Lithium modulates the chronic stress-induced effect on blood glucose level of male rats

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Popović Nataša

2010-01-01

Full Text Available In the present study we examined gross changes in the mass of whole adrenal glands and that of the adrenal cortex, as well as the serum corticosterone and glucose level of mature male Wistar rats subjected to three different treatments: animals subjected to chronic restraint-stress, animals injected with lithium (Li and chronically stressed rats treated with Li. Under all three conditions we observed hypertrophy of whole adrenals, as well as the adrenal cortices. Chronic restraint stress, solely or in combination with Li treatment, significantly elevated the corticosterone level, but did not change the blood glucose level. Animals treated only with Li exhibited an elevated serum corticosterone level and blood glucose level. The aim of our study was to investigate the modulation of the chronic stress-induced effect on the blood glucose level by lithium, as a possible mechanism of avoiding the damage caused by chronic stress. Our results showed that lithium is an agent of choice which may help to reduce stress-elevated corticosterone and replenish exhausted glucose storages in an organism.

Myo-inositol inhibits intestinal glucose absorption and promotes muscle glucose uptake: a dual approach study.

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

2016-12-01

The present study investigated the effects of myo-inositol on muscle glucose uptake and intestinal glucose absorption ex vivo as well as in normal and type 2 diabetes model of rats. In ex vivo study, both intestinal glucose absorption and muscle glucose uptake were studied in isolated rat jejunum and psoas muscle respectively in the presence of increasing concentrations (2.5 % to 20 %) of myo-inositol. In the in vivo study, the effect of a single bolus dose (1 g/kg bw) of oral myo-inositol on intestinal glucose absorption, blood glucose, gastric emptying and digesta transit was investigated in normal and type 2 diabetic rats after 1 h of co-administration with 2 g/kg bw glucose, when phenol red was used as a recovery marker. Myo-inositol inhibited intestinal glucose absorption (IC 50  = 28.23 ± 6.01 %) and increased muscle glucose uptake, with (GU 50  = 2.68 ± 0.75 %) or without (GU 50  = 8.61 ± 0.55 %) insulin. Additionally, oral myo-inositol not only inhibited duodenal glucose absorption and reduced blood glucose increase, but also delayed gastric emptying and accelerated digesta transit in both normal and diabetic animals. Results of this study suggest that dietary myo-inositol inhibits intestinal glucose absorption both in ex vivo and in normal or diabetic rats and also promotes muscle glucose uptake in ex vivo condition. Hence, myo-inositol may be further investigated as a possible anti-hyperglycaemic dietary supplement for diabetic foods and food products.

Effect of sulfonylureas administered centrally on the blood glucose level in immobilization stress model.

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

2015-05-01

Sulfonylureas are widely used as an antidiabetic drug. In the present study, the effects of sulfonylurea administered supraspinally on immobilization stress-induced blood glucose level were studied in ICR mice. Mice were once enforced into immobilization stress for 30 min and returned to the cage. The blood glucose level was measured 30, 60, and 120 min after immobilization stress initiation. We found that intracerebroventricular (i.c.v.) injection with 30 µg of glyburide, glipizide, glimepiride or tolazamide attenuated the increased blood glucose level induced by immobilization stress. Immobilization stress causes an elevation of the blood corticosterone and insulin levels. Sulfonylureas pretreated i.c.v. caused a further elevation of the blood corticosterone level when mice were forced into the stress. In addition, sulfonylureas pretreated i.c.v. alone caused an elevation of the plasma insulin level. Furthermore, immobilization stress-induced insulin level was reduced by i.c.v. pretreated sulfonylureas. Our results suggest that lowering effect of sulfonylureas administered supraspinally against immobilization stress-induced increase of the blood glucose level appears to be primarily mediated via elevation of the plasma insulin level.

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

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

2012-03-01

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

C-myb Regulates Autophagy for Pulp Vitality in Glucose Oxidative Stress.

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Lee, Y H; Kim, H S; Kim, J S; Yu, M K; Cho, S D; Jeon, J G; Yi, H K

2016-04-01

Diabetes mellitus is closely related to oral-complicated diseases by oxidative stress. This study investigates whether cellular myeloblastosis (c-myb) could protect human dental pulp cells against glucose oxidative stress and regulate autophagy activity for pulp vitality. Diabetes mellitus was induced by streptozotocin in Sprague-Dawley rats, and their pulp tissue in teeth was analyzed in terms of pulp cavity and molecules by hematoxylin and eosin and immunohistochemistry staining. Human dental pulp cells were serially subcultured and treated with glucose oxidase in the presence of elevated glucose to generate glucose oxidative stress. The replication-deficient adenovirus c-myb and small interfering RNA c-myb were introduced for c-myb expression. The pulp tissue from the diabetic rats was structurally different from normal tissue in terms of narrow pulp capacity, reduced c-myb, and dentinogenesis molecules. Glucose oxidase treatment decreased c-myb and dentinogenesis molecules (bone morphogenetic protein 2 and 7, dentin matrix protein 1, and dentin sialophosphoprotein) in human dental pulp cells. However, overexpression of c-myb by adenovirus c-myb increased dentinogenesis, autophagy molecules (autophagy protein 5, microtubule-associated protein 1A/1B-light chain 3, and Beclin-1), and cell survival via p-AMPK/AKT signaling even with glucose oxidative stress. In contrast, the lack of c-myb decreased the above molecules and cell survival by downregulating p-AMPK/AKT signaling. The results indicate that diabetes leads to irreversible damage to dental pulp, which is related to downexpression of autophagy via the p-AMPK/AKT pathway by decline of c-myb. The findings of this study provide a new insight that c-myb could ameliorate autophagy activity and that it is applicable for monitoring complicated diseases of dental pulp. The involvement of c-myb in pulp pathology could serve a therapeutic target in oral-complicated diseases. © International & American Associations

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

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

2017-11-01

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

Chronic variable stress improves glucose tolerance in rats with sucrose-induced prediabetes

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Packard, Amy E. B.; Ghosal, Sriparna; Herman, James P.; Woods, Stephen C.; Ulrich-Lai, Yvonne M.

2014-01-01

The incidence of type-2 diabetes (T2D) and the burden it places on individuals, as well as society as a whole, compels research into the causes, factors and progression of this disease. Epidemiological studies suggest that chronic stress exposure may contribute to the development and progression of T2D in human patients. To address the interaction between chronic stress and the progression of T2D, we developed a dietary model of the prediabetic state in rats utilizing unlimited access to 30% sucrose solution (in addition to unlimited access to normal chow and water), which led to impaired glucose tolerance despite elevated insulin levels. We then investigated the effects of a chronic variable stress paradigm (CVS; twice daily exposure to an unpredictable stressor for 2 weeks) on metabolic outcomes in this prediabetic model. Chronic stress improved glucose tolerance in prediabetic rats following a glucose challenge. Importantly, pair-fed control groups revealed that the beneficial effect of chronic stress did not result from the decreased food intake or body weight gain that occurred during chronic stress. The present work suggests that chronic stress in rodents can ameliorate the progression of diet-induced prediabetic disease independent of chronic stress-induced decreases in food intake and body weight. PMID:25001967

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

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

2010-11-11

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

Glucose metabolism in pigs expressing human genes under an insulin promoter.

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Wijkstrom, Martin; Bottino, Rita; Iwase, Hayoto; Hara, Hidetaka; Ekser, Burcin; van der Windt, Dirk; Long, Cassandra; Toledo, Frederico G S; Phelps, Carol J; Trucco, Massimo; Cooper, David K C; Ayares, David

2015-01-01

Xenotransplantation of porcine islets can reverse diabetes in non-human primates. The remaining hurdles for clinical application include safe and effective T-cell-directed immunosuppression, but protection against the innate immune system and coagulation dysfunction may be more difficult to achieve. Islet-targeted genetic manipulation of islet-source pigs represents a powerful tool to protect against graft loss. However, whether these genetic alterations would impair islet function is unknown. On a background of α1,3-galactosyltransferase gene-knockout (GTKO)/human (h)CD46, additional genes (hCD39, human tissue factor pathway inhibitor, porcine CTLA4-Ig) were inserted in different combinations under an insulin promoter to promote expression in islets (confirmed by immunofluorescence). Seven pigs were tested for baseline and glucose/arginine-challenged levels of glucose, insulin, C-peptide, and glucagon. This preliminary study did not show definite evidence of β-cell deficiencies, even when three transgenes were expressed under the insulin promoter. Of seven animals, all were normoglycemic at fasting, and five of seven had normal glucose disposal rates after challenge. All animals exhibited insulin, C-peptide, and glucagon responses to both glucose and arginine challenge; however, significant interindividual variation was observed. Multiple islet-targeted transgenic expression was not associated with an overtly detrimental effect on islet function, suggesting that complex genetic constructs designed for islet protection warrants further testing in islet xenotransplantation models. © 2014 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Effect of food-related stress conditions and loss of agr and sigB on seb promoter activity in S. aureus.

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Sihto, Henna-Maria; Stephan, Roger; Engl, Christoph; Chen, John; Johler, Sophia

2017-08-01

Staphylococcal enterotoxin B (SEB) causes staphylococcal food poisoning and is produced in up to ten times higher quantities than other major enterotoxins. While Staphylococcus aureus growth is often repressed by competing flora, the organism exhibits a decisive growth advantage under some stress conditions. So far, data on the influence of food-related stressors and regulatory mutations on seb expression is limited and largely based on laboratory strains, which were later reported to harbor mutations. Therefore, the aim of this study was to investigate the influence of stress and regulatory mutations on seb promoter activity. To this end, transcriptional fusions were created in two strains, USA300 and HG003, carrying different seb upstream sequences fused to a blaZ reporter. NaCl, nitrite, and glucose stress led to significantly decreased seb promoter activity, while lactic acid stress resulted in significantly increased seb promoter activity. Loss of agr decreased seb promoter activity and loss of sigB increased promoter activity, with the magnitude of change depending on the strain. These results demonstrate that mild stress conditions encountered during food production and preservation can induce significant changes in seb promoter activity. Copyright © 2017 Elsevier Ltd. All rights reserved.

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

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Konitzer, K.; Voigt, S.

1980-01-01

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

Davallialactone reduces inflammation and repairs dentinogenesis on glucose oxidase-induced stress in dental pulp cells.

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Lee, Young-Hee; Kim, Go-Eun; Song, Yong-Beom; Paudel, Usha; Lee, Nan-Hee; Yun, Bong-Sik; Yu, Mi-Kyung; Yi, Ho-Keun

2013-11-01

The chronic nature of diabetes mellitus (DM) raises the risk of oral complication diseases. In general, DM causes oxidative stress to organs. This study aimed to evaluate the cellular change of dental pulp cells against glucose oxidative stress by glucose oxidase with a high glucose state. The purpose of this study was to test the antioxidant character of davallialactone and to reduce the pathogenesis of dental pulp cells against glucose oxidative stress. The glucose oxidase with a high glucose concentration was tested for hydroxy peroxide (H2O2) production, cellular toxicity, reactive oxygen species (ROS) formation, induction of inflammatory molecules and disturbance of dentin mineralization in human dental pulp cells. The anti-oxidant effect of Davallilactone was investigated to restore dental pulp cells' vitality and dentin mineralization via reduction of H2O2 production, cellular toxicity, ROS formation and inflammatory molecules. The treatment of glucose oxidase with a high glucose concentration increased H2O2 production, cellular toxicity, and inflammatory molecules and disturbed dentin mineralization by reducing pulp cell activity. However, davallialactone reduced H2O2 production, cellular toxicity, ROS formation, inflammatory molecules, and dentin mineralization disturbances even with a long-term glucose oxidative stress state. The results of this study imply that the development of oral complications is related to the irreversible damage of dental pulp cells by DM-induced oxidative stress. Davallialactone, a natural antioxidant, may be useful to treat complicated oral disease, representing an improvement for pulp vital therapy. Copyright © 2013 American Association of Endodontists. Published by Elsevier Inc. All rights reserved.

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

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Torres I.L.S.

2001-01-01

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

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

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Xuemei Shi

2017-11-01

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

Involvement of α(2)-adrenergic receptor in the regulation of the blood glucose level induced by immobilization stress.

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Kang, Yu-Jung; Sim, Yun-Beom; Park, Soo-Hyun; Sharma, Naveen; Suh, Hong-Won

2015-01-01

The blood glucose profiles were characterized after mice were forced into immobilization stress with various exposure durations. The blood glucose level was significantly enhanced by immobilization stress for 30 min or 1 h, respectively. On the other hand, the blood glucose level was not affected in the groups which were forced into immobilization stress for 2 or 4 h. We further examined the effect of yohimbine (an α2-adrenergic receptor antagonist) administered systemically or centrally in the immobilization stress model. Mice were pretreated intraperitoneally (i.p.; from 0.5 to 5 mg/kg), intracerebroventricularly (i.c.v.; from 1 to 10 µg/5 µl), or intrathecally (i.t.; from 1 to 10 µg/5 µl) with yohimbine for 10 min and then, forced into immobilization stress for 30 min. The blood glucose level was measured right after immobilization stress. We found that up-regulation of the blood glucose level induced by immobilization stress was abolished by i.p. pretreatment with yohimbine. And the immobilization stress-induced blood glucose level was not inhibited by i.c.v. or i.t. pretreatment with yohimbine at a lower dose (1 µg/5 µl). However, immobilization stress-induced blood glucose level was significantly inhibited by i.c.v. or i.t. pretreatment with yohimbine at higher doses (5 and 10 µg/5 µl). In addition, the i.p. (5 mg/kg), i.c.v. (10 µg/5 µl), or i.t. (10 µg/5 µl) pretreatment with yohimbine reduced hypothalamic glucose transporter 4 expression. The involvement of α2-adrenergic receptor in regulation of immobilization stress- induced blood glucose level was further confirmed by the i.p, i.c.v, or i.t pretreatment with idazoxan, another specific α2-adrenergic receptor antagonist. Finally, i.p., i.c.v., or i.t. pretreatment with yohimbine attenuated the blood glucose level in D-glucose-fed model. We suggest that α2-adrenergic receptors located at the peripheral, the brain and the spinal cord play important roles in the up

Post-stress recovery of pituitary-adrenal hormones and glucose, but not the response during exposure to the stressor, is a marker of stress intensity in highly stressful situations.

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Márquez, Cristina; Belda, Xavier; Armario, Antonio

2002-02-01

Acute immobilization in male rats elicited the same ACTH, corticosterone and glucose response as foot shock when measured immediately after stress. However, post-stress recovery of plasma ACTH, corticosterone and glucose levels were delayed in immobilized versus shocked rats. Similarly, stress-induced anorexia was much greater in the former animals. All these data suggest that post-stress speed of recovery of some physiological variables is positively related to stressor intensity and could be used to evaluate it.

High Glucose-Induced Oxidative Stress Mediates Apoptosis and Extracellular Matrix Metabolic Imbalances Possibly via p38 MAPK Activation in Rat Nucleus Pulposus Cells

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Xiaofei Cheng

2016-01-01

Full Text Available Objectives. To investigate whether high glucose-induced oxidative stress is implicated in apoptosis of rat nucleus pulposus cells (NPCs and abnormal expression of critical genes involved in the metabolic balance of extracellular matrix (ECM. Methods. NPCs were cultured with various concentrations of glucose to detect cell viability and apoptosis. Cells cultured with high glucose (25 mM were untreated or pretreated with N-acetylcysteine or a p38 MAPK inhibitor SB 202190. Reactive oxygen species (ROS production was evaluated. Activation of p38 MAPK was measured by Western blot. The expression of ECM metabolism-related genes, including type II collagen, aggrecan, SRY-related high-mobility-group box 9 (Sox-9, matrix metalloproteinase 3 (MMP-3, and tissue inhibitor of metalloproteinase 1 (TIMP-1, was analyzed by semiquantitative RT-PCR. Results. High glucose reduced viability of NPCs and induced apoptosis. High glucose resulted in increased ROS generation and p38 MAPK activation. In addition, it negatively regulated the expression of type II collagen, aggrecan, Sox-9, and TIMP-1 and positively regulated MMP-3 expression. These results were changed by pretreatment with N-acetylcysteine or SB 202190. Conclusions. High glucose might promote apoptosis of NPCs, trigger ECM catabolic pathways, and inhibit its anabolic activities, possibly through a p38 MAPK-dependent oxidative stress mechanism.

Simulation and qualitative analysis of glucose variability, mean glucose, and hypoglycemia after subcutaneous insulin therapy for stress hyperglycemia.

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Strilka, Richard J; Stull, Mamie C; Clemens, Michael S; McCaver, Stewart C; Armen, Scott B

2016-01-27

The critically ill can have persistent dysglycemia during the "subacute" recovery phase of their illness because of altered gene expression; it is also not uncommon for these patients to receive continuous enteral nutrition during this time. The optimal short-acting subcutaneous insulin therapy that should be used in this clinical scenario, however, is unknown. Our aim was to conduct a qualitative numerical study of the glucose-insulin dynamics within this patient population to answer the above question. This analysis may help clinicians design a relevant clinical trial. Eight virtual patients with stress hyperglycemia were simulated by means of a mathematical model. Each virtual patient had a different combination of insulin resistance and insulin deficiency that defined their unique stress hyperglycemia state; the rate of gluconeogenesis was also doubled. The patients received 25 injections of subcutaneous regular or Lispro insulin (0-6 U) with 3 rates of continuous nutrition. The main outcome measurements were the change in mean glucose concentration, the change in glucose variability, and hypoglycemic episodes. These end points were interpreted by how the ultradian oscillations of glucose concentration were affected by each insulin preparation. Subcutaneous regular insulin lowered both mean glucose concentrations and glucose variability in a linear fashion. No hypoglycemic episodes were noted. Although subcutaneous Lispro insulin lowered mean glucose concentrations, glucose variability increased in a nonlinear fashion. In patients with high insulin resistance and nutrition at goal, "rebound hyperglycemia" was noted after the insulin analog was rapidly metabolized. When the nutritional source was removed, hypoglycemia tended to occur at higher Lispro insulin doses. Finally, patients with severe insulin resistance seemed the most sensitive to insulin concentration changes. Subcutaneous regular insulin consistently lowered mean glucose concentrations and glucose

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

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

2013-09-20

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

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

International Nuclear Information System (INIS)

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

2013-01-01

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

Direct electron transfer of glucose oxidase promoted by carbon nanotubes is without value in certain mediator-free applications

International Nuclear Information System (INIS)

Wang, Y.; Yao, Y.

2012-01-01

We have investigated the direct electron transfer (DET) promoted by carbon nanotubes (CNTs) on an electrode containing immobilized glucose oxidase (GOx) with the aim to develop a third-generation glucose biosensor and a mediator-free glucose biofuel cell anode. GOx was immobilized via chitosan (CS) on a glassy carbon electrode (GCE) modified with multi-walled carbon nanotubes (MWCNTs). Cyclic voltammetric revealed that the GOx on the surface of such an electrode is unable to simultaneously demonstrate DET with the electrode and to retain its catalytic activity towards glucose, although the MWCNTs alone can promote electron transfer between GOx and electrode. This is interpreted in terms of two types of GOx on the surface, the distribution and properties of which are quite different. The first type exhibits DET capability that results from the collaboration of MWCNTs and metal impurities, but is unable to catalyze the oxidation of glucose. The second type maintains its glucose-specific catalytic capability in the presence of a mediator, which can be enhanced by MWCNTs, but cannot undergo DET with the electrode. As a result, the MWCNTs are capable of promoting the electron transfer, but this is without value in some mediator-free applications such as in third-generation glucose biosensors and in mediator-free anodes for glucose biofuel cells. (author)

Long-term blood glucose monitoring with implanted telemetry device in conscious and stress-free cynomolgus monkeys.

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Wang, B; Sun, G; Qiao, W; Liu, Y; Qiao, J; Ye, W; Wang, H; Wang, X; Lindquist, R; Wang, Y; Xiao, Y-F

2017-09-01

Continuous blood glucose monitoring, especially long-term and remote, in diabetic patients or research is very challenging. Nonhuman primate (NHP) is an excellent model for metabolic research, because NHPs can naturally develop Type 2 diabetes mellitus (T2DM) similarly to humans. This study was to investigate blood glucose changes in conscious, moving-free cynomolgus monkeys (Macaca fascicularis) during circadian, meal, stress and drug exposure. Blood glucose, body temperature and physical activities were continuously and simultaneously recorded by implanted HD-XG telemetry device for up to 10 weeks. Blood glucose circadian changes in normoglycemic monkeys significantly differed from that in diabetic animals. Postprandial glucose increase was more obvious after afternoon feeding. Moving a monkey from its housing cage to monkey chair increased blood glucose by 30% in both normoglycemic and diabetic monkeys. Such increase in blood glucose declined to the pre-procedure level in 30 min in normoglycemic animals and >2 h in diabetic monkeys. Oral gavage procedure alone caused hyperglycemia in both normoglycemic and diabetic monkeys. Intravenous injection with the stress hormones, angiotensin II (2 μg/kg) or norepinephrine (0.4 μg/kg), also increased blood glucose level by 30%. The glucose levels measured by the telemetry system correlated significantly well with glucometer readings during glucose tolerance tests (ivGTT or oGTT), insulin tolerance test (ITT), graded glucose infusion (GGI) and clamp. Our data demonstrate that the real-time telemetry method is reliable for monitoring blood glucose remotely and continuously in conscious, stress-free, and moving-free NHPs with the advantages highly valuable to diabetes research and drug discovery.

Metal‐Free Dehydration of Glucose to 5‐(Hydroxymethyl)furfural in Ionic Liquids with Boric Acid as a Promoter

DEFF Research Database (Denmark)

Ståhlberg, Tim; Rodriguez, Sergio; Fristrup, Peter

2011-01-01

The dehydration of glucose and other hexose carbohydrates to 5‐(hydroxymethyl)furfural (HMF) was investigated in imidazolium‐based ionic liquids with boric acid as a promoter. A yield of up to 42 % from glucose and as much as 66 % from sucrose was obtained. The yield of HMF decreased as the conce......The dehydration of glucose and other hexose carbohydrates to 5‐(hydroxymethyl)furfural (HMF) was investigated in imidazolium‐based ionic liquids with boric acid as a promoter. A yield of up to 42 % from glucose and as much as 66 % from sucrose was obtained. The yield of HMF decreased...

Effect of degree of lipomobilization on results of glucose test in dairy cows in heat stress

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Cincović M.R.

2012-01-01

Full Text Available Cows exposed to heat stress exhibit a decreased ability to mobilize lipids due to increased sensitivity to insulin, which is expressed in a decreased concentration of NEFA. However, certain cows can preserve the level of lipid mobilization after adapting to heat stress. We assumed that cows that have a preserved ability to mobilize lipids are less sensitive to insulin and that they have a lower tolerance for glucose. The aim of this work was to compare the results of an intravenous glucose tolerance test in cows that exhibited, in prolonged heat stress, a decreased (NEFA0.30 mmol/l ability for lipid mobilization. Glucose concentration and NEFA concentration were measured following intravenous application of glucose. The mean glycaemic index value did not differ statistically significantly between the two groups of cows at 10, 15 and 20 minutes after glucose application (p>0.05, but there was a tendency at 10 and 15 minutes for the glycaemia to be higher in cows with preserved lipomobilization (p<0.1. At 30, 60 and 90 minutes after glucose application, glycaemia was statistically significantly higher (p<0.01; p<0.05 and p<0.05 in the group of cows with preserved lipomobilization. The glycaemic index values (mmol/l shown in the same order (30, 60 and 90 minutes were as follows 9.91±0.21: 9.23±0.41; 5.41±0.5: 4.67±0.33 and 4.31±0.39: 3.47±0.37. The mean value for NEFA concentration in samples originating from the two experimental groups of cows did not differ statistically significantly following glucose application. The NEFA concentration showed a tendency to be higher in cows with preserved lipid mobilization in comparison with cows with decreased lipomobilization at 20 and 30 minutes after glucose application (p<0.1. Following the intravenous glucose tolerance test, NEFA and glucose concentrations were in a significant negative correlation, and that correlation was more expressed in cows with decreased lipomobilization. Cows with preserved

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

OpenAIRE

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

2017-01-01

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

A study on work stress, stress coping strategies and health promoting lifestyle among district hospital nurses in Taiwan.

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Lee, Wei-Lun; Tsai, Shieunt-Han; Tsai, Chao-Wen; Lee, Chia-Ying

2011-01-01

To determine work stress, and stress-coping strategies, and to analyze their the relationships in order to improve health-promoting lifestyle of nurses in Taiwan. Three hundred eighty-five nurses who had work experience for more than 6 mo, were selected from four district hospitals in Kaohsiung and Ping Tung. We used a stratified cluster random sampling method for the selection. The nurses answered a self-report questionnaire, which was categorized into four sections: personal background data, work stress, stress-coping strategies, and health-promoting lifestyle. The findings indicate work stress and the health promoting lifestyle of nurses are at a higher level, with stress-coping strategies being at a medium level. Work stress and stress-coping strategies were significantly and positively correlated. Professional relationships, managerial role, personal responsibility, and recognition of work stress and the responsibilities of a health-promoting lifestyle were negatively correlated. Managerial role, personal responsibility, and organizational atmosphere of work stress as well as realization, an item of health-promoting lifestyle, were negatively correlated. Recognition of work stress and stress management, items of health-promoting lifestyle, were negatively correlated. Health responsibility, and self-actualization, items of health-promoting lifestyle, as well as stress-coping strategies were negatively correlated. Nutrition, an item of health-promoting lifestyle, and the support stress-coping strategy was negatively correlated. Nurses have greater work pressure and better work stress-coping strategies, but worse health responsibility and realization of a health-promoting lifestyle. We suggest hospitals build good relationships and appropriately increase employment of nurses through a good work atmosphere to achieve nurses' realization of a health-promoting lifestyle.

ALDH2 Inhibition Potentiates High Glucose Stress-Induced Injury in Cultured Cardiomyocytes

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Guodong Pan

2016-01-01

Full Text Available Aldehyde dehydrogenase (ALDH gene superfamily consists of 19 isozymes. They are present in various organs and involved in metabolizing aldehydes that are biologically generated. For instance, ALDH2, a cardiac mitochondrial ALDH isozyme, is known to detoxify 4-hydroxy-2-nonenal, a reactive aldehyde produced upon lipid peroxidation in diabetic conditions. We hypothesized that inhibition of ALDH leads to the accumulation of unmetabolized 4HNE and consequently exacerbates injury in cells subjected to high glucose stress. H9C2 cardiomyocyte cell lines were pretreated with 10 μM disulfiram (DSF, an inhibitor of ALDH2 or vehicle (DMSO for 2 hours, and then subjected to high glucose stress {33 mM D-glucose (HG or 33 mM D-mannitol as an osmotic control (Ctrl} for 24 hrs. The decrease in ALDH2 activity with DSF pretreatment was higher in HG group when compared to Ctrl group. Increased 4HNE adduct formation with DSF pretreatment was higher in HG group compared to Ctrl group. Pretreatment with DSF leads to potentiated HG-induced cell death in cultured H9C2 cardiomyocytes by lowering mitochondrial membrane potential. Our results indicate that ALDH2 activity is important in preventing high glucose induced cellular dysfunction.

Promotion or suppression of glucose isomerization in subcritical aqueous straight- and branched-chain alcohols.

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Gao, Da-Ming; Kobayashi, Takashi; Adachi, Shuji

2015-01-01

The influence of water-miscible alcohols (methanol, 1-propanol, 2-propanol, and t-butyl alcohol) on the isomerization of glucose to fructose and mannose was investigated under subcritical aqueous conditions (180-200 °C). Primary and secondary alcohols promoted the conversion and isomerization of glucose to afford fructose and mannose with high and low selectivity, respectively. On the other hand, the decomposition (side-reaction) of glucose was suppressed in the presence of the primary and secondary alcohols compared with that in subcritical water. The yield of fructose increased with increasing concentration of the primary and secondary alcohols, and the species of the primary and secondary alcohols tested had little effect on the isomerization behavior of glucose. In contrast, the isomerization of glucose was suppressed in subcritical aqueous t-butyl alcohol. Both the conversion of glucose and the yield of fructose decreased with increasing concentration of t-butyl alcohol. In addition, mannose was not detected in reactions using subcritical aqueous t-butyl alcohol.

Glucose Induces Slow-Wave Sleep by Exciting the Sleep-Promoting Neurons in the Ventrolateral Preoptic Nucleus: A New Link between Sleep and Metabolism.

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Varin, Christophe; Rancillac, Armelle; Geoffroy, Hélène; Arthaud, Sébastien; Fort, Patrice; Gallopin, Thierry

2015-07-08

Sleep-active neurons located in the ventrolateral preoptic nucleus (VLPO) play a crucial role in the induction and maintenance of slow-wave sleep (SWS). However, the cellular and molecular mechanisms responsible for their activation at sleep onset remain poorly understood. Here, we test the hypothesis that a rise in extracellular glucose concentration in the VLPO can promote sleep by increasing the activity of sleep-promoting VLPO neurons. We find that infusion of a glucose concentration into the VLPO of mice promotes SWS and increases the density of c-Fos-labeled neurons selectively in the VLPO. Moreover, we show in patch-clamp recordings from brain slices that VLPO neurons exhibiting properties of sleep-promoting neurons are selectively excited by glucose within physiological range. This glucose-induced excitation implies the catabolism of glucose, leading to a closure of ATP-sensitive potassium (KATP) channels. The extracellular glucose concentration monitors the gating of KATP channels of sleep-promoting neurons, highlighting that these neurons can adapt their excitability according to the extracellular energy status. Together, these results provide evidence that glucose may participate in the mechanisms of SWS promotion and/or consolidation. Although the brain circuitry underlying vigilance states is well described, the molecular mechanisms responsible for sleep onset remain largely unknown. Combining in vitro and in vivo experiments, we demonstrate that glucose likely contributes to sleep onset facilitation by increasing the excitability of sleep-promoting neurons in the ventrolateral preoptic nucleus (VLPO). We find here that these neurons integrate energetic signals such as ambient glucose directly to regulate vigilance states accordingly. Glucose-induced excitation of sleep-promoting VLPO neurons should therefore be involved in the drowsiness that one feels after a high-sugar meal. This novel mechanism regulating the activity of VLPO neurons reinforces the

Insulin-like peptide 5 is a microbially regulated peptide that promotes hepatic glucose production

DEFF Research Database (Denmark)

Lee, Ying Shiuan; De Vadder, Filipe; Tremaroli, Valentina

2016-01-01

expression in the brain was higher in CONV-R versus GF mice. We also observed that colonic Insl5 expression was suppressed by increasing the energy supply in GF mice by colonization or high-fat feeding. We did not observe any differences in food intake, gut transit or oral glucose tolerance between Insl5......-/- and wild-type mice. However, we showed impaired intraperitoneal glucose tolerance in Insl5-/- mice. We also observed improved insulin tolerance and reduced hepatic glucose production in Insl5-/- mice. CONCLUSIONS: We have shown that colonic Insl5 expression is regulated by the gut microbiota and energy...... availability. We propose that INSL5 is a hormone that could play a role in promoting hepatic glucose production during periods of energy deprivation....

The effect of glucose concentration and sodium phenylbutyrate treatment on mitochondrial bioenergetics and ER stress in 3T3-L1 adipocytes.

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Tanis, Ross M; Piroli, Gerardo G; Day, Stani D; Frizzell, Norma

2015-01-01

While the 3T3-L1 adipocyte model is routinely used for the study of obesity and diabetes, the mitochondrial respiratory profile in normal versus high glucose has not been examined in detail. We matured adipocytes in normal (5mM) or high (30 mM) glucose and insulin and examined the mitochondrial bioenergetics. We also assessed the requirement for the Unfolded Protein Response (UPR) and ER stress under these conditions. Basal respiration was ~1.7-fold greater in adipocytes that had matured in 30 mM glucose; however, their ability to increase oxygen consumption in response to stress was impaired. Adipogenesis proceeded in both normal and high glucose with concomitant activation of the UPR, but only high glucose was associated with increased levels of ER stress and mitochondrial stress as observed by parallel increases in CHOP and protein succination. Treatment of adipocytes with sodium phenylbutyrate relieved mitochondrial stress through a reduction in mitochondrial respiration. Our data suggests that mitochondrial stress, protein succination and ER stress are uniquely linked in adipocytes matured in high glucose. Copyright © 2014 Elsevier B.V. All rights reserved.

Studies of genetic variability of the glucose transporter 2 promoter in patients with type 2 diabetes mellitus

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Møller, A M; Jensen, N M; Pildal, J

2001-01-01

This study was performed to test the hypothesis that genetic variation in the promoter of the glucose transporter 2 (GLUT2) might predispose to prediabetic phenotypes or type 2 diabetes. A total of 1611 bp comprising the minimal promoter region of the GLUT2 gene were examined by combined single-s......-tolerant subjects. In conclusion, we found no evidence supporting the hypothesis that genetic variability in the minimal promoter of the GLUT2 is associated with type 2 diabetes or prediabetic phenotypes in the Danish population.......This study was performed to test the hypothesis that genetic variation in the promoter of the glucose transporter 2 (GLUT2) might predispose to prediabetic phenotypes or type 2 diabetes. A total of 1611 bp comprising the minimal promoter region of the GLUT2 gene were examined by combined single...

Cardiac damage associated with stress hyperglycaemia and acute coronary syndrome changes according to level of presenting blood glucose.

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Al Jumaily, Talib; Rose'Meyer, Roselyn B; Sweeny, Amy; Jayasinghe, Rohan

2015-10-01

To determine the prevalence of stress hyperglycaemia in people presenting with acute coronary syndrome (ACS), and the relationships between admission glucose and cardiac damage, cardiovascular mortality and morbidity. In a prospective observational study people presenting with ACS at the Gold Coast Hospital had their admission glucose (AG) level tested to determine stress hyperglycaemia. A range of measurements supplemented this data including troponin levels, category of ACS and major adverse coronary events (MACEs) were obtained through hospital records and patient follow-up post-discharge. One hundred eighty-eight participants were recruited. The prevalence of stress hyperglycaemia in ACS was 44% with 31% having a previous diagnosis of type 2 diabetes and 7.7% had undiagnosed diabetes. The stress hyperglycaemic group had a significantly higher median troponin levels compared to participants with normal blood glucose levels on admission (pglucose group (>15 mmol/L) had troponin levels similar to people presenting with normal blood glucose levels and ACS (p>0.05). Cardiac necrosis as measured by troponin levels is significantly increased in people with ACS and stress hyperglycaemia. This study found that one in four participants presenting with ACS and an admission glucose of >7.0 had no previous diagnosis for diabetes. Consistently ordering HbA1C testing on patients with high AG can enable earlier diagnosis and treatment of diabetes. Copyright © 2015. Published by Elsevier Ireland Ltd.

The Major Chromophore Arising from Glucose Degradation and Oxidative Stress Occurrence during Lens Proteins Glycation Induced by Glucose

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Felipe Ávila

2017-12-01

Full Text Available Glucose autoxidation has been proposed as a key reaction associated with deleterious effects induced by hyperglycemia in the eye lens. Little is known about chromophores generated during glucose autoxidation. In this study, we analyzed the effect of oxidative and dicarbonyl stress in the generation of a major chromophore arising from glucose degradation (GDC and its association with oxidative damage in lens proteins. Glucose (5 mM was incubated with H2O2 (0.5–5 mM, Cu2+ (5–50 μM, glyoxal (0.5–5 mM or methylglyoxal (0.5–5 mM at pH 7.4, 5% O2, 37 °C, from 0 to 30 days. GDC concentration increased with incubation time, as well as when incubated in the presence of H2O2 and/or Cu2+, which were effective even at the lowest concentrations. Dicarbonylic compounds did not increase the levels of GDC during incubations. 1H, 13C and FT-IR spectra from the purified fraction containing the chromophore (detected by UV/vis spectroscopy showed oxidation products of glucose, including gluconic acid. Lens proteins solutions (10 mg/mL incubated with glucose (30 mM presented increased levels of carboxymethyl-lysine and hydrogen peroxide that were associated with GDC increase. Our results suggest a possible use of GDC as a marker of autoxidative reactions occurring during lens proteins glycation induced by glucose.

The neuroenergetics of stress hormones in the hippocampus and implications for memory

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Osborne, Danielle M.; Pearson-Leary, Jiah; McNay, Ewan C.

2015-01-01

Acute stress causes rapid release of norepinephrine (NE) and glucocorticoids (GCs), both of which bind to hippocampal receptors. This release continues, at varying concentrations, for several hours following the stressful event, and has powerful effects on hippocampally-dependent memory that generally promote acquisition and consolidation while impairing retrieval. Several studies have characterized the brain's energy usage both at baseline and during memory processing, but there are few data on energy requirements of memory processes under stressful conditions. Because memory is enhanced by emotional arousal such as during stress, it is likely that molecular memory processes under these conditions differ from those under non-stressful conditions that do not activate the hypothalamic-pituitary-adrenal (HPA) axis. Mobilization of peripheral and central energy stores during stress may increase hippocampal glucose metabolism that enhances salience and detail to facilitate memory enhancement. Several pathways activated by the HPA axis affect neural energy supply and metabolism, and may also prevent detrimental damage associated with chronic stress. We hypothesize that alterations in hippocampal metabolism during stress are key to understanding the effects of stress hormones on hippocampally-dependent memory formation. Second, we suggest that the effects of stress on hippocampal metabolism are bi-directional: within minutes, NE promotes glucose metabolism, while hours into the stress response GCs act to suppress metabolism. These bi-directional effects of NE and GCs on glucose metabolism may occur at least in part through direct modulation of glucose transporter-4. In contrast, chronic stress and prolonged elevation of hippocampal GCs cause chronically suppressed glucose metabolism, excitotoxicity and subsequent memory deficits. PMID:25999811

The Neuroenergetics of Stress Hormones in the Hippocampus and Implications for Memory

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Danielle eOsborne

2015-05-01

Full Text Available Acute stress causes rapid release of norepinephrine (NE and glucocorticoids (GCs, both of which bind to hippocampal receptors. This release continues, at varying concentrations, for several hours following the stressful event, and has powerful effects on hippocampally-dependent memory that generally promote acquisition and consolidation while impairing retrieval. Several studies have characterized the brain's energy usage both at baseline and during memory processing, but there are few data on energy requirements of memory processes under stressful conditions. Because memory is enhanced by emotional arousal such as during stress, it is likely that molecular memory processes under these conditions differ from those under non-stressful conditions that do not activate the hypothalamic-pituitary-adrenal (HPA axis. Mobilization of peripheral and central energy stores during stress may increase hippocampal glucose metabolism that enhances salience and detail to facilitate memory enhancement. Several pathways activated by the HPA axis affect neural energy supply and metabolism, and may also prevent detrimental damage associated with chronic stress. We hypothesize that alterations in hippocampal metabolism during stress are key to understanding the effects of stress hormones on hippocampally-dependent memory formation. Second, we suggest that the effects of stress on hippocampal metabolism are bi-directional: within minutes, NE promotes glucose metabolism, while hours into the stress response GCs act to suppress metabolism. These bi-directional effects of NE and GCs on glucose metabolism may occur at least in part through direct modulation of glucose transporter-4. In contrast, chronic stress and prolonged elevation of hippocampal GCs cause chronically suppressed glucose metabolism, excitotoxicity and subsequent memory deficits.

Heritable transmission of stress resistance by high dietary glucose in Caenorhabditis elegans.

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Arnaud Tauffenberger

2014-05-01

Full Text Available Glucose is a major energy source and is a key regulator of metabolism but excessive dietary glucose is linked to several disorders including type 2 diabetes, obesity and cardiac dysfunction. Dietary intake greatly influences organismal survival but whether the effects of nutritional status are transmitted to the offspring is an unresolved question. Here we show that exposing Caenorhabditis elegans to high glucose concentrations in the parental generation leads to opposing negative effects on fecundity, while having protective effects against cellular stress in the descendent progeny. The transgenerational inheritance of glucose-mediated phenotypes is dependent on the insulin/IGF-like signalling pathway and components of the histone H3 lysine 4 trimethylase complex are essential for transmission of inherited phenotypes. Thus dietary over-consumption phenotypes are heritable with profound effects on the health and survival of descendants.

Glucose homeostasis in Egyptian children and adolescents with β-Thalassemia major: Relationship to oxidative stress

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Kotb Abbass Metwalley

2014-01-01

Full Text Available Background: Oxidative stress in children with β-thalassemia may contribute to shortened life span of erythrocytes and endocrinal abnormalities. Aim: This study was aimed to evaluate glucose homeostasis in Egyptian children and adolescents with β-thalassemia major and its relation to oxidative stress. Materials and Methods: Sixty children and adolescents with β-thalassemia major were studied in comparison to 30 healthy age and sex-matched subjects. Detailed medical history, thorough clinical examination, and laboratory assessment of oral glucose tolerance test (OGTT, serum ferritin, alanine transferase (ALT, fasting insulin levels, plasma malondialdehyde (MDA as oxidant marker and serum total antioxidants capacity (TAC were performed. Patients were divided into two groups according to the presence of abnormal OGTT. Results: The prevalence of diabetes was 5% (3 of 60 and impaired glucose tolerance test (IGT was 8% (5 of 60. Fasting blood glucose, 2-hour post-load plasma glucose, serum ferritin, ALT, fasting insulin level, homeostatic model assessment for insulin resistance index (HOMA-IR and MDA levels were significantly elevated while TAC level was significantly decreased in thalassemic patients compared with healthy controls (P < 0.001 for each. The difference was more evident in patients with abnormal OGTT than those with normal oral glucose tolerance (P < 0.001 for each. We also observed that thalassemic patients not receiving or on irregular chelation therapy had significantly higher fasting, 2-h post-load plasma glucose, serum ferritin, ALT, fasting insulin, HOMA-IR, oxidative stress markers OSI and MDA levels and significantly lower TAC compared with either those on regular chelation or controls. HOMA-IR was positively correlated with age, serum ferritin, ALT, MDA, and negatively correlated with TAC. Conclusions: The development of abnormal glucose tolerance in Egyptian children and adolescents with β--thalassemia is associated with

Hydrogen Sulphide modulating mitochondrial morphology to promote mitophagy in endothelial cells under high-glucose and high-palmitate.

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Liu, Ning; Wu, Jichao; Zhang, Linxue; Gao, Zhaopeng; Sun, Yu; Yu, Miao; Zhao, Yajun; Dong, Shiyun; Lu, Fanghao; Zhang, Weihua

2017-12-01

Endothelial cell dysfunction is one of the main reasons for type II diabetes vascular complications. Hydrogen sulphide (H 2 S) has antioxidative effect, but its regulation on mitochondrial dynamics and mitophagy in aortic endothelial cells under hyperglycaemia and hyperlipidaemia is unclear. Rat aortic endothelial cells (RAECs) were treated with 40 mM glucose and 200 μM palmitate to imitate endothelium under hyperglycaemia and hyperlipidaemia, and 100 μM NaHS was used as an exogenous H 2 S donor. Firstly, we demonstrated that high glucose and palmitate decreased H 2 S production and CSE expression in RAECs. Then, the antioxidative effect of H 2 S was proved in RAECs under high glucose and palmitate to reduce mitochondrial ROS level. We also showed that exogenous H 2 S inhibited mitochondrial apoptosis in RAECs under high glucose and palmitate. Using Mito Tracker and transmission electron microscopy assay, we revealed that exogenous H 2 S decreased mitochondrial fragments and significantly reduced the expression of p-Drp-1/Drp-1 and Fis1 compared to high-glucose and high-palmitate group, whereas it increased mitophagy by transmission electron microscopy assay. We demonstrated that exogenous H 2 S facilitated Parkin recruited by PINK1 by immunoprecipitation and immunostaining assays and then ubiquitylated mitofusin 2 (Mfn2), which illuminated the mechanism of exogenous H 2 S on mitophagy. Parkin siRNA suppressed the expression of Mfn2, Nix and LC3B, which revealed that it eliminated mitophagy. In summary, exogenous H 2 S could protect RAECs against apoptosis under high glucose and palmitate by suppressing oxidative stress, decreasing mitochondrial fragments and promoting mitophagy. Based on these results, we proposed a new mechanism of H 2 S on protecting endothelium, which might provide a new strategy for type II diabetes vascular complication. © 2017 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for

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

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Miao Xu

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

Glucose-6-phosphate dehydrogenase protects Escherichia coli from tellurite-mediated oxidative stress.

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Juan M Sandoval

Full Text Available The tellurium oxyanion tellurite induces oxidative stress in most microorganisms. In Escherichia coli, tellurite exposure results in high levels of oxidized proteins and membrane lipid peroxides, inactivation of oxidation-sensitive enzymes and reduced glutathione content. In this work, we show that tellurite-exposed E. coli exhibits transcriptional activation of the zwf gene, encoding glucose 6-phosphate dehydrogenase (G6PDH, which in turn results in augmented synthesis of reduced nicotinamide adenine dinucleotide phosphate (NADPH. Increased zwf transcription under tellurite stress results mainly from reactive oxygen species (ROS generation and not from a depletion of cellular glutathione. In addition, the observed increase of G6PDH activity was paralleled by accumulation of glucose-6-phosphate (G6P, suggesting a metabolic flux shift toward the pentose phosphate shunt. Upon zwf overexpression, bacterial cells also show increased levels of antioxidant molecules (NADPH, GSH, better-protected oxidation-sensitive enzymes and decreased amounts of oxidized proteins and membrane lipids. These results suggest that by increasing NADPH content, G6PDH plays an important role in E. coli survival under tellurite stress.

High glucose modifies transient receptor potential canonical type 6 channels via increased oxidative stress and syndecan-4 in human podocytes

DEFF Research Database (Denmark)

Thilo, Florian; Lee, Marlene; Xia, Shengqiang

2014-01-01

oxidative stress and syndecan-4 (SDC-4) in human podocytes. Human podocytes were exposed to control conditions (5.6 mmol/L D-glucose), high glucose (30 mmol/L D-glucose or L-glucose), 100 μmol/L peroxynitrite, or high glucose and the superoxide dismutase mimetic tempol (100 μmol/L). TRPC6 and SDC-4...... transcripts and protein expression were measured using RT-PCR and in-cell Western assay. Intracellular reactive oxygen species (ROS) and cytosolic calcium were measured using fluorescent dye techniques. High D-glucose increased TRPC6 transcripts to 8.66±4.08 (p....44±0.07 (poxidative stress using peroxynitrite significantly increased TRPC6 transcripts to 4.29±1.26 (p

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

Science.gov (United States)

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

2018-03-01

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

Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress

International Nuclear Information System (INIS)

Liao, Y.Y.; Seto, K.; Saito, H.; Kawakami, M.

1980-01-01

A study was made of the effect of acupuncture on citrate and glucose metabolism in the liver in terms of incorporation of 14 C-1, 5-citric acid and 14 C-u-glucose in some metabolites. The effect of acupuncture on citrate metabolism in the liver under control conditions was such as to increase production of G and reduce that of KB, FC and FFA. No effect of acupuncture on glucose metabolism in the liver under such conditions was observed. Both citrate and glucose metabolism were affected to a marked extent by immobilization stress or exposure to heat or cold. The deleterious effect of these types of stress was less prominent in animals receiving acupuncture at the Tsu-San-Li locus than in those treated otherwise or receiving no treatment

Effects of acupuncture on the citrate and glucose metabolism in the liver under various types of stress

Energy Technology Data Exchange (ETDEWEB)

Liao, Y.Y.; Seto, K.; Saito, H.; Kawakami, M.

A study was made of the effect of acupuncture on citrate and glucose metabolism in the liver in terms of incorporation of /sup 14/C-1, 5-citric acid and /sup 14/C-u-glucose in some metabolites. The effect of acupuncture on citrate metabolism in the liver under control conditions was such as to increase production of G and reduce that of KB, FC and FFA. No effect of acupuncture on glucose metabolism in the liver under such conditions was observed. Both citrate and glucose metabolism were affected to a marked extent by immobilization stress or exposure to heat or cold. The deleterious effect of these types of stress was less prominent in animals receiving acupuncture at the Tsu-San-Li locus than in those treated otherwise or receiving no treatment.

Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

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Hsu, Ya-Yun [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Tseng, Yu-Ting [Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Lo, Yi-Ching, E-mail: yichlo@kmu.edu.tw [Department of Pharmacology, School of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Medicine, College of Medicine, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China); Graduate Institute of Natural Products, Kaohsiung Medical University, Kaohsiung 80708, Taiwan (China)

2013-11-01

Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H{sub 2}O{sub 2} neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS

Berberine, a natural antidiabetes drug, attenuates glucose neurotoxicity and promotes Nrf2-related neurite outgrowth

International Nuclear Information System (INIS)

Hsu, Ya-Yun; Tseng, Yu-Ting; Lo, Yi-Ching

2013-01-01

Reactive oxygen intermediates production and apoptotic damage induced by high glucose are major causes of neuronal damage in diabetic neuropathy. Berberine (BBR), a natural antidiabetes drug with PI3K-activating activity, holds promise for diabetes because of its dual antioxidant and anti-apoptotic activities. We have previously reported that BBR attenuated H 2 O 2 neurotoxicity via activating the PI3K/Akt/Nrf2-dependent pathway. In this study, we further explored the novel protective mechanism of BBR on high glucose-induced apoptotic death and neurite damage of SH-SY5Y cells. Results indicated BBR (0.1–10 nM) significantly attenuated reactive oxygen species (ROS) production, nucleus condensation, and apoptotic death in high glucose-treated cells. However, AG1024, an inhibitor of insulin growth factor-1 (IGF-1) receptor, significantly abolished BBR protection against high glucose-induced neuronal death. BBR also increased Bcl-2 expression and decreased cytochrome c release. High glucose down-regulated IGF-1 receptor and phosphorylation of Akt and GSK-3β, the effects of which were attenuated by BBR treatment. BBR also activated nuclear erythroid 2-related factor 2 (Nrf2), the key antioxidative transcription factor, which is accompanied with up-regulation of hemeoxygenase-1 (HO-1). Furthermore, BBR markedly enhanced nerve growth factor (NGF) expression and promoted neurite outgrowth in high glucose-treated cells. To further determine the role of the Nrf2 in BBR neuroprotection, RNA interference directed against Nrf2 was used. Results indicated Nrf2 siRNA abolished BBR-induced HO-1, NGF, neurite outgrowth and ROS decrease. In conclusion, BBR attenuated high glucose-induced neurotoxicity, and we are the first to reveal this novel mechanism of BBR as an Nrf2 activator against glucose neurotoxicity, providing another potential therapeutic use of BBR on the treatment of diabetic complications. - Highlights: • BBR attenuates high glucose-induced ROS production and

High glucose alters retinal astrocytes phenotype through increased production of inflammatory cytokines and oxidative stress.

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Eui Seok Shin

Full Text Available Astrocytes are macroglial cells that have a crucial role in development of the retinal vasculature and maintenance of the blood-retina-barrier (BRB. Diabetes affects the physiology and function of retinal vascular cells including astrocytes (AC leading to breakdown of BRB. However, the detailed cellular mechanisms leading to retinal AC dysfunction under high glucose conditions remain unclear. Here we show that high glucose conditions did not induce the apoptosis of retinal AC, but instead increased their rate of DNA synthesis and adhesion to extracellular matrix proteins. These alterations were associated with changes in intracellular signaling pathways involved in cell survival, migration and proliferation. High glucose conditions also affected the expression of inflammatory cytokines in retinal AC, activated NF-κB, and prevented their network formation on Matrigel. In addition, we showed that the attenuation of retinal AC migration under high glucose conditions, and capillary morphogenesis of retinal endothelial cells on Matrigel, was mediated through increased oxidative stress. Antioxidant proteins including heme oxygenase-1 and peroxiredoxin-2 levels were also increased in retinal AC under high glucose conditions through nuclear localization of transcription factor nuclear factor-erythroid 2-related factor-2. Together our results demonstrated that high glucose conditions alter the function of retinal AC by increased production of inflammatory cytokines and oxidative stress with significant impact on their proliferation, adhesion, and migration.

Stress ratings and health promotion practices among RNs: a case for action.

Science.gov (United States)

Tucker, Sharon J; Weymiller, Audrey J; Cutshall, Susanne M; Rhudy, Lori M; Lohse, Christine M

2012-05-01

: The objective of this study was to investigate associations between RN perceptions of their stress levels, health-promoting behaviors, and associated demographic variables. : Stress and burnout are occupational hazards resulting in absenteeism, illness, and staff turnover, factors important to nurse administrators. Personal health behaviors among nurses have been linked to less stress and the delivery of health-promotion teaching. : An electronic survey with 2 standardized measures and demographic questions was completed by 2,247 staff nurses from a large Midwestern academic medical center. : Stress levels were inversely correlated with overall health-promoting behavior scores. Outside caregiver responsibilities were associated with higher stress and lower health-promoting behaviors scores. : Findings support work-site interventions that promote nurses' health and wellness, reduce work and home stress, and influence positive patient care and outcomes.

Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress.

Science.gov (United States)

Wang, Zhen; do Carmo, Jussara M; Aberdein, Nicola; Zhou, Xinchun; Williams, Jan M; da Silva, Alexandre A; Hall, John E

2017-05-01

Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK-AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar-AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK-AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. © 2017 American Heart Association, Inc.

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

DEFF Research Database (Denmark)

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

2014-01-01

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

Effects of Red Wine Tannat on Oxidative Stress Induced by Glucose and Fructose in Erythrocytes in Vitro

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Pazzini, Camila Eliza Fernandes; Colpo, Ana Ceolin; Poetini, Márcia Rósula; Pires, Cauê Ferreira; de Camargo, Vanessa Brum; Mendez, Andreas Sebastian Loureiro; Azevedo, Miriane Lucas; Soares, Júlio César Mendes; Folmer, Vanderlei

2015-01-01

The literature indicates that red wine presents in its composition several substances that are beneficial to health. This study has investigated the antioxidant effects of Tannat red wine on oxidative stress induced by glucose and fructose in erythrocytes in vitro, with the purpose to determine some of its majoritarian phenolic compounds and its antioxidant capacity. Erythrocytes were incubated using different concentrations of glucose and fructose in the presence or absence of wine. From these erythrocytes were determined the production of thiobarbituric acid reactive species (TBARS), glucose consumption, and osmotic fragility. Moreover, quantification of total phenolic, gallic acid, caffeic acid, epicatechin, resveratrol, and DPPH scavenging activity in wine were also assessed. Red wine showed high levels of polyphenols analyzed, as well as high antioxidant potential. Erythrocytes incubated with glucose and fructose had an increase in lipid peroxidation and this was prevented by the addition of wine. The wine increased glucose uptake into erythrocytes and was able to decrease the osmotic fragility of erythrocytes incubated with fructose. Altogether, these results suggest that wine leads to a reduction of the oxidative stress induced by high concentrations of glucose and fructose. PMID:26078708

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

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Roberta Palorini

2016-03-01

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

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

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Thomas E. Jensen

2014-10-01

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

Protective role of morin, a flavonoid, against high glucose induced oxidative stress mediated apoptosis in primary rat hepatocytes.

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Radhika Kapoor

Full Text Available Apoptosis is an early event of liver damage in diabetes and oxidative stress has been linked to accelerate the apoptosis in hepatocytes. Therefore, the compounds that can scavenge ROS may confer regulatory effects on high-glucose induced apoptosis. In the present study, primary rat hepatocytes were exposed to high concentration (40 mM of glucose. At this concentration decreased cell viability and enhanced ROS generation was observed. Depleted antioxidant status of hepatocytes under high glucose stress was also observed as evident from transcriptional level and activities of antioxidant enzymes. Further, mitochondrial depolarisation was accompanied by the loss of mitochondrial integrity and altered expression of Bax and Bcl-2. Increased translocation of apoptotic proteins like AIF (Apoptosis inducing factor & Endo-G (endonuclease-G from its resident place mitochondria to nucleus was also observed. Cyt-c residing in the inter-membrane space of mitochondria also translocated to cytoplasm. These apoptotic proteins initiated caspase activation, DNA fragmentation, chromatin condensation, increased apoptotic DNA content in glucose treated hepatocytes, suggesting mitochondria mediated apoptotic mode of cell death. Morin, a dietary flavonoid from Psidium guajava was effective in increasing the cell viability and decreasing the ROS level. It maintained mitochondrial integrity, inhibited release of apoptotic proteins from mitochondria, prevented DNA fragmentation, chromatin condensation and hypodiploid DNA upon exposure to high glucose. This study confirms the capacity of dietary flavonoid Morin in regulating apoptosis induced by high glucose via mitochondrial mediated pathway through intervention of oxidative stress.

The predictive role of health-promoting behaviours and perceived stress in aneurysmal rupture.

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Lee, Mi-Sun; Park, Chang G; Hughes, Tonda L; Jun, Sang-Eun; Whang, Kum; Kim, Nahyun

2018-03-01

To examine the roles of two modifiable factors-health-promoting behaviours and perceived stress-in predicting aneurysmal rupture. Unruptured intracranial aneurysm detection produces significant stress and anxiety in patients because of the risk of rupture. Compared to nonmodifiable risk factors for rupture such as age, gender and aneurysm size/location, less attention has been given to modifiable risk factors. Two modifiable factors, health-promoting behaviours and perceived stress, have hardly been examined as potential predictors of rupture. This study used a cross-sectional design. We assessed 155 patients with intracranial aneurysms-that is, subarachnoid haemorrhage (n = 77) or unruptured intracranial aneurysm (n = 78)-to examine (i) baseline characteristics (patient and aneurysmal factors), (ii) health-related factors (lifestyle habits and health-promoting behaviour) and (iii) perceived stress levels (psychological stress and physical stress). Patient records provided medical histories and aneurysmal factors; other data were collected using a structured questionnaire addressing lifestyle habits, the Health-Promoting Lifestyle Profile-II to measure health-promoting behaviour and the Perceived Stress Questionnaire to measure perceived-psychological stress and perceived-physical stress levels. Bivariate analysis indicated that aneurysm rupture risk was associated with female gender, aneurysm size/location, defecation frequency, hyperlipidaemia, sedentary time, low Health-Promoting Lifestyle Profile-II mean scores and high perceived-psychological stress scores. After adjusting for known risk factors, the mean Health-Promoting Lifestyle Profile-II and perceived-psychological stress scores remained robust predictors of rupture. Furthermore, known risk factors combined with these scores had greater predictive power than known risk factors alone. Health-promoting behaviour and psychological stress are promising modifiable factors for reducing risk of aneurysmal

NEDDylation promotes stress granule assembly.

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Jayabalan, Aravinth Kumar; Sanchez, Anthony; Park, Ra Young; Yoon, Sang Pil; Kang, Gum-Yong; Baek, Je-Hyun; Anderson, Paul; Kee, Younghoon; Ohn, Takbum

2016-07-06

Stress granules (SGs) harbour translationally stalled messenger ribonucleoproteins and play important roles in regulating gene expression and cell fate. Here we show that neddylation promotes SG assembly in response to arsenite-induced oxidative stress. Inhibition or depletion of key components of the neddylation machinery concomitantly inhibits stress-induced polysome disassembly and SG assembly. Affinity purification and subsequent mass-spectrometric analysis of Nedd8-conjugated proteins from translationally stalled ribosomal fractions identified ribosomal proteins, translation factors and RNA-binding proteins (RBPs), including SRSF3, a previously known SG regulator. We show that SRSF3 is selectively neddylated at Lys85 in response to arsenite. A non-neddylatable SRSF3 (K85R) mutant do not prevent arsenite-induced polysome disassembly, but fails to support the SG assembly, suggesting that the neddylation pathway plays an important role in SG assembly.

Cap-proximal nucleotides via differential eIF4E binding and alternative promoter usage mediate translational response to energy stress.

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Tamarkin-Ben-Harush, Ana; Vasseur, Jean-Jacques; Debart, Françoise; Ulitsky, Igor; Dikstein, Rivka

2017-02-08

Transcription start-site (TSS) selection and alternative promoter (AP) usage contribute to gene expression complexity but little is known about their impact on translation. Here we performed TSS mapping of the translatome following energy stress. Assessing the contribution of cap-proximal TSS nucleotides, we found dramatic effect on translation only upon stress. As eIF4E levels were reduced, we determined its binding to capped-RNAs with different initiating nucleotides and found the lowest affinity to 5'cytidine in correlation with the translational stress-response. In addition, the number of differentially translated APs was elevated following stress. These include novel glucose starvation-induced downstream transcripts for the translation regulators eIF4A and Pabp, which are also translationally-induced despite general translational inhibition. The resultant eIF4A protein is N-terminally truncated and acts as eIF4A inhibitor. The induced Pabp isoform has shorter 5'UTR removing an auto-inhibitory element. Our findings uncovered several levels of coordination of transcription and translation responses to energy stress.

Relationships between the pituitary-adrenal hormones, insulin, and glucose in middle-aged men: moderating influence of psychosocial stress.

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Keltikangas-Järvinen, L; Ravaja, N; Räikkönen, K; Hautanen, A; Adlercreutz, H

1998-12-01

We examined whether the relationships between the pituitary-adrenal hormones (corticotropin [ACTH) and cortisol), insulin, and glucose differ as a function of psychosocial stress defined in terms of vital exhaustion (VE) and depressive behavior (DB). The participants were 69 normotensive and 21 unmedicated borderline hypertensive (BH) middle-aged men whose work is stressful. Hormonal and metabolic variables were measured during an oral glucose tolerance test (OGTT), and the cortisol response to dexamethasone (DXM) suppression and intravenous ACTH stimulation was also measured. We found that the basal ACTH level during the OGTT was positively associated with the cortisol response to ACTH at 60 minutes, the fasting insulin level, and the insulin to glucose ratio among exhausted and high DB men, while the reverse was true for nonexhausted and low DB men. Also, a high cortisol response to ACTH, a low cortisol level during the OGTT, and a high ratio of these cortisol determinations (cortisol ratio) were associated with high fasting insulin and glucose levels, the summed insulin values, and the insulin to glucose ratio only among nonexhausted and low DB men; among exhausted and high DB men, these associations were less pronounced, absent, or in the opposite direction. The findings suggest that VE and DB have a moderating influence on the relationships among the hormonal and metabolic parameters studied. Psychosocial stress may affect the pituitary-adrenocortical system in complex ways, contributing thereby to insulin resistance, hyperinsulinemia, and coronary heart disease (CHD) risk.

Ayurvedic Amalaki Rasayana promotes improved stress tolerance

Indian Academy of Sciences (India)

Ayurvedic Amalaki Rasayana promotes improved stress tolerance and thus ... and some otheringredients, and is used for general good health and healthy aging. ... Wild-type larvae/flies rearedon AR-supplemented food survived the various ...

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

Science.gov (United States)

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

2010-03-01

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

daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival.

Science.gov (United States)

Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca Ew; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D; Baugh, L Ryan

2017-10-24

daf-16 /FoxO is required to survive starvation in Caenorhabditis elegans , but how daf-16I FoxO promotes starvation resistance is unclear. We show that daf-16 /FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16 /FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant.

daf-16/FoxO promotes gluconeogenesis and trehalose synthesis during starvation to support survival

Science.gov (United States)

Hibshman, Jonathan D; Doan, Alexander E; Moore, Brad T; Kaplan, Rebecca EW; Hung, Anthony; Webster, Amy K; Bhatt, Dhaval P; Chitrakar, Rojin; Hirschey, Matthew D

2017-01-01

daf-16/FoxO is required to survive starvation in Caenorhabditis elegans, but how daf-16IFoxO promotes starvation resistance is unclear. We show that daf-16/FoxO restructures carbohydrate metabolism by driving carbon flux through the glyoxylate shunt and gluconeogenesis and into synthesis of trehalose, a disaccharide of glucose. Trehalose is a well-known stress protectant, capable of preserving membrane organization and protein structure during abiotic stress. Metabolomic, genetic, and pharmacological analyses confirm increased trehalose synthesis and further show that trehalose not only supports survival as a stress protectant but also serves as a glycolytic input. Furthermore, we provide evidence that metabolic cycling between trehalose and glucose is necessary for this dual function of trehalose. This work demonstrates that daf-16/FoxO promotes starvation resistance by shifting carbon metabolism to drive trehalose synthesis, which in turn supports survival by providing an energy source and acting as a stress protectant. PMID:29063832

Production of water-soluble yellow pigments via high glucose stress fermentation of Monascus ruber CGMCC 10910.

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Wang, Meihua; Huang, Tao; Chen, Gong; Wu, Zhenqiang

2017-04-01

Monascus pigments are secondary metabolites of Monascus species and are mainly composed of yellow pigments, orange pigments and red pigments. In this study, a larger proportion of Monascus yellow pigments could be obtained through the selection of the carbon source. Hydrophilic yellow pigments can be largely produced extracellularly by Monascus ruber CGMCC 10910 under conditions of high glucose fermentation with low oxidoreduction potential (ORP). However, keeping high glucose levels later in the culture causes translation or a reduction of yellow pigment. We presume that the mechanism behind this phenomenon may be attributed to the redox level of the culture broth and the high glucose stress reaction of M. ruber CGMCC 10910 during high glucose fermentation. These yellow pigments were produced via high glucose bio-fermentation without citrinin. Therefore, these pigments can act as natural pigments for applications as food additives.

The dipeptidyl peptidase-4 (DPP-4) inhibitor teneligliptin functions as antioxidant on human endothelial cells exposed to chronic hyperglycemia and metabolic high-glucose memory.

Science.gov (United States)

Pujadas, Gemma; De Nigris, Valeria; Prattichizzo, Francesco; La Sala, Lucia; Testa, Roberto; Ceriello, Antonio

2017-06-01

Dipeptidyl peptidase-4 inhibitors are widely used in type 2 diabetes. Endothelium plays a crucial role maintaining vascular integrity and function. Chronic exposure to high glucose drives to endothelial dysfunction generating oxidative stress. Teneligliptin is a novel dipeptidyl peptidase-4 inhibitor with antioxidant properties. This study is aimed to verify a potential protective action of teneligliptin in endothelial cells exposed to high glucose. Human umbilical vein endothelial cells were cultured under normal (5 mmol/L) or high glucose (25 mmol/L) during 21 days, or at high glucose during 14 days followed by 7 days at normal glucose, to reproduce the high-metabolic memory state. During this period, different concentrations of teneligliptin (0.1, 1.0 and 3.0 µmol/L) or sitagliptin (0.5 µmol/L) were added to cells. Ribonucleic acid and protein expression were assessed for antioxidant response, proliferation, apoptosis and endoplasmic reticulum stress markers. Teneligliptin promotes the antioxidant response in human umbilical vein endothelial cells, reducing ROS levels and inducing Nrf2-target genes messenger ribonucleic acid expression. Teneligliptin, but not sitagliptin, reduces the expression of the nicotine amide adenine dinucleotide phosphate oxidase regulatory subunit P22 -phox , however, both blunt the high glucose-induced increase of TXNIP. Teneligliptin improves proliferation rates in human umbilical vein endothelial cells exposed to high glucose, regulating the expression of cell-cycle inhibitors markers (P53, P21 and P27), and reducing proapoptotic genes (BAX and CASP3), while promotes BCL2 expression. Teneligliptin ameliorates high glucose-induced endoplasmic reticulum stress reducing the expression of several markers (BIP, PERK, ATF4, CHOP, IRE1a and ATF6). Teneligliptin has antioxidant properties, ameliorates oxidative stress and apoptotic phenotype and it can overcome the metabolic memory effect, induced by chronic exposure to high

Glucose concentration and blood acid-basis status in high-yielding dairy cows during heat stress

Directory of Open Access Journals (Sweden)

Vujanac Ivan

2011-01-01

Full Text Available The objective of this work was to examine the effect of heat stress on glucose and pH values in blood of high-yielding dairy cows in the early stage of lactation, as well as to determine whether the changes in these parameters are interdependent under such conditions. An experiment was performed on high-yielding dairy cows during the summer and the spring periods. Forty cows were selected, twenty each for the two periods under investigation. In the course of the experiment, the temperature humidity index (THI was determined for the entire period of investigations, and then also the average daily THI, nightmorning THI (average value of hourly THI measured from 22h on the previous day until 10h of the current day, as well as the day-night THI (average value of hourly THI measured during the period from 10h to 22h of the current day. The pH and glucose concentration were determined in blood samples taken in the morning and afternoon of days 30, 60, and 90 of lactation during the spring and summer periods of the investigations. Based on the results for the THI, it was established that the animals were not exposed to the effect of extreme heat stress during the spring period of investigations, while they were periodically exposed to moderate but also extreme heat stress during the summer, in particular in the afternoon hours. It can be concluded from the results obtained for the blood pH that the cows were in respiratory alkalosis during the summer in the morning and afternoon hours on day 30, in the afternoon hours of days 60 and 90 of lactation, as well as in the afternoon on day 90 of lactation during the spring period of investigations. During the summer period, there were no statistically significant differences between the pH value determined in the morning and afternoon hours on day 30 of lactation, while the pH value was significantly higher in the afternoon hours than in the morning hours on days 60 and 90 of lactation. There were no

Mitochondrial oxidative stress contributes differently to rat pancreatic islet cell apoptosis and insulin secretory defects after prolonged culture in a low non-stimulating glucose concentration.

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Roma, L P; Pascal, S M; Duprez, J; Jonas, J-C

2012-08-01

Pancreatic beta cells chronically exposed to low glucose concentrations show signs of oxidative stress, loss of glucose-stimulated insulin secretion (GSIS) and increased apoptosis. Our aim was to confirm the role of mitochondrial oxidative stress in rat islet cell apoptosis under these culture conditions and to evaluate whether its reduction similarly improves survival and GSIS. Apoptosis, oxidative stress-response gene mRNA expression and glucose-induced stimulation of mitochondrial metabolism, intracellular Ca(2+) concentration and insulin secretion were measured in male Wistar rat islets cultured for 1 week in RPMI medium containing 5-10 mmol/l glucose with or without manganese(III)tetrakis(4-benzoic acid)porphyrin (MnTBAP) or N-acetyl-L-: cysteine (NAC). Oxidative stress was measured in islet cell clusters cultured under similar conditions using cytosolic and mitochondrial redox-sensitive green fluorescent protein (roGFP1/mt-roGFP1). Prolonged culture in 5 vs 10 mmol/l glucose increased mt-roGFP1 (but not roGFP1) oxidation followed by beta cell apoptosis and loss of GSIS resulting from reduced insulin content, mitochondrial metabolism, Ca(2+) influx and Ca(2+)-induced secretion. Tolbutamide-induced, but not high K(+)-induced, Ca(2+) influx was also suppressed. Under these conditions, MnTBAP, but not NAC, triggered parallel ~50-70% reductions in mt-roGFP1 oxidation and beta cell apoptosis, but failed to protect against the loss of GSIS despite significant improvement in glucose-induced and tolbutamide-induced Ca(2+) influx. Mitochondrial oxidative stress contributes differently to rat pancreatic islet cell apoptosis and insulin secretory defects during culture in a low glucose concentration. Thus, targeting beta cell survival may not be sufficient to restore insulin secretion when beta cells suffer from prolonged mitochondrial oxidative stress, e.g. in the context of reduced glucose metabolism.

Brain glucose metabolism in an animal model of depression.

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Detka, J; Kurek, A; Kucharczyk, M; Głombik, K; Basta-Kaim, A; Kubera, M; Lasoń, W; Budziszewska, B

2015-06-04

An increasing number of data support the involvement of disturbances in glucose metabolism in the pathogenesis of depression. We previously reported that glucose and glycogen concentrations in brain structures important for depression are higher in a prenatal stress model of depression when compared with control animals. A marked rise in the concentrations of these carbohydrates and glucose transporters were evident in prenatally stressed animals subjected to acute stress and glucose loading in adulthood. To determine whether elevated levels of brain glucose are associated with a change in its metabolism in this model, we assessed key glycolytic enzymes (hexokinase, phosphofructokinase and pyruvate kinase), products of glycolysis, i.e., pyruvate and lactate, and two selected enzymes of the tricarboxylic acid cycle (pyruvate dehydrogenase and α-ketoglutarate dehydrogenase) in the hippocampus and frontal cortex. Additionally, we assessed glucose-6-phosphate dehydrogenase activity, a key enzyme in the pentose phosphate pathway (PPP). Prenatal stress increased the levels of phosphofructokinase, an important glycolytic enzyme, in the hippocampus and frontal cortex. However, prenatal stress had no effect on hexokinase or pyruvate kinase levels. The lactate concentration was elevated in prenatally stressed rats in the frontal cortex, and pyruvate levels remained unchanged. Among the tricarboxylic acid cycle enzymes, prenatal stress decreased the level of pyruvate dehydrogenase in the hippocampus, but it had no effect on α-ketoglutarate dehydrogenase. Like in the case of glucose and its transporters, also in the present study, differences in markers of glucose metabolism between control animals and those subjected to prenatal stress were not observed under basal conditions but in rats subjected to acute stress and glucose load in adulthood. Glucose-6-phosphate dehydrogenase activity was not reduced by prenatal stress but was found to be even higher in animals exposed to

CTRP7 deletion attenuates obesity-linked glucose intolerance, adipose tissue inflammation, and hepatic stress.

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Petersen, Pia S; Lei, Xia; Wolf, Risa M; Rodriguez, Susana; Tan, Stefanie Y; Little, Hannah C; Schweitzer, Michael A; Magnuson, Thomas H; Steele, Kimberley E; Wong, G William

2017-04-01

Chronic low-grade inflammation and cellular stress are important contributors to obesity-linked metabolic dysfunction. Here, we uncover an immune-metabolic role for C1q/TNF-related protein 7 (CTRP7), a secretory protein of the C1q family with previously unknown function. In obese humans, circulating CTRP7 levels were markedly elevated and positively correlated with body mass index, glucose, insulin, insulin resistance index, hemoglobin A1c, and triglyceride levels. Expression of CTRP7 in liver was also significantly upregulated in obese humans and positively correlated with gluconeogenic genes. In mice, Ctrp7 expression was differentially modulated in various tissues by fasting and refeeding and by diet-induced obesity. A genetic loss-of-function mouse model was used to determine the requirement of CTRP7 for metabolic homeostasis. When fed a control low-fat diet, male or female mice lacking CTRP7 were indistinguishable from wild-type littermates. In obese male mice consuming a high-fat diet, however, CTRP7 deficiency attenuated insulin resistance and enhanced glucose tolerance, effects that were independent of body weight, metabolic rate, and physical activity level. Improved glucose metabolism in CTRP7-deficient mice was associated with reduced adipose tissue inflammation, as well as decreased liver fibrosis and cellular oxidative and endoplasmic reticulum stress. These results provide a link between elevated CTRP7 levels and impaired glucose metabolism, frequently associated with obesity. Inhibiting CTRP7 action may confer beneficial metabolic outcomes in the setting of obesity and diabetes. Copyright © 2017 the American Physiological Society.

The impact of stress on tumor growth: peripheral CRF mediates tumor-promoting effects of stress

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Stathopoulos Efstathios N

2010-09-01

Full Text Available Abstract Introduction Stress has been shown to be a tumor promoting factor. Both clinical and laboratory studies have shown that chronic stress is associated with tumor growth in several types of cancer. Corticotropin Releasing Factor (CRF is the major hypothalamic mediator of stress, but is also expressed in peripheral tissues. Earlier studies have shown that peripheral CRF affects breast cancer cell proliferation and motility. The aim of the present study was to assess the significance of peripheral CRF on tumor growth as a mediator of the response to stress in vivo. Methods For this purpose we used the 4T1 breast cancer cell line in cell culture and in vivo. Cells were treated with CRF in culture and gene specific arrays were performed to identify genes directly affected by CRF and involved in breast cancer cell growth. To assess the impact of peripheral CRF as a stress mediator in tumor growth, Balb/c mice were orthotopically injected with 4T1 cells in the mammary fat pad to induce breast tumors. Mice were subjected to repetitive immobilization stress as a model of chronic stress. To inhibit the action of CRF, the CRF antagonist antalarmin was injected intraperitoneally. Breast tissue samples were histologically analyzed and assessed for neoangiogenesis. Results Array analysis revealed among other genes that CRF induced the expression of SMAD2 and β-catenin, genes involved in breast cancer cell proliferation and cytoskeletal changes associated with metastasis. Cell transfection and luciferase assays confirmed the role of CRF in WNT- β-catenin signaling. CRF induced 4T1 cell proliferation and augmented the TGF-β action on proliferation confirming its impact on TGFβ/SMAD2 signaling. In addition, CRF promoted actin reorganization and cell migration, suggesting a direct tumor-promoting action. Chronic stress augmented tumor growth in 4T1 breast tumor bearing mice and peripheral administration of the CRF antagonist antalarmin suppressed this

Photoactivation of GLUT4 translocation promotes glucose uptake via PI3-K/Akt2 signaling in 3T3-L1 adipocytes

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Lei Huang

2014-05-01

Full Text Available Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes. Dysfunction of PI-3K/Akt signaling was involved in insulin resistance. Glucose transporter 4 (GLUT4 is a key factor for glucose uptake in muscle and adipose tissues, which is closely regulated by PI-3K/Akt signaling in response to insulin treatment. Low-power laser irradiation (LPLI has been shown to regulate various physiological processes and induce the synthesis or release of multiple molecules such as growth factors, which (especially red and near infrared light is mainly through the activation of mitochondrial respiratory chain and the initiation of intracellular signaling pathways. Nevertheless, it is unclear whether LPLI could promote glucose uptake through activation of PI-3K/Akt/GLUT4 signaling in 3T3L-1 adipocytes. In this study, we investigated how LPLI promoted glucose uptake through activation of PI-3K/Akt/GLUT4 signaling pathway. Here, we showed that GLUT4 was localized to the Golgi apparatus and translocated from cytoplasm to cytomembrane upon LPLI treatment in 3T3L-1 adipocytes, which enhanced glucose uptake. Moreover, we found that glucose uptake was mediated by the PI3-K/Akt2 signaling, but not Akt1 upon LPLI treatment with Akt isoforms gene silence and PI3-K/Akt inhibitors. Collectively, our results indicate that PI3-K/Akt2/GLUT4 signaling act as the key regulators for improvement of glucose uptake under LPLI treatment in 3T3L-1 adipocytes. More importantly, our findings suggest that activation of PI3-K/Akt2/GLUT4 signaling by LPLI may provide guidance in practical applications for promotion of glucose uptake in insulin-resistant adipose tissue.

Adenovirus E4ORF1-induced MYC activation promotes host cell anabolic glucose metabolism and virus replication.

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Thai, Minh; Graham, Nicholas A; Braas, Daniel; Nehil, Michael; Komisopoulou, Evangelia; Kurdistani, Siavash K; McCormick, Frank; Graeber, Thomas G; Christofk, Heather R

2014-04-01

Virus infections trigger metabolic changes in host cells that support the bioenergetic and biosynthetic demands of viral replication. Although recent studies have characterized virus-induced changes in host cell metabolism (Munger et al., 2008; Terry et al., 2012), the molecular mechanisms by which viruses reprogram cellular metabolism have remained elusive. Here, we show that the gene product of adenovirus E4ORF1 is necessary for adenovirus-induced upregulation of host cell glucose metabolism and sufficient to promote enhanced glycolysis in cultured epithelial cells by activation of MYC. E4ORF1 localizes to the nucleus, binds to MYC, and enhances MYC binding to glycolytic target genes, resulting in elevated expression of specific glycolytic enzymes. E4ORF1 activation of MYC promotes increased nucleotide biosynthesis from glucose intermediates and enables optimal adenovirus replication in primary lung epithelial cells. Our findings show how a viral protein exploits host cell machinery to reprogram cellular metabolism and promote optimal progeny virion generation. Copyright © 2014 Elsevier Inc. All rights reserved.

Neonatal hypothyroidism affects testicular glucose homeostasis through increased oxidative stress in prepubertal mice: effects on GLUT3, GLUT8 and Cx43.

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Sarkar, D; Singh, S K

2017-07-01

Thyroid hormones (THs) play an important role in maintaining the link between metabolism and reproduction and the altered THs status is associated with induction of oxidative stress in various organs like brain, heart, liver and testis. Further, reactive oxygen species play a pivotal role in regulation of glucose homeostasis in several organs, and glucose utilization by Leydig cells is essential for testosterone biosynthesis and thus is largely dependent on glucose transporter 8 (GLUT8). Glucose uptake by Sertoli cells is mediated through glucose transporter 3 (GLUT3) under the influence of THs to meet energy requirement of developing germ cells. THs also modulate level of gap junctional protein such as connexin 43 (Cx43), a potential regulator of cell proliferation and apoptosis in the seminiferous epithelium. Although the role of transient neonatal hypothyroidism in adult testis in terms of testosterone production is well documented, the effect of THs deficiency in early developmental period and its role in testicular glucose homeostasis and oxidative stress with reference to Cx43 in immature mice remain unknown. Therefore, the present study was conducted to evaluate the effect of neonatal hypothyroidism on testicular glucose homeostasis and oxidative stress at postnatal days (PND) 21 and 28 in relation to GLUT3, GLUT8 and Cx43. Hypothyroidism induced by 6-propyl-2-thiouracil (PTU) markedly decreased testicular glucose level with considerable reduction in expression level of GLUT3 and GLUT8. Likewise, lactate dehydrogenase (LDH) activity and intratesticular concentration of lactate were also decreased in hypothyroid mice. There was also a rise in germ cell apoptosis with increased expression of caspase-3 in PTU-treated mice. Further, neonatal hypothyroidism affected germ cell proliferation with decreased expression of proliferating cell nuclear antigen (PCNA) and Cx43. In conclusion, our results suggest that neonatal hypothyroidism alters testicular glucose

Correlations between blood glucose,lipid,oxidative stress and pancreatic β-cell function in patients with type 2 diabetes mellitus

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Yong-ling LI

2011-06-01

Full Text Available Objective To investigate the relationship between glucose,lipid,oxidative stress and the first-phase of pancreatic β-cell insulin secretion in individuals with different degrees of glucose tolerance.Methods The intravenous glucose tolerance test(IVGTT was performed in 40 patients with newly diagnosed type 2 diabetes mellitus(DM group,37 patients with impaired glucose tolerance(IGT group,and 43 subjects with normal glucose tolerance(NGT group.Glucose,lipid,fasting plasma 8-hydroxydeoxyguanosin(8-OHdG,malondialdehyde(MDA and the activity of superoxide dismutase(SOD were measured.0-10 minutes of insulin area under the curve(AUC,acute insulin response(AIR3-5,homeostasis model assessment(HOMA-IR and homeostasis model assessment-B(HOMA-B were calculated to analyze the relationship between oxidative stress and the fasting plasma glucose(FPG,high density lipoprotein cholesterol(HDL-C,low density lipoprotein cholesterol(LDL-C,triglyceride(TG,total cholesterol(TC,AUC,AIR3-5,HOMA-B and HOMA-IR.Results SOD,AIR3-5 and AUC were significantly lower in DM and IGT group than in NGT group(P < 0.05;LDL-C,TG,8-OHdG and MDA were significantly higher in IGT and DM group than in NGT group(P < 0.05;SOD,AIR3-5 and AUC were significantly lower in DM group than in IGT group(P < 0.05;LDL-C,TG,8-OHdG and MDA were significantly higher in DM group than in IGT group(P < 0.05.MDA and 8-OHdG were positively correlated with FPG,TG and LDL-C,and negatively correlated with FINS,HOMA-B,AUC and AIR3-5.SOD was positively correlated with FINS,HOMA-B,AUC and AIR3-5,and negatively correlated with FPG,TG and LDL-C.Multiple stepwise regression analysis showed that FPG and LDL-C were the independent factors of plasma 8-OHdG and SOD,while 8-OHdG and SOD were the independent factors of AIR3-5.Conclusion Patients with type 2 diabetes have obvious glycometabolic disorder,lipoidosis and oxidative stress.Oxidative stress takes a significant effect on the first phase of pancreatic β cell insulin

High glucose-induced oxidative stress represses sirtuin deacetylase expression and increases histone acetylation leading to neural tube defects.

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Yu, Jingwen; Wu, Yanqing; Yang, Peixin

2016-05-01

Aberrant epigenetic modifications are implicated in maternal diabetes-induced neural tube defects (NTDs). Because cellular stress plays a causal role in diabetic embryopathy, we investigated the possible role of the stress-resistant sirtuin (SIRT) family histone deacetylases. Among the seven sirtuins (SIRT1-7), pre-gestational maternal diabetes in vivo or high glucose in vitro significantly reduced the expression of SIRT 2 and SIRT6 in the embryo or neural stem cells, respectively. The down-regulation of SIRT2 and SIRT6 was reversed by superoxide dismutase 1 (SOD1) over-expression in the in vivo mouse model of diabetic embryopathy and the SOD mimetic, tempol and cell permeable SOD, PEGSOD in neural stem cell cultures. 2,3-dimethoxy-1,4-naphthoquinone (DMNQ), a superoxide generating agent, mimicked high glucose-suppressed SIRT2 and SIRT6 expression. The acetylation of histone 3 at lysine residues 56 (H3K56), H3K14, H3K9, and H3K27, putative substrates of SIRT2 and SIRT6, was increased by maternal diabetes in vivo or high glucose in vitro, and these increases were blocked by SOD1 over-expression or tempol treatment. SIRT2 or SIRT6 over-expression abrogated high glucose-suppressed SIRT2 or SIRT6 expression, and prevented the increase in acetylation of their histone substrates. The potent sirtuin activator (SRT1720) blocked high glucose-increased histone acetylation and NTD formation, whereas the combination of a pharmacological SIRT2 inhibitor and a pan SIRT inhibitor mimicked the effect of high glucose on increased histone acetylation and NTD induction. Thus, diabetes in vivo or high glucose in vitro suppresses SIRT2 and SIRT6 expression through oxidative stress, and sirtuin down-regulation-induced histone acetylation may be involved in diabetes-induced NTDs. The mechanism underlying pre-gestational diabetes-induced neural tube defects (NTDs) is still elusive. Our study unravels a new epigenetic mechanism in which maternal diabetes-induced oxidative stress represses

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

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

2014-08-01

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

A randomized clinical trial comparing the effect of basal insulin and inhaled mealtime insulin on glucose variability and oxidative stress

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Siegelaar, S. E.; Kulik, W.; van Lenthe, H.; Mukherjee, R.; Hoekstra, J. B. L.; DeVries, J. H.

2009-01-01

To assess the effect of three times daily mealtime inhaled insulin therapy compared with once daily basal insulin glargine therapy on 72-h glucose profiles, glucose variability and oxidative stress in type 2 diabetes patients. In an inpatient crossover study, 40 subjects with type 2 diabetes were

Caveolin-1 and glucose transporter 4 involved in the regulation of glucose-deprivation stress in PC12 cells.

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Zhang, Qi-Qi; Huang, Liang; Han, Chao; Guan, Xin; Wang, Ya-Jun; Liu, Jing; Wan, Jing-Hua; Zou, Wei

2015-08-25

Recent evidence suggests that caveolin-1 (Cav-1), the major protein constituent of caveolae, plays a prominent role in neuronal nutritional availability with cellular fate regulation besides in several cellular processes such as cholesterol homeostasis, regulation of signal transduction, integrin signaling and cell growth. Here, we aimed to investigate the function of Cav-1 and glucose transporter 4 (GLUT4) upon glucose deprivation (GD) in PC12 cells. The results demonstrated firstly that both Cav-1 and GLUT4 were up-regulated by glucose withdrawal in PC12 cells by using Western blot and laser confocal technology. Also, we found that the cell death rate, mitochondrial membrane potential (MMP) and intracellular free Ca(2+) concentration ([Ca(2+)]i) were also respectively changed followed the GD stress tested by CCK8 and flow cytometry. After knocking down of Cav-1 in the cells by siRNA, the level of [Ca(2+)]i was increased, and MMP was reduced further in GD-treated PC12 cells. Knockdown of Cav-1 or methylated-β-Cyclodextrin (M-β-CD) treatment inhibited the expression of GLUT4 protein upon GD. Additionally, we found that GLUT4 could translocate from cytoplasm to cell membrane upon GD. These findings might suggest a neuroprotective role for Cav-1, through coordination of GLUT4 in GD.

Photoelectrocatalytic Glucose Oxidation to Promote Hydrogen Production over Periodically Ordered TiO2 Nanotube Arrays Assembled of Pd Quantum Dots

International Nuclear Information System (INIS)

Zhang, Yajun; Zhao, Guohua; Shi, Huijie; Zhang, Ya-nan; Huang, Wenna; Huang, Xiaofeng; Wu, Zhongyi

2015-01-01

Highlights: • Solar-driven PEC glucose oxidation to promote hydrogen production was presented. • The excellent PEC activity of Pd QDs@TNTAs was investigated. • The rate of hydrogen production from glucose was about 15 times than water. • A low-cost and efficient method in renewables-to-hydrogen conversion was put forward. - Abstract: The development of highly efficient and low-cost approaches for catalytic hydrogen production from renewable energy is of tremendous importance for a truly sustainable hydrogen-based energy carrier in future life. Herein, the probability of utilizing solar light to product hydrogen from biomass derivative, glucose, was systematically demonstrated by using the periodically ordered TiO 2 nanotube arrays (TNTAs) assembled of Palladium quantum dots (Pd QDs), i.e. Pd QDs@ TNTAs as photoanode. The results showed that remarkably increased photocurrent density was obtained in the glucose solution compared to the pure KOH electrolyte over as-prepared photoelectrode, which indicated that the glucose could be faster oxidized than water oxidation, and thus could promote the hydrogen production on Pt cathode. The yield of hydrogen production from glucose oxidation reached as high as 164.8 μmol cm −1 over Pd QDs@TNTAs photoanode and Pt cathode system (denoted as Pd QDs@TNTAs/Pt) under the solar light irradiation for 6 h, which was about 15 times higher than that from pure water splitting. The superior hydrogen production performance could be attributed to the less endergonic process of the glucose oxidation than water, as well as the efficient synergistic photoelectrocatalytic (PEC) glucose oxidation over Pd QDs@TNTAs photoanode which possesses excellent photoelectrochemical performance and structure characteristics. Moreover, a probable mechanism for the PEC hydrogen production from biomass derivatives oxidation was proposed and discussed

Gardening promotes neuroendocrine and affective restoration from stress.

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Van Den Berg, Agnes E; Custers, Mariëtte H G

2011-01-01

Stress-relieving effects of gardening were hypothesized and tested in a field experiment. Thirty allotment gardeners performed a stressful Stroop task and were then randomly assigned to 30 minutes of outdoor gardening or indoor reading on their own allotment plot. Salivary cortisol levels and self-reported mood were repeatedly measured. Gardening and reading each led to decreases in cortisol during the recovery period, but decreases were significantly stronger in the gardening group. Positive mood was fully restored after gardening, but further deteriorated during reading. These findings provide the first experimental evidence that gardening can promote relief from acute stress.

The Promoter of AtUSP Is Co-regulated by Phytohormones and Abiotic Stresses in Arabidopsis thaliana.

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Bhuria, Monika; Goel, Parul; Kumar, Sanjay; Singh, Anil K

2016-01-01

Universal stress proteins (USPs) are known to be expressed in response to various abiotic stresses in a wide variety of organisms, such as bacteria, archaebacteria, protists, algae, fungi, plants, and animals. However, in plants, biological function of most of the USPs still remains obscure. In the present study, Arabidopsis USP gene ( AtUSP ) showed induction in response to abscisic acid (ABA) and various abiotic stresses viz . heat, dehydration, salt, osmotic, and cold stresses. Additionally, in silico analysis of AtUSP promoter identified several cis -elements responsive to phytohormones and abiotic stresses such as ABRE, ERE, DRE, and HSE, etc. To functionally validate the AtUSP promoter, the 1115 bp region of promoter was characterized under phytohormone and abiotic stress treatments. Deletion analysis of promoter was carried out by cloning the full length promoter (D0) and its three 5' deletion derivatives, D1 (964 bp), D2 (660 bp), and D3 (503 bp) upstream of the β-glucuronidase (GUS) reporter gene, which were then stably transformed in Arabidopsis plants. The AtUSP promoter (D0) showed minimal activity under non-stress conditions which was enhanced in response to phytohormone treatments (ABA and ACC) and abiotic stresses such as dehydration, heat, cold, salt, and osmotic stresses. The seedlings harboring D1 and D2 deletion fragments showed constitutive GUS expression even under control condition with increased activity almost under all the treatments. However, D3 seedlings exhibited complete loss of activity under control condition with induction under ACC treatment, dehydration, heat, oxidative, salt, and osmotic stresses. Thus, present study clearly showed that AtUSP promoter is highly inducible by phytohormones and multiple abiotic stresses and it can be exploited as stress inducible promoter to generate multi-stress tolerant crops with minimal effects on their other important traits.

Carnosol promotes endothelial differentiation under H2O2-induced oxidative stress

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Ou Shulin

2017-01-01

Full Text Available Oxidative stress causes deregulation of endothelial cell differentiation. Carnosol is a potent antioxidant and antiinflammatory compound. In the present study, we examined whether the antioxidant effect of carnosol might protect bone marrow stem cells against H2O2-induced oxidative stress and promote endothelial differentiation. We examined cell viability by the MTT assay; oxidative stress and apoptosis were analyzed through changes in ROS levels, apoptotic ratio and caspase-3 activity; changes in protein expression of OCT-4, Flk-1, CD31 and Nrf-2 were assessed by Western blot analysis. H2O2 treatment increased oxidative stress and reduced cell viability, while the stem cell marker OCT-4 and endothelial markers Flk-1, CD31 were significantly downregulated as a result of the treatment with H2O2. Treatment with carnosol improved the antioxidant status, increased OCT-4 expression and promoted endothelial differentiation. This study provides evidence that carnosol could increase the antioxidant defense mechanism and promote endothelial differentiation.

Attenuation of oxidative stress and inflammation by gravinol in high glucose-exposed renal tubular epithelial cells

International Nuclear Information System (INIS)

Kim, You Jung; Kim, Young Ae; Yokozawa, Takako

2010-01-01

Gravinol, a proanthocyanidin from grape seeds, has polyphenolic properties with powerful anti-oxidative effects. Although, increasing evidence strongly suggests that polyphenolic antioxidants suppress diabetic nephropathy that is causally associated with oxidative stress and inflammation, gravinol's protective action against diabetic nephropathy has not been fully explored to date. In the current study, we investigated the protective action of gravinol against oxidative stress and inflammation using the experimental diabetic nephropathy cell model, high glucose-exposed renal tubular epithelial cells. To elucidate the underlying actions of gravinol, several oxidative and inflammatory markers were estimated. Included are measurements of lipid peroxidation, total reactive species (RS), superoxide (·O 2 ), nitric oxide (NO·), and peroxynitrite (ONOO - ), as well as nuclear factor-kappa B (NF-κB) nuclear translocation. Results indicate that gravinol had a potent inhibitory action against lipid peroxidation, total RS, ·O 2 , NO·, ONOO - , the reduced glutathione (GSH)/oxidized glutathione (GSSG) ratio and more importantly, against NF-κB nuclear translocation. We propose that gravinol's strong protective effect against high glucose-induced renal tubular epithelial cell damage attenuates diabetic nephropathy by suppressing oxidative stress and inflammation.

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

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

2018-01-01

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

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

Science.gov (United States)

Kosse, C; Gonzalez, A; Burdakov, D

2015-01-01

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

AAV delivery of GRP78/BiP promotes adaptation of human RPE cell to ER stress.

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Ghaderi, Shima; Ahmadian, Shahin; Soheili, Zahra-Soheila; Ahmadieh, Hamid; Samiei, Shahram; Kheitan, Samira; Pirmardan, Ehsan R

2018-02-01

Adeno associated virus (AAV)-mediated gene delivery of GRP78 (78 kDa glucose-regulated protein) attenuates the condition of endoplasmic reticulum (ER) stress and prevents apoptotic loss of photoreceptors in Retinitis pigmentosa (RP) rats. In the current study we overexpressed Grp78 with the help of AAV-2 in primary human retinal pigmented epithelium (hRPE) cell cultures and examined its effect on cell response to ER stress. The purpose of this work was studying potential stimulating effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress, as an in vitro model for RPE degeneration. To investigate the effect of Grp78 overexpression on unfolded protein response (UPR) markers under ER stress, hRPE primary cultures were transduced by recombinant virus rAAV/Grp78, and treated with ER stressor drug, tunicamycin. Expression changes of four UPR markers including GRP78, PERK, ATF6α, and GADD153/CHOP, were assessed by real-time PCR and western blotting. We found that GRP78 has a great contribution in modulation of UPR markers to favor adaptive response in ER-stressed hRPE cells. In fact, GRP78 overexpression affected adaptation and apoptotic phases of early UPR, through enhancement of two master regulators/ER stress sensors (PERK and ATF6α) and down-regulation of a key pro-apoptotic cascade activator (GADD153/CHOP). Together these findings demonstrate the promoting effect of GRP78 on adaptation/pro-survival of hRPE cells under ER stress. This protein with anti-apoptotic actions in the early UPR and important role in cell fate regulation, can be recruited as a useful candidate for future investigations of RPE degenerative diseases. © 2017 Wiley Periodicals, Inc.

Effect of low glycemic index food and postprandial exercise on blood glucose level, oxidative stress and antioxidant capacity.

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Kasuya, Noriaki; Ohta, Shoichiro; Takanami, Yoshikazu; Kawai, Yukari; Inoue, Yutaka; Murata, Isamu; Kanamoto, Ikuo

2015-04-01

Low glycemic index (GI) food and postprandial exercise are non-drug therapies for improving postprandial hyperglycemia. The present randomized, crossover study investigated the effect of low GI food combined with postprandial exercise on postprandial blood glucose level, oxidative stress and antioxidant capacity. A total of 13 healthy subjects were each used in four experiments: i) rice only (control), ii) salad prior to rice (LGI), iii) exercise following rice (EX) and iv) salad prior to rice and exercise following rice (MIX). The blood glucose level, oxidative stress and antioxidant capacity were then measured. At 60 min after the meal, the blood glucose level was observed to be increased in the MIX group compared with that in the LGI group. Furthermore, at 180 min, the antioxidant capacity was found to be reduced in the MIX group compared with those of the LGI and EX groups. These findings suggest that low GI food combined with postprandial exercise does not improve postprandial hyperglycemia. It may be necessary to establish optimal timing and intensity when combining low GI food with postprandial exercise to improve postprandial hyperglycemia.

Metformin is synthetically lethal with glucose withdrawal in cancer cells.

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Menendez, Javier A; Oliveras-Ferraros, Cristina; Cufí, Sílvia; Corominas-Faja, Bruna; Joven, Jorge; Martin-Castillo, Begoña; Vazquez-Martin, Alejandro

2012-08-01

Glucose deprivation is a distinctive feature of the tumor microecosystem caused by the imbalance between poor supply and an extraordinarily high consumption rate. The metabolic reprogramming from mitochondrial respiration to aerobic glycolysis in cancer cells (the "Warburg effect") is linked to oncogenic transformation in a manner that frequently implies the inactivation of metabolic checkpoints such as the energy rheostat AMP-activated protein kinase (AMPK). Because the concept of synthetic lethality in oncology can be applied not only to genetic and epigenetic intrinsic differences between normal and cancer cells but also to extrinsic ones such as altered microenvironment, we recently hypothesized that stress-energy mimickers such as the AMPK agonist metformin should produce metabolic synthetic lethality in a glucose-starved cell culture milieu imitating the adverse tumor growth conditions in vivo. Under standard high-glucose conditions, metformin supplementation mostly caused cell cycle arrest without signs of apoptotic cell death. Under glucose withdrawal stress, metformin supplementation circumvented the ability of oncogenes (e.g., HER2) to protect breast cancer cells from glucose-deprivation apoptosis. Significantly, representative cell models of breast cancer heterogeneity underwent massive apoptosis (by >90% in some cases) when glucose-starved cell cultures were supplemented with metformin. Our current findings may uncover crucial issues regarding the cell-autonomous metformin's anti-cancer actions: (1) The offently claimed clinically irrelevant, non-physiological concentrations needed to observe the metformin's anti-cancer effects in vitro merely underlie the artifactual interference of erroneous glucose-rich experimental conditions that poorly reflect glucose-starved in vivo conditions; (2) the preferential killing of cancer stem cells (CSC) by metformin may simply expose the best-case scenario for its synthetically lethal activity because an increased

N-Methyl-D aspartate receptor-mediated effect on glucose transporter-3 levels of high glucose exposed-SH-SY5Y dopaminergic neurons.

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Engin, Ayse Basak; Engin, Evren Doruk; Karakus, Resul; Aral, Arzu; Gulbahar, Ozlem; Engin, Atilla

2017-11-01

High glucose and insulin lead to neuronal insulin resistance. Glucose transport into the neurons is achieved by regulatory induction of surface glucose transporter-3 (GLUT3) instead of the insulin. N-methyl-D aspartate (NMDA) receptor activity increases GLUT3 expression. This study explored whether an endogenous NMDA receptor antagonist, kynurenic acid (KynA) affects the neuronal cell viability at high glucose concentrations. SH-SY5Y neuroblastoma cells were exposed to 150-250 mg/dL glucose and 40 μU/mL insulin. In KynA and N-nitro-l-arginine methyl ester (L-NAME) supplemented cultures, oxidative stress, mitochondrial metabolic activity (MTT), nitric oxide as nitrite+nitrate (NOx) and GLUT3 were determined at the end of 24 and 48-h incubation periods. Viable cells were counted by trypan blue dye. High glucose-exposed SH-SY5Y cells showed two-times more GLUT3 expression at second 24-h period. While GLUT3-stimulated glucose transport and oxidative stress was increased, total mitochondrial metabolic activity was significantly reduced. Insulin supplementation to high glucose decreased NOx synthesis and GLUT3 levels, in contrast oxidative stress increased three-fold. KynA significantly reduced oxidative stress, and increased MTT by regulating NOx production and GLUT3 expression. KynA is a noteworthy compound, as an endogenous, specific NMDA receptor antagonist; it significantly reduces oxidative stress, while increasing cell viability at high glucose and insulin concentrations. Copyright © 2017 Elsevier Ltd. All rights reserved.

A mathematical model of brain glucose homeostasis

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Kimura Hidenori

2009-11-01

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

2-deoxy-D-glucose-induced metabolic stress enhances resistance to Listeria monocytogenes infection in mice

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Miller, E. S.; Bates, R. A.; Koebel, D. A.; Fuchs, B. B.; Sonnenfeld, G.

1998-01-01

Exposure to different forms of psychological and physiological stress can elicit a host stress response, which alters normal parameters of neuroendocrine homeostasis. The present study evaluated the influence of the metabolic stressor 2-deoxy-D-glucose (2-DG; a glucose analog, which when administered to rodents, induces acute periods of metabolic stress) on the capacity of mice to resist infection with the facultative intracellular bacterial pathogen Listeria monocytogenes. Female BDF1 mice were injected with 2-DG (500 mg/kg b. wt.) once every 48 h prior to, concurrent with, or after the onset of a sublethal dose of virulent L. monocytogenes. Kinetics of bacterial growth in mice were not altered if 2-DG was applied concurrently or after the start of the infection. In contrast, mice exposed to 2-DG prior to infection demonstrated an enhanced resistance to the listeria challenge. The enhanced bacterial clearance in vivo could not be explained by 2-DG exerting a toxic effect on the listeria, based on the results of two experiments. First, 2-DG did not inhibit listeria replication in trypticase soy broth. Second, replication of L. monocytogenes was not inhibited in bone marrow-derived macrophage cultures exposed to 2-DG. Production of neopterin and lysozyme, indicators of macrophage activation, were enhanced following exposure to 2-DG, which correlated with the increased resistance to L. monocytogenes. These results support the contention that the host response to 2-DG-induced metabolic stress can influence the capacity of the immune system to resist infection by certain classes of microbial pathogens.

Emerging importance of helicases in plant stress tolerance: characterization of Oryza sativa repair helicase XPB2 promoter and its functional validation in tobacco under multiple stresses

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Shailendra eRaikwar

2015-12-01

Full Text Available Genetic material always remains at the risk of spontaneous or induced damage which challenges the normal functioning of DNA molecule, thus, DNA repair is vital to protect the organisms against genetic damage. DNA hHelicases, the unique molecular motors, are emerged as potentialprospective molecules to engineer stress tolerance in plants and are involved in a variety of DNA nucleic acid metabolismc processes including DNA repair. The DNA repair helicase, OsXPB2 is an evolutionary conserved protein present in different organisms, including plants. Availability of few efficient promoters for gene expression in plants provoked us to study the promoter of XPB for better understanding of gene regulation under stress The analysis of promoter sequence from plant genome is important in understanding the gene regulation. Hereconditions. Here, we report the in silico analysis of novel stress inducible promoter of rice Oryza sativa OsXPB2 (OsXPB2. gene is reported. The in vivo validation of functionality/activity of novel stress inducible promoter of rice OsXPB2 gene promoter under abiotic and hormonal stress conditions was performed by Agrobacterium-mediated transient assay in tobacco leaves using OsXPB2::GUS chimeric construct. Our resultsThe present research revealed that OsXPB2 promoter contains cis-elements accounting for various abiotic stresses (salt, dehydration or cold and hormone (Auxin, ABA or MeJA induced GUS expression/activity in the promoter-reporter assay. The promoter region of OsXPB2 contains CACG, GTAACG, CACGTG, CGTCA CCGCCGCGCT cis acting-elements which are reported to be salt, dehydration, cold, MeJA or ABA responsive, respectively. Functional analysis was done by Agrobacterium-transient assays using agroinfiltration in tobacco leaves, followed by GUS staining and fluorescence quantitative analyses. The results revealed high induction of GUS activity under multiple abiotic stresses as compared to mock treated control. The present

Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

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Cronin, Katherine R; Mangan, Thomas P; Carew, Josephine A

2012-01-01

Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, pfactor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

Prioritized expression of BTN2 of Saccharomyces cerevisiae under pronounced translation repression induced by severe ethanol stress

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Yukina Yamauchi

2016-08-01

Full Text Available Severe ethanol stress (>9% ethanol, v/v as well as glucose deprivation rapidly induces a pronounced repression of overall protein synthesis in budding yeast Saccharomyces cerevisiae. Therefore, transcriptional activation in yeast cells under severe ethanol stress does not always indicate the production of expected protein levels. Messenger RNAs of genes containing heat shock elements can be intensively translated under glucose deprivation, suggesting that some mRNAs are preferentially translated even under severe ethanol stress. In the present study, we tried to identify the mRNA that can be preferentially translated under severe ethanol stress. BTN2 encodes a v-SNARE binding protein, and its null mutant shows hypersensitivity to ethanol. We found that BTN2 mRNA was efficiently translated under severe ethanol stress but not under mild ethanol stress. Moreover, the increased Btn2 protein levels caused by severe ethanol stress were smoothly decreased with the elimination of ethanol stress. These findings suggested that severe ethanol stress extensively induced BTN2 expression. Further, the BTN2 promoter induced protein synthesis of non-native genes such as CUR1, GIC2, and YUR1 in the presence of high ethanol concentrations, indicating that this promoter overcame severe ethanol stress-induced translation repression. Thus, our findings provide an important clue about yeast response to severe ethanol stress and suggest that the BTN2 promoter can be used to improve the efficiency of ethanol production and stress tolerance of yeast cells by modifying gene expression in the presence of high ethanol concentration.

Emerging Importance of Helicases in Plant Stress Tolerance: Characterization of Oryza sativa Repair Helicase XPB2 Promoter and Its Functional Validation in Tobacco under Multiple Stresses.

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Raikwar, Shailendra; Srivastava, Vineet K; Gill, Sarvajeet S; Tuteja, Renu; Tuteja, Narendra

2015-01-01

Genetic material always remains at the risk of spontaneous or induced damage which challenges the normal functioning of DNA molecule, thus, DNA repair is vital to protect the organisms against genetic damage. Helicases, the unique molecular motors, are emerged as prospective molecules to engineer stress tolerance in plants and are involved in nucleic acid metabolism including DNA repair. The repair helicase, XPB is an evolutionary conserved protein present in different organisms, including plants. Availability of few efficient promoters for gene expression in plants provoked us to study the promoter of XPB for better understanding of gene regulation under stress conditions. Here, we report the in silico analysis of novel stress inducible promoter of Oryza sativa XPB2 (OsXPB2). The in vivo validation of functionality/activity of OsXPB2 promoter under abiotic and hormonal stress conditions was performed by Agrobacterium-mediated transient assay in tobacco leaves using OsXPB2::GUS chimeric construct. The present research revealed that OsXPB2 promoter contains cis-elements accounting for various abiotic stresses (salt, dehydration, or cold) and hormone (Auxin, ABA, or MeJA) induced GUS expression/activity in the promoter-reporter assay. The promoter region of OsXPB2 contains CACG, GTAACG, CACGTG, CGTCA CCGCCGCGCT cis acting-elements which are reported to be salt, dehydration, cold, MeJA, or ABA responsive, respectively. Functional analysis was done by Agrobacterium-mediated transient assay using agroinfiltration in tobacco leaves, followed by GUS staining and fluorescence quantitative analyses. The results revealed high induction of GUS activity under multiple abiotic stresses as compared to mock treated control. The present findings suggest that OsXPB2 promoter is a multi-stress inducible promoter and has potential applications in sustainable crop production under abiotic stresses by regulating desirable pattern of gene expression.

Upregulation of the coagulation factor VII gene during glucose deprivation is mediated by activating transcription factor 4.

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Katherine R Cronin

Full Text Available BACKGROUND: Constitutive production of blood coagulation proteins by hepatocytes is necessary for hemostasis. Stressful conditions trigger adaptive cellular responses and delay processing of most proteins, potentially affecting plasma levels of proteins secreted exclusively by hepatocytes. We examined the effect of glucose deprivation on expression of coagulation proteins by the human hepatoma cell line, HepG2. METHODOLOGY/PRINCIPAL FINDINGS: Expression of coagulation factor VII, which is required for initiation of blood coagulation, was elevated by glucose deprivation, while expression of other coagulation proteins decreased. Realtime PCR and ELISA demonstrated that the relative percentage expression +/- SD of steady-state F7 mRNA and secreted factor VII antigen were significantly increased (from 100+/-15% to 188+/-27% and 100+/-8.8% to 176.3+/-17.3% respectively, p<0.001 at 24 hr of treatment. The integrated stress response was induced, as indicated by upregulation of transcription factor ATF4 and of additional stress-responsive genes. Small interfering RNAs directed against ATF4 potently reduced basal F7 expression, and prevented F7 upregulation by glucose deprivation. The response of the endogenous F7 gene was replicated in reporter gene assays, which further indicated that ATF4 effects were mediated via interaction with an amino acid response element in the F7 promoter. CONCLUSIONS/SIGNIFICANCE: Our data indicated that glucose deprivation enhanced F7 expression in a mechanism reliant on prior ATF4 upregulation primarily due to increased transcription from the ATF4 gene. Of five coagulation protein genes examined, only F7 was upregulated, suggesting that its functions may be important in a systemic response to glucose deprivation stress.

Glucose intolerance induced by blockade of central FGF receptors is linked to an acute stress response

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Jennifer M. Rojas

2015-08-01

Conclusions: The effect of acute inhibition of central FGFR signaling to impair glucose tolerance likely involves a stress response associated with pronounced, but transient, sympathoadrenal activation and an associated reduction of insulin secretion. Whether this effect is a true consequence of FGFR blockade or involves an off-target effect of the FGFR inhibitor requires additional study.

An Association between College Students' Health Promotion Practices and Perceived Stress

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Li, Ying; Lindsey, Billie J.

2013-01-01

This study was undertaken to gain a better understanding of health promotion practices among college students and the relationship of stress and the practice of various health behaviors. Method: In Fall 2008, 319 students from a mid-size university participated in a cross-sectional survey utilizing the Perceived Stress Scale (PSS) and the Health…

SREBP-1c regulates glucose-stimulated hepatic clusterin expression

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Kim, Gukhan [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Geun Hyang; Oh, Gyun-Sik; Yoon, Jin [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Hae Won [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Min-Seon [Department of Internal Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Kim, Seung-Whan, E-mail: swkim7@amc.seoul.kr [Department of Pharmacology, Asan Medical Center, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of); Bio-Medical Institute of Technology, University of Ulsan College of Medicine, Seoul 138-736 (Korea, Republic of)

2011-05-20

Highlights: {yields} This is the first report to show nutrient-regulated clusterin expression. {yields} Clusterin expression in hepatocytes was increased by high glucose concentration. {yields} SREBP-1c is directly involved in the transcriptional activation of clusterin by glucose. {yields} This glucose-stimulated activation process is mediated through tandem E-box motifs. -- Abstract: Clusterin is a stress-response protein that is involved in diverse biological processes, including cell proliferation, apoptosis, tissue differentiation, inflammation, and lipid transport. Its expression is upregulated in a broad spectrum of diverse pathological states. Clusterin was recently reported to be associated with diabetes, metabolic syndrome, and their sequelae. However, the regulation of clusterin expression by metabolic signals was not addressed. In this study we evaluated the effects of glucose on hepatic clusterin expression. Interestingly, high glucose concentrations significantly increased clusterin expression in primary hepatocytes and hepatoma cell lines, but the conventional promoter region of the clusterin gene did not respond to glucose stimulation. In contrast, the first intronic region was transcriptionally activated by high glucose concentrations. We then defined a glucose response element (GlRE) of the clusterin gene, showing that it consists of two E-box motifs separated by five nucleotides and resembles carbohydrate response element (ChoRE). Unexpectedly, however, these E-box motifs were not activated by ChoRE binding protein (ChREBP), but were activated by sterol regulatory element binding protein-1c (SREBP-1c). Furthermore, we found that glucose induced recruitment of SREBP-1c to the E-box of the clusterin gene intronic region. Taken together, these results suggest that clusterin expression is increased by glucose stimulation, and SREBP-1c plays a crucial role in the metabolic regulation of clusterin.

Cover Picture: Metal‐Free Dehydration of Glucose to 5‐(Hydroxymethyl)furfural in Ionic Liquids with Boric Acid as a Promoter (Chem. Eur. J. 5/2011)

DEFF Research Database (Denmark)

Ståhlberg, Tim Johannes Bjarki; Rodriguez, Sergio; Fristrup, Peter

2011-01-01

Boric acid promotes the dehydration of glucose to 5-(hydroxy)methylfurfural in ionic liquids. Computational analyses by DFT calculations show a significant decrease in energy for the isomerization of glucose to fructose when the sugars are bound to boric acid and isotopic labeling NMR studies con...

PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation

KAUST Repository

Hou, Xu; Liu, Yaohua; Liu, Huailei; Chen, Xin; Liu, Min; Che, Hui; Guo, Fei; Wang, Chunlei; Zhang, Daming; Wu, Jianing; Chen, Xiaofeng; Shen, Chen; Li, Chenguang; Peng, Fei; Bi, Yunke; Yang, Zhuowen; Yang, Guang; Ai, Jing; Gao, Xin; Zhao, Shiguang

2015-01-01

Glioma relies on glycolysis to obtain energy and sustain its survival under low glucose microenvironment in vivo. The mechanisms on glioma cell glycolysis regulation are still unclear. Signaling mediated by Double-stranded RNA-activated protein kinase (PKR) - like ER kinase (PERK) is one of the important pathways of unfolded protein response (UPR) which is comprehensively activated in cancer cells upon the hypoxic and low glucose stress. Here we show that PERK is significantly activated in human glioma tissues. PERK silencing results in decreased glioma cell viability and ATP/lactate production upon low glucose stress, which is mediated by partially blocked AKT activation and subsequent inhibition of Hexokinase II (HK2)'s mitochondria translocation. More importantly, PERK silenced glioma cells show decreased tumor formation capacity. Our results reveal that PERK activation is involved in glioma glycolysis regulation and may be a potential molecular target for glioma treatment.

PERK silence inhibits glioma cell growth under low glucose stress by blockage of p-AKT and subsequent HK2's mitochondria translocation

KAUST Repository

Hou, Xu

2015-03-12

Glioma relies on glycolysis to obtain energy and sustain its survival under low glucose microenvironment in vivo. The mechanisms on glioma cell glycolysis regulation are still unclear. Signaling mediated by Double-stranded RNA-activated protein kinase (PKR) - like ER kinase (PERK) is one of the important pathways of unfolded protein response (UPR) which is comprehensively activated in cancer cells upon the hypoxic and low glucose stress. Here we show that PERK is significantly activated in human glioma tissues. PERK silencing results in decreased glioma cell viability and ATP/lactate production upon low glucose stress, which is mediated by partially blocked AKT activation and subsequent inhibition of Hexokinase II (HK2)\\'s mitochondria translocation. More importantly, PERK silenced glioma cells show decreased tumor formation capacity. Our results reveal that PERK activation is involved in glioma glycolysis regulation and may be a potential molecular target for glioma treatment.

FMRFamide signaling promotes stress-induced sleep in Drosophila.

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Lenz, Olivia; Xiong, Jianmei; Nelson, Matthew D; Raizen, David M; Williams, Julie A

2015-07-01

Enhanced sleep in response to cellular stress is a conserved adaptive behavior across multiple species, but the mechanism of this process is poorly understood. Drosophila melanogaster increases sleep following exposure to septic or aseptic injury, and Caenorhabditis elegans displays sleep-like quiescence following exposure to high temperatures that stress cells. We show here that, similar to C. elegans, Drosophila responds to heat stress with an increase in sleep. In contrast to Drosophila infection-induced sleep, heat-induced sleep is not sensitive to the time-of-day of the heat pulse. Moreover, the sleep response to heat stress does not require Relish, the NFκB transcription factor that is necessary for infection-induced sleep, indicating that sleep is induced by multiple mechanisms from different stress modalities. We identify a sleep-regulating role for a signaling pathway involving FMRFamide neuropeptides and their receptor FR. Animals mutant for either FMRFamide or for the FMRFamide receptor (FR) have a reduced recovery sleep in response to heat stress. FR mutants, in addition, show reduced sleep responses following infection with Serratia marcescens, and succumb to infection at a faster rate than wild-type controls. Together, these findings support the hypothesis that FMRFamide and its receptor promote an adaptive increase in sleep following stress. Because an FMRFamide-like neuropeptide plays a similar role in C. elegans, we propose that FRMFamide neuropeptide signaling is an ancient regulator of recovery sleep which occurs in response to cellular stress. Copyright © 2015 Elsevier Inc. All rights reserved.

ALA/LA ameliorates glucose toxicity on HK-2 cells by attenuating oxidative stress and apoptosis through the ROS/p38/TGF-β1 pathway.

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Jiang, Mingxia; Zhang, Haifen; Zhai, Lijie; Ye, Bianliang; Cheng, Yin; Zhai, Chengkai

2017-11-16

Growing evidence indicates that oxidative stress (OS) plays a pivotal role in Diabetic nephropathy (DN). In a previous study we demonstrated that ALA/LA protected HK-2 cells against high glucose-induced cytotoxicity. So we aimed to establish the glucose injury model of HK-2 cells and investigate the beneficial effects of ALA/LA on high glucose-induced excessive production of TGF-β1 and the possible mechanisms mediating the effects. The expression of OS markers in high glucose-induced HK-2 cells treated with ALA/LA., including the antioxidant enzymes and reactive oxygen species (ROS) production, as well as the apoptosis rate were assayed by ELISA and flow cytometry. The p38/transforming growth factor β 1 (TGF-β 1 ) signal pathway were measured by real-time RT-PCR and western blot. The modeling condition of glucose toxicity on HK-2 cells was at the glucose concentration of 40.9 mM. ALA/LA can significantly increase the activities of antioxidant enzymes and decrease ROS production stimulated by high glucose. The study also found that ALA/LA caused a decrease in the apoptosis rate and TGF-β 1 level of HK-2 cells under high glucose stress through the ROS/p38 pathway. ALA/LA exerts protective effects in vitro through inhibition of ROS generation, down regulation of the activation of the p38MAPK pathway and the expression of TGF-β 1 in HK-2 cells.

Assessment of glucose homeostasis in crossbred steer progeny sired by Brahman bulls that experienced prenatal transportation stress

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The objective of this experiment was to assess glucose homeostasis of crossbred male progeny whose Brahman sires experienced prenatal transportation stress (PS) in utero. Sixteen steers (PNS group) sired by 3 PS bulls gestating dams were transported for 2 h at 60, 80, 100, 120, and 140 ± 5 d of gest...

Radiation and Heat Stress Impact on Plasma Levels of Thyroid Hormones, Lipid Fractions, Glucose and Liver Glycogen in rats

International Nuclear Information System (INIS)

Abdel-Fattah, K.I.; Abou-Safi, H.M.

2003-01-01

Since Egypt is classified as a hot country, the present work has been directed to study the combined effect of heat stress and gamma radiation exposure on blood thyroid hormonal levels and some other parameters. Four groups of rats were served as: control, whole-body gamma irradiated (6Gy), exposed to ambient heat stress (38 C-40 C) and a group exposed to heat stress and irradiation. Four time intervals 1, 3, 5 and 7 days were determined for heat stress or exposure to heat followed by irradiation. Blood samples and liver specimens were taken at the end of each time interval in the third group and after one hour of irradiation in the second and fourth groups. To detect the radiation effects after the different periods of heat stress, plasma levels of thyroid hormones (T3 and T4), lipid fractions (triglycerides, total cholesterol, HDL- and LDL-cholesterol), glucose and liver glycogen content were determined. The results revealed that exposure to heat and ionizing radiation leads to a decrease in the levels of thyroid hormones, which was mostly pronounced in the T3 levels. Plasma glucose levels showed significant elevations in both, the heat-stressed group and the heat-treated then irradiated group. While, liver glycogen content exhibited similar elevations only during the 1st, 3 rd and 5 th days of heating followed by irradiation treatment as compared to the heat stressed group. Yet, it showed significant declines in comparison with both control and irradiated groups. Enormous increments in all determined plasma lipid fractions were induced by heat stress and / or gamma radiation

Metformin and liraglutide ameliorate high glucose-induced oxidative stress via inhibition of PKC-NAD(P)H oxidase pathway in human aortic endothelial cells.

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Batchuluun, Battsetseg; Inoguchi, Toyoshi; Sonoda, Noriyuki; Sasaki, Shuji; Inoue, Tomoaki; Fujimura, Yoshinori; Miura, Daisuke; Takayanagi, Ryoichi

2014-01-01

Metformin and glucagon like peptide-1 (GLP-1) prevent diabetic cardiovascular complications and atherosclerosis. However, the direct effects on hyperglycemia-induced oxidative stress in endothelial cells are not fully understood. Thus, we aimed to evaluate the effects of metformin and a GLP-1 analog, liraglutide on high glucose-induced oxidative stress. Production of reactive oxygen species (ROS), activation of protein kinase C (PKC) and NAD(P)H oxidase, and changes in signaling molecules in response to high glucose exposure were evaluated in human aortic endothelial cells with and without treatment of metformin and liraglutide, alone or in combination. PKC-NAD(P)H oxidase pathway was assessed by translocation of GFP-fused PKCβ2 isoform and GFP-fused p47phox, a regulatory subunit of NAD(P)H oxidase, in addition to endogenous PKC phosphorylation and NAD(P)H oxidase activity. High glucose-induced ROS overproduction was blunted by metformin or liraglutide treatment, with a further decrease by a combination of these drugs. Exposure to high glucose caused PKCβ2 translocation and a time-dependent phosphorylation of endogenous PKC but failed to induce its translocation and phosphorylation in the cells treated with metformin and liraglutide. Furthermore, both drugs inhibited p47phox translocation and NAD(P)H oxidase activation, and prevented the high glucose-induced changes in intracellulalr diacylglycerol (DAG) level and phosphorylation of AMP-activated protein kinase (AMPK). A combination of these drugs further enhanced all of these effects. Metformin and liraglutide ameliorate high glucose-induced oxidative stress by inhibiting PKC-NAD(P)H oxidase pathway. A combination of these two drugs provides augmented protective effects, suggesting the clinical usefulness in prevention of diabetic vascular complications. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Oxidative Stress-Related Mechanisms and Antioxidant Therapy in Diabetic Retinopathy

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Cheng Li

2017-01-01

Full Text Available Diabetic retinopathy (DR is one of the most common microvascular complications of diabetes and is the leading cause of blindness in young adults. Oxidative stress has been implicated as a critical cause of DR. Metabolic abnormalities induced by high-glucose levels are involved in the development of DR and appear to be influenced by oxidative stress. The imbalance between reactive oxygen species (ROS production and the antioxidant defense system activates several oxidative stress-related mechanisms that promote the pathogenesis of DR. The damage caused by oxidative stress persists for a considerable time, even after the blood glucose concentration has returned to a normal level. Animal experiments have proved that the use of antioxidants is a beneficial therapeutic strategy for the treatment of DR, but more data are required from clinical trials. The aims of this review are to highlight the improvements to our understanding of the oxidative stress-related mechanisms underlying the development of DR and provide a summary of the main antioxidant therapy strategies used to treat the disease.

Studies of genetic variability of the glucose transporter 2 promoter in patients with type 2 diabetes mellitus

DEFF Research Database (Denmark)

Møller, A M; Jensen, N M; Pildal, J

2001-01-01

This study was performed to test the hypothesis that genetic variation in the promoter of the glucose transporter 2 (GLUT2) might predispose to prediabetic phenotypes or type 2 diabetes. A total of 1611 bp comprising the minimal promoter region of the GLUT2 gene were examined by combined single......-tolerant subjects. In conclusion, we found no evidence supporting the hypothesis that genetic variability in the minimal promoter of the GLUT2 is associated with type 2 diabetes or prediabetic phenotypes in the Danish population.......-strand conformational polymorphism and heteroduplex analysis followed by direct sequencing of identified variants on genomic DNA from 96 randomly recruited Danish type 2 diabetic patients. We identified 4 nucleotide variants, -447g-->a, -149c-->a, -122t-->c, and -44g-->a. None of the variants were positioned in known...

Pro-aging effects of glucose signaling through a G protein-coupled glucose receptor in fission yeast.

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Antoine E Roux

2009-03-01

Full Text Available Glucose is the preferred carbon and energy source in prokaryotes, unicellular eukaryotes, and metazoans. However, excess of glucose has been associated with several diseases, including diabetes and the less understood process of aging. On the contrary, limiting glucose (i.e., calorie restriction slows aging and age-related diseases in most species. Understanding the mechanism by which glucose limits life span is therefore important for any attempt to control aging and age-related diseases. Here, we use the yeast Schizosaccharomyces pombe as a model to study the regulation of chronological life span by glucose. Growth of S. pombe at a reduced concentration of glucose increased life span and oxidative stress resistance as reported before for many other organisms. Surprisingly, loss of the Git3 glucose receptor, a G protein-coupled receptor, also increased life span in conditions where glucose consumption was not affected. These results suggest a role for glucose-signaling pathways in life span regulation. In agreement, constitutive activation of the Galpha subunit acting downstream of Git3 accelerated aging in S. pombe and inhibited the effects of calorie restriction. A similar pro-aging effect of glucose was documented in mutants of hexokinase, which cannot metabolize glucose and, therefore, are exposed to constitutive glucose signaling. The pro-aging effect of glucose signaling on life span correlated with an increase in reactive oxygen species and a decrease in oxidative stress resistance and respiration rate. Likewise, the anti-aging effect of both calorie restriction and the Deltagit3 mutation was accompanied by increased respiration and lower reactive oxygen species production. Altogether, our data suggest an important role for glucose signaling through the Git3/PKA pathway to regulate S. pombe life span.

Wheat chloroplast targeted sHSP26 promoter confers heat and abiotic stress inducible expression in transgenic Arabidopsis Plants.

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Neetika Khurana

Full Text Available The small heat shock proteins (sHSPs have been found to play a critical role in physiological stress conditions in protecting proteins from irreversible aggregation. To characterize the hloroplast targeted sHSP26 promoter in detail, deletion analysis of the promoter is carried out and analysed via transgenics in Arabidopsis. In the present study, complete assessment of the importance of CCAAT-box elements along with Heat shock elements (HSEs in the promoter of sHSP26 was performed. Moreover, the importance of 5' untranslated region (UTR has also been established in the promoter via Arabidopsis transgenics. An intense GUS expression was observed after heat stress in the transgenics harbouring a full-length promoter, confirming the heat-stress inducibility of the promoter. Transgenic plants without UTR showed reduced GUS expression when compared to transgenic plants with UTR as was confirmed at the RNA and protein levels by qRT-PCR and GUS histochemical assays, thus suggesting the possible involvement of some regulatory elements present in the UTR in heat-stress inducibility of the promoter. Promoter activity was also checked under different abiotic stresses and revealed differential expression in different deletion constructs. Promoter analysis based on histochemical assay, real-time qPCR and fluorimetric analysis revealed that HSEs alone could not transcribe GUS gene significantly in sHSP26 promoter and CCAAT box elements contribute synergistically to the transcription. Our results also provide insight into the importance of 5`UTR of sHsp26 promoter thus emphasizing the probable role of imperfect CCAAT-box element or some novel cis-element with respect to heat stress.

Best combination of promoter and micellar catalyst for the rapid conversion of sorbitol to glucose

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Mukherjee, Kakali; Ghosh, Aniruddha; Saha, Rumpa; Sar, Pintu; Malik, Susanta; Saha, Bidyut

2014-03-01

Kinetic data for oxidation of D-sorbitol to glucose by hexavalent chromium in aqueous medium and aqueous surfactant medium (SDS, TX-100) have been reported. Effect of promoter such as PA, bipy and phenanthroline on the reaction has been investigated. The reaction is performed under pseudo first order condition with an excess of substrate over the oxidant. The reaction is first order with respect to substrate and oxidant. The micelles have a catalytic effect on the reaction. Combination of phen and TX-100 produces almost twelve times increase in rate of oxidation.

Glucose-dependent insulinotropic polypeptide promotes lipid deposition in subcutaneous adipocytes in obese type 2 diabetes patients

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Thondam, Sravan K; Daousi, Christina; Wilding, John P H

2017-01-01

is anabolic in human subcutaneous adipose tissue (SAT) promoting triacylglycerol (TAG) deposition through reesterification of nonesterified fatty acids (NEFA), and this effect may differ according to obesity status or glucose tolerance. Twenty-three subjects categorized into four groups, normoglycemic lean (n...... = 6), normoglycemic obese (n = 6), obese with impaired glucose regulation (IGR; n = 6), and obese T2DM (n = 5), participated in a double-blind, randomized, crossover study involving a hyperglycemic clamp with a 240-min GIP infusion (2 pmol·kg(-1)·min(-1)) or normal saline. Insulin, NEFA, SAT......-TAG content, and gene expression of key lipogenic enzymes were determined before and immediately after GIP/saline infusions. GIP lowered NEFA concentrations in the obese T2DM group despite diminished insulinotropic activity (mean NEFA AUC0-4 h ± SE, 41,992 ± 9,843 µmol·l(-1)·min(-1) vs. 71,468 ± 13...

Change in blood glucose level in rats after immobilization

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Platonov, R. D.; Baskakova, G. M.; Chepurnov, S. A.

1981-01-01

Experiments were carried out on male white rats divided into four groups. In group one the blood glucose level was determined immediately after immobilization. In the other three groups, two hours following immobilization, the blood glucose level was determined every 20 minutes for 3 hours 40 minutes by the glucose oxidase method. Preliminary immobilization for 2 hours removed the increase in the blood glucose caused by the stress reaction. By the 2nd hour of immobilization in the presence of continuing stress, the blood glucose level stabilized and varied within 42 + or - 5.5 and 47 + or - 8.1 mg %. Within 2 hours after the immobilization, the differences in the blood glucose level of the rats from the control groups were statistically insignificant.

Long-term impact of earthquake stress on fasting glucose control and diabetes prevalence among Chinese adults of Tangshan.

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An, Cuixia; Zhang, Yun; Yu, Lulu; Li, Na; Song, Mei; Wang, Lan; Zhao, Xiaochuan; Gao, Yuanyuan; Wang, Xueyi

2014-01-01

To investigate the long-term influence of stresses from the 1976 Tangshan earthquake on blood glucose control and the incidence of diabetes mellitus in Chinese people of Tangshan. 1,551 adults ≥ 37 years of age were recruited for this investigation in Tangshan city of China, where one of the deadliest earthquakes occurred in 1796. All subjects finished a questionnaire. 1,030 of them who experienced that earthquake were selected into the exposure group, while 521 were gathered as the control group who have not exposed to any earthquake. The numbers of subjects who were first identified with diabetes or had normal FBG but with diabetic history were added for the calculation of diabetes prevalence. Statistic-analysis was applied on the baseline data, and incidences of IFG as well as diabetes among all groups. Statistic comparisons indicate there is no significant difference on average fasting glucose levels between the control group and the exposure group. However, the prevalence of IFG and diabetes among the exposure group displays significant variance with the control group. The prevalence of diabetes among exposure groups is significantly higher than the control group. Women are more likely to have diabetes after experiencing earthquake stresses compared to men. The earthquake stress was linked to higher diabetes incidence as an independent factor. The earthquake stress has long-term impacts on diabetes incidence as an independent risk factor. Emerging and long-term managements regarding the care of IFG and diabetes in populations exposed to earthquake stress should be concerned.

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

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

2015-06-19

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

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

International Nuclear Information System (INIS)

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

2015-01-01

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

Drought stress promotes the colonization success of a herbivorous mite that manipulates plant defenses.

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Ximénez-Embún, Miguel G; Glas, Joris J; Ortego, Felix; Alba, Juan M; Castañera, Pedro; Kant, Merijn R

2017-12-01

Climate change is expected to bring longer periods of drought and this may affect the plant's ability to resist pests. We assessed if water deficit affects the tomato russet mite (TRM; Aculops lycopersici), a key tomato-pest. TRM thrives on tomato by suppressing the plant's jamonate defenses while these defenses typically are modulated by drought stress. We observed that the TRM population grows faster and causes more damage on drought-stressed plants. To explain this observation we measured several nutrients, phytohormones, defense-gene expression and the activity of defensive proteins in plants with or without drought stress or TRM. TRM increased the levels of total protein and several free amino acids. It also promoted the SA-response and upregulated the accumulation of jasmonates but down-regulated the downstream marker genes while promoting the activity of cysteine-but not serine-protease inhibitors, polyphenol oxidase and of peroxidase (POD). Drought stress, in turn, retained the down regulation of JA-marker genes and reduced the activity of serine protease inhibitors and POD, and altered the levels of some free-amino acids. When combined, drought stress antagonized the accumulation of POD and JA by TRM and synergized accumulation of free sugars and SA. Our data show that drought stress interacts with pest-induced primary and secondary metabolic changes and promotes pest performance.

Acute, but not Chronic, Exposure to Arsenic Provokes Glucose Intolerance in Rats: Possible Roles for Oxidative Stress and the Adrenergic Pathway.

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Rezaei, Mohsen; Khodayar, Mohammd Javad; Seydi, Enayatollah; Soheila, Alboghobeish; Parsi, Isa Kazemzadeh

2017-06-01

Health problems due to heavy metals have become a worldwide concern. Along with its carcinogenicity, arsenic exposure results in impairment of glucose metabolism and insulin secretion as well as altered gene expression and signal transduction. However, the exact mechanism behind the behaviour of arsenic on glucose homeostasis and insulin secretion has not yet been fully understood. Fasting blood sugar and glucose tolerance tests were evaluated. In this study, we demonstrated that arsenic, when acutely administered, induced glucose intolerance in rats, although its chronic oral exposure did not provoke any glucose intolerance or hyperglycemia in rats. The protective activity of N-acetylcysteine, carvedilol and propranolol in male rats exposed to arsenic were also assessed, and N-acetylcysteine, particularly at 40 and 80 mg/kg, prevented the glucose intolerance induced in rats by arsenic. The present study showed that acute, but not chronic, contact with arsenic generates significant changes in the normal glucose tolerance pattern that may be due fundamentally to overproduction of reactive oxygen species and oxidative stress and is preventable by using N-acetylcysteine, a thiol-containing antioxidant. Copyright © 2017 Diabetes Canada. Published by Elsevier Inc. All rights reserved.

The role of stress in the relationships between gender and health-promoting behaviours.

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Soffer, Michal

2010-09-01

Studies have shown that in Western societies, women live longer than men. Among other factors, this has been attributed to health behaviours; men engage in health-risking behaviours, while women perform health-promoting behaviours. These tendencies were argued to align with cultural notions of masculinity and femininity. There may be some evidence, however, that men and women engage in different types of health-promoting behaviours, and stress may play a role in these tendencies. This study attempts to examine the various types of health-promoting behaviours women engage in and compare them to the tendencies of men. Secondly, it examines the mediating role of stress in the relationships between gender and health-promoting behaviours. The sample was comprised of 402 young Israeli adults. Half were undergraduate university students majoring in social work. The remaining participants were sampled by 'snowball sampling'. Participants completed a questionnaire containing 63 closed-ended questions on various health issues. For the purpose of this study, gender, stress and health-promoting behaviours measures were used. Data were collected over three academic years by the teacher responsible for the course and were received by the author at the end of the data collection phase. The study was approved by the institution's internal review board. The results indicate that,-while women engage in 'type 2 behaviours'- refraining from smoking and drinking, eating breakfast regularly and sleeping 7-8 hours per night-men engage in 'type 1 behaviours'- physical exercise, refraining from snacking, and maintaining an appropriate body mass. We also found that, to some extent, women refrain from 'type 1 behaviours' because of their levels of general stress. Our study suggests that the social construction of masculinity and femininity which undermines individuals' health needs to be challenged and addressed. In particular, the enduring role of stress in women's health outcomes should be

Guava leaf extracts promote glucose metabolism in SHRSP.Z-Leprfa/Izm rats by improving insulin resistance in skeletal muscle.

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Guo, Xiangyu; Yoshitomi, Hisae; Gao, Ming; Qin, Lingling; Duan, Ying; Sun, Wen; Xu, Tunhai; Xie, Peifeng; Zhou, Jingxin; Huang, Liansha; Liu, Tonghua

2013-03-01

Metabolic syndrome (MS) and type 2 diabetes mellitus (T2DM) have been associated with insulin-resistance; however, the effective therapies in improving insulin sensitivity are limited. This study is aimed at investigating the effect of Guava Leaf (GL) extracts on glucose tolerance and insulin resistance in SHRSP.Z-Leprfa/Izm rats (SHRSP/ZF), a model of spontaneously metabolic syndrome. Male rats at 7 weeks of age were administered with vehicle water or treated by gavage with 2 g/kg GL extracts daily for six weeks, and their body weights, water and food consumption, glucose tolerance, and insulin resistance were measured. Compared with the controls, treatment with GL extracts did not modulate the amounts of water and food consumption, but significantly reduced the body weights at six weeks post treatment. Treatment with GL extracts did not alter the levels of fasting plasma glucose and insulin, but significantly reduced the levels of plasma glucose at 60 and 120 min post glucose challenge, also reduced the values of AUC and quantitative insulin sensitivity check index (QUICKI) at 42 days post treatment. Furthermore, treatment with GL extracts promoted IRS-1, AKT, PI3Kp85 expression, then IRS-1, AMKP, and AKT308, but not AKT473, phosphorylation, accompanied by increasing the ratios of membrane to total Glut 4 expression and adiponectin receptor 1 transcription in the skeletal muscles. These data indicated that GL extracts improved glucose metabolism and insulin sensitivity in the skeletal muscles of rats by modulating the insulin-related signaling.

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

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

2017-05-02

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

GADD34 Function in Protein Trafficking Promotes Adaptation to Hyperosmotic Stress in Human Corneal Cells

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Dawid Krokowski

2017-12-01

Full Text Available Summary: GADD34, a stress-induced regulatory subunit of the phosphatase PP1, is known to function in hyperosmotic stress through its well-known role in the integrated stress response (ISR pathway. Adaptation to hyperosmotic stress is important for the health of corneal epithelial cells exposed to changes in extracellular osmolarity, with maladaptation leading to dry eye syndrome. This adaptation includes induction of SNAT2, an endoplasmic reticulum (ER-Golgi-processed protein, which helps to reverse the stress-induced loss of cell volume and promote homeostasis through amino acid uptake. Here, we show that GADD34 promotes the processing of proteins synthesized on the ER during hyperosmotic stress independent of its action in the ISR. We show that GADD34/PP1 phosphatase activity reverses hyperosmotic-stress-induced Golgi fragmentation and is important for cis- to trans-Golgi trafficking of SNAT2, thereby promoting SNAT2 plasma membrane localization and function. These results suggest that GADD34 is a protective molecule for ocular diseases such as dry eye syndrome. : Here, Krokowski et al. show that GADD34/PP1 protects the microtubule network, prevents Golgi fragmentation, and preserves protein trafficking independent of its action in the integrated stress response (ISR. In osmoadaptation, GADD34 facilitates trans-Golgi-mediated processing of the endoplasmic reticulum (ER-synthesized amino acid transporter SNAT2, which in turn increases amino acid uptake. Keywords: SNAT2, GADD34, hyperosmotic stress, amino acid transport, Golgi fragmentation, ISR

A common polymorphism in the promoter of the IGF-I gene associates with increased fasting serum triglyceride levels in glucose-tolerant subjects

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Nielsen, Eva-Maria D; Hansen, Lars; Lajer, Maria

2004-01-01

The aim of the present study was to examine if absence of a common allele in a microsatellite polymorphism in the insulin-like growth factor I (IGF-I) promoter was associated with type 2 diabetes and alterations in quantitative traits in glucose-tolerant subjects....

Adaptation of Escherichia coli to glucose promotes evolvability in lactose.

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Phillips, Kelly N; Castillo, Gerardo; Wünsche, Andrea; Cooper, Tim F

2016-02-01

The selective history of a population can influence its subsequent evolution, an effect known as historical contingency. We previously observed that five of six replicate populations that were evolved in a glucose-limited environment for 2000 generations, then switched to lactose for 1000 generations, had higher fitness increases in lactose than populations started directly from the ancestor. To test if selection in glucose systematically increased lactose evolvability, we started 12 replay populations--six from a population subsample and six from a single randomly selected clone--from each of the six glucose-evolved founder populations. These replay populations and 18 ancestral populations were evolved for 1000 generations in a lactose-limited environment. We found that replay populations were initially slightly less fit in lactose than the ancestor, but were more evolvable, in that they increased in fitness at a faster rate and to higher levels. This result indicates that evolution in the glucose environment resulted in genetic changes that increased the potential of genotypes to adapt to lactose. Genome sequencing identified four genes--iclR, nadR, spoT, and rbs--that were mutated in most glucose-evolved clones and are candidates for mediating increased evolvability. Our results demonstrate that short-term selective costs during selection in one environment can lead to changes in evolvability that confer longer term benefits. © 2016 The Author(s). Evolution © 2016 The Society for the Study of Evolution.

A potent class of GPR40 full agonists engages the enteroinsular axis to promote glucose control in rodents.

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Jian Luo

Full Text Available Type 2 diabetes is characterized by impaired glucose homeostasis due to defects in insulin secretion, insulin resistance and the incretin response. GPR40 (FFAR1 or FFA1 is a G-protein-coupled receptor (GPCR, primarily expressed in insulin-producing pancreatic β-cells and incretin-producing enteroendocrine cells of the small intestine. Several GPR40 agonists, including AMG 837 and TAK-875, have been disclosed, but no GPR40 synthetic agonists have been reported that engage both the insulinogenic and incretinogenic axes. In this report we provide a molecular explanation and describe the discovery of a unique and potent class of GPR40 full agonists that engages the enteroinsular axis to promote dramatic improvement in glucose control in rodents. GPR40 full agonists AM-1638 and AM-6226 stimulate GLP-1 and GIP secretion from intestinal enteroendocrine cells and increase GSIS from pancreatic islets, leading to enhanced glucose control in the high fat fed, streptozotocin treated and NONcNZO10/LtJ mouse models of type 2 diabetes. The improvement in hyperglycemia by AM-1638 was reduced in the presence of the GLP-1 receptor antagonist Ex(9-39NH(2.

Neuronal nitric oxide synthase mediates insulin- and oxidative stress-induced glucose uptake in skeletal muscle myotubes.

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Kellogg, Dean L; McCammon, Karen M; Hinchee-Rodriguez, Kathryn S; Adamo, Martin L; Roman, Linda J

2017-09-01

Previously published studies strongly suggested that insulin- and exercise-induced skeletal muscle glucose uptake require nitric oxide (NO) production. However, the signal transduction mechanisms by which insulin and contraction regulated NO production and subsequent glucose transport are not known. In the present study, we utilized the myotube cell lines treated with insulin or hydrogen peroxide, the latter to mimic contraction-induced oxidative stress, to characterize these mechanisms. We found that insulin stimulation of neuronal nitric oxide synthase (nNOS) phosphorylation, NO production, and GLUT4 translocation were all significantly reduced by inhibition of either nNOS or Akt2. Hydrogen peroxide (H 2 O 2 ) induced phosphorylation of nNOS at the same residue as did insulin, and also stimulated NO production and GLUT4 translocation. nNOS inhibition prevented H 2 O 2 -induced GLUT4 translocation. AMP activated protein kinase (AMPK) inhibition prevented H 2 O 2 activation and phosphorylation of nNOS, leading to reduced NO production and significantly attenuated GLUT4 translocation. We conclude that nNOS phosphorylation and subsequently increased NO production are required for both insulin- and H 2 O 2 -stimulated glucose transport. Although the two stimuli result in phosphorylation of the same residue on nNOS, they do so through distinct protein kinases. Thus, insulin and H 2 O 2 -activated signaling pathways converge on nNOS, which is a common mediator of glucose uptake in both pathways. However, the fact that different kinases are utilized provides a basis for the use of exercise to activate glucose transport in the face of insulin resistance. Copyright © 2017. Published by Elsevier Inc.

The UPR reduces glucose metabolism via IRE1 signaling.

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

2017-04-01

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

Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

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Riad, Sandra; Bougherara, Habiba

2015-01-01

Cisplatin (CisPt) is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2) cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death). Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death). PMID:25685789

Mechanical Stress Promotes Cisplatin-Induced Hepatocellular Carcinoma Cell Death

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Laila Ziko

2015-01-01

Full Text Available Cisplatin (CisPt is a commonly used platinum-based chemotherapeutic agent. Its efficacy is limited due to drug resistance and multiple side effects, thereby warranting a new approach to improving the pharmacological effect of CisPt. A newly developed mathematical hypothesis suggested that mechanical loading, when coupled with a chemotherapeutic drug such as CisPt and immune cells, would boost tumor cell death. The current study investigated the aforementioned mathematical hypothesis by exposing human hepatocellular liver carcinoma (HepG2 cells to CisPt, peripheral blood mononuclear cells, and mechanical stress individually and in combination. HepG2 cells were also treated with a mixture of CisPt and carnosine with and without mechanical stress to examine one possible mechanism employed by mechanical stress to enhance CisPt effects. Carnosine is a dipeptide that reportedly sequesters platinum-based drugs away from their pharmacological target-site. Mechanical stress was achieved using an orbital shaker that produced 300 rpm with a horizontal circular motion. Our results demonstrated that mechanical stress promoted CisPt-induced death of HepG2 cells (~35% more cell death. Moreover, results showed that CisPt-induced death was compromised when CisPt was left to mix with carnosine 24 hours preceding treatment. Mechanical stress, however, ameliorated cell death (20% more cell death.

The wake-promoting drug modafinil stimulates specific hypothalamic circuits to promote adaptive stress responses in an animal model of PTSD.

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Cohen, S; Ifergane, G; Vainer, E; Matar, M A; Kaplan, Z; Zohar, J; Mathé, A A; Cohen, H

2016-10-11

Pharmacotherapeutic intervention during traumatic memory consolidation has been suggested to alleviate or even prevent the development of posttraumatic stress disorder (PTSD). We recently reported that, in a controlled, prospective animal model, depriving rats of sleep following stress exposure prevents the development of a PTSD-like phenotype. Here, we report that administering the wake-promoting drug modafinil to rats in the aftermath of a stressogenic experience has a similar prophylactic effect, as it significantly reduces the prevalence of PTSD-like phenotype. Moreover, we show that the therapeutic value of modafinil appears to stem from its ability to stimulate a specific circuit within the hypothalamus, which ties together the neuropeptide Y, the orexin system and the HPA axis, to promote adaptive stress responses. The study not only confirms the value of sleep prevention and identifies the mechanism of action of a potential prophylactic treatment after traumatic exposure, but also contributes to understanding mechanisms underlying the shift towards adaptive behavioral response.

A glucose oxidase-coupled DNAzyme sensor for glucose detection in tears and saliva.

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Liu, Chengcheng; Sheng, Yongjie; Sun, Yanhong; Feng, Junkui; Wang, Shijin; Zhang, Jin; Xu, Jiacui; Jiang, Dazhi

2015-08-15

Biosensors have been widely investigated and utilized in a variety of fields ranging from environmental monitoring to clinical diagnostics. Glucose biosensors have triggered great interest and have been widely exploited since glucose determination is essential for diabetes diagnosis. In here, we designed a novel dual-enzyme biosensor composed of glucose oxidase (GOx) and pistol-like DNAzyme (PLDz) to detect glucose levels in tears and saliva. First, GOx, as a molecular recognition element, catalyzes the oxidation of glucose forming H2O2; then PLDz recognizes the produced H2O2 as a secondary signal and performs a self-cleavage reaction promoted by Mn(2+), Co(2+) and Cu(2+). Thus, detection of glucose could be realized by monitoring the cleavage rate of PLDz. The slope of the cleavage rate of PLDz versus glucose concentration curve was fitted with a Double Boltzmann equation, with a range of glucose from 100 nM to 10mM and a detection limit of 5 μM. We further applied the GOx-PLDz 1.0 biosensor for glucose detection in tears and saliva, glucose levels in which are 720±81 μM and 405±56 μM respectively. Therefore, the GOx-PLDz 1.0 biosensor is able to determine glucose levels in tears and saliva as a noninvasive glucose biosensor, which is important for diabetic patients with frequent/continuous glucose monitoring requirements. In addition, induction of DNAzyme provides a new approach in the development of glucose biosensors. Copyright © 2015 Elsevier B.V. All rights reserved.

Chronic erythropoietin treatment improves diet-induced glucose intolerance in rats

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Caillaud, Corinne; Mechta, Mie; Ainge, Heidi

2015-01-01

Erythropoietin (EPO) ameliorates glucose metabolism through mechanisms not fully understood. In this study, we investigated the effect of EPO on glucose metabolism and insulin signaling in skeletal muscle. A 2-week EPO treatment of rats fed with a high-fat diet (HFD) improved fasting glucose levels...... and glucose tolerance, without altering total body weight or retroperitoneal fat mass. Concomitantly, EPO partially rescued insulin-stimulated AKT activation, reduced markers of oxidative stress, and restored heat-shock protein 72 expression in soleus muscles from HFD-fed rats. Incubation of skeletal muscle...... not directly activate the phosphorylation of AKT in muscle cells. We propose that the reduced systemic inflammation or oxidative stress that we observed after treatment with EPO could contribute to the improvement of whole-body glucose metabolism....

In adenosine A2B knockouts acute treatment with inorganic nitrate improves glucose disposal, oxidative stress and AMPK signaling in the liver

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Maria ePeleli

2015-08-01

Full Text Available Rationale: Accumulating studies suggest that nitric oxide (NO deficiency and oxidative stress are central pathological mechanisms in type 2 diabetes. Recent findings demonstrate therapeutic effects by boosting a nitrate-nitrite-NO pathway, an alternative pathway for NO formation. This study aimed at investigating the acute effects of inorganic nitrate on glucose and insulin signaling in adenosine A2B receptor knockout mice (A2B-/-, a genetic model of impaired metabolic regulation.Methods: Acute effects of nitrate treatment were investigated in aged wild-type (WT and A2B-/- mice. One hour after injection with nitrate or placebo, metabolic regulation was evaluated by glucose and insulin tolerance tests. NADPH oxidase-mediated superoxide production and AMPK phosphorylation were measured in livers obtained from non-treated or glucose-treated mice, with or without prior nitrate injection. Plasma was used to determine insulin resistance (HOMA-IR and NO signaling.Results: A2B-/- displayed increased body weight, reduced glucose clearance and attenuated overall insulin responses compared with age-matched WT. Nitrate treatment increased circulating levels of nitrate, nitrite and cGMP in A2B-/-, and improved glucose clearance. In WT mice, however, nitrate treatment did not influence glucose clearance. HOMA-IR increased following glucose injection in A2B-/-, but remained at basal levels in mice pretreated with nitrate. NADPH oxidase activity in livers from A2B-/-, but not WT mice, was reduced by nitrate. Livers from A2B-/- displayed reduced AMPK phosphorylation compared with WT mice, and this was increased by nitrate treatment. Injection with the anti-diabetic agent metformin induced similar therapeutic effects in the A2B-/- as observed with nitrate. Conclusion: The A2B-/- mouse is a genetic model of metabolic syndrome. Acute treatment with nitrate improved the metabolic profile, at least partly via reduction in oxidative stress and improved AMPK signaling

Red Yeast Rice Protects Circulating Bone Marrow-Derived Proangiogenic Cells against High-Glucose-Induced Senescence and Oxidative Stress: The Role of Heme Oxygenase-1

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Jung-Tung Liu

2017-01-01

Full Text Available The inflammation and oxidative stress of bone marrow-derived proangiogenic cells (PACs, also named endothelial progenitor cells, triggered by hyperglycemia contributes significantly to vascular dysfunction. There is supporting evidence that the consumption of red yeast rice (RYR; Monascus purpureus-fermented rice reduces the vascular complications of diabetes; however, the underlying mechanism remains unclear. This study aimed to elucidate the effects of RYR extract in PACs, focusing particularly on the role of a potent antioxidative enzyme, heme oxygenase-1 (HO-1. We found that treatment with RYR extract induced nuclear factor erythroid-2-related factor nuclear translocation and HO-1 mRNA and protein levels in PACs. RYR extract inhibited high-glucose-induced (30 mM PAC senescence and the development of reactive oxygen species (ROS in a dose-dependent manner. The HO-1 inducer cobalt protoporphyrin IX also decreased high-glucose-induced cell senescence and oxidative stress, whereas the HO-1 enzyme inhibitor zinc protoporphyrin IX and HO-1 small interfering RNA significantly reversed RYR extract-caused inhibition of senescence and reduction of oxidative stress in high-glucose-treated PACs. These results suggest that RYR extract serves as alternative and complementary medicine in the treatment of these diseases, by inducing HO-1, thereby decreasing the vascular complications of diabetes.

Phosphorylation of stress protein pp80 is related to promotion of transformation

International Nuclear Information System (INIS)

Smith, B.M.; Gindhart, T.D.; Hirano, K.; Colburn, N.H.

1986-01-01

The JB6 mouse epidermal cell system is an in vitro model of late stage promotion, and includes cell lines sensitive (P+) or resistant (P-) to phorbol ester-induced anchorage independent transformation, and transformed (T/sub x/) lines. Certain promoter-induced changes in phosphoproteins, identified by gel electrophoresis, are unique to cells of one phenotype, and occur only with specific promoters. An 80Kd protein is inversely correlated with phenotype: P- cells have a constitutively higher level (p 35 S-methionine. pp80 shares properties with the 80Kd heat stress protein: molecular weight relative abundance, and isoelectric point (4.5). Pharmacological analogs of calcium, the lanthanides, promote transformation of JB6 cells, but have no effect on phosphorylation of the 80Kd protein. If pp80 is on the promotion pathway, it is limited to a specific subset of transformation promoters

Optogenetic activation of leptin- and glucose-regulated GABAergic neurons in dorsomedial hypothalamus promotes food intake via inhibitory synaptic transmission to paraventricular nucleus of hypothalamus

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Zesemdorj Otgon-Uul

2016-08-01

Full Text Available Objective: The dorsomedial hypothalamus (DMH has been considered an orexigenic nucleus, since the DMH lesion reduced food intake and body weight and induced resistance to diet-induced obesity. The DMH expresses feeding regulatory neuropeptides and receptors including neuropeptide Y (NPY, cocaine- and amphetamine-regulated transcript (CART, cholecystokinin (CCK, leptin receptor, and melanocortin 3/4 receptors. However, the principal neurons generating the orexigenic function in the DMH remain to be defined. This study aimed to clarify the role of the DMH GABAergic neurons in feeding regulation by using optogenetics and electrophysiological techniques. Methods: We generated the mice expressing ChRFR-C167A, a bistable chimeric channelrhodopsin, selectively in GABAergic neurons of DMH via locally injected adeno-associated virus 2. Food intake after optogenetic activation of DMH GABAergic neurons was measured. Electrophysiological properties of DMH GABAergic neurons were measured using slice patch clamp. Results: Optogenetic activation of DMH GABAergic neurons promoted food intake. Leptin hyperpolarized and lowering glucose depolarized half of DMH GABAergic neurons, suggesting their orexigenic property. Optical activation of axonal terminals of DMH GABAergic neurons at the paraventricular nucleus of hypothalamus (PVN, where anorexigenic neurons are localized, increased inhibitory postsynaptic currents on PVN neurons and promoted food intake. Conclusion: DMH GABAergic neurons are regulated by metabolic signals leptin and glucose and, once activated, promote food intake via inhibitory synaptic transmission to PVN. Keywords: Dorsomedial hypothalamus, GABAergic neuron, Feeding, Leptin, Glucose, Optogenetics

Effects of Berberine on Amelioration of Hyperglycemia and Oxidative Stress in High Glucose and High Fat Diet-Induced Diabetic Hamsters In Vivo

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Cong Liu

2015-01-01

Full Text Available This study investigated the effects of berberine on amelioration of hyperglycemia and hyperlipidemia and the mechanism involved in high glucose and high fat diet-induced diabetic hamsters. Golden hamsters fed with high glucose and high fat diet were medicated with metformin, simvastatin, and low or high dose of berberine (50 and 100 mg·kg−1 for 6 weeks. The results showed that the body weights were significantly lower in berberine-treated groups than control group. Histological analyses revealed that the treatment of berberine inhibited hepatic fat accumulation. Berberine significantly reduced plasma total cholesterol, triglyceride, free fatty acid, low density lipoprotein cholesterol, malondialdehyde, thiobarbituric acid-reactive substance, and 8-isoprostane level but significantly increased plasma superoxide dismutase activity. Glucose and insulin levels were significantly reduced in metformin and berberine-treated groups. Glucose tolerance tests documented that berberine-treated mice were more glucose tolerant. Berberine treatment increased expression of skeletal muscle glucose transporter 4 mRNA and significantly decreased liver low density lipoprotein receptor mRNA expression. The study suggested that berberine was effective in lowering blood glucose and lipids levels, reducing the body weight, and alleviating the oxidative stress in diabetic hamsters, which might be beneficial in reducing the cardiovascular risk factors in diabetes.

Functional Characterization of TaSnRK2.8 Promoter in Response to Abiotic Stresses by Deletion Analysis in Transgenic Arabidopsis

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Hongying Zhang

2017-07-01

Full Text Available Drought, salinity, and cold are the major factors limiting wheat quality and productivity; it is thus highly desirable to characterize the abiotic-stress-inducible promoters suitable for the genetic improvement of plant resistance. The sucrose non-fermenting 1-related protein kinase 2 (SnRK2 family genes show distinct regulatory properties in response to abiotic stresses. The present study characterized the approximately 3000-bp upstream sequence (the 313 bp upstream of the ATG was the transcription start site of the Triticum aestivum TaSnRK2.8 promoter under abscisic acid (ABA and abiotic stresses. Four different-length 5′ deletion fragments of TaSnRK2.8 promoter were fused with the GUS reporter gene and transformed into Arabidopsis. Tissue expression analysis showed that the TaSnRK2.8 promoter region from position -1481 to -821 contained the stalk-specific elements, and the region from position -2631 to -1481 contained the leaf- and root-specific elements. In the ABA-treated seedlings, the deletion analysis showed that the TaSnRK2.8 promoter region from position -821 to -2631 contained ABA response elements. The abiotic stress responses of the TaSnRK2.8 promoter derivatives demonstrated that they harbored abiotic-stress response elements: the region from position -821 to -408 harbored the osmotic-stress response elements, whereas the region from position -2631 to -1481 contained the positive regulatory motifs and the region from position -1481 to -821 contained the leaf- and stalk-specific enhancers. Further deletion analysis of the promoter region from position -821 to -408 indicated that a 125-bp region from position -693 to -568 was required to induce an osmotic-stress response. These results contribute to a better understanding of the molecular mechanisms of TaSnRK2.8 in response to abiotic stresses, and the TaSnRK2.8 promoter seems to be a candidate for regulating the expression of abiotic stress response genes in transgenic plants.

Higher glucose level and systemic oxidative stress decrease the mean velocity index of the retinal artery during flickering light stimulation in type 1 diabetes.

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Debelić, Vladimir; Drnovšek Olup, Brigita; Žižek, Bogomir; Skitek, Milan; Jerin, Aleš

2016-10-31

To determine whether higher glucose level and systemic oxidative stress decrease mean velocity (MV) index of the central retinal artery (CRA) during flickering light stimulation in type 1 diabetes (T1D). The study was performed in the period from 2008 to 2015 at the University Eye Clinic in Ljubljana. 41 patients with T1D and 37 participants without diabetes were included. MV in the CRA was measured using Doppler ultrasound diagnostics in basal conditions and during 8 Hz flickering light irritation. The plasma levels of glucose, fructosamine, 8-hydroxy-2'-deoxyguanosine (8-OHdG), triglycerides, cholesterol, and low-density lipoprotein (LDL) were measured. Patients with T1D had significantly higher levels of blood glucose (Ptriglycerides (P=0.108), cholesterol (P=0.531), and LDL (P=0.645) between the groups. Patients with T1D also had a significantly lower MV index in the CRA (1.11±0.15 vs 1.24±0.23; P=0.010). In the T1D group, a significant negative correlation was found between the level of glucose (r=0.58; Pindex in the CRA. At the same time, in this group fructosamine and 8-OHdG levels had a separate effect on the MV index (adjusted R2=0.38, Pglucose levels, the medium-term glucose level, and systemic oxidative stress could importantly reduce retinal vasodilatation during flickering light irritation in patients with T1D.

Low-level shear stress promotes migration of liver cancer stem cells via the FAK-ERK1/2 signalling pathway.

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Sun, Jinghui; Luo, Qing; Liu, Lingling; Song, Guanbin

2018-07-28

Cancer stem cells (CSCs) are a small subpopulation of tumour cells that have been proposed to be responsible for cancer initiation, chemotherapy resistance and cancer recurrence. Shear stress activated cellular signalling is involved in cellular migration, proliferation and differentiation. However, little is known about the effects of shear stress on the migration of liver cancer stem cells (LCSCs). Here, we studied the effects of shear stress that are generated from a parallel plated flow chamber system, on LCSC migration and the activation of focal adhesion kinase (FAK) and extracellular signal regulated kinase1/2 (ERK1/2), using transwell assay and western blot, respectively. We found that 2 dyne/cm 2 shear stress loading for 6 h promotes LCSC migration and activation of the FAK and ERK1/2 signalling pathways, whereas treatment with the FAK phosphorylation inhibitor PF573228 or the ERK1/2 phosphorylation inhibitor PD98059 suppressed the shear stress-promoted migration, indicating the involvement of FAK and ERK1/2 activation in shear stress-induced LCSC migration. Additionally, atomic force microscopy (AFM) analysis showed that shear stress lowers LCSC stiffness via the FAK and ERK1/2 pathways, suggesting that the mechanism by which shear stress promotes LCSC migration might partially be responsible for the decrease in cell stiffness. Further experiments focused on the role of the actin cytoskeleton, demonstrating that the F-actin filaments in LCSCs are less well-defined after shear stress treatment, providing an explanation for the reduction in cell stiffness and the promotion of cell migration. Overall, our study demonstrates that shear stress promotes LCSC migration through the activation of the FAK-ERK1/2 signalling pathways, which further results in a reduction of organized actin and softer cell bodies. Copyright © 2018 Elsevier B.V. All rights reserved.

Geniposide regulates glucose-stimulated insulin secretion possibly through controlling glucose metabolism in INS-1 cells.

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Jianhui Liu

Full Text Available Glucose-stimulated insulin secretion (GSIS is essential to the control of metabolic fuel homeostasis. The impairment of GSIS is a key element of β-cell failure and one of causes of type 2 diabetes mellitus (T2DM. Although the KATP channel-dependent mechanism of GSIS has been broadly accepted for several decades, it does not fully describe the effects of glucose on insulin secretion. Emerging evidence has suggested that other mechanisms are involved. The present study demonstrated that geniposide enhanced GSIS in response to the stimulation of low or moderately high concentrations of glucose, and promoted glucose uptake and intracellular ATP levels in INS-1 cells. However, in the presence of a high concentration of glucose, geniposide exerted a contrary role on both GSIS and glucose uptake and metabolism. Furthermore, geniposide improved the impairment of GSIS in INS-1 cells challenged with a high concentration of glucose. Further experiments showed that geniposide modulated pyruvate carboxylase expression and the production of intermediates of glucose metabolism. The data collectively suggest that geniposide has potential to prevent or improve the impairment of insulin secretion in β-cells challenged with high concentrations of glucose, likely through pyruvate carboxylase mediated glucose metabolism in β-cells.

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

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Choi, Kevin; Weber, Jean-Michel

2016-03-15

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

Stretch-stimulated glucose transport in skeletal muscle is regulated by Rac1.

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Sylow, Lykke; Møller, Lisbeth L V; Kleinert, Maximilian; Richter, Erik A; Jensen, Thomas E

2015-02-01

Rac1 regulates stretch-stimulated (i.e. mechanical stress) glucose transport in muscle. Actin depolymerization decreases stretch-induced glucose transport in skeletal muscle. Rac1 is a required part of the mechanical stress-component of the contraction-stimulus to glucose transport in skeletal muscle. An alternative to the canonical insulin signalling pathway for glucose transport is muscle contraction/exercise. Mechanical stress is an integrated part of the muscle contraction/relaxation cycle, and passive stretch stimulates muscle glucose transport. However, the signalling mechanism regulating stretch-stimulated glucose transport is not well understood. We recently reported that the actin cytoskeleton regulating GTPase, Rac1, was activated in mouse muscle in response to stretching. Rac1 is a regulator of contraction- and insulin-stimulated glucose transport, however, its role in stretch-stimulated glucose transport and signalling is unknown. We therefore investigated whether stretch-induced glucose transport in skeletal muscle required Rac1 and the actin cytoskeleton. We used muscle-specific inducible Rac1 knockout mice as well as pharmacological inhibitors of Rac1 and the actin cytoskeleton in isolated soleus and extensor digitorum longus muscles. In addition, the role of Rac1 in contraction-stimulated glucose transport during conditions without mechanical load on the muscles was evaluated in loosely hanging muscles and muscles in which cross-bridge formation was blocked by the myosin ATPase inhibitors BTS and Blebbistatin. Knockout as well as pharmacological inhibition of Rac1 reduced stretch-stimulated glucose transport by 30-50% in soleus and extensor digitorum longus muscle. The actin depolymerizing agent latrunculin B similarly decreased glucose transport in response to stretching by 40-50%. Rac1 inhibition reduced contraction-stimulated glucose transport by 30-40% in tension developing muscle but did not affect contraction-stimulated glucose transport in

Adipocyte spliced form of X-box-binding protein 1 promotes adiponectin multimerization and systemic glucose homeostasis

NARCIS (Netherlands)

Sha, H.; Yang, L.; Liu, M.; Xia, S.; Liu, Y.; Liu, F.; Kersten, A.H.; Qi, L.

2014-01-01

The physiological role of the spliced form of X-box–binding protein 1 (XBP1s), a key transcription factor of the endoplasmic reticulum (ER) stress response, in adipose tissue remains largely unknown. In this study, we show that overexpression of XBP1s promotes adiponectin multimerization in

6-Paradol and 6-Shogaol, the Pungent Compounds of Ginger, Promote Glucose Utilization in Adipocytes and Myotubes, and 6-Paradol Reduces Blood Glucose in High-Fat Diet-Fed Mice

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Chien-Kei Wei

2017-01-01

Full Text Available The anti-diabetic activity of ginger powder (Zingiber officinale has been recently promoted, with the recommendation to be included as one of the dietary supplements for diabetic patients. However, previous studies presented different results, which may be caused by degradation and metabolic changes of ginger components, gingerols, shogaols and paradols. Therefore, we prepared 10 ginger active components, namely 6-, 8-, 10-paradols, 6-, 8-, 10-shogaols, 6-, 8-, 10-gingerols and zingerone, and evaluated their anti-hyperglycemic activity. Among the tested compounds, 6-paradol and 6-shogaol showed potent activity in stimulating glucose utilization by 3T3-L1 adipocytes and C2C12 myotubes. The effects were attributed to the increase in 5′ adenosine monophosphate-activated protein kinase (AMPK phosphorylation in 3T3-L1 adipocytes. 6-Paradol, the major metabolite of 6-shogaol, was utilized in an in vivo assay and significantly reduced blood glucose, cholesterol and body weight in high-fat diet-fed mice.

Factors and symptoms associated with work stress and health-promoting lifestyles among hospital staff: a pilot study in Taiwan

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Tsai Yueh-Chi

2012-07-01

Full Text Available Abstract Background Healthcare workers including physicians, nurses, medical technicians and administrative staff experience high levels of occupational stress as a result of heavy workloads, extended working hours and time-related pressure. The aims of this study were to investigate factors associated with work stress among hospital staff members and to evaluate their health-promoting lifestyle behaviors. Methods We conducted a cross-sectional study from May 1, 2010 to July 30, 2010 and recruited 775 professional staff from two regional hospitals in Taiwan using purposive sampling. Demographic data and self-reported symptoms related to work-related stress were collected. Each subject completed the Chinese versions of the Job Content Questionnaire (C-JCQ and The Health-Promoting Lifestyle Profile (HPLSP. Linear and binary regression analyses were applied to identify associations between these two measurements and subjects’ characteristics, and associations between the two measurements and stress symptoms. Results Self-reported symptoms of work-related stress included 64.4% of subjects reporting nervousness, 33.7% nightmares, 44.1% irritability, 40.8% headaches, 35.0% insomnia, and 41.4% gastrointestinal upset. C-JCQ scores for psychological demands of the job and discretion to utilize skills had a positive correlation with stress-related symptoms; however, the C-JCQ scores for decision-making authority and social support correlated negatively with stress-related symptoms except for nightmares and irritability. All items on the HPLSP correlated negatively with stress-related symptoms except for irritability, indicating an association between subjects’ symptoms and a poor quality of health-promoting lifestyle behaviors. Conclusions We found that high demands, little decision-making authority, and low levels of social support were associated with the development of stress-related symptoms. The results also suggested that better performance on

Factors and symptoms associated with work stress and health-promoting lifestyles among hospital staff: a pilot study in Taiwan.

Science.gov (United States)

Tsai, Yueh-Chi; Liu, Chieh-Hsing

2012-07-16

Healthcare workers including physicians, nurses, medical technicians and administrative staff experience high levels of occupational stress as a result of heavy workloads, extended working hours and time-related pressure. The aims of this study were to investigate factors associated with work stress among hospital staff members and to evaluate their health-promoting lifestyle behaviors. We conducted a cross-sectional study from May 1, 2010 to July 30, 2010 and recruited 775 professional staff from two regional hospitals in Taiwan using purposive sampling. Demographic data and self-reported symptoms related to work-related stress were collected. Each subject completed the Chinese versions of the Job Content Questionnaire (C-JCQ) and The Health-Promoting Lifestyle Profile (HPLSP). Linear and binary regression analyses were applied to identify associations between these two measurements and subjects' characteristics, and associations between the two measurements and stress symptoms. Self-reported symptoms of work-related stress included 64.4% of subjects reporting nervousness, 33.7% nightmares, 44.1% irritability, 40.8% headaches, 35.0% insomnia, and 41.4% gastrointestinal upset. C-JCQ scores for psychological demands of the job and discretion to utilize skills had a positive correlation with stress-related symptoms; however, the C-JCQ scores for decision-making authority and social support correlated negatively with stress-related symptoms except for nightmares and irritability. All items on the HPLSP correlated negatively with stress-related symptoms except for irritability, indicating an association between subjects' symptoms and a poor quality of health-promoting lifestyle behaviors. We found that high demands, little decision-making authority, and low levels of social support were associated with the development of stress-related symptoms. The results also suggested that better performance on or a higher frequency of health-promoting life-style behaviors might

Set2 Methyltransferase Facilitates DNA Replication and Promotes Genotoxic Stress Responses through MBF-Dependent Transcription.

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Pai, Chen-Chun; Kishkevich, Anastasiya; Deegan, Rachel S; Keszthelyi, Andrea; Folkes, Lisa; Kearsey, Stephen E; De León, Nagore; Soriano, Ignacio; de Bruin, Robertus Antonius Maria; Carr, Antony M; Humphrey, Timothy C

2017-09-12

Chromatin modification through histone H3 lysine 36 methylation by the SETD2 tumor suppressor plays a key role in maintaining genome stability. Here, we describe a role for Set2-dependent H3K36 methylation in facilitating DNA replication and the transcriptional responses to both replication stress and DNA damage through promoting MluI cell-cycle box (MCB) binding factor (MBF)-complex-dependent transcription in fission yeast. Set2 loss leads to reduced MBF-dependent ribonucleotide reductase (RNR) expression, reduced deoxyribonucleoside triphosphate (dNTP) synthesis, altered replication origin firing, and a checkpoint-dependent S-phase delay. Accordingly, prolonged S phase in the absence of Set2 is suppressed by increasing dNTP synthesis. Furthermore, H3K36 is di- and tri-methylated at these MBF gene promoters, and Set2 loss leads to reduced MBF binding and transcription in response to genotoxic stress. Together, these findings provide new insights into how H3K36 methylation facilitates DNA replication and promotes genotoxic stress responses in fission yeast. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

Set2 Methyltransferase Facilitates DNA Replication and Promotes Genotoxic Stress Responses through MBF-Dependent Transcription

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Chen-Chun Pai

2017-09-01

Full Text Available Chromatin modification through histone H3 lysine 36 methylation by the SETD2 tumor suppressor plays a key role in maintaining genome stability. Here, we describe a role for Set2-dependent H3K36 methylation in facilitating DNA replication and the transcriptional responses to both replication stress and DNA damage through promoting MluI cell-cycle box (MCB binding factor (MBF-complex-dependent transcription in fission yeast. Set2 loss leads to reduced MBF-dependent ribonucleotide reductase (RNR expression, reduced deoxyribonucleoside triphosphate (dNTP synthesis, altered replication origin firing, and a checkpoint-dependent S-phase delay. Accordingly, prolonged S phase in the absence of Set2 is suppressed by increasing dNTP synthesis. Furthermore, H3K36 is di- and tri-methylated at these MBF gene promoters, and Set2 loss leads to reduced MBF binding and transcription in response to genotoxic stress. Together, these findings provide new insights into how H3K36 methylation facilitates DNA replication and promotes genotoxic stress responses in fission yeast.

Halophytes: Potential Resources for Salt Stress Tolerance Genes and Promoters.

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Mishra, Avinash; Tanna, Bhakti

2017-01-01

Halophytes have demonstrated their capability to thrive under extremely saline conditions and thus considered as one of the best germplasm for saline agriculture. Salinity is a worldwide problem, and the salt-affected areas are increasing day-by-day because of scanty rainfall, poor irrigation system, salt ingression, water contamination, and other environmental factors. The salinity stress tolerance mechanism is a very complex phenomenon, and some pathways are coordinately linked for imparting salinity tolerance. Though a number of salt responsive genes have been reported from the halophytes, there is always a quest for promising stress-responsive genes that can modulate plant physiology according to the salt stress. Halophytes such as Aeluropus, Mesembryanthemum, Suaeda, Atriplex, Thellungiella, Cakile , and Salicornia serve as a potential candidate for the salt-responsive genes and promoters. Several known genes like antiporters ( NHX, SOS, HKT, VTPase ), ion channels (Cl - , Ca 2+ , aquaporins), antioxidant encoding genes ( APX, CAT, GST, BADH, SOD ) and some novel genes such as USP, SDR1, SRP etc. were isolated from halophytes and explored for developing stress tolerance in the crop plants (glycophytes). It is evidenced that stress triggers salt sensors that lead to the activation of stress tolerance mechanisms which involve multiple signaling proteins, up- or down-regulation of several genes, and finally the distinctive or collective effects of stress-responsive genes. In this review, halophytes are discussed as an excellent platform for salt responsive genes which can be utilized for developing salinity tolerance in crop plants through genetic engineering.

Salt and alkali stresses reduction in wheat by plant growth promoting haloalkaliphilic bacteria

OpenAIRE

Torbaghan, Mehrnoush Eskandari; Lakzian, Amir; Astaraei, Ali Reza; Fotovat, Amir; Besharati, Hossein

2017-01-01

Haloalkaliphilic bacteria have plant growth promoting characteristics that can be used to deal with different environmental stresses. To study the effect of haloalkaliphilic bacteria to reduce salinity and alkalinity stress in wheat, 48 isolates were isolated and grouped into halophiles, alkaliphiles and haloalkaliphiles based on growth characteristics. The ammonia, 3-indole acetic acid and ACC (1-aminocyclopropane-1-carboxylate) deaminase production were studied. Wheat yield was evaluated in...

Hydrogen improves glycemic control in type1 diabetic animal model by promoting glucose uptake into skeletal muscle.

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Haruka Amitani

Full Text Available Hydrogen (H(2 acts as a therapeutic antioxidant. However, there are few reports on H(2 function in other capacities in diabetes mellitus (DM. Therefore, in this study, we investigated the role of H(2 in glucose transport by studying cultured mouse C2C12 cells and human hepatoma Hep-G2 cells in vitro, in addition to three types of diabetic mice [Streptozotocin (STZ-induced type 1 diabetic mice, high-fat diet-induced type 2 diabetic mice, and genetically diabetic db/db mice] in vivo. The results show that H(2 promoted 2-[(14C]-deoxy-d-glucose (2-DG uptake into C2C12 cells via the translocation of glucose transporter Glut4 through activation of phosphatidylinositol-3-OH kinase (PI3K, protein kinase C (PKC, and AMP-activated protein kinase (AMPK, although it did not stimulate the translocation of Glut2 in Hep G2 cells. H(2 significantly increased skeletal muscle membrane Glut4 expression and markedly improved glycemic control in STZ-induced type 1 diabetic mice after chronic intraperitoneal (i.p. and oral (p.o. administration. However, long-term p.o. administration of H(2 had least effect on the obese and non-insulin-dependent type 2 diabetes mouse models. Our study demonstrates that H(2 exerts metabolic effects similar to those of insulin and may be a novel therapeutic alternative to insulin in type 1 diabetes mellitus that can be administered orally.

Xbp1s in Pomc neurons connects ER stress with energy balance and glucose homeostasis.

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Williams, Kevin W; Liu, Tiemin; Kong, Xingxing; Fukuda, Makoto; Deng, Yingfeng; Berglund, Eric D; Deng, Zhuo; Gao, Yong; Liu, Tianya; Sohn, Jong-Woo; Jia, Lin; Fujikawa, Teppei; Kohno, Daisuke; Scott, Michael M; Lee, Syann; Lee, Charlotte E; Sun, Kai; Chang, Yongsheng; Scherer, Philipp E; Elmquist, Joel K

2014-09-02

The molecular mechanisms underlying neuronal leptin and insulin resistance in obesity and diabetes remain unclear. Here we show that induction of the unfolded protein response transcription factor spliced X-box binding protein 1 (Xbp1s) in pro-opiomelanocortin (Pomc) neurons alone is sufficient to protect against diet-induced obesity as well as improve leptin and insulin sensitivity, even in the presence of strong activators of ER stress. We also demonstrate that constitutive expression of Xbp1s in Pomc neurons contributes to improved hepatic insulin sensitivity and suppression of endogenous glucose production. Notably, elevated Xbp1s levels in Pomc neurons also resulted in activation of the Xbp1s axis in the liver via a cell-nonautonomous mechanism. Together our results identify critical molecular mechanisms linking ER stress in arcuate Pomc neurons to acute leptin and insulin resistance as well as liver metabolism in diet-induced obesity and diabetes. Copyright © 2014 Elsevier Inc. All rights reserved.

Organization of cis-acting regulatory elements in osmotic- and cold-stress-responsive promoters.

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Yamaguchi-Shinozaki, Kazuko; Shinozaki, Kazuo

2005-02-01

cis-Acting regulatory elements are important molecular switches involved in the transcriptional regulation of a dynamic network of gene activities controlling various biological processes, including abiotic stress responses, hormone responses and developmental processes. In particular, understanding regulatory gene networks in stress response cascades depends on successful functional analyses of cis-acting elements. The ever-improving accuracy of transcriptome expression profiling has led to the identification of various combinations of cis-acting elements in the promoter regions of stress-inducible genes involved in stress and hormone responses. Here we discuss major cis-acting elements, such as the ABA-responsive element (ABRE) and the dehydration-responsive element/C-repeat (DRE/CRT), that are a vital part of ABA-dependent and ABA-independent gene expression in osmotic and cold stress responses.

Molecular characterization of the sweet potato peroxidase SWPA4 promoter which responds to abiotic stresses and pathogen infection.

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Ryu, Sun-Hwa; Kim, Yun-Hee; Kim, Cha Young; Park, Soo-Young; Kwon, Suk-Yoon; Lee, Haeng-Soon; Kwak, Sang-Soo

2009-04-01

Previously, the swpa4 peroxidase gene has been shown to be inducible by a variety of abiotic stresses and pathogenic infections in sweet potato (Ipomoea batatas). To elucidate its regulatory mechanism at the transcriptional level under various stress conditions, we isolated and characterized the promoter region (2374 bp) of swpa4 (referred to as SWPA4). We performed a transient expression assay in tobacco protoplasts with deletions from the 5'-end of SWPA4 promoter fused to the beta-glucuronidase (GUS) reporter gene. The -1408 and -374 bp deletions relative to the transcription start site (+1) showed 8 and 4.5 times higher GUS expression than the cauliflower mosaic virus 35S promoter, respectively. In addition, transgenic tobacco plants expressing GUS under the control of -2374, -1408 or -374 bp region of SWPA4 promoter were generated and studied in various tissues under abiotic stresses and pathogen infection. Gel mobility shift assays revealed that nuclear proteins from sweet potato cultured cells specifically interacted with 60-bp fragment (-178/-118) in -374 bp promoter region. In silico analysis indicated that four kinds of cis-acting regulatory sequences, reactive oxygen species-related element activator protein 1 (AP1), CCAAT/enhancer-binding protein alpha element, ethylene-responsive element (ERE) and heat-shock element, are present in the -60 bp region (-178/-118), suggesting that the -60 bp region might be associated with stress inducibility of the SWPA4 promoter.

Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring.

Science.gov (United States)

Zheng, Jia; Xiao, Xinhua; Zhang, Qian; Yu, Miao; Xu, Jianping; Wang, Zhixin; Qi, Cuijuan; Wang, Tong

2015-10-01

Substantial evidence demonstrated that maternal dietary nutrients can significantly determine the susceptibility to developing metabolic disorders in the offspring. Therefore, we aimed to investigate the later-life effects of maternal and postweaning diets interaction on epigenetic modification of the central nervous system in the offspring. We examined the effects of dams fed a high-fat, high-sucrose (FS) diet during pregnancy and lactation and weaned to FS diet continuously until 32 weeks of age. Then, DNA methylation and gene expressions of hypothalamic proopiomelanocortin (POMC) and melanocortin receptor 4 (MC4R) were determined in the offspring. Offspring of FS diet had heavier body weight, impaired glucose tolerance, decreased insulin sensitivity and higher serum leptin level at 32-week age (p diet during gestation, lactation and into 32-week age (p diet offspring (p fat diet predisposes the offspring for obesity, glucose intolerance and insulin resistance in later life. Our findings can advance our thinking around the DNA methylation status of the promoter of the POMC and MC4R genes between long-term high-fat, high-sucrose diet and glucose homeostasis in mouse.

Identification of a novel promoter from banana aquaporin family gene (MaTIP1;2) which responses to drought and salt-stress in transgenic Arabidopsis thaliana.

Science.gov (United States)

Song, Shun; Xu, Yi; Huang, Dongmei; Miao, Hongxia; Liu, Juhua; Jia, Caihong; Hu, Wei; Valarezo, Ana Valeria; Xu, Biyu; Jin, Zhiqiang

2018-07-01

Drought and salt stresses often affect plant growth and crop yields. Identification of promoters involved in drought and salt stress responses is of great significance for genetic improvement of crop resistance. Our previous studies showed that aquaporin can respond to drought and salt stresses, but its promoter has not yet been reported in plants. In the present study, cis-acting elements of MaAQP family member promoters were systematically analyzed in banana. Expression of MaTIP1; 2 was induced by drought and salt stresses but not sensitive to cold stress, waterlogging stress, or mechanical damage, and its promoter contained five stress-related cis-acting elements. The MaTIP1; 2 promoter (841 bp upstream of translation initiation site) from banana (Musa acuminata L. AAA group cv. Brazilian) was isolated through genome walking polymerase chain reaction, and found to contain a TATA Box, CAAT box, ABRE element, CCGTCC box, CGTCA motif, and TCA element. Transformation of the MaTIP1; 2 promoter into Arabidopsis to assess its function indicated that it responds to both drought and salt stress treatments. These results suggest that MaTIP1; 2 utilization may improve drought and salt stresses resistance of the transgenic plants by promoting banana aquaporin expression. Copyright © 2018 Elsevier Masson SAS. All rights reserved.

Localized Failure Promoted by Heterogeneous Stresses in Tectonic Mélanges

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Phillips, N. J.; Rowe, C. D.; Ujiie, K.

2017-12-01

Within the shallow (PLC) toolbox developed at the University of Maine, which uses Asymptotic Expansion Homogenization (AEH) over a finite element mesh to determine the instantaneous stress distributions in a multiphase system. We model the shale matrix mélange to be deforming through a modified flow law for viscous creep based on coupled frictional sliding and pressure solution, where at a strain rate of 10-12 s-1 the flow stress is 10 MPa under the temperature (190 ºC) and pressure ( 100 MPa) conditions during deformation, and describe the behaviour of the basaltic blocks using experimentally-derived power law flow laws. The results show that at the strain rates calculated based on plate-rate motion, differential stresses high enough to cause comminution of the basalts ( 300 MPa) correspond strongly to areas around the blocks with basalt derived cataclasites. Within the basalt derived cataclasites, thin zones of ultracataclasite record localized slip. We hypothesize that the heterogeneous stress distributions within subduction mélanges: 1) fractures the strong basalt thereby facilitating weakening through fluid-rock interactions, and 2) promotes localized slip (and occasionally seismicity) within these zones of altered basalt along the margins of strong intact basalt.

P-body proteins regulate transcriptional rewiring to promote DNA replication stress resistance.

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Loll-Krippleber, Raphael; Brown, Grant W

2017-09-15

mRNA-processing (P-) bodies are cytoplasmic granules that form in eukaryotic cells in response to numerous stresses to serve as sites of degradation and storage of mRNAs. Functional P-bodies are critical for the DNA replication stress response in yeast, yet the repertoire of P-body targets and the mechanisms by which P-bodies promote replication stress resistance are unknown. In this study we identify the complete complement of mRNA targets of P-bodies during replication stress induced by hydroxyurea treatment. The key P-body protein Lsm1 controls the abundance of HHT1, ACF4, ARL3, TMA16, RRS1 and YOX1 mRNAs to prevent their toxic accumulation during replication stress. Accumulation of YOX1 mRNA causes aberrant downregulation of a network of genes critical for DNA replication stress resistance and leads to toxic acetaldehyde accumulation. Our data reveal the scope and the targets of regulation by P-body proteins during the DNA replication stress response.P-bodies form in response to stress and act as sites of mRNA storage and degradation. Here the authors identify the mRNA targets of P-bodies during DNA replication stress, and show that P-body proteins act to prevent toxic accumulation of these target transcripts.

A Mutator Phenotype Promoting the Emergence of Spontaneous Oxidative Stress-Resistant Mutants in Campylobacter jejuni.

Science.gov (United States)

Dai, Lei; Sahin, Orhan; Tang, Yizhi; Zhang, Qijing

2017-12-15

Campylobacter jejuni is a leading cause of foodborne illnesses worldwide. As a microaerophilic organism, C. jejuni must be able to defend against oxidative stress encountered both in the host and in the environment. How Campylobacter utilizes a mutation-based mechanism for adaptation to oxidative stress is still unknown. Here we present a previously undescribed phenotypic and genetic mechanism that promotes the emergence of oxidative stress-resistant mutants. Specifically, we showed that a naturally occurring mutator phenotype, resulting from a loss of function mutation in the DNA repair enzyme MutY, increased oxidative stress resistance (OX R ) in C. jejuni We further demonstrated that MutY malfunction did not directly contribute to the OX R phenotype but increased the spontaneous mutation rate in the peroxide regulator gene perR , which functions as a repressor for multiple genes involved in oxidative stress resistance. Mutations in PerR resulted in loss of its DNA binding function and derepression of PerR-controlled oxidative stress defense genes, thereby conferring an OX R phenotype and facilitating Campylobacter survival under oxidative stress. These findings reveal a new mechanism that promotes the emergence of spontaneous OX R mutants in bacterial organisms. IMPORTANCE Although a mutator phenotype has been shown to promote antibiotic resistance in many bacterial species, little is known about its contribution to the emergence of OX R mutants. This work describes the link between a mutator phenotype and the enhanced emergence of OX R mutants as well as its underlying mechanism involving DNA repair and mutations in PerR. Since DNA repair systems and PerR are well conserved in many bacterial species, especially in Gram positives, the same mechanism may operate in multiple bacterial species. Additionally, we developed a novel method that allows for rapid quantification of spontaneous OX R mutants in a bacterial population. This method represents a technical

Halophytes: Potential Resources for Salt Stress Tolerance Genes and Promoters

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Avinash Mishra

2017-05-01

Full Text Available Halophytes have demonstrated their capability to thrive under extremely saline conditions and thus considered as one of the best germplasm for saline agriculture. Salinity is a worldwide problem, and the salt-affected areas are increasing day-by-day because of scanty rainfall, poor irrigation system, salt ingression, water contamination, and other environmental factors. The salinity stress tolerance mechanism is a very complex phenomenon, and some pathways are coordinately linked for imparting salinity tolerance. Though a number of salt responsive genes have been reported from the halophytes, there is always a quest for promising stress-responsive genes that can modulate plant physiology according to the salt stress. Halophytes such as Aeluropus, Mesembryanthemum, Suaeda, Atriplex, Thellungiella, Cakile, and Salicornia serve as a potential candidate for the salt-responsive genes and promoters. Several known genes like antiporters (NHX, SOS, HKT, VTPase, ion channels (Cl−, Ca2+, aquaporins, antioxidant encoding genes (APX, CAT, GST, BADH, SOD and some novel genes such as USP, SDR1, SRP etc. were isolated from halophytes and explored for developing stress tolerance in the crop plants (glycophytes. It is evidenced that stress triggers salt sensors that lead to the activation of stress tolerance mechanisms which involve multiple signaling proteins, up- or down-regulation of several genes, and finally the distinctive or collective effects of stress-responsive genes. In this review, halophytes are discussed as an excellent platform for salt responsive genes which can be utilized for developing salinity tolerance in crop plants through genetic engineering.

A Comparison of American and Chinese Students' Perceived Stress, Coping Styles, and Health Promotion Practices

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Li, Ying; Lindsey, Billie J.; Yin, Xiaoqin; Chen, William

2012-01-01

A cross-sectional survey utilized the Perceived Stress Scale, Brief COPE, and Health Promotion Lifestyle Profile II to ascertain similarities and differences between American (n=319) and Chinese (n=335) college students and between higher and lower stressed students in both samples. The results suggested the existence of a country difference in…

Hyperglycemia (High Blood Glucose)

Medline Plus

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

Plant Growth Promoting Rhizobacteria in Amelioration of Salinity Stress: A Systems Biology Perspective

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Gayathri Ilangumaran

2017-10-01

Full Text Available Salinity affects plant growth and is a major abiotic stress that limits crop productivity. It is well-understood that environmental adaptations and genetic traits regulate salinity tolerance in plants, but imparting the knowledge gained towards crop improvement remain arduous. Harnessing the potential of beneficial microorganisms present in the rhizosphere is an alternative strategy for improving plant stress tolerance. This review intends to elucidate the understanding of salinity tolerance mechanisms attributed by plant growth promoting rhizobacteria (PGPR. Recent advances in molecular studies have yielded insights into the signaling networks of plant–microbe interactions that contribute to salt tolerance. The beneficial effects of PGPR involve boosting key physiological processes, including water and nutrient uptake, photosynthesis, and source-sink relationships that promote growth and development. The regulation of osmotic balance and ion homeostasis by PGPR are conducted through modulation of phytohormone status, gene expression, protein function, and metabolite synthesis in plants. As a result, improved antioxidant activity, osmolyte accumulation, proton transport machinery, salt compartmentalization, and nutrient status reduce osmotic stress and ion toxicity. Furthermore, in addition to indole-3-acetic acid and 1-aminocyclopropane-1-carboxylic acid deaminase biosynthesis, other extracellular secretions of the rhizobacteria function as signaling molecules and elicit stress responsive pathways. Application of PGPR inoculants is a promising measure to combat salinity in agricultural fields, thereby increasing global food production.

Toward CMOS image sensor based glucose monitoring.

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Devadhasan, Jasmine Pramila; Kim, Sanghyo

2012-09-07

Complementary metal oxide semiconductor (CMOS) image sensor is a powerful tool for biosensing applications. In this present study, CMOS image sensor has been exploited for detecting glucose levels by simple photon count variation with high sensitivity. Various concentrations of glucose (100 mg dL(-1) to 1000 mg dL(-1)) were added onto a simple poly-dimethylsiloxane (PDMS) chip and the oxidation of glucose was catalyzed with the aid of an enzymatic reaction. Oxidized glucose produces a brown color with the help of chromogen during enzymatic reaction and the color density varies with the glucose concentration. Photons pass through the PDMS chip with varying color density and hit the sensor surface. Photon count was recognized by CMOS image sensor depending on the color density with respect to the glucose concentration and it was converted into digital form. By correlating the obtained digital results with glucose concentration it is possible to measure a wide range of blood glucose levels with great linearity based on CMOS image sensor and therefore this technique will promote a convenient point-of-care diagnosis.

Long-term impact of earthquake stress on fasting glucose control and diabetes prevalence among Chinese adults of Tangshan

OpenAIRE

An, Cuixia; Zhang, Yun; Yu, Lulu; Li, Na; Song, Mei; Wang, Lan; Zhao, Xiaochuan; Gao, Yuanyuan; Wang, Xueyi

2014-01-01

Objective: To investigate the long-term influence of stresses from the 1976 Tangshan earthquake on blood glucose control and the incidence of diabetes mellitus in Chinese people of Tangshan. Methods: 1,551 adults ≥ 37 years of age were recruited for this investigation in Tangshan city of China, where one of the deadliest earthquakes occurred in 1796. All subjects finished a questionnaire. 1,030 of them who experienced that earthquake were selected into the exposure group, while 521 were gathe...

The relationship between serum cortisol, adrenaline, blood glucose ...

African Journals Online (AJOL)

Background: Stress is an extremely adaptive phenomenon in human beings and cortisol is a known stress hormone. Examination has been described as a naturalistic stressor capable of affecting human health. Objectives: To estimate the relationship between serum cortisol, adrenaline, fasting blood glucose (FBG) and ...

Stress-activated miR-21/miR-21* in hepatocytes promotes lipid and glucose metabolic disorders associated with high-fat diet consumption.

Science.gov (United States)

Calo, Nicolas; Ramadori, Pierluigi; Sobolewski, Cyril; Romero, Yannick; Maeder, Christine; Fournier, Margot; Rantakari, Pia; Zhang, Fu-Ping; Poutanen, Matti; Dufour, Jean-François; Humar, Bostjan; Nef, Serge; Foti, Michelangelo

2016-11-01

miR-21 is an oncomir highly upregulated in hepatocellular carcinoma and in early stages of liver diseases characterised by the presence of steatosis. Whether upregulation of miR-21 contributes to hepatic metabolic disorders and their progression towards cancer is unknown. This study aims at investigating the role of miR-21/miR-21* in early stages of metabolic liver disorders associated with diet-induced obesity (DIO). Constitutive miR-21/miR-21* knockout (miR21KO) and liver-specific miR-21/miR-21* knockout (LImiR21KO) mice were generated. Mice were then fed with high-fat diet (HFD) and alterations of the lipid and glucose metabolism were investigated. Serum and ex vivo explanted liver tissue were analysed. Under normal breeding conditions and standard diet, miR-21/miR-21* deletion in mice was not associated with any detectable phenotypic alterations. However, when mice were challenged with an obesogenic diet, glucose intolerance, steatosis and adiposity were improved in mice lacking miR-21/miR-21* . Deletion of miR-21/miR-21* specifically in hepatocytes led to similar improvements in mice fed an HFD, indicating a crucial role for hepatic miR-21/miR-21* in metabolic disorders associated with DIO. Further molecular analyses demonstrated that miR-21/miR-21* deletion in hepatocytes increases insulin sensitivity and modulates the expression of multiple key metabolic transcription factors involved in fatty acid uptake, de novo lipogenesis, gluconeogenesis and glucose output. Hepatic miR-21/miR-21* deficiency prevents glucose intolerance and steatosis in mice fed an obesogenic diet by altering the expression of several master metabolic regulators. This study points out miR-21/miR-21 * as a potential therapeutic target for non-alcoholic fatty liver disease and the metabolic syndrome. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/.

The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 mediates environmental stress responses in plants.

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Hong, Jeum Kyu; Hwang, Byung Kook

2009-01-01

The promoter of the pepper pathogen-induced membrane protein gene CaPIMP1 was analyzed by an Agrobacterium-mediated transient expression assay in tobacco leaves. Several stress-related cis-acting elements (GT-1, W-box and ABRE) are located within the CaPIMP1 promoter. In tobacco leaf tissues transiently transformed with a CaPIMP1 promoter-beta-glucuronidase (GUS) gene fusion, serially 5'-deleted CaPIMP1 promoters were differentially activated by Pseudomonas syringae pv. tabaci, ethylene, methyl jasmonate, abscisic acid, and nitric oxide. The -1,193 bp region of the CaPIMP1 gene promoter sequence exhibited full promoter activity. The -417- and -593 bp promoter regions were sufficient for GUS gene activation by ethylene and methyl jasmonate treatments, respectively. However, CaPIMP1 promoter sequences longer than -793 bp were required for promoter activation by abscisic acid and sodium nitroprusside treatments. CaPIMP1 expression was activated in pepper leaves by treatment with ethylene, methyl jasmonate, abscisic acid, beta-amino-n-butyric acid, NaCl, mechanical wounding, and low temperature, but not with salicylic acid. Overexpression of CaPIMP1 in Arabidopsis conferred hypersensitivity to mannitol, NaCl, and ABA during seed germination but not during seedling development. In contrast, transgenic plants overexpressing CaPIMP1 exhibited enhanced tolerance to oxidative stress induced by methyl viologen during germination and early seedling stages. These results suggest that CaPIMP1 expression may alter responsiveness to environmental stress, as well as to pathogen infection.

Glucose oxidase and graphene bionanocomposite bridged by ionic liquid unit for glucose biosensing application

DEFF Research Database (Denmark)

Jiang, Yuanyuan; Zhang, Qixian; Li, Fenghua

2012-01-01

activity towards the reduction of O2 and H2O2. Then negatively charged glucose oxidase (GOD) was immobilized onto the composite matrix simply by ionic exchange. The ionic liquid here could improve the dispersibility of graphene and provide a favorable conductive microenvironment for the immobilized GOD......, thus promote its direct electron transfer at the GC electrode. This novel IL-graphene–GOD bionanocomposite could act as a biosensor towards the detection of glucose with a linear response up to 16mM. In this report, the method for immobilizing GOD by ionic interaction is of universality and has...... widespread use, even in other biological systems, which brings a forceful combination between GOD and IL-graphene. Besides, the biosensor is easy to prepare, have good stability, and will have potential application in glucose detection....

Risk factors for glucose intolerance in active acromegaly

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Kreze A.

2001-01-01

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

A halotolerant Enterobacter sp. displaying ACC deaminase activity promotes rice seedling growth under salt stress.

Science.gov (United States)

Sarkar, Anumita; Ghosh, Pallab Kumar; Pramanik, Krishnendu; Mitra, Soumik; Soren, Tithi; Pandey, Sanjeev; Mondal, Monohar Hossain; Maiti, Tushar Kanti

2018-01-01

Agricultural productivity is proven to be hampered by the synthesis of reactive oxygen species (ROS) and production of stress-induced ethylene under salinity stress. One-aminocyclopropane-1-carboxylic acid (ACC) is the direct precursor of ethylene synthesized by plants. Bacteria possessing ACC deaminase activity can use ACC as a nitrogen source preventing ethylene production. Several salt-tolerant bacterial strains displaying ACC deaminase activity were isolated from rice fields, and their plant growth-promoting (PGP) properties were determined. Among them, strain P23, identified as an Enterobacter sp. based on phenotypic characteristics, matrix-assisted laser desorption ionization-time of flight mass spectrometry data and the 16S rDNA sequence, was selected as the best-performing isolate for several PGP traits, including phosphate solubilization, IAA production, siderophore production, HCN production, etc. Enterobacter sp. P23 was shown to promote rice seedling growth under salt stress, and this effect was correlated with a decrease in antioxidant enzymes and stress-induced ethylene. Isolation of an acdS mutant strain enabled concluding that the reduction in stress-induced ethylene content after inoculation of strain P23 was linked to ACC deaminase activity. Copyright © 2017 Institut Pasteur. Published by Elsevier Masson SAS. All rights reserved.

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

Science.gov (United States)

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

2015-09-01

Equine metabolic syndrome is characterized by obesity and insulin resistance (IR). Currently, there is no effective pharmacological treatment for this insidious disease. Glucose uptake is mediated by a family of glucose transporters (GLUT), and is regulated by insulin-dependent and -independent pathways, including 5-AMP-activated protein kinase (AMPK). Importantly, the activation of AMPK, by 5-aminoimidazole-4-carboxamide-1-D-ribofuranoside (AICAR) stimulates glucose uptake in both healthy and diabetic humans. However, whether AICAR promotes glucose uptake in horses has not been established. It is hypothesized that AICAR administration would enhance glucose transport in equine skeletal muscle through AMPK activation. In this study, the effect of an intravenous AICAR infusion on blood glucose and insulin concentrations, as well as on GLUT expression and AMPK activation in equine skeletal muscle (quantified by Western blotting) was examined. Upon administration, plasma AICAR rapidly reached peak concentration. Treatment with AICAR resulted in a decrease (P change in lactate concentration. The ratio of phosphorylated to total AMPK was increased (P managing IR requires investigation. Copyright © 2015 Elsevier Ltd. All rights reserved.

Oxidative stress promotes pathologic polyploidization in nonalcoholic fatty liver disease.

Science.gov (United States)

Gentric, Géraldine; Maillet, Vanessa; Paradis, Valérie; Couton, Dominique; L'Hermitte, Antoine; Panasyuk, Ganna; Fromenty, Bernard; Celton-Morizur, Séverine; Desdouets, Chantal

2015-03-02

Polyploidization is one of the most dramatic changes that can occur in the genome. In the liver, physiological polyploidization events occur during both liver development and throughout adult life. Here, we determined that a pathological polyploidization takes place in nonalcoholic fatty liver disease (NAFLD), a widespread hepatic metabolic disorder that is believed to be a risk factor for hepatocellular carcinoma (HCC). In murine models of NAFLD, the parenchyma of fatty livers displayed alterations of the polyploidization process, including the presence of a large proportion of highly polyploid mononuclear cells, which are rarely observed in normal hepatic parenchyma. Biopsies from patients with nonalcoholic steatohepatitis (NASH) revealed the presence of alterations in hepatocyte ploidy compared with tissue from control individuals. Hepatocytes from NAFLD mice revealed that progression through the S/G2 phases of the cell cycle was inefficient. This alteration was associated with activation of a G2/M DNA damage checkpoint, which prevented activation of the cyclin B1/CDK1 complex. Furthermore, we determined that oxidative stress promotes the appearance of highly polyploid cells, and antioxidant-treated NAFLD hepatocytes resumed normal cell division and returned to a physiological state of polyploidy. Collectively, these findings indicate that oxidative stress promotes pathological polyploidization and suggest that this is an early event in NAFLD that may contribute to HCC development.

Environmental stress affects DNA methylation of a CpG rich promoter region of serotonin transporter gene in a nurse cohort.

Directