuntalam S.; Ghosh-Choudhury, Nandini; Choudhury, Goutam Ghosh

    2016-01-01

    Elevated IGF-1/insulin-like growth factor-1 receptor (IGF-1R) autocrine/paracrine signaling in patients with renal cell carcinoma is associated with poor prognosis of the disease independent of their von Hippel-Lindau (VHL) status. Increased expression of IGF-1R in renal cancer cells correlates with their potency of tumor development and progression. The mechanism by which expression of IGF-1R is increased in renal carcinoma is not known. We report that VHL-deficient and VHL-positive renal cancer cells possess significantly decreased levels of mature, pre-, and pri-miR-214 than normal proximal tubular epithelial cells. We identified an miR-214 recognition element in the 3′UTR of IGF-1R mRNA and confirmed its responsiveness to miR-214. Overexpression of miR-214 decreased the IGF-1R protein levels, resulting in the inhibition of Akt kinase activity in both types of renal cancer cells. IGF-1 provoked phosphorylation and inactivation of PRAS40 in an Akt-dependent manner, leading to the activation of mTORC1 signal transduction to increase phosphorylation of S6 kinase and 4EBP-1. Phosphorylation-deficient mutants of PRAS40 and 4EBP-1 significantly inhibited IGF-1R-driven proliferation of renal cancer cells. Expression of miR-214 suppressed IGF-1R-induced phosphorylation of PRAS40, S6 kinase, and 4EBP-1, indicating inhibition of mTORC1 activity. Finally, miR-214 significantly blocked IGF-1R-forced renal cancer cell proliferation, which was reversed by expression of 3′UTR-less IGF-1R and constitutively active mTORC1. Together, our results identify a reciprocal regulation of IGF-1R levels and miR-214 expression in renal cancer cells independent of VHL status. Our data provide evidence for a novel mechanism for IGF-1R-driven renal cancer cell proliferation involving miR-214 and mTORC1. PMID:27226530

  5. A model to estimate insulin sensitivity in dairy cows

    OpenAIRE

    Holtenius, Paul; Holtenius, Kjell

    2007-01-01

    Abstract Impairment of the insulin regulation of energy metabolism is considered to be an etiologic key component for metabolic disturbances. Methods for studies of insulin sensitivity thus are highly topical. There are clear indications that reduced insulin sensitivity contributes to the metabolic disturbances that occurs especially among obese lactating cows. Direct measurements of insulin sensitivity are laborious and not suitable for epidemiological studies. We have therefore adopted an i...

  6. Insulin resistance in drug naive patients with multiple sclerosis

    OpenAIRE

    Kostić Smiljana; Kolić Ivana; Raičević Ranko; Stojanović Zvezdana; Kostić Dejan; Dinčić Evica

    2017-01-01

    Background/Aim. Due to the fact that there is a relatively small number of data related to systemic insulin abnormalities in the multiple sclerosis (MS), the main objective of our study was to determine whether a dysbalance of glucose and insulin metabolism exist in patients with natural course of MS. Our hypothesis was that the metabolic disorder that characterizes state of the insulin resistance (IR) and reduced insulin sensitivity (IS) in untreated patie...

  7. Arabidopsis thaliana ggt1 photorespiratory mutants maintain leaf carbon/nitrogen balance by reducing RuBisCO content and plant growth.

    Science.gov (United States)

    Dellero, Younès; Lamothe-Sibold, Marlène; Jossier, Mathieu; Hodges, Michael

    2015-09-01

    Metabolic and physiological analyses of glutamate:glyoxylate aminotransferase 1 (GGT1) mutants were performed at the global leaf scale to elucidate the mechanisms involved in their photorespiratory growth phenotype. Air-grown ggt1 mutants showed retarded growth and development, that was not observed at high CO2 (3000 μL L(-1) ). When compared to wild-type (WT) plants, air-grown ggt1 plants exhibited glyoxylate accumulation, global changes in amino acid amounts including a decrease in serine content, lower organic acid levels, and modified ATP/ADP and NADP(+) /NADPH ratios. When compared to WT plants, their net CO2 assimilation rates (An ) were 50% lower and this mirrored decreases in ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) contents. High CO2 -grown ggt1 plants transferred to air revealed a rapid decrease of An and photosynthetic electron transfer rate while maintaining a high energetic state. Short-term (a night period and 4 h of light) transferred ggt1 leaves accumulated glyoxylate and exhibited low serine contents, while other amino acid levels were not modified. RuBisCO content, activity and activation state were not altered after a short-term transfer while the ATP/ADP ratio was lowered in ggt1 rosettes. However, plant growth and RuBisCO levels were both reduced in ggt1 leaves after a long-term (12 days) acclimation to air from high CO2 when compared to WT plants. The data are discussed with respect to a reduced photorespiratory carbon recycling in the mutants. It is proposed that the low An limits nitrogen-assimilation, this decreases leaf RuBisCO content until plants attain a new homeostatic state that maintains a constant C/N balance and leads to smaller, slower growing plants. © 2015 The Authors The Plant Journal © 2015 John Wiley & Sons Ltd.

  8. [Effect of twirling-reinforcing-reducing needling manipulations on contents of serum acetylcholine and arterial NOS and cGMP in stress-induced hypertension rats].

    Science.gov (United States)

    Liu, Wei; Zhu, Ling-Qun; Chen, Si-Si; Lu, Shu-Chao; Tang, Jie; Liu, Qing-Guo

    2015-04-01

    To observe the effect of twirling-reinforcing or reducing needling manipulations on plasma acetylcholine (Ach) content and expression of nitric oxide synthetase (NOS) and cyclic guanosine monophosphate (cGMP) in thoracic artery tissue in stress-induced hypertension rats. A total of 60 male rats were randomly divided into blank control, model, acupuncture (no-needle-manipulation) , twirling-reinforcing needling and twirling-reducing needling groups (n = 12 in each group). The stress hypertension model was established by giving the animals with noise and electric shock stimulation (paw), twice a day for 15 days. Acupuncture stimulation was applied to bilateral "Taichong" (LR 3) for 1 min, followed by retaining the needles for 20 min. The treatment was conducted once daily for 7 days. Systolic blood pressure of the rat's tail was detected with non-invasive method and plasma Ach, and NOS and cGMP contents in the thoracic artery tissue were measured using ELISA method. Compared with the control group, the systolic blood pressure was significantly higher in the model group after 15 days' stress stimulation (P arterial NOS and cGMP were markedly down-regulated (P arterial cGMP content was found in the no-needle-manipulation group (P > 0.05). The effect of the twirling-reducing needling was superior to that of no-needle-manipulation and twirling-reinforcing needling in lowering blood pressure and raising plasma Ach content (P hypertensive effect in stress hypertension rats, which may be associated with its effects in raising blood Ach, and arterial NOS and cGMP levels.

  9. Insulin resistance in porphyria cutanea tarda.

    Science.gov (United States)

    Calcinaro, F; Basta, G; Lisi, P; Cruciani, C; Pietropaolo, M; Santeusanio, F; Falorni, A; Calafiore, R

    1989-06-01

    It has been reported that patients with porphyria cutanea tarda (PCT) develop carbohydrate (CHO) intolerance and manifest diabetes melitus (DM) more frequently than the normal population. In order to verify whether this is due to insulin resistance we studied 5 patients with PCT and 5 normal subjects matched for age, sex and weight. In all the patients an evaluation consisted of the glycemic curve and insulin response to an iv glucose tolerance test (IVGTT: 0.33 g/kg) as well as of an evaluation of the circulating monocyte insulin receptors. Blood samples were drawn in the basal state to measure plasma levels of NEFA, glycerol, and intermediate metabolites. The patients with PCT showed normal glucose tolerance which was obtained, however, at the expense of the elevated insulin levels: therefore a condition of insulin resistance was demonstrated in these subjects. An involvement of the lipid metabolism, observed by the raised levels of plasma NEFA and glycerol, was also evident. The insulin binding to circulating monocytes was reduced but not enough to justify the degree of insulin resistance observed. Therefore, it could be hypothesized, in agreement with similar studies, that a postreceptor defect is responsible for the insulin-resistance observed in patients with PCT and that the reduction of insulin receptors is determined by the down regulation in response to elevated insulinemic levels. An alteration of the porphyrin metabolism might be responsible for this disorder.

  10. Dimethylarginine Dimethylaminohydrolase Overexpression enhances Insulin Sensitivity

    Science.gov (United States)

    Sydow, Karsten; Mondon, Carl E.; Schrader, Joerg; Konishi, Hakuoh; Cooke, John P.

    2011-01-01

    Objective Previous studies suggest that nitric oxide (NO) may modulate insulin-induced uptake of glucose in insulin-sensitive tissues. Asymmetric dimethylarginine (ADMA) is an endogenous inhibitor of NO synthase (NOS). We hypothesized that a reduction in endogenous ADMA would increase NO synthesis and thereby enhance insulin sensitivity. Methods and Results To test this hypothesis we employed a transgenic mouse in which we overexpressed human dimethylarginine dimethylaminohydrolase (DDAH-I). The DDAH-I mice had lower plasma ADMA at all ages (22–70 weeks) by comparison to wild-type (WT) littermates. With a glucose challenge, WT mice showed a prompt increase in ADMA, whereas DDAH-I mice had a blunted response. Furthermore, DDAH-I mice had a blunted increase in plasma insulin and glucose levels after glucose challenge, with a 50% reduction in the insulin resistence index, consistent with enhanced sensitivity to insulin. In liver, we observed an increased Akt phosphorylation in the DDAH-I mice after i.p. glucose challenge. Incubation of skeletal muscle from WT mice ex vivo with ADMA (2μM) markedly suppressed insulin-induced glycogen synthesis in fast-twitch but not slow-twitch muscle. Conclusions These findings suggest that the endogenous NOS inhibitor ADMA reduces insulin sensitivity, consistent with previous observations that NO plays a role in insulin sensitivity. PMID:18239148

  11. Optimization of Protein Extraction from Spirulina platensis to Generate a Potential Co-Product and a Biofuel Feedstock with Reduced Nitrogen Content

    Energy Technology Data Exchange (ETDEWEB)

    Parimi, Naga Sirisha; Singh, Manjinder; Kastner, James R.; Das, Keshav C., E-mail: kdas@engr.uga.edu [College of Engineering, The University of Georgia, Athens, GA (United States); Forsberg, Lennart S.; Azadi, Parastoo [Complex Carbohydrate Research Center, The University of Georgia, Athens, GA (United States)

    2015-06-23

    The current work reports protein extraction from Spirulina platensis cyanobacterial biomass in order to simultaneously generate a potential co-product and a biofuel feedstock with reduced nitrogen content. S. platensis cells were subjected to cell disruption by high-pressure homogenization and subsequent protein isolation by solubilization at alkaline pH followed by precipitation at acidic pH. Response surface methodology was used to optimize the process parameters – pH, extraction (solubilization/precipitation) time and biomass concentration for obtaining maximum protein yield. The optimized process conditions were found to be pH 11.38, solubilization time of 35 min and biomass concentration of 3.6% (w/w) solids for the solubilization step, and pH 4.01 and precipitation time of 60 min for the precipitation step. At the optimized conditions, a high protein yield of 60.7% (w/w) was obtained. The protein isolate (co-product) had a higher protein content [80.6% (w/w)], lower ash [1.9% (w/w)] and mineral content and was enriched in essential amino acids, the nutritious γ-linolenic acid and other high-value unsaturated fatty acids compared to the original biomass. The residual biomass obtained after protein extraction had lower nitrogen content and higher total non-protein content than the original biomass. The loss of about 50% of the total lipids from this fraction did not impact its composition significantly owing to the low lipid content of S. platensis (8.03%).

  12. Optimization of Protein Extraction from Spirulina platensis to Generate a Potential Co-Product and a Biofuel Feedstock with Reduced Nitrogen Content

    International Nuclear Information System (INIS)

    Parimi, Naga Sirisha; Singh, Manjinder; Kastner, James R.; Das, Keshav C.; Forsberg, Lennart S.; Azadi, Parastoo

    2015-01-01

    The current work reports protein extraction from Spirulina platensis cyanobacterial biomass in order to simultaneously generate a potential co-product and a biofuel feedstock with reduced nitrogen content. S. platensis cells were subjected to cell disruption by high-pressure homogenization and subsequent protein isolation by solubilization at alkaline pH followed by precipitation at acidic pH. Response surface methodology was used to optimize the process parameters – pH, extraction (solubilization/precipitation) time and biomass concentration for obtaining maximum protein yield. The optimized process conditions were found to be pH 11.38, solubilization time of 35 min and biomass concentration of 3.6% (w/w) solids for the solubilization step, and pH 4.01 and precipitation time of 60 min for the precipitation step. At the optimized conditions, a high protein yield of 60.7% (w/w) was obtained. The protein isolate (co-product) had a higher protein content [80.6% (w/w)], lower ash [1.9% (w/w)] and mineral content and was enriched in essential amino acids, the nutritious γ-linolenic acid and other high-value unsaturated fatty acids compared to the original biomass. The residual biomass obtained after protein extraction had lower nitrogen content and higher total non-protein content than the original biomass. The loss of about 50% of the total lipids from this fraction did not impact its composition significantly owing to the low lipid content of S. platensis (8.03%).

  13. Decrease in glutathione content in boar sperm after cryopreservation. Effect of the addition of reduced glutathione to the freezing and thawing extenders.

    Science.gov (United States)

    Gadea, Joaquín; Sellés, Elena; Marco, Marco Antonio; Coy, Pilar; Matás, Carmen; Romar, Raquel; Ruiz, Salvador

    2004-08-01

    Although glutathione content in boar spermatozoa has been previously reported, the effect of reduced glutathione (GSH) on semen parameters and the fertilizing ability of boar spermatozoa after cryopreservation has never been evaluated. In this study, GSH content was determined in ejaculated boar spermatozoa before and after cryopreservation. Semen samples were centrifuged and GSH content in the resulting pellet monitored spectrophotometrically. The fertilizing ability of frozen-thawed boar sperm was also tested in vitro by incubating sperm with in vitro matured oocytes obtained from gilts. GSH content in fresh semen was 3.84 +/- 0.21 nM GSH/10(8) sperm. Following semen cryopreservation, there was a 32% decrease in GSH content (P boars and after various preservation protocols (P = 0.0102 ). The effect of addition of GSH to the freezing and thawing extenders was also evaluated. Addition of 5 mM GSH to the freezing extender did not have a significant effect on standard semen parameters or sperm fertilizing ability after thawing. In contrast, when GSH was added to the thawing extender, a dose-dependent tendency to increase in sperm fertilizing ability was observed, although no differences were observed in standard semen parameters. In summary, (i) there was a loss in GSH content after cryopreservation of boar semen; (ii) addition of GSH to the freezing extender did not result in any improvement in either standard semen parameters or sperm fertilizing ability; and (iii) addition of GSH to the thawing extender resulted in a significant increase in sperm fertilizing ability. Nevertheless, future studies must conclude if this is the case for all boars. Furthermore, since addition of GSH to the thawing extender did not result in an improvement in standard semen parameters, this suggests that during the thawing process, GSH prevents damage of a sperm property that is critical in the fertilization process but that is not measured in the routine semen analysis.

  14. Insulin signaling pathways in lepidopteran steroidogenesis

    Directory of Open Access Journals (Sweden)

    Wendy eSmith

    2014-02-01

    Full Text Available Molting and metamorphosis are stimulated by the secretion of ecdysteroid hormones from the prothoracic glands. Insulin-like hormones have been found to enhance prothoracic gland activity, providing a mechanism to link molting to nutritional state. In silk moths (Bombyx mori, the prothoracic glands are directly stimulated by insulin and the insulin-like hormone bombyxin. Further, in Bombyx , the neuropeptide prothoracicotropic hormone (PTTH appears to act at least in part through the insulin-signaling pathway. In the prothoracic glands of Manduca sexta, while insulin stimulates the phosphorylation of the insulin receptor and Akt, neither insulin nor bombyxin II stimulate ecdysone secretion. Involvement of the insulin-signaling pathway in Manduca prothoracic glands was explored using two inhibitors of phosphatidylinositol-3-kinase (PI3K, LY294002 and wortmannin. PI3K inhibitors block the phosphorylation of Akt and 4EBP but have no effect on ecdysone secretion, or on the phosphorylation of the MAPkinase, ERK. Inhibitors that block phosphorylation of ERK, including the MEK inhibitor U0126, and high doses of the RSK inhibitor SL0101, effectively inhibit ecdysone secretion. The results highlight differences between the two lepidopteran insects most commonly used to directly study ecdysteroid secretion. In Bombyx, the PTTH and insulin-signaling pathways intersect; both insulin and PTTH enhance the phosphorylation of Akt and stimulate ecdysteroid secretion, and inhibition of PI3K reduces ecdysteroid secretion. By contrast, in Manduca, the action of PTTH is distinct from insulin. The results highlight species differences in the roles of translational regulators such as 4EBP, and members of the MAPkinase pathway such as ERK and RSK, in the effects of nutritionally-sensitive hormones such as insulin on ecdysone secretion and molting.

  15. Dietary fiber, plasma insulin, and obesity.

    Science.gov (United States)

    Albrink, M J

    1978-10-01

    The relationship between obesity, insulin resistance, and hyperinsulinemia is briefly reviewed. The possibility is considered that excess insulin secretion is the cause rather than the result of insulin resistance and obesity. Glucose administration is one of the most frequently studied of those factors known to stimulate insulin secretion. Much less well documented is the fact that meals of equal protein, fat, and carbohydrate content may cause different responses of plasma glucose and insulin. An experiment is reported in which the effects of a high-carbohydrate, high-fiber meal administered to seven healthy young adults were compared with the effects of a meal equally high in carbohydrate but composed largely of glucose in liquid formula form. The high-fiber meal caused an insulin rise less than half that caused by the liquid formula meal although the plasma glucose response to the two meals was not significantly different. The hypothesis is proposed that a high-carbohydrate, fiber-depleted diet, high in simple sugars, by repeatedly stimulating an excessive insulin response, may lead to insulin resistance and obesity in susceptible individuals and may play a role in the common occurrence of obesity in industrialized societies.

  16. Soybean and sunflower oil-induced insulin resistance correlates with impaired GLUT4 protein expression and translocation specifically in white adipose tissue.

    Science.gov (United States)

    Poletto, Ana Cláudia; Anhê, Gabriel Forato; Eichler, Paula; Takahashi, Hilton Kenji; Furuya, Daniela Tomie; Okamoto, Maristela Mitiko; Curi, Rui; Machado, Ubiratan Fabres

    2010-03-01

    Free fatty acids are known for playing a crucial role in the development of insulin resistance. High fat intake is known for impairing insulin sensitivity; however, the effect of vegetable-oil injections have never been investigated. The present study investigated the effects of daily subcutaneous injections (100 microL) of soybean (SB) and sunflower (SF) oils, during 7 days. Both treated groups developed insulin resistance as assessed by insulin tolerance test. The mechanism underlying the SB- and SF-induced insulin resistance was shown to involve GLUT4. In SB- and SF-treated animals, the GLUT4 protein expression was reduced approximately 20% and 10 min after an acute in vivo stimulus with insulin, the plasma membrane GLUT4 content was approximately 60% lower in white adipose tissue (WAT). No effects were observed in skeletal muscle. Additionally, both oil treatments increased mainly the content of palmitic acid ( approximately 150%) in WAT, which can contribute to explain the GLUT4 regulations. Altogether, the present study collects evidence that those oil treatments might generate insulin resistance by targeting GLUT4 expression and translocation specifically in WAT. These alterations are likely to be caused due to the specific local increase in saturated fatty acids that occurred as a consequence of oil daily injections. 2010 John Wiley & Sons, Ltd.

  17. Alteration in insulin action

    DEFF Research Database (Denmark)

    Tanti, J F; Gual, P; Grémeaux, T

    2004-01-01

    Insulin resistance, when combined with impaired insulin secretion, contributes to the development of type 2 diabetes. Insulin resistance is characterised by a decrease in insulin effect on glucose transport in muscle and adipose tIssue. Tyrosine phosphorylation of insulin receptor substrate 1 (IRS......-1) and its binding to phosphatidylinositol 3-kinase (PI 3-kinase) are critical events in the insulin signalling cascade leading to insulin-stimulated glucose transport. Modification of IRS-1 by serine phosphorylation could be one of the mechanisms leading to a decrease in IRS-1 tyrosine...... to phosphorylate these serine residues have been identified. These exciting results suggest that serine phosphorylation of IRS-1 is a possible hallmark of insulin resistance in biologically insulin responsive cells or tIssues. Identifying the pathways by which "diabetogenic" factors activate IRS-1 kinases...

  18. Dipeptidyl peptidase-4 impairs insulin signaling and promotes lipid accumulation in hepatocytes

    International Nuclear Information System (INIS)

    Rufinatscha, Kerstin; Radlinger, Bernhard; Dobner, Jochen; Folie, Sabrina; Bon, Claudia; Profanter, Elisabeth; Ress, Claudia; Salzmann, Karin; Staudacher, Gabriele; Tilg, Herbert; Kaser, Susanne

    2017-01-01

    Dipeptidyl-peptidase 4 [DPP-4) has evolved into an important target in diabetes therapy due to its role in incretin hormone metabolism. In contrast to its systemic effects, cellular functions of membranous DPP-4 are less clear. Here we studied the role of DPP-4 in hepatic energy metabolism. In order to distinguish systemic from cellular effects we established a cell culture model of DPP-4 knockdown in human hepatoma cell line HepG2. DPP-4 suppression was associated with increased basal glycogen content due to enhanced insulin signaling as shown by increased phosphorylation of insulin-receptor substrate 1 (IRS-1), protein kinase B/Akt and mitogen-activated protein kinases (MAPK)/ERK, respectively. Additionally, glucose-6-phosphatase cDNA expression was significantly decreased in DPP-4 deficiency. Reduced triglyceride content in DPP-4 knockdown cells was paralleled by enhanced expressions of peroxisome proliferator-activated receptor alpha (PPARα) and carnitine palmitoyltransferase −1 (CPT-1) while sterol regulatory element-binding protein 1c (SREBP-1c) expression was significantly decreased. Our data suggest that hepatic DPP-4 induces a selective pathway of insulin resistance with reduced glycogen storage, enhanced glucose output and increased lipid accumulation in the liver. Hepatic DPP-4 might be a novel target in fatty liver disease in patients with glucose intolerance. - Highlights: • DPP-IV knockdown results in increased insulin signaling in hepatocytes. • Increased fatty acid oxidation and decreased lipogenesis result in reduced hepatic triglyceride content in DPP-IV deficiency. • Hepatic DPP-IV induces a selective pathway of insulin resistance with increased triglyceride accumulation in the liver.

  19. Effects of reduction temperature to Ni and Fe content and the morphology of agglomerate of reduced laterite limonitic nickel ore by coal-bed method

    Science.gov (United States)

    Abdul, Fakhreza; Pintowantoro, Sungging; Kawigraha, Adji; Nursidiq, Ahlidin

    2018-04-01

    As the current drop of nickel sulfide ore on earth, the attention to nickel laterite ore processing was inscreased in order to fulfill the future nickel demand needs. This research aims to optimized the process of nickel laterite ore extraction using coal bed method. This research was conducted by reducing low grade nickel laterite ore (limonitic) with nickel content of 1.25 %. The reduction process was carried out using CO gas which formed by the reaction of coal and dolomite. The Briquette of nickel ore, coal, Na2SO4 mixtures incorporated in the crucible with bed, then reduced for 6 hours at the temperature of 1200 °C. 1400 °C, and 1400 °C. The result of the research shown that the highest increase of Ni content and Ni recovery value was in the reduction temperature of 1400 °C with the increase of 3.44 %, and the recovery value of Ni equal to 86.75 %. While the highest increase of Fe content and Fe recovery value, respectively, was in the reduction temperature of 1300 °C with the increase of 22.67 % and 1200 °C with Fe recovery value of 89.41 %.

  20. A Phenylurea Cytokinin, CPPU, Elevated Reducing Sugar and Correlated to Andrographolide Contents in Leaves of Andrographis paniculata (Burm. F.) Wall. Ex Nees.

    Science.gov (United States)

    Worakan, Phapawee; Karaket, Netiya; Maneejantra, Nuchada; Supaibulwatana, Kanyaratt

    2017-02-01

    Cytokinins are phytohormones that play multiple roles to control plant growth and development. In this study, leaf biomass and the production of andrographolide compounds in a medicinal plant Andrographis paniculata were significantly increased after exogenously treating with the synthetic cytokinin cytokinin-1-(2-chloro-4-pyridyl)-3-phenylurea (CPPU) at 0 (water), 5, or 10 mg L -1 and observed the results for 24 h, 48 h, and 7 days of treatment. It was found that CPPU could significantly enhance new axillary bud formation and further promote branching 4.6-5.6-fold higher, resulting in higher fresh weight (FW) and dry weight (DW) than the control. Application of CPPU at 5 mg L -1 significantly promoted the highest contents of total reducing sugar at 2.5-fold in leaves and at 1.5-fold in roots. Although treatments of CPPU significantly affected the increasing contents of chlorophyll and carotenoid (1.2-1.6-fold), CPPU at 10 mg L -1 slightly caused leaf stress and chlorophyll reduction. Interestingly, 5 mg L -1 CPPU could enhance andrographolide content, an active anti-infectious compound in Andrographis paniculata (2.2-fold higher than the control) that reached the highest content at 24 h after treatment. This study suggested that CPPU should be suitable for field application to promote leaf yields and induce the production of useful pharmaceutical compounds in Andrographis paniculata.

  1. Short-term fasting promotes insulin expression in rat hypothalamus.

    Science.gov (United States)

    Dakic, Tamara B; Jevdjovic, Tanja V; Peric, Mina I; Bjelobaba, Ivana M; Markelic, Milica B; Milutinovic, Bojana S; Lakic, Iva V; Jasnic, Nebojsa I; Djordjevic, Jelena D; Vujovic, Predrag Z

    2017-07-01

    In the hypothalamus, insulin takes on many roles involved in energy homoeostasis. Therefore, the aim of this study was to examine hypothalamic insulin expression during the initial phase of the metabolic response to fasting. Hypothalamic insulin content was assessed by both radioimmunoassay and Western blot. The relative expression of insulin mRNA was examined by qPCR. Immunofluorescence and immunohistochemistry were used to determine the distribution of insulin immunopositivity in the hypothalamus. After 6-h fasting, both glucose and insulin levels were decreased in serum but not in the cerebrospinal fluid. Our study showed for the first time that, while the concentration of circulating glucose and insulin decreased, both insulin mRNA expression and insulin content in the hypothalamic parenchyma were increased after short-term fasting. Increased insulin immunopositivity was detected specifically in the neurons of the hypothalamic periventricular nucleus and in the ependymal cells of fasting animals. These novel findings point to the complexity of mechanisms regulating insulin expression in the CNS in general and in the hypothalamus in particular. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

  2. Reducing crude protein content with supplementation of synthetic lysine and threonine in barley - rapeseed meal - pea diets for growing pigs

    Directory of Open Access Journals (Sweden)

    Jarmo Valaja

    1993-03-01

    Full Text Available This study was conducted to determine the possibility to use synthetic amino acids to lower the nitrogen output from pig production. A performance experiment was carried out with 120triplet-fed growing pigs whose dietary crude protein was reduced from 179 g/feed unit (FU= 0.7 kg starch equivalent to 160, 140 and 122 g/FU, respectively. The diets were supplemented with synthetic lysine and threonine to keep the level of these amino acids constant. Dietary protein reduction did not affect the growth performance or feed conversion ratio of the pigs, but it did linearly increase the portion of fat to lean in the carcass. Significant linear effect was found in back fat (p

  3. Effect of Thiamine, Ascorbic acid and Gibberellic acid (GA3 on Growth Characteristics, Pigment Content and Reduced Sugars of Petunia

    Directory of Open Access Journals (Sweden)

    moslem salehi

    2017-02-01

    Full Text Available Introduction: Bedding plants, especially petunia is important element for urban landscaping and attracted the attention of landscapers. This is due to some properties such as growth habit and color. The petunia (Petunia hybrida L. belongs to Solanaceae family that has annual and perennial varieties. This plant is originally from Argentina, Brazil and Uruguay. Some plant growth regulators such as gibberellic acid (GA3 and vitamins including thiamine and ascorbic acid affect plant growth and development and may extend flowering period. Vitamin C affects cell division and cell growth in plants and is effective on the feeding cycle activity in higher plants and it has an important role in electron transport system. The concentrations of 50 and 100 ppm of vitamin C and thiamine can increase the plant height, leaf number, leaf area, fresh and dry weight, and chemical compounds of the Syngonium plant. The application of 100 mg/l of GA3 significantly increased plant height and the number of leaves of gladiolus. Material and methods: The experiment was arranged in a factorial based on a completely randomized design with five replications. In this research, growth characteristics (lateral branch number, flower number, flower diameter, stem diameter, root length, and lateral branch length and biochemical characteristics (chlorophyll a, chlorophyll b, total chlorophyll, carotenoids, and reducing sugar were measured. After seeding and transplanting the seedling at 6 leaf stage, plants sprayed at 4 various growth stages with following treatments: 1-\tControl 2-\tVitamin C(100 mg/l 3-\tThiamin (100 mg/l 4-\tGibberellic acid (100 mg/l 5-\tVitamin C and Thiamin (The concentration of both 100 mg/l 6-\tVitamin C and Gibberellic acid (The concentration of both 100 mg/l 7-\tThiamin and Gibberellic acid (The concentration of both 100 mg/l 8-\tVitamin C, Thiamin and Gibberellic acid (The concentration of three 100 mg/l Data obtained from the measured parameters

  4. Why is VO2 max after altitude acclimatization still reduced despite normalization of arterial O2 content?

    DEFF Research Database (Denmark)

    Calbet, J A L; Boushel, Robert Christopher; Radegran, G

    2003-01-01

    Acute hypoxia (AH) reduces maximal O2 consumption (VO2 max), but after acclimatization, and despite increases in both hemoglobin concentration and arterial O2 saturation that can normalize arterial O2 concentration ([O2]), VO2 max remains low. To determine why, seven lowlanders were studied at VO2......% of the cardiac output perfused the legs, in CH the legs received only 67%. Pulmonary VO2 max (4.1 +/- 0.3 l/min at SL) fell to 2.2 +/- 0.1 l/min in AH (P normalization...... of arterial [O2] is explained by two circulatory effects of altitude: 1) failure of cardiac output to normalize and 2) preferential redistribution of cardiac output to nonexercising tissues. Oxygen transport from blood to muscle mitochondria, on the other hand, appears unaffected by CH....

  5. Insulin Detemir Is Transported From Blood to Cerebrospinal Fluid and Has Prolonged Central Anorectic Action Relative to NPH Insulin

    Science.gov (United States)

    Begg, Denovan P.; May, Aaron A.; Mul, Joram D.; Liu, Min; D’Alessio, David A.; Seeley, Randy J.

    2015-01-01

    Insulin detemir (DET) reduces glycemia comparably to other long-acting insulin formulations but causes less weight gain. Insulin signaling in the brain is catabolic, reducing food intake. We hypothesized that DET reduces weight gain, relative to other insulins, owing to increased transport into the central nervous system and/or increased catabolic action within the brain. Transport of DET and NPH insulin into the cerebrospinal fluid (CSF) was compared over several hours and after the administration of different doses peripherally in rats. DET and NPH had comparable saturable, receptor-mediated transport into the CSF. CSF insulin remained elevated significantly longer after intraperitoneal DET than after NPH. When administered acutely into the 3rd cerebral ventricle, both DET and NPH insulin reduced food intake and body weight at 24 h, and both food intake and body weight remained lower after DET than after NPH after 48 h. In direct comparison with another long-acting insulin, insulin glargine (GLAR), DET led to more prolonged increases in CSF insulin despite a shorter plasma half-life in both rats and mice. Additionally, peripheral DET administration reduced weight gain and increased CSF insulin compared with saline or GLAR in mice. Overall, these data support the hypothesis that DET has distinct effects on energy balance through enhanced and prolonged centrally mediated reduction of food intake. PMID:25667307

  6. High-oleic canola oil consumption enriches LDL particle cholesteryl oleate content and reduces LDL proteoglycan binding in humans.

    Science.gov (United States)

    Jones, Peter J H; MacKay, Dylan S; Senanayake, Vijitha K; Pu, Shuaihua; Jenkins, David J A; Connelly, Philip W; Lamarche, Benoît; Couture, Patrick; Kris-Etherton, Penny M; West, Sheila G; Liu, Xiaoran; Fleming, Jennifer A; Hantgan, Roy R; Rudel, Lawrence L

    2015-02-01

    Oleic acid consumption is considered cardio-protective according to studies conducted examining effects of the Mediterranean diet. However, animal models have shown that oleic acid consumption increases LDL particle cholesteryl oleate content which is associated with increased LDL-proteoglycan binding and atherosclerosis. The objective was to examine effects of varying oleic, linoleic and docosahexaenoic acid consumption on human LDL-proteoglycan binding in a non-random subset of the Canola Oil Multi-center Intervention Trial (COMIT) participants. COMIT employed a randomized, double-blind, five-period, cross-over trial design. Three of the treatment oil diets: 1) a blend of corn/safflower oil (25:75); 2) high oleic canola oil; and 3) DHA-enriched high oleic canola oil were selected for analysis of LDL-proteoglycan binding in 50 participants exhibiting good compliance. LDL particles were isolated from frozen plasma by gel filtration chromatography and LDL cholesteryl esters quantified by mass-spectrometry. LDL-proteoglycan binding was assessed using surface plasmon resonance. LDL particle cholesterol ester fatty acid composition was sensitive to the treatment fatty acid compositions, with the main fatty acids in the treatments increasing in the LDL cholesterol esters. The corn/safflower oil and high-oleic canola oil diets lowered LDL-proteoglycan binding relative to their baseline values (p = 0.0005 and p = 0.0012, respectively). At endpoint, high-oleic canola oil feeding resulted in lower LDL-proteoglycan binding than corn/safflower oil (p = 0.0243) and DHA-enriched high oleic canola oil (p = 0.0249), although high-oleic canola oil had the lowest binding at baseline (p = 0.0344). Our findings suggest that high-oleic canola oil consumption in humans increases cholesteryl oleate percentage in LDL, but in a manner not associated with a rise in LDL-proteoglycan binding. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

  7. Ablation of the Right Cardiac Vagus Nerve Reduces Acetylcholine Content without Changing the Inflammatory Response during Endotoxemia

    Directory of Open Access Journals (Sweden)

    Konstanze Plaschke

    2018-02-01

    acetylcholine concentration and an increase in cardiac acetylcholinesterase activity. Without LPS, VGX changed rat hemodynamic parameters, including heart frequency, cardiac output, and end-diastolic volume. In contrast, VGX during endotoxemia did not significantly change the concentration and expression of proinflammatory cytokines in the heart. In conclusion we demonstrate that right cardiac vagal innervation regulates cardiac acetylcholine content but neither improves nor worsens systemic inflammation.

  8. Ablation of the Right Cardiac Vagus Nerve Reduces Acetylcholine Content without Changing the Inflammatory Response during Endotoxemia.

    Science.gov (United States)

    Plaschke, Konstanze; Do, Thuc Quyen Monica; Uhle, Florian; Brenner, Thorsten; Weigand, Markus A; Kopitz, Jürgen

    2018-02-01

    concentration and an increase in cardiac acetylcholinesterase activity. Without LPS, VGX changed rat hemodynamic parameters, including heart frequency, cardiac output, and end-diastolic volume. In contrast, VGX during endotoxemia did not significantly change the concentration and expression of proinflammatory cytokines in the heart. In conclusion we demonstrate that right cardiac vagal innervation regulates cardiac acetylcholine content but neither improves nor worsens systemic inflammation.

  9. Exogenous insulin antibody syndrome (EIAS: a clinical syndrome associated with insulin antibodies induced by exogenous insulin in diabetic patients

    Directory of Open Access Journals (Sweden)

    Xiaolei Hu

    2018-01-01

    Full Text Available Insulin has been used for diabetes therapy and has achieved significant therapeutic effect. In recent years, the use of purified and recombinant human insulin preparations has markedly reduced, but not completely suppressed, the incidence of insulin antibodies (IAs. IAs induced by exogenous insulin in diabetic patients is associated with clinical events, which is named exogenous insulin antibody syndrome (EIAS. The present review is based on our research and summarizes the characterization of IAs, the factors affecting IA development, the clinical significance of IAs and the treatments for EIAS.

  10. Glucose delays the insulin-induced increase in thyroid hormone-mediated signaling in adipose of prolong-fasted elephant seal pups

    Science.gov (United States)

    Soñanez-Organis, José G.; Viscarra, Jose A.; Jaques, John T.; MacKenzie, Duncan S.; Crocker, Daniel E.; Ortiz, Rudy M.

    2016-01-01

    Prolonged food deprivation in mammals typically reduces glucose, insulin, and thyroid hormone (TH) concentrations, as well as tissue deiodinase (DI) content and activity, which, collectively, suppress metabolism. However, in elephant seal pups, prolonged fasting does not suppress TH levels; it is associated with upregulation of adipose TH-mediated cellular mechanisms and adipose-specific insulin resistance. The functional relevance of this apparent paradox and the effects of glucose and insulin on TH-mediated signaling in an insulin-resistant tissue are not well defined. To address our hypothesis that insulin increases adipose TH signaling in pups during extended fasting, we assessed the changes in TH-associated genes in response to an insulin infusion in early- and late-fasted pups. In late fasting, insulin increased DI1, DI2, and THrβ-1 mRNA expression by 566%, 44%, and 267% at 60 min postinfusion, respectively, with levels decreasing by 120 min. Additionally, we performed a glucose challenge in late-fasted pups to differentiate between insulin- and glucose-mediated effects on TH signaling. In contrast to the insulin-induced effects, glucose infusion did not increase the expressions of DI1, DI2, and THrβ-1 until 120 min, suggesting that glucose delays the onset of the insulin-induced effects. The data also suggest that fasting duration increases the sensitivity of adipose TH-mediated mechanisms to insulin, some of which may be mediated by increased glucose. These responses appear to be unique among mammals and to have evolved in elephant seals to facilitate their adaptation to tolerate an extreme physiological condition. PMID:26739649

  11. High passage MIN6 cells have impaired insulin secretion with impaired glucose and lipid oxidation.

    Directory of Open Access Journals (Sweden)

    Kim Cheng

    Full Text Available Type 2 diabetes is a metabolic disorder characterized by the inability of beta-cells to secrete enough insulin to maintain glucose homeostasis. MIN6 cells secrete insulin in response to glucose and other secretagogues, but high passage (HP MIN6 cells lose their ability to secrete insulin in response to glucose. We hypothesized that metabolism of glucose and lipids were defective in HP MIN6 cells causing impaired glucose stimulated insulin secretion (GSIS. HP MIN6 cells had no first phase and impaired second phase GSIS indicative of global functional impairment. This was coupled with a markedly reduced ATP content at basal and glucose stimulated states. Glucose uptake and oxidation were higher at basal glucose but ATP content failed to increase with glucose. HP MIN6 cells had decreased basal lipid oxidation. This was accompanied by reduced expressions of Glut1, Gck, Pfk, Srebp1c, Ucp2, Sirt3, Nampt. MIN6 cells represent an important model of beta cells which, as passage numbers increased lost first phase but retained partial second phase GSIS, similar to patients early in type 2 diabetes onset. We believe a number of gene expression changes occurred to produce this defect, with emphasis on Sirt3 and Nampt, two genes that have been implicated in maintenance of glucose homeostasis.

  12. Iontophoresis of monomeric insulin analogues in vitro: effects of insulin charge and skin pretreatment.

    Science.gov (United States)

    Langkjaer, L; Brange, J; Grodsky, G M; Guy, R H

    1998-01-23

    The aim of this study was to investigate the influence of association state and net charge of human insulin analogues on the rate of iontophoretic transport across hairless mouse skin, and the effect of different skin pretreatments on said transport. No insulin flux was observed with anodal delivery probably because of degradation at the Ag/AgCl anode. The flux during cathodal iontophoresis through intact skin was insignificant for human hexameric insulin, and only low and variable fluxes were observed for monomeric insulins. Using stripped skin on the other hand, the fluxes of monomeric insulins with two extra negative charges were 50-100 times higher than that of hexameric human insulin. Introducing three additional charges led to a further 2-3-fold increase in flux. Wiping the skin gently with absolute alcohol prior to iontophoresis resulted in a 1000-fold increase in transdermal transport of insulin relative to that across untreated skin, i.e. to almost the same level as stripping the skin. The alcohol pretreatment reduced the electrical resistance of the skin, presumably by lipid extraction. In conclusion, monomeric insulin analogues with at least two extra negative charges can be iontophoretically delivered across hairless mouse skin, whereas insignificant flux is observed with human, hexameric insulin. Wiping the skin with absolute alcohol prior to iontophoresis gave substantially improved transdermal transport of monomeric insulins resulting in clinically relevant delivery rates for basal treatment.

  13. Abnormal subcellular distribution of GLUT4 protein in obese and insulin-treated diabetic female dogs

    Directory of Open Access Journals (Sweden)

    A.M. Vargas

    2004-07-01

    Full Text Available The GLUT4 transporter plays a key role in insulin-induced glucose uptake, which is impaired in insulin resistance. The objective of the present study was to investigate the tissue content and the subcellular distribution of GLUT4 protein in 4- to 12-year-old control, obese and insulin-treated diabetic mongrel female dogs (4 animals per group. The parametrial white adipose tissue was sampled and processed to obtain both plasma membrane and microsome subcellular fractions for GLUT4 analysis by Western blotting. There was no significant difference in glycemia and insulinemia between control and obese animals. Diabetic dogs showed hyperglycemia (369.9 ± 89.9 mg/dl. Compared to control, the plasma membrane GLUT4, reported per g tissue, was reduced by 55% (P < 0.01 in obese dogs, and increased by 30% (P < 0.05 in diabetic dogs, and the microsomal GLUT4 was increased by ~45% (P < 0.001 in both obese and diabetic animals. Considering the sum of GLUT4 measured in plasma membrane and microsome as total cellular GLUT4, percent GLUT4 present in plasma membrane was reduced by ~65% (P < 0.001 in obese compared to control and diabetic animals. Since insulin stimulates GLUT4 translocation to the plasma membrane, percent GLUT4 in plasma membrane was divided by the insulinemia at the time of tissue removal and was found to be reduced by 75% (P < 0.01 in obese compared to control dogs. We conclude that the insulin-stimulated translocation of GLUT4 to the cell surface is reduced in obese female dogs. This probably contributes to insulin resistance, which plays an important role in glucose homeostasis in dogs.

  14. Will the next generation of basal insulins offer clinical advantages?

    Science.gov (United States)

    Garber, A J

    2014-06-01

    The 21st century has seen the arrival of several insulin analogue products and the refinement of insulin regimens, with widespread advocacy of continuous titration algorithms and earlier initiation of supplementary insulin therapy (predominantly using basal insulins) in type 2 diabetes. Nevertheless, many insulin-treated diabetes patients remain in poor glycaemic control. This might reflect insufficient titration effort or lax adherence, but these issues could in some cases result from concerns about hypoglycaemia. Certainly there is scope for improving the pharmacokinetic/pharmacodynamic (PK/PD) profile of basal insulin, and three new products offer this prospect. Insulin degludec, now in clinical use, and PEGylated insulin lispro, in development, have greatly extended action profiles that result from two very different, but unique, mechanisms. With once-daily dosing, these insulins produce stable PK/PD profiles at steady state, associated with a low incidence of hypoglycaemia. The feasibility of varied daily dose timing has also been confirmed with insulin degludec. High strength formulations of insulin glargine and insulin degludec offer the prospect of a reduced injection number/volume in high dose users, and in the case of glargine, the PK/PD profile might also be favourably modified. This review considers critically the clinical evidence and expectations we should have for these new basal insulins. © 2013 John Wiley & Sons Ltd.

  15. Peripheral nervous system insulin resistance in ob/ob mice

    Science.gov (United States)

    2013-01-01

    Background A reduction in peripheral nervous system (PNS) insulin signaling is a proposed mechanism that may contribute to sensory neuron dysfunction and diabetic neuropathy. Neuronal insulin resistance is associated with several neurological disorders and recent evidence has indicated that dorsal root ganglion (DRG) neurons in primary culture display altered insulin signaling, yet in vivo results are lacking. Here, experiments were performed to test the hypothesis that the PNS of insulin-resistant mice displays altered insulin signal transduction in vivo. For these studies, nondiabetic control and type 2 diabetic ob/ob mice were challenged with an intrathecal injection of insulin or insulin-like growth factor 1 (IGF-1) and downstream signaling was evaluated in the DRG and sciatic nerve using Western blot analysis. Results The results indicate that insulin signaling abnormalities documented in other “insulin sensitive” tissues (i.e. muscle, fat, liver) of ob/ob mice are also present in the PNS. A robust increase in Akt activation was observed with insulin and IGF-1 stimulation in nondiabetic mice in both the sciatic nerve and DRG; however this response was blunted in both tissues from ob/ob mice. The results also suggest that upregulated JNK activation and reduced insulin receptor expression could be contributory mechanisms of PNS insulin resistance within sensory neurons. Conclusions These findings contribute to the growing body of evidence that alterations in insulin signaling occur in the PNS and may be a key factor in the pathogenesis of diabetic neuropathy. PMID:24252636

  16. Enhancement of the electrical characteristics of MOS capacitors by reducing the organic content of H2O-diluted Spin-On-Glass based oxides

    International Nuclear Information System (INIS)

    Molina, Joel; Munoz, Ana; Torres, Alfonso; Landa, Mauro; Alarcon, Pablo; Escobar, Manuel

    2011-01-01

    In this work, the physical, chemical and electrical properties of Metal-Oxide-Semiconductor (MOS) capacitors with Spin-On-Glass (SOG)-based thin films as gate dielectric have been investigated. Experiments of SOG diluted with two different solvents (2-propanol and deionized water) were done in order to reduce the viscosity of the SOG solution so that thinner films (down to ∼20 nm) could be obtained and their general characteristics compared. Thin films of SOG were deposited on silicon by the sol-gel technique and they were thermally annealed using conventional oxidation furnace and Rapid Thermal Processing (RTP) systems within N 2 ambient after deposition. SOG dilution using non-organic solvents like deionized water and further annealing (at relatively high temperatures ≥450 deg. C) are important processes intended to reduce the organic content of the films. Fourier-Transform Infrared (FTIR) Spectroscopy results have shown that water-diluted SOG films have a significant reduction in their organic content after increasing annealing temperature and/or dilution percentage when compared to those of undiluted SOG films. Both current-voltage (I-V) and capacitance-voltage (C-V) measurements show better electrical characteristics for SOG-films diluted in deionized water compared to those diluted in 2-propanol (which is an organic solvent). The electrical characteristics of H 2 O-diluted SOG thin films are very similar to those obtained from high quality thermal oxides so that their application as gate dielectrics in MOS devices is promising. Finally, it has been demonstrated that by reducing the organic content of SOG-based thin films, it is possible to obtain MOS devices with better electrical properties.

  17. Giving an insulin injection

    Science.gov (United States)

    ... hand. The bubbles will float to the top. Push the bubbles back into the insulin bottle, then pull back to ... hand. The bubbles will float to the top. Push the bubbles back into the insulin bottle, then pull back to ...

  18. Insulin Resistance and Prediabetes

    Science.gov (United States)

    ... Your Baby is Born Monogenic Diabetes Insulin Resistance & Prediabetes Insulin resistance and prediabetes occur when your body ... will stay in the healthy range. What is prediabetes? Prediabetes means your blood glucose levels are higher ...

  19. Defective insulin signaling pathway and increased glycogen synthase kinase-3 activity in the brain of diabetic mice: parallels with Alzheimer's disease and correction by insulin.

    Science.gov (United States)

    Jolivalt, C G; Lee, C A; Beiswenger, K K; Smith, J L; Orlov, M; Torrance, M A; Masliah, E

    2008-11-15

    We have evaluated the effect of peripheral insulin deficiency on brain insulin pathway activity in a mouse model of type 1 diabetes, the parallels with Alzheimer's disease (AD), and the effect of treatment with insulin. Nine weeks of insulin-deficient diabetes significantly impaired the learning capacity of mice, significantly reduced insulin-degrading enzyme protein expression, and significantly reduced phosphorylation of the insulin-receptor and AKT. Phosphorylation of glycogen synthase kinase-3 (GSK3) was also significantly decreased, indicating increased GSK3 activity. This evidence of reduced insulin signaling was associated with a concomitant increase in tau phosphorylation and amyloid beta protein levels. Changes in phosphorylation levels of insulin receptor, GSK3, and tau were not observed in the brain of db/db mice, a model of type 2 diabetes, after a similar duration (8 weeks) of diabetes. Treatment with insulin from onset of diabetes partially restored the phosphorylation of insulin receptor and of GSK3, partially reduced the level of phosphorylated tau in the brain, and partially improved learning ability in insulin-deficient diabetic mice. Our data indicate that mice with systemic insulin deficiency display evidence of reduced insulin signaling pathway activity in the brain that is associated with biochemical and behavioral features of AD and that it can be corrected by insulin treatment.

  20. Insulin inhalation for diabetic patients: Nursing considerations

    Directory of Open Access Journals (Sweden)

    Hanan Mohammed Mohammed

    2016-04-01

    Full Text Available Scientific knowledge has advanced to enable the development of inhaled insulin. It is a form of diabetes medication administered via the pulmonary system that studies have shown to be efficacious in the treatment of both type 1 and type 2 diabetes. Inhaled insulin is a new, safe means to deliver insulin that may increase patient compliance with insulin therapy, helping them to achieve optimal glycemic control and possibly reducing their risk of developing cardiovascular complications. However, diabetes is a chronic illness requiring lifetime intervention. Empowering patients with the knowledge of the diabetes disease process may give them the confidence to be more autonomous in managing their diabetes. HIIP gives nurse practitioners a new option that may improve their patients’ acceptance of insulin therapy, and improve glycemic control.

  1. Fasting in Ramadan with an insulin pump.

    Science.gov (United States)

    Kesavadev, Jothydev

    2015-05-01

    A good majority of subjects with diabetes on insulin therapies observe fasting during Ramadan. The challenge for the physician and the patient is to manage diabetes without an interruption to fasting by avoiding hypoglycaemia and simultaneously ensuring that blood glucose remain at acceptable safe levels. Insulin Pumps differ from syringes and insulin pens in that it offers a variable basal rate, different type of boluses and associated calculators. The technological advances that pumps offer, help educated subjects pre-programme a reduced basal rate throughout the day. Pumps ensure avoidance of hypoglycaemia and hyperglycaemia and preserve quality of life and enhance confidence in patients during fasting. Due to multiple benefits, insulin pumps are considered the best delivery systems for insulin during the holy month of Ramadan, despite the prerequisites for its optimal output and cost concerns.

  2. Populus balsamifera Extract and Its Active Component Salicortin Reduce Obesity and Attenuate Insulin Resistance in a Diet-Induced Obese Mouse Model

    Directory of Open Access Journals (Sweden)

    Despina Harbilas

    2013-01-01

    Full Text Available Populus balsamifera L. (BP is a medicinal plant stemming from the traditional pharmacopoeia of the Cree of Eeyou Istchee (CEI—Northern Quebec. In vitro screening studies revealed that it strongly inhibited adipogenesis in 3T3-L1 adipocytes, suggesting potential antiobesity activity. Salicortin was identified, through bioassay-guided fractionation, as the active component responsible for BP’s activity. The present study aimed to assess the potential of BP and salicortin at reducing obesity and features of the metabolic syndrome, in diet-induced obese C57Bl/6 mice. Mice were subjected to high fat diet (HFD for sixteen weeks, with BP (125 or 250 mg/kg or salicortin (12.5 mg/kg introduced in the HFD for the last eight of the sixteen weeks. BP and salicortin effectively reduced whole body and retroperitoneal fat pad weights, as well as hepatic triglyceride accumulation. Glycemia, insulinemia, leptin, and adiponectin levels were also improved. This was accompanied by a small yet significant reduction in food intake in animals treated with BP. BP and salicortin (slightly also modulated key components in signaling pathways involved with glucose regulation and lipid oxidation in the liver, muscle, and adipose tissue. These results confirm the validity of the CEI pharmacopoeia as alternative and complementary antiobesity and antidiabetic therapies.

  3. Adverse effects of reduced oxygen tension on the proliferative capacity of rat kidney and insulin-secreting cell lines involve DNA damage and stress responses

    International Nuclear Information System (INIS)

    Chen Jianhua; Jones, R. Huw; Tarry-Adkins, Jane; Smith, Noel H.; Ozanne, Susan E.

    2008-01-01

    Standard cell culture conditions do not reflect the physiological environment in terms of oxygen tension (20% vs 3%). The effects of lowering oxygen tension on cell proliferation in culture can be beneficial as well as detrimental depending on the cell line studied, but the molecular mechanism underlying such effects is not fully understood. We observed that the proliferative capacity of the rat cell lines NRK and INS-1 was inhibited when cultured under 3% oxygen as compared to 20% oxygen. Suppression of proliferation in NRK cells was accompanied by induction of DNA double strand breaks whereas in INS-1 cells it was accompanied by up-regulation of p53 and p27. Although Sirt1 was up-regulated in both cell lines by 3% oxygen the effects on antioxidant enzymes (MnSOD, CuZnSOD and catalase) were cell line specific. Marked up-regulation of heme oxygenase-1 (HO-1) was detected in both NRK and INS-1 cells when cultured in 3% oxygen. HO-1 expression can be readily induced by exposure to hydrogen peroxide in culture. These results suggest that reduced oxygen tension suppresses the proliferative capacity of these two cell lines through a stress response that is similar to an oxidative stress response but the molecular events that lead to the reduced cell proliferation are cell line specific

  4. PYY(3-36) reduces food intake and body weight and improves insulin sensitivity in rodent models of diet-induced obesity

    DEFF Research Database (Denmark)

    Vrang, Niels; Madsen, Andreas Nygaard; Tang-Christensen, Mads

    2006-01-01

    The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3-36) in mice and rats, as well as metabolic effects of chronic PYY(3-36) administration to diet-induced obese (DIO) mice and rats. A single intraperit......The gut hormone peptide YY (PYY) was recently proposed to comprise an endogenous satiety factor. We have studied acute anorectic functions of PYY(3-36) in mice and rats, as well as metabolic effects of chronic PYY(3-36) administration to diet-induced obese (DIO) mice and rats. A single...... intraperitoneal injection of PYY(3-36) inhibited food intake in mice, but not in rats. We next investigated the effects of increasing doses (100, 300, and 1,000 microg.kg-1.day-1) of PYY(3-36) administered subcutaneously via osmotic minipumps on food intake and body weight in DIO C57BL/6J mice. Whereas only...... the highest dose (1,000 microg.kg-1.day-1) of PYY(3-36) significantly reduced food intake over the first 3 days, body weight gain was dose dependently reduced, and on day 28 the group treated with 1,000 microg.kg-1.day-1 PYY(3-36) weighed approximately 10% less than the vehicle-treated group. Mesenteric...

  5. Excellent Tribological Properties of Lower Reduced Graphene Oxide Content Copper Composite by Using a One-Step Reduction Molecular-Level Mixing Process

    Directory of Open Access Journals (Sweden)

    Haibin Nie

    2018-04-01

    Full Text Available Reduced graphene oxide (RGO composite copper matrix powders were fabricated successfully by using a modified molecular-level mixing (MLM method. Divalent copper ions (Cu2+ were adsorbed in oxygen functional groups of graphene oxide (GO as a precursor, then were reduced simultaneously by one step chemical reduction. RGO showed a distribution converting from a random to a three-dimensional network in the copper matrix when its content increased to above 1.0 wt.% The tribological tests indicated that the friction coefficient of the composite with 1.0 wt.% RGO decreased markedly from 0.6 to 0.07 at an applied load of 10 N, and the wear rate was about one-third of pure copper. The excellent tribological properties were attributed to a three-dimensional and uniform distribution, which contributes to improving toughness and adhesion strength.

  6. Skeletal muscle and hepatic insulin signaling is maintained in heat-stressed lactating Holstein cows.

    Science.gov (United States)

    Xie, G; Cole, L C; Zhao, L D; Skrzypek, M V; Sanders, S R; Rhoads, M L; Baumgard, L H; Rhoads, R P

    2016-05-01

    Multiparous cows (n=12; parity=2; 136±8 d in milk, 560±32kg of body weight) housed in climate-controlled chambers were fed a total mixed ration (TMR) consisting primarily of alfalfa hay and steam-flaked corn. During the first experimental period (P1), all 12 cows were housed in thermoneutral conditions (18°C, 20% humidity) with ad libitum intake for 9 d. During the second experimental period (P2), half of the cows were fed for ad libitum intake and subjected to heat-stress conditions [WFHS, n=6; cyclical temperature 31.1 to 38.9°C, 20% humidity: minimum temperature humidity index (THI)=73, maximum THI=80.5], and half of the cows were pair-fed to match the intake of WFHS cows in thermal neutral conditions (TNPF, n=6) for 9 d. Rectal temperature and respiration rate were measured thrice daily at 0430, 1200, and 1630 h. To evaluate muscle and liver insulin responsiveness, biopsies were obtained immediately before and after an insulin tolerance test on the last day of each period. Insulin receptor (IR), insulin receptor substrate 1 (IRS-1), AKT/protein kinase B (AKT), and phosphorylated AKT (p-AKT) were measured by Western blot analyses for both tissues. During P2, WFHS increased rectal temperature and respiration rate by 1.48°C and 2.4-fold, respectively. Heat stress reduced dry matter intake by 8kg/d and, by design, TNPF cows had similar intake reductions. Milk yield was decreased similarly (30%) in WFHS and TNPF cows, and both groups entered into a similar (-4.5 Mcal/d) calculated negative energy balance during P2. Insulin infusion caused a less rapid glucose disposal in P2 compared with P1, but glucose clearance did not differ between environments in P2. In liver, insulin increased p-AKT protein content in each period. Phosphorylation ratio of AKT increased 120% in each period after insulin infusion. In skeletal muscle, protein abundance of the IR, IRS, and AKT remained stable between periods and environment. Insulin increased skeletal muscle p-AKT in each

  7. Classifying insulin regimens

    DEFF Research Database (Denmark)

    Neu, A; Lange, K; Barrett, T

    2015-01-01

    Modern insulin regimens for the treatment of type 1 diabetes are highly individualized. The concept of an individually tailored medicine accounts for a broad variety of different insulin regimens applied. Despite clear recommendations for insulin management in children and adolescents with type 1...

  8. Glycosphingolipids and insulin resistance

    NARCIS (Netherlands)

    Langeveld, Mirjam; Aerts, Johannes M. F. G.

    2009-01-01

    Obesity is associated with an increased risk for insulin resistance, a state characterized by impaired responsiveness of liver, muscle and adipose tissue to insulin. One class of lipids involved in the development of insulin resistance are the (glyco)sphingolipids. Ceramide, the most simple

  9. Estradiol Protects Proopiomelanocortin Neurons Against Insulin Resistance.

    Science.gov (United States)

    Qiu, Jian; Bosch, Martha A; Meza, Cecilia; Navarro, Uyen-Vy; Nestor, Casey C; Wagner, Edward J; Rønnekleiv, Oline K; Kelly, Martin J

    2018-02-01

    Insulin resistance is at the core of the metabolic syndrome, and men exhibit a higher incidence of metabolic syndrome than women in early adult life, but this sex advantage diminishes sharply when women reach the postmenopausal state. Because 17β-estradiol (E2) augments the excitability of the anorexigenic proopiomelanocortin (POMC) neurons, we investigated the neuroprotective effects of E2 against insulin resistance in POMC neurons from diet-induced obese (DIO) female and male mice. The efficacy of insulin to activate canonical transient receptor potential 5 (TRPC5) channels and depolarize POMC neurons was significantly reduced in DIO male mice but not in DIO female mice. However, the insulin response in POMC neurons was abrogated in ovariectomized DIO females but restored with E2 replacement. E2 increased T-type calcium channel Cav3.1 messenger RNA (mRNA) expression and whole-cell currents but downregulated stromal-interaction molecule 1 mRNA, which rendered POMC neurons more excitable and responsive to insulin-mediated TRPC5 channel activation. Moreover, E2 prevented the increase in suppressor of cytokine signaling-3 mRNA expression with DIO as seen in DIO males. As proof of principle, insulin [intracerebroventricular injection into the third ventricle (ICV)] decreased food intake and increased metabolism in female but not male guinea pigs fed a high-fat diet. The uncoupling of the insulin receptor from its downstream effector system was corroborated by the reduced expression of phosphorylated protein kinase B in the arcuate nucleus of male but not female guinea pigs following insulin. Therefore, E2 protects female POMC neurons from insulin resistance by enhancing POMC neuronal excitability and the coupling of insulin receptor to TRPC5 channel activation. Copyright © 2018 Endocrine Society.

  10. Topical application of a cleanser containing extracts of Diospyros kaki folium, Polygonum cuspidatum and Castanea crenata var. dulcis reduces skin oil content and pore size in human skin.

    Science.gov (United States)

    Lee, Bo Mi; An, Sungkwan; Kim, Soo-Yeon; Han, Hyun Joo; Jeong, Yu-Jin; Lee, Kyoung-Rok; Roh, Nam Kyung; Ahn, Kyu Joong; An, In-Sook; Cha, Hwa Jun

    2015-05-01

    The effects of skin pores on skin topographic features can be reduced by decreasing excessive production and accumulation of sebum and elimination of comedones. Therefore, a cosmetic cleanser that regulates sebum homeostasis is required. In the present study, the effects of a cosmetic cleanser that contained Diospyros kaki folium, Polygonum cuspidatum and Castanea crenata var. dulcis (DPC) was examined on the removal of sebum and on skin pore size. Healthy volunteers (n=23) aged 20-50 years were asked to apply the test materials to the face. Skin oil content, pore size, pore number and extracted sebum surface area were measured using various measurement methods. All the measurements were performed at pre- and post-application of the test materials. When the cosmetic cleanser containing DPC was applied to the skin, the oil content decreased by 77.3%, from 6.19 to 1.40. The number of skin pores decreased by 24.83%, from 125.39 to 94.23. Skin pore size decreased from 0.07 to 0.02 µm 3 (71.43% decrease). The amount of extracted sebum increased by 335% when the DPC cleanser was used. Compared to the control cleanser, skin oil content was significantly decreased when the cleanser that contained DPC was used. The cleanser containing DPC also decreased pore size and number. Finally, the DPC cleanser easily removed solidified sebum from the skin.

  11. Nutritional Modulation of Insulin Resistance

    Directory of Open Access Journals (Sweden)

    Martin O. Weickert

    2012-01-01

    Full Text Available Insulin resistance has been proposed as the strongest single predictor for the development of Type 2 Diabetes (T2DM. Chronic oversupply of energy from food, together with inadequate physical activity, have been recognized as the most relevant factors leading to overweight, abdominal adiposity, insulin resistance, and finally T2DM. Conversely, energy reduced diets almost invariably to facilitate weight loss and reduce abdominal fat mass and insulin resistance. However, sustained weight loss is generally difficult to achieve, and distinct metabolic characteristics in patients with T2DM further compromise success. Therefore, investigating the effects of modulating the macronutrient composition of isoenergetic diets is an interesting concept that may lead to additional important insights. Metabolic effects of various different dietary concepts and strategies have been claimed, but results from randomized controlled studies and particularly from longer-term-controlled interventions in humans are often lacking. However, some of these concepts are supported by recent research, at least in animal models and short-term studies in humans. This paper provides an update of the current literature regarding the role of nutrition in the modulation of insulin resistance, which includes the discussion of weight-loss-independent metabolic effects of commonly used dietary concepts.

  12. Obesity genes and insulin resistance.

    Science.gov (United States)

    Belkina, Anna C; Denis, Gerald V

    2010-10-01

    The exploding prevalence of insulin resistance and Type 2 diabetes (T2D) linked to obesity has become an alarming public health concern. Worldwide, approximately 171 million people suffer from obesity-induced diabetes and public health authorities expect this situation to deteriorate rapidly. An interesting clinical population of 'metabolically healthy but obese' (MHO) cases is relatively protected from T2D and its associated cardiovascular risk. The molecular basis for this protection is not well understood but is likely to involve reduced inflammatory responses. The inflammatory cells and pathways that respond to overnutrition are the primary subject matter for this review. The chance discovery of a genetic mutation in the Brd2 gene, which is located in the class II major histocompatibility complex and makes mice enormously fat but protects them from diabetes, offers revolutionary new insights into the cellular mechanisms that link obesity to insulin resistance and T2D. These Brd2-hypomorphic mice have reduced inflammation in fat that is normally associated with insulin resistance, and resemble MHO patients, suggesting novel therapeutic pathways for obese patients at risk for T2D. Deeper understanding of the functional links between genes that control inflammatory responses to diet-induced obesity is crucial to the development of therapies for obese, insulin-resistant patients.

  13. Use of Novel High-Protein Functional Food Products as Part of a Calorie-Restricted Diet to Reduce Insulin Resistance and Increase Lean Body Mass in Adults: A Randomized Controlled Trial

    Directory of Open Access Journals (Sweden)

    Carol S. Johnston

    2017-10-01

    Full Text Available Significant reductions in insulin resistance (IR can be achieved by either calorie restriction or by the increase of lean mass. However, calorie restriction usually results in significant loss of lean mass. A 6-week randomized controlled feeding trial was conducted to determine if a calorie-restricted, high-protein diet (~125 g protein/day consumed evenly throughout the day using novel functional foods would be more successful for reducing IR in comparison to a conventional diet (~80 g protein/day with a similar level of calorie restriction. Healthy adults (age 20–75 years; body mass index, 20–42 kg/m2 with raised triglyceride/high-density lipoprotein ratios were randomly assigned to the control group (CON: test foods prepared using gluten-free commercial pasta and cereal or to the high-protein group (HPR: test foods prepared using novel high-protein pasta and cereal both rich in wheat gluten. Mean weight loss did not differ between groups (−2.7 ± 2.6 and −3.2 ± 3.0 kg for CON (n = 11 and HPR (n = 10 respectively, p = 0.801; however, the 6-week change in fat-free mass (FFM differed significantly between groups (−0.5 ± 1.5 and +1.5 ± 3.8 kg for CON and HPR respectively, p = 0.008. IR improved in HPR vs. CON participants (homeostasis model assessment-estimated insulin resistance [HOMAIR] change: −1.7 ± 1.4 and −0.7 ± 0.7 respectively; p = 0.020. The change in HOMA-IR was related to the change in FFM among participants (r = −0.511, p = 0.021. Thus, a high-protein diet using novel functional foods combined with modest calorie restriction was 140% more effective for reducing HOMA-IR in healthy adults compared to a lower protein, standard diet with an equal level of calorie restriction.

  14. Attrition during a randomized controlled trial of reduced nicotine content cigarettes as a proxy for understanding acceptability of nicotine product standards.

    Science.gov (United States)

    Mercincavage, Melissa; Wileyto, E Paul; Saddleson, Megan L; Lochbuehler, Kirsten; Donny, Eric C; Strasser, Andrew A

    2017-06-01

    To determine (1) if nicotine content affects study attrition-a potential behavioral measure of acceptability-in a trial that required compliance with three levels of reduced nicotine content (RNC) cigarettes, and (2) if attrition is associated with subjective and behavioral responses to RNC cigarettes. Secondary analysis of a 35-day, parallel-design, open-label, randomized controlled trial. After a 5-day baseline period, participants were randomized to smoke for three 10-day periods: their preferred brand (control group) or RNC cigarettes with three nicotine levels in a within-subject stepdown (one group: high-moderate-low) or non-stepdown (five groups: high-low-moderate, low-moderate-high, low-high-moderate, moderate-low-high, moderate-high-low) fashion. A single site in Philadelphia, PA, USA. A total of 246 non-treatment-seeking daily smokers [mean age = 39.52, cigarettes per day (CPD) = 20.95, 68.3% white] were recruited from October 2007 to June 2013. The primary outcome was attrition. Key predictors were nicotine content transition and study period. Exploratory predictors were taste and strength subjective ratings, total puff volume and carbon monoxide (CO) boost. Covariates included: age, gender, race, education and nicotine dependence. Overall attrition was 31.3% (n = 77): 24.1% of the control and 25.0% of the stepdown RNC cigarette groups dropped out versus 44.6% of non-stepdown groups (P = 0.006). Compared with controls, attrition odds were 4.5 and 4.7 times greater among smokers transitioning from preferred and the highest RNC cigarettes to the lowest RNC cigarettes, respectively (P = 0.001 and 0.003). Providing more favorable initial taste ratings of study cigarettes decreased attrition odds by 2% (P = 0.012). The majority of participants completed a 35-day trial of varying levels of reduced nicotine content cigarettes. Participant dropout was greater for cigarettes with lower nicotine content and less in smokers reporting more favorable

  15. Insulin structure and stability.

    Science.gov (United States)

    Brange, J; Langkjoer, L

    1993-01-01

    Insulin is composed of 51 amino acids in two peptide chains (A and B) linked by two disulfide bonds. The three-dimensional structure of the insulin molecule (insulin monomer), essentially the same in solution and in solid phase, exists in two main conformations. These differ in the extent of helix in the B chain which is governed by the presence of phenol or its derivatives. In acid and neutral solutions, in concentrations relevant for pharmaceutical formulation, the insulin monomer assembles to dimers and at neutral pH, in the presence of zinc ions, further to hexamers. Many crystalline modifications of insulin have been identified but only those with the hexamer as the basic unit are utilized in preparations for therapy. The insulin hexamer forms a relatively stable unit but some flexibility remains within the individual molecules. The intrinsic flexibility at the ends of the B chain plays an important role in governing the physical and chemical stability of insulin. A variety of chemical changes of the primary structure (yielding insulin derivatives), and physical modifications of the secondary to quaternary structures (resulting in "denaturation," aggregation, and precipitation) are known to affect insulin and insulin preparations during storage and use (Fig. 8). The tendency of insulin to undergo structural transformation resulting in aggregation and formation of insoluble insulin fibrils has been one of the most intriguing and widely studied phenomena in relation to insulin stability. Although the exact mechanism of fibril formation is still obscure, it is now clear that the initial step is an exposure of certain hydrophobic residues, normally buried in the three-dimensional structure, to the surface of the insulin monomer. This requires displacement of the COOH-terminal B-chain residues from their normal position which can only be accomplished via monomerization of the insulin. Therefore, most methods stabilizing insulin against fibrillation share the

  16. The application of non-Saccharomyces yeast in fermentations with limited aeration as a strategy for the production of wine with reduced alcohol content.

    Science.gov (United States)

    Contreras, A; Hidalgo, C; Schmidt, S; Henschke, P A; Curtin, C; Varela, C

    2015-07-16

    High alcohol concentrations reduce the complexity of wine sensory properties. In addition, health and economic drivers have the wine industry actively seeking technologies that facilitate the production of wines with lower alcohol content. One of the simplest approaches to achieve this aim would be the use of wine yeast strains which are less efficient at transforming grape sugars into ethanol, however commercially available wine yeasts produce very similar ethanol yields. Non-conventional yeast, in particular non-Saccharomyces species, have shown potential for producing wines with lower alcohol content. These yeasts are naturally present in the early stages of fermentation but in general are not capable of completing alcoholic fermentation. We have evaluated 48 non-Saccharomyces isolates to identify strains that, with limited aeration and in sequential inoculation regimes with S. cerevisiae, could be used for the production of wine with lower ethanol concentration. Two of these, Torulaspora delbrueckii AWRI1152 and Zygosaccharomyces bailii AWRI1578, enabled the production of wine with reduced ethanol concentration under limited aerobic conditions. Depending on the aeration regime T. delbrueckii AWRI1152 and Z. bailii AWRI1578 showed a reduction in ethanol concentration of 1.5% (v/v) and 2.0% (v/v) respectively, compared to the S. cerevisiae anaerobic control. Copyright © 2015 Elsevier B.V. All rights reserved.

  17. Effects of B Vitamins Overload on Plasma Insulin Level and Hydrogen Peroxide Generation in Rats.

    Science.gov (United States)

    Sun, Wuping; Zhai, Mingzhu; Zhou, Qian; Qian, Chengrui; Jiang, Changyu

    2017-08-31

    It has been reported that nicotinamide-overload induces oxidative stress associated with insulin resistance, the key feature of type 2 diabetes mellitus (T2DM). This study aimed to investigate the effects of B vitamins in T2DM. Glucose tolerance tests were carried out in adult Sprague-Dawley rats treated with or without cumulative doses of B vitamins. More specifically, insulin tolerance tests were also carried out in adult Sprague-Dawley rats treated with or without cumulative doses of Vitamin B3. We found that cumulative Vitamin B1 and Vitamin B3 administration significantly increased the plasma H₂O₂ levels associated with high insulin levels. Only Vitamin B3 reduced muscular and hepatic glycogen contents. Cumulative administration of nicotinic acid, another form of Vitamin B3, also significantly increased plasma insulin level and H₂O₂ generation. Moreover, cumulative administration of nicotinic acid or nicotinamide impaired glucose metabolism. This study suggested that excess Vitamin B1 and Vitamin B3 caused oxidative stress and insulin resistance.

  18. Glycosides from Stevia rebaudiana Bertoni Possess Insulin-Mimetic and Antioxidant Activities in Rat Cardiac Fibroblasts

    Directory of Open Access Journals (Sweden)

    Cecilia Prata

    2017-01-01

    Full Text Available Stevia rebaudiana Bertoni is a shrub having a high content of sweet diterpenoid glycosides in its leaves, mainly stevioside and rebaudioside A, which are used as noncaloric, natural sweeteners. The aim of this study was to deepen the knowledge about the insulin-mimetic effect exerted by four different mixtures of steviol glycosides, rich in stevioside and rebaudioside A, in neonatal rat cardiac fibroblasts. The potential antioxidant activity of these steviol glycosides was also assessed, as oxidative stress is associated with diabetes. Likewise the insulin effect, steviol glycosides caused an increase in glucose uptake into rat fibroblasts by activating the PI3K/Akt pathway, thus inducing Glut4 translocation to the plasma membrane. The presence of S961, an insulin antagonist, completely abolished these effects, allowing to hypothesize that steviol glycosides could act as ligands of the same receptor engaged by insulin. Moreover, steviol glycosides counteracted oxidative stress by increasing reduced glutathione intracellular levels and upregulating expression and activity of the two antioxidant enzymes superoxide dismutase and catalase. The present work unravels the insulin-mimetic effect and the antioxidant property exerted by steviol glycosides, suggesting their potential beneficial role in the cotreatment of diabetes and in health maintenance.

  19. Glycosides from Stevia rebaudiana Bertoni Possess Insulin-Mimetic and Antioxidant Activities in Rat Cardiac Fibroblasts

    Science.gov (United States)

    Prata, Cecilia; Zambonin, Laura; Rizzo, Benedetta; Vieceli Dalla Sega, Francesco

    2017-01-01

    Stevia rebaudiana Bertoni is a shrub having a high content of sweet diterpenoid glycosides in its leaves, mainly stevioside and rebaudioside A, which are used as noncaloric, natural sweeteners. The aim of this study was to deepen the knowledge about the insulin-mimetic effect exerted by four different mixtures of steviol glycosides, rich in stevioside and rebaudioside A, in neonatal rat cardiac fibroblasts. The potential antioxidant activity of these steviol glycosides was also assessed, as oxidative stress is associated with diabetes. Likewise the insulin effect, steviol glycosides caused an increase in glucose uptake into rat fibroblasts by activating the PI3K/Akt pathway, thus inducing Glut4 translocation to the plasma membrane. The presence of S961, an insulin antagonist, completely abolished these effects, allowing to hypothesize that steviol glycosides could act as ligands of the same receptor engaged by insulin. Moreover, steviol glycosides counteracted oxidative stress by increasing reduced glutathione intracellular levels and upregulating expression and activity of the two antioxidant enzymes superoxide dismutase and catalase. The present work unravels the insulin-mimetic effect and the antioxidant property exerted by steviol glycosides, suggesting their potential beneficial role in the cotreatment of diabetes and in health maintenance. PMID:28947927

  20. Nuclear SREBP-1a causes loss of pancreatic β-cells and impaired insulin secretion

    International Nuclear Information System (INIS)

    Iwasaki, Yuko; Iwasaki, Hitoshi; Yatoh, Shigeru; Ishikawa, Mayumi; Kato, Toyonori; Matsuzaka, Takashi; Nakagawa, Yoshimi; Yahagi, Naoya; Kobayashi, Kazuto; Takahashi, Akimitsu; Suzuki, Hiroaki; Yamada, Nobuhiro; Shimano, Hitoshi

    2009-01-01

    Transgenic mice expressing nuclear sterol regulatory element-binding protein-1a under the control of the insulin promoter were generated to determine the role of SREBP-1a in pancreatic β-cells. Only low expressors could be established, which exhibited mild hyperglycemia, impaired glucose tolerance, and reduced plasma insulin levels compared to C57BL/6 controls. The islets isolated from the transgenic mice were fewer and smaller, and had decreased insulin content and unaltered glucagon staining. Both glucose- and potassium-stimulated insulin secretions were decreased. The transgenic islets consistently expressed genes for fatty acids and cholesterol synthesis, resulting in accumulation of triglycerides but not cholesterol. PDX-1, ΒΕΤΑ2, MafA, and IRS-2 were suppressed, partially explaining the loss and dysfunction of β-cell mass. The transgenic mice on a high fat/high sucrose diet still exhibited impaired insulin secretion and continuous β-cell growth defect. Therefore, nuclear SREBP-1a, even at a low level, strongly disrupts β-cell mass and function.

  1. Insulin and the Lung

    DEFF Research Database (Denmark)

    Singh, Suchita; Prakash, Y S; Linneberg, Allan

    2013-01-01

    , molecular understanding is necessary. Insulin resistance is a strong, independent risk factor for asthma development, but it is unknown whether a direct effect of insulin on the lung is involved. This review summarizes current knowledge regarding the effect of insulin on cellular components of the lung...... and highlights the molecular consequences of insulin-related metabolic signaling cascades that could adversely affect lung structure and function. Examples include airway smooth muscle proliferation and contractility and regulatory signaling networks that are associated with asthma. These aspects of insulin...

  2. Riboflavin Reduces Pro-Inflammatory Activation of Adipocyte-Macrophage Co-culture. Potential Application of Vitamin B2 Enrichment for Attenuation of Insulin Resistance and Metabolic Syndrome Development.

    Science.gov (United States)

    Mazur-Bialy, Agnieszka Irena; Pocheć, Ewa

    2016-12-15

    Due to the progressive increase in the incidence of obese and overweight individuals, cardiometabolic syndrome has become a worldwide pandemic in recent years. Given the immunomodulatory properties of riboflavin, the current study was performed to investigate the potency of riboflavin in reducing obesity-related inflammation, which is the main cause of insulin resistance, diabetes mellitus 2 or arteriosclerosis. We determined whether pretreatment with a low dose of riboflavin (10.4-1000 nM) affected the pro-inflammatory activity of adipocyte-macrophage co-culture (3T3 L1-RAW 264.7) following lipopolysaccharide stimulation (LPS; 100 ng/mL) which mimics obesity-related inflammation. The apoptosis of adipocytes and macrophages as well as tumor necrosis factor-alpha (TNF-α), interleukin 6 (IL-6), interleukin 1beta (IL-1β), monocyte chemotactic protein 1 (MCP-1), high-mobility group box 1 (HMGB1), transforming growth factor-beta 1 (TGFβ), interleukin 10 (IL-10), inducible nitric oxide synthase (iNOS), nitric oxide (NO), matrix metalloproteinase 9 (MMP-9), tissue inhibitor of metalloproteinases-1 (TIMP-1) expression and release, macrophage migration and adipokines (adiponectin and leptin) were determined. Our results indicated an efficient reduction in pro-inflammatory factors (TNFα, IL-6, MCP-1, HMGB1) upon culture with riboflavin supplementation (500-1000 nM), accompanied by elevation in anti-inflammatory adiponectin and IL-10. Moreover, macrophage migration was reduced by the attenuation of chemotactic MCP-1 release and degradation of the extracellular matrix by MMP-9. In conclusion, riboflavin effectively inhibits the pro-inflammatory activity of adipocyte and macrophage co-cultures, and therefore we can assume that its supplementation may reduce the likelihood of conditions associated with the mild inflammation linked to obesity.

  3. Riboflavin Reduces Pro-Inflammatory Activation of Adipocyte-Macrophage Co-culture. Potential Application of Vitamin B2 Enrichment for Attenuation of Insulin Resistance and Metabolic Syndrome Development

    Directory of Open Access Journals (Sweden)

    Agnieszka Irena Mazur-Bialy

    2016-12-01

    Full Text Available Due to the progressive increase in the incidence of obese and overweight individuals, cardiometabolic syndrome has become a worldwide pandemic in recent years. Given the immunomodulatory properties of riboflavin, the current study was performed to investigate the potency of riboflavin in reducing obesity-related inflammation, which is the main cause of insulin resistance, diabetes mellitus 2 or arteriosclerosis. We determined whether pretreatment with a low dose of riboflavin (10.4–1000 nM affected the pro-inflammatory activity of adipocyte-macrophage co-culture (3T3 L1-RAW 264.7 following lipopolysaccharide stimulation (LPS; 100 ng/mL which mimics obesity-related inflammation. The apoptosis of adipocytes and macrophages as well as tumor necrosis factor-alpha (TNF-α, interleukin 6 (IL-6, interleukin 1beta (IL-1β, monocyte chemotactic protein 1 (MCP-1, high-mobility group box 1 (HMGB1, transforming growth factor–beta 1 (TGFβ, interleukin 10 (IL-10, inducible nitric oxide synthase (iNOS, nitric oxide (NO, matrix metalloproteinase 9 (MMP-9, tissue inhibitor of metalloproteinases-1 (TIMP-1 expression and release, macrophage migration and adipokines (adiponectin and leptin were determined. Our results indicated an efficient reduction in pro-inflammatory factors (TNFα, IL-6, MCP-1, HMGB1 upon culture with riboflavin supplementation (500–1000 nM, accompanied by elevation in anti-inflammatory adiponectin and IL-10. Moreover, macrophage migration was reduced by the attenuation of chemotactic MCP-1 release and degradation of the extracellular matrix by MMP-9. In conclusion, riboflavin effectively inhibits the pro-inflammatory activity of adipocyte and macrophage co-cultures, and therefore we can assume that its supplementation may reduce the likelihood of conditions associated with the mild inflammation linked to obesity.

  4. Effects of elevated root zone CO2 and air temperature on photosynthetic gas exchange, nitrate uptake, and total reduced nitrogen content in aeroponically grown lettuce plants.

    Science.gov (United States)

    He, Jie; Austin, Paul T; Lee, Sing Kong

    2010-09-01

    Effects of elevated root zone (RZ) CO(2) and air temperature on photosynthesis, productivity, nitrate (NO(3)(-)), and total reduced nitrogen (N) content in aeroponically grown lettuce plants were studied. Three weeks after transplanting, four different RZ [CO(2)] concentrations [ambient (360 ppm) and elevated concentrations of 2000, 10,000, and 50,000 ppm] were imposed on plants grown at two air temperature regimes of 28 degrees C/22 degrees C (day/night) and 36 degrees C/30 degrees C. Photosynthetic CO(2) assimilation (A) and stomatal conductance (g(s)) increased with increasing photosynthetically active radiation (PAR). When grown at 28 degrees C/22 degrees C, all plants accumulated more biomass than at 36 degrees C/30 degrees C. When measured under a PAR >or=600 micromol m(-2) s(-1), elevated RZ [CO(2)] resulted in significantly higher A, lower g(s), and higher midday leaf relative water content in all plants. Under elevated RZ [CO(2)], the increase of biomass was greater in roots than in shoots, causing a lower shoot/root ratio. The percentage increase in growth under elevated RZ [CO(2)] was greater at 36 degrees C/30 degrees C although the total biomass was higher at 28 degrees C/22 degrees C. NO(3)(-) and total reduced N concentrations of shoot and root were significantly higher in all plants under elevated RZ [CO(2)] than under ambient RZ [CO(2)] of 360 ppm at both temperature regimes. At each RZ [CO(2)], NO(3)(-) and total reduced N concentration of shoots were greater at 28 degrees C/22 degrees C than at 36 degrees C/30 degrees C. At all RZ [CO(2)], roots of plants at 36 degrees C/30 degrees C had significantly higher NO(3)(-) and total reduced N concentrations than at 28 degrees C/22 degrees C. Since increased RZ [CO(2)] caused partial stomatal closure, maximal A and maximal g(s) were negatively correlated, with a unique relationship for each air temperature. However, across all RZ [CO(2)] and temperature treatments, there was a close correlation between

  5. Sitagliptin reduces cardiac apoptosis, hypertrophy and fibrosis primarily by insulin-dependent mechanisms in experimental type-II diabetes. Potential roles of GLP-1 isoforms.

    Directory of Open Access Journals (Sweden)

    Belén Picatoste

    Full Text Available BACKGROUND: Myocardial fibrosis is a key process in diabetic cardiomyopathy. However, their underlying mechanisms have not been elucidated, leading to a lack of therapy. The glucagon-like peptide-1 (GLP-1 enhancer, sitagliptin, reduces hyperglycemia but may also trigger direct effects on the heart. METHODS: Goto-Kakizaki (GK rats developed type-II diabetes and received sitagliptin, an anti-hyperglycemic drug (metformin or vehicle (n=10, each. After cardiac structure and function assessment, plasma and left ventricles were isolated for biochemical studies. Cultured cardiomyocytes and fibroblasts were used for in vitro assays. RESULTS: Untreated GK rats exhibited hyperglycemia, hyperlipidemia, plasma GLP-1 decrease, and cardiac cell-death, hypertrophy, fibrosis and prolonged deceleration time. Moreover, cardiac pro-apoptotic/necrotic, hypertrophic and fibrotic factors were up-regulated. Importantly, both sitagliptin and metformin lessened all these parameters. In cultured cardiomyocytes and cardiac fibroblasts, high-concentration of palmitate or glucose induced cell-death, hypertrophy and fibrosis. Interestingly, GLP-1 and its insulinotropic-inactive metabolite, GLP-1(9-36, alleviated these responses. In addition, despite a specific GLP-1 receptor was only detected in cardiomyocytes, GLP-1 isoforms attenuated the pro-fibrotic expression in cardiomyocytes and fibroblasts. In addition, GLP-1 receptor signalling may be linked to PPARδ activation, and metformin may also exhibit anti-apoptotic/necrotic and anti-fibrotic direct effects in cardiac cells. CONCLUSIONS: Sitagliptin, via GLP-1 stabilization, promoted cardioprotection in type-II diabetic hearts primarily by limiting hyperglycemia e hyperlipidemia. However, GLP-1 and GLP-1(9-36 promoted survival and anti-hypertrophic/fibrotic effects on cultured cardiac cells, suggesting cell-autonomous cardioprotective actions.

  6. Exercise, pregnancy, and insulin sensitivity--what is new?

    DEFF Research Database (Denmark)

    Damm, Peter; Breitowicz, Bettina; Hegaard, Hanne Kristine

    2007-01-01

    Pregnancy is characterized by a marked physiological insulin resistance. Overweight and obesity or lack of physical activity can aggravate this reduced insulin sensitivity further. Increased insulin resistance has been associated with serious pregnancy complications, such as gestational diabetes...... mellitus (GDM) and pre-eclampsia. Recent studies clearly indicate that physical activity before and during pregnancy can reduce the risk of GDM and pre-eclampsia....

  7. Insulin aspart in diabetic pregnancy

    DEFF Research Database (Denmark)

    Mathiesen, Elisabeth R

    2008-01-01

    in insulin requirements during pregnancy necessitate short-acting insulins for postprandial control of hyperglycemia. The fast-acting insulin analogue insulin aspart has been tested in a large, randomized trial of pregnant women with Type 1 diabetes and offers benefits in control of postprandial...... hyperglycemia with a tendency towards fewer episodes of severe hypoglycemia compared with human insulin. Treatment with insulin aspart was associated with a tendency toward fewer fetal losses and preterm deliveries than treatment with human insulin. Insulin aspart could not be detected in the fetal circulation...... and no increase in insulin antibodies was found. Thus, the use of insulin aspart in pregnancy is regarded safe....

  8. User Preferences for Content, Features, and Style for an App to Reduce Harmful Drinking in Young Adults: Analysis of User Feedback in App Stores and Focus Group Interviews.

    Science.gov (United States)

    Milward, Joanna; Khadjesari, Zarnie; Fincham-Campbell, Stephanie; Deluca, Paolo; Watson, Rod; Drummond, Colin

    2016-05-24

    Electronic screening and brief intervention (eSBI) is effective in reducing weekly alcohol consumption when delivered by a computer. Mobile phone apps demonstrate promise in delivering eSBI; however, few have been designed with an evidence-based and user-informed approach. This study aims to explore from a user perspective, preferences for content, appearance, and operational features to inform the design of a mobile phone app for reducing quantity and frequency of drinking in young adults engaged in harmful drinking (18-30 year olds). Phase 1 included a review of user reviews of available mobile phone apps that support a reduction in alcohol consumption. Apps were identified on iTunes and Google Play and were categorized into alcohol reduction support, entertainment, blood alcohol content measurement (BAC), or other. eSBI apps with ≥18 user reviews were subject to a content analysis, which coded praise, criticism, and recommendations for app content, functionality, and esthetics. Phase 2 included four focus groups with young adults drinking at harmful levels and residing in South London to explore their views on existing eSBI apps and preferences for future content, functionality, and appearance. Detailed thematic analysis of the data was undertaken. In Phase 1, of the 1584 apps extracted, 201 were categorized as alcohol reduction, 154 as BAC calculators, 509 as entertainment, and 720 as other. We classified 32 apps as eSBI apps. Four apps had ≥18 user reviews: Change for Life Drinks Tracker, Drinksmeter, Drinkaware, and Alcohol Units Calculator. The highest proportion of content praises were for information and feedback provided in the apps (12/27, 44%), followed by praise for the monitoring features (5/27, 19%). Many (8/12, 67%) criticisms were for the drinking diary; all of these were related to difficulty entering drinks. Over half (18/32, 56%) of functionality criticisms were descriptions of software bugs, and over half of those (10/18, 56%) were for app

  9. N-acetylcysteine is able to reduce the oxidation status and the endothelial activation after a high-glucose content meal in patients with Type 2 diabetes mellitus.

    Science.gov (United States)

    Masha, A; Brocato, L; Dinatale, S; Mascia, C; Biasi, F; Martina, V

    2009-04-01

    Post-prandial hyperglycemia seems to play a pivotal role in the pathogenesis of the cardiovascular complications of diabetes mellitus, as it leads to an oxidative stress which in turn causes a reduced NO bioavailability. These conditions produce an endothelial activation. The aim of this study was to assure that the administration of N-acetylcysteine (NAC), thiolic antioxidant, is able to decrease the oxidation status and endothelial activation after a high-glucose content meal. Ten patients with Type 2 diabetes mellitus (DMT2) (Group 1) and 10 normal subjects (Group 2) were studied. They assumed a high-glucose content meal without (phase A) or after (phase B) the administration of NAC. Glycemia, insulinemia, intercellular adhesion molecule 1, vascular adhesion molecule 1 (VCAM-1), E-selectin, malonaldehyde (MDA), and 4-hydroxynonenal (HNE) were assessed at -30, 0, +30, +60, +90, +120, and +180 min with respect to the meal consumption. During the phase A in Group 1, only HNE and MDA levels increased after the meal assumption; all parameters remained unchanged in Group 2. During the phase B, in Group 1, HNE, MDA, VCAM-1, and E-selectin levels after the meal were lower than those in phase A, while no change for all variables were observed in Group 2. A high-glucose meal produces an increase in oxidation parameters in patients with DMT2. The administration of NAC reduces the oxidative stress and, by doing so, reduces the endothelial activation. In conclusion, NAC could be efficacious in the slackening of the progression of vascular damage in DMT2.

  10. Decreased insulin response in dairy cows following a four-day fast to induce hepatic lipidosis.

    Science.gov (United States)

    Oikawa, S; Oetzel, G R

    2006-08-01

    Negative energy balance has been implicated in the development of fatty liver, insulin resistance, and impaired health in dairy cows. A 4-d fasting model previously was reported to increase liver triglycerides more than 2.5-fold. The purpose of the present study was to evaluate insulin response in this fasting model. Nonlactating, nonpregnant Holstein cows were fasted for 4 d (6 cows) or fed continuously as control cows (4 cows). Samples were collected 5 d before fasting, during fasting, and immediately after the 4-d fast, 8 d after the fast, and 16 d after the fast. Fasted cows had greater liver triglyceride content (49.4 vs. 16.2 mg/g, wet-weight basis) at the end of the fasting period compared with control cows. Fasted cows also had increased plasma nonesterified fatty acid (NEFA) concentrations (1.24 vs. 0.21 mmol/L) and increased plasma beta-hydroxybutyrate (BHBA) concentrations at the end of the fasting period. Liver triglyceride, plasma NEFA, and plasma BHBA in fasted cows returned to prefasting concentrations by the end of the experiment. Plasma glucose concentrations were not affected by fasting. Plasma insulin concentrations were decreased (6.3 vs. 14.1 microU/mL) and insulin-stimulated blood glucose reduction was decreased (24.9 vs. 48.6%) in the fasted cows compared with control cows at the end of the fast, indicating reduced insulin response. Insulin response was negatively correlated with plasma NEFA and liver triglycerides. Decreased insulin response may be an important complication of negative energy balance and hepatic lipidosis.

  11. Hyperinsulinism and polycystic ovary syndrome (PCOS): role of insulin clearance.

    Science.gov (United States)

    Amato, M C; Vesco, R; Vigneri, E; Ciresi, A; Giordano, C

    2015-12-01

    Insulin resistance and compensatory hyperinsulinism are the predominant metabolic defects in polycystic ovary syndrome (PCOS). However, hyperinsulinism, as well as being compensatory, can also express a condition of reduced insulin clearance. Our aim was to evaluate the differences in insulin action and metabolism between women with PCOS (with normal glucose tolerance) and age- and BMI-matched women with prediabetes (without hyperandrogenism and ovulatory disorders). 22 women with PCOS and 21 age/BMI-matched women with prediabetes were subjected to a Hyperinsulinemic-euglycemic clamp and an Oral Glucose tolerance Test (OGTT). Insulin sensitivity was assessed by the glucose infusion rate during clamp (M value); insulin secretion by Insulinogenic index, Oral Disposition Index (DIo) and AUC(2h-insulin) during OGTT; and insulin clearance by the metabolic clearance rate of insulin (MCRI) during clamp. Women with PCOS showed significantly higher levels of AUC(2h-insulin) (p PCOS [420 (IQR 227-588) vs. 743 (IQR 597-888) ml m(-2) min(-1): p PCOS group, a strong independent inverse correlation was only observed between MCRI and AUC(2h-insulin) (PCOS: β:-0.878; p PCOS there is peripheral insulin sensitivity similar to that of women with prediabetes. What sets PCOS apart is the hyperinsulinism, today still simplistically defined "compensatory"; actually this is mainly related to decreased insulin clearance whose specific causes and dynamics have yet to be clarified.

  12. Radioimmunologic study of insulin secretion during acute radiation sickness

    International Nuclear Information System (INIS)

    Barkalaya, A.I.

    1977-01-01

    Insulin secretion in irradiated (750 R) albino rats has been studied radioimmunologically. The data obtained were correlated with the corticosterone and glucose contents of blood. It has been shown that there is a risk of relative incompetence of insulin secretion during the hypercorticoidism and hyperglycemia

  13. Radioimmunologic study of insulin secretion during acute radiation sickness

    Energy Technology Data Exchange (ETDEWEB)

    Barkalaya, A I

    1977-01-01

    Insulin secretion in irradiated (750 R) albino rats has been studied radioimmunologically. The data obtained were correlated with the corticosterone and glucose contents of blood. It has been shown that there is a risk of relative incompetence of insulin secretion during the hypercorticoidism and hyperglycemia.

  14. Patient safety and minimizing risk with insulin administration - role of insulin degludec.

    Science.gov (United States)

    Aye, Myint M; Atkin, Stephen L

    2014-01-01

    Diabetes is a lifelong condition requiring ongoing medical care and patient self-management. Exogenous insulin therapy is essential in type 1 diabetes and becomes a necessity in patients with longstanding type 2 diabetes who fail to achieve optimal control with lifestyle modification, oral agents, and glucagon-like peptide 1-based therapy. One of the risks that hinders insulin use is hypoglycemia. Optimal insulin therapy should therefore minimize the risk of hypoglycemia while improving glycemic control. Insulin degludec (IDeg) is a novel basal insulin that, following subcutaneous injection, assembles into a depot of soluble multihexamer chains. These subsequently release IDeg monomers that are absorbed at a slow and steady rate into the circulation, with the terminal half-life of IDeg being ~25 hours. Thus, it requires only once-daily dosing unlike other basal insulin preparations that often require twice-daily dosing. Despite its long half-life, once-daily IDeg does not cause accumulation of insulin in the circulation after reaching steady state. IDeg once a day will produce a steady-state profile with a lower peak:trough ratio than other basal insulins. In clinical trials, this profile translates into a lower frequency of nocturnal hypoglycemia compared with insulin glargine, as well as an ability to allow some flexibility in dose timing without compromising efficacy and safety. Indeed, a study that tested the extremes of dosing intervals of 8 and 40 hours showed no detriment in either glycemic control or hypoglycemic frequency versus insulin glargine given at the same time each day. While extreme flexibility in dose timing is not recommended, these findings are reassuring. This may be particularly beneficial to elderly patients, patients with learning difficulties, or others who have to rely on health-care professionals for their daily insulin injections. Further studies are required to confirm whether this might benefit adherence to treatment, reduce long

  15. Dissociation between insulin secretion and DNA synthesis in cultured pancreatic islets

    DEFF Research Database (Denmark)

    Nielsen, Jens Høiriis

    1985-01-01

    -Tdr incorporation. However, long-term exposure to IBMX did not result in increased DNA content of the islets. Inhibition of the DNA synthesis by 5 mM hydroxyurea resulted in a marked reduction in DNA content of the islets but no decrease in either insulin release or insulin content when expressed per ng DNA...

  16. Maternal periodontal disease in rats decreases insulin sensitivity and insulin signaling in adult offspring.

    Science.gov (United States)

    Shirakashi, Daisy J; Leal, Rosana P; Colombo, Natalia H; Chiba, Fernando Y; Garbin, Cléa A S; Jardim, Elerson G; Antoniali, Cristina; Sumida, Doris H

    2013-03-01

    Periodontal disease during pregnancy has been recognized as one of the causes of preterm and low-birth-weight (PLBW) babies. Several studies have demonstrated that PLBW babies are prone to developing insulin resistance as adults. Although there is controversy over the association between periodontal disease and PLBW, the phenomenon known as programming can translate any stimulus or aggression experienced during intrauterine growth into physiologic and metabolic alterations in adulthood. The purpose of the present study is to investigate whether the offspring of rats with periodontal disease develop insulin resistance in adulthood. Ten female Wistar rats were divided into periodontal disease (PED) and control (CN) groups. All rats were mated at 7 days after induction of periodontal disease. Male offspring were divided into two groups: 1) periodontal disease offspring (PEDO; n = 24); and 2) control offspring (CNO; n = 24). Offspring body weight was measured from birth until 75 days. When the offspring reached 75 days old, the following parameters were measured: 1) plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and tumor necrosis factor-α (TNF-α); 2) insulin sensitivity (IS); and 3) insulin signal transduction (IST) in insulin-sensitive tissues. Low birth weight was not detected in the PEDO group. However, plasma concentrations of glucose, insulin, fructosamine, lipase, amylase, and TNF-α were increased and IS and IST were reduced (P PEDO group compared with the CNO group. Maternal periodontal disease may induce insulin resistance and reduce IST in adult offspring, but such alterations are not attributable to low birth weight.

  17. Insulin-like growth factor-1 (IGF-1) promotes primordial follicle growth and reduces DNA fragmentation through the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) signalling pathway.

    Science.gov (United States)

    Bezerra, Maria É S; Barberino, Ricássio S; Menezes, Vanúzia G; Gouveia, Bruna B; Macedo, Taís J S; Santos, Jamile M S; Monte, Alane P O; Barros, Vanessa R P; Matos, Maria H T

    2018-05-30

    We investigated the effects of insulin-like growth factor 1 (IGF-1) on the morphology and follicular activation of ovine preantral follicles cultured in situ and whether the phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway is involved in IGF-1 action in the sheep ovary. Ovine ovarian fragments were fixed for histological and terminal deoxynucleotidyl transferase dUTP nick-end labelling (TUNEL) analyses (fresh control) or cultured in supplemented alpha-minimum essential medium (α-MEM+; control) or α-MEM+ with IGF-1 (1, 10, 50, 100 or 200ngmL-1) for 7 days. Follicles were classified as normal or atretic, primordial or growing and the oocyte and follicle diameters were measured. DNA fragmentation was evaluated by TUNEL assay. Proliferating cell nuclear antigen (PCNA) immunohistochemistry was performed on the fresh control, α-MEM+ and 100ngmL-1 IGF-1 samples. Inhibition of PI3K activity was performed through pretreatment with the PI3K inhibitor LY294002 and phosphorylated AKT (pAKT) expression was analysed after culture in the absence or presence of LY294002. IGF-1 at 100ngmL-1 increased (PIGF-1. LY294002 significantly inhibited follicular activation stimulated by α-MEM+ and 100ngmL-1 IGF-1 and reduced pAKT expression in follicles. Overall, IGF-1 at 100ngmL-1 promoted primordial follicle activation, cell proliferation and reduced DNA fragmentation after in situ culture through the PI3K/AKT pathway.

  18. Mental performance in 8-year-old children fed reduced protein content formula during the 1st year of life: safety analysis of a randomised clinical trial.

    Science.gov (United States)

    Escribano, J; Luque, V; Canals-Sans, J; Ferré, N; Koletzko, B; Grote, V; Weber, M; Gruszfeld, D; Szott, K; Verduci, E; Riva, E; Brasselle, G; Poncelet, P; Closa-Monasterolo, R

    2016-01-22

    In humans, maximum brain development occurs between the third trimester of gestation and 2 years of life. Nutrition during these critical windows of rapid brain development might be essential for later cognitive functioning and behaviour. In the last few years, trends on protein recommendations during infancy and childhood have tended to be lower than that in the past. It remains to be demonstrated that lower protein intakes among healthy infants, a part of being able to reduce obesity risk, is safe in terms of mental performance achievement. Secondary analyses of the EU CHOP, a clinical trial in which infants from five European countries were randomised to be fed a higher or a lower protein content formula during the 1st year of life. Children were assessed at the age of 8 years with a neuropsychological battery of tests that included assessments of memory (visual and verbal), attention (visual, selective, focused and sustained), visual-perceptual integration, processing speed, visual-motor coordination, verbal fluency and comprehension, impulsivity/inhibition, flexibility/shifting, working memory, reasoning, visual-spatial skills and decision making. Internalising, externalising and total behaviour problems were assessed using the Child Behaviour Checklist 4-18. Adjusted analyses considering factors that could influence neurodevelopment, such as parental education level, maternal smoking, child's gestational age at birth and head circumference, showed no differences between feeding groups in any of the assessed neuropsychological domains and behaviour. In summary, herewith we report on the safety of lower protein content in infant formulae (closer to the content of human milk) according to long-term mental performance.

  19. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet.

    Science.gov (United States)

    Balbaa, Mahmoud; El-Zeftawy, Marwa; Ghareeb, Doaa; Taha, Nabil; Mandour, Abdel Wahab

    2016-01-01

    The black cumin (Nigella sativa) "NS" or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO) in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride) and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling.

  20. Nigella sativa Relieves the Altered Insulin Receptor Signaling in Streptozotocin-Induced Diabetic Rats Fed with a High-Fat Diet

    Directory of Open Access Journals (Sweden)

    Mahmoud Balbaa

    2016-01-01

    Full Text Available The black cumin (Nigella sativa “NS” or the black seeds have many pharmacological activities such as antioxidant, anticarcinogenic, antihypertensive, and antidiabetic properties. In this work, streptozotocin-induced diabetic rats fed with a high-fat diet were treated daily with NS oil (NSO in order to study the effect on the blood glucose, lipid profile, oxidative stress parameters, and the gene expression of some insulin receptor-induced signaling molecules. This treatment was combined also with some drugs (metformin and glimepiride and the insulin receptor inhibitor I-OMe-AG538. The administration of NSO significantly induced the gene expression of insulin receptor compared to rats that did not receive NSO. Also, it upregulated the expression of insulin-like growth factor-1 and phosphoinositide-3 kinase, whereas the expression of ADAM-17 was downregulated. The expression of ADAM-17 is corroborated by the analysis of TIMP-3 content. In addition, the NSO significantly reduced blood glucose level, components of the lipid profile, oxidative stress parameters, serum insulin/insulin receptor ratio, and the tumor necrosis factor-α, confirming that NSO has an antidiabetic activity. Thus, the daily NSO treatment in our rat model indicates that NSO has a potential in the management of diabetes as well as improvement of insulin-induced signaling.

  1. Combining insulins for optimal blood glucose control in type 1 and 2 diabetes: focus on insulin glulisine

    Directory of Open Access Journals (Sweden)

    Heather Ulrich

    2007-07-01

    Full Text Available Heather Ulrich1,4, Benjamin Snyder1,Satish K Garg1,2,31Barbara Davis Center for Childhood Diabetes; 2Department of Medicine; 3Pediatrics; 4Department of Clinical Pharmacy, School of Pharmacy, University of Colorado at Denver and Health Sciences Center, Denver, CO, USAAbstract: Normalization of blood glucose is essential for the prevention of diabetes mellitus (DM-related microvascular and macrovascular complications. Despite substantial literature to support the benefits of glucose lowering and clear treatment targets, glycemic control remains suboptimal for most people with DM in the United States. Pharmacokinetic limitations of conventional insulins have been a barrier to achieving treatment targets secondary to adverse effects such as hypoglycemia and weight gain. Recombinant DNA technology has allowed modification of the insulin molecule to produce insulin analogues that overcome these pharmacokinetic limitations. With time action profiles that more closely mimic physiologic insulin secretion, rapid acting insulin analogues (RAAs reduce post-prandial glucose excursions and hypoglycemia when compared to regular human insulin (RHI. Insulin glulisine (Apidra® is a rapid-acting insulin analogue created by substituting lysine for asparagine at position B3 and glutamic acid for lysine at position B29 on the B chain of human insulin. The quick absorption of insulin glulisine more closely reproduces physiologic first-phase insulin secretion and its rapid acting profile is maintained across patient subtypes. Clinical trials have demonstrated comparable or greater efficacy of insulin glulisine versus insulin lispro or RHI, respectively. Efficacy is maintained even when insulin glulisine is administered post-meal. In addition, glulisine appears to have a more rapid time action profile compared with insulin lispro across various body mass indexes (BMIs. The safety and tolerability profile of insulin glulisine is also comparable to that of insulin

  2. Effect of tributyltin on adenylate content and enzyme activities of teleost sperm: a biochemical approach to study the mechanisms of toxicant reduced spermatozoa motility.

    Science.gov (United States)

    Rurangwa, E; Biegniewska, A; Slominska, E; Skorkowski, E F; Ollevier, F

    2002-03-01

    The effects of tributyltin (TBT) on the energy metabolism and motility of fish spermatozoa were investigated in vitro in African catfish and common carp. A significant (PTBT for 24 h. Exposure of catfish spermatozoa to 2.7-27 microg/l TBT caused an instant decrease in ATP content. In the presence of 27 microg/l TBT approximately 55% of the initial ATP concentration in catfish semen was lost after 60 min incubation while AMP concentrations increased and the total adenine nucleotide (TAN) pool remained unchanged. The reduction in sperm ATP levels could not be attributed to cell death since viability decreased only slightly over the period of exposure. In carp by contrast, none of the adenylates concentrations studied (ATP, ADP and AMP) were affected by TBT exposure at any experimental condition. However, carp sperm motility was significantly reduced by exposure to 2.7 microg/l TBT. Among the enzymes investigated only lactate dehydrogenase (LDH) in catfish sperm was significantly (PTBT treatment with a reduction in activity of approximately 75%. Compared with carp sperm before TBT exposure, that of catfish had lower adenylate contents and overall lower enzymatic activities; this explains its slower sperm velocity and shorter duration of movement as measured by computer assisted sperm analysis (CASA). The present in vitro study shows that catfish spermatozoa are more sensitive to TBT exposure (and probably to other toxicants) than those of carp.

  3. Insulin receptor isoforms A and B as well as insulin receptor substrates-1 and -2 are differentially expressed in prostate cancer.

    Science.gov (United States)

    Heni, Martin; Hennenlotter, Jörg; Scharpf, Marcus; Lutz, Stefan Z; Schwentner, Christian; Todenhöfer, Tilman; Schilling, David; Kühs, Ursula; Gerber, Valentina; Machicao, Fausto; Staiger, Harald; Häring, Hans-Ulrich; Stenzl, Arnulf

    2012-01-01

    In different cancers types, insulin receptor isoform composition or insulin receptor substrate (IRS) isoforms are different to healthy tissue. This may be a molecular link to increased cancer risk in diabetes and obesity. Since this is yet unclear for prostate cancer, we investigated IR isoform composition and IRS balance in prostate cancer compared to benign and tumor adjacent benign prostate tissue and brought this into relation to cell proliferation. We studied 23 benign prostate samples from radical cystectomy or benign prostatic hyperplasia surgery, 30 samples from benign tissue directly adjacent to prostate cancer foci and 35 cancer samples from different patients. RNA expression levels for insulin receptor isoforms A and B, IRS-1, IRS-2, and IGF-1 receptor were assessed by quantitative real-time RT-PCR. In addition, RNA- and protein expression of the cell cycle regulator p27(Kip1) was quantified by real-time RT-PCR and immunohistochemistry. Insulin receptor isoform A to B ratio was significantly higher in cancer as well as in tumor adjacent benign prostate tissue compared to purely benign prostates (pprostatic tissue (pcancer and adjacent tissue were significantly associated with reduced p27(Kip1) content (preceptor levels were significantly lower in patients with type 2 diabetes (p = 0.0019). We found significant differences in the insulin signaling cascade between benign prostate tissue and prostate cancer. Histological benign tissue adjacent to cancer showed expression patterns similar to the malignancies. Our findings suggest a role of the insulin signaling pathway in prostate cancer and surrounding tissue and can hence be relevant for both novel diagnostic and therapeutic approaches in this malignancy.

  4. Insulin resistance in dairy cows.

    Science.gov (United States)

    De Koster, Jenne D; Opsomer, Geert

    2013-07-01

    Glucose is the molecule that drives milk production, and insulin plays a pivotal role in the glucose metabolism of dairy cows. The effect of insulin on the glucose metabolism is regulated by the secretion of insulin by the pancreas and the insulin sensitivity of the skeletal muscles, the adipose tissue, and the liver. Insulin resistance may develop as part of physiologic (pregnancy and lactation) and pathologic processes, which may manifest as decreased insulin sensitivity or decreased insulin responsiveness. A good knowledge of the normal physiology of insulin is needed to measure the in vivo insulin resistance of dairy cows. Copyright © 2013 Elsevier Inc. All rights reserved.

  5. Skeletal muscle insulin resistance associated with cholesterol-induced activation of macrophages is prevented by high density lipoprotein.

    Directory of Open Access Jour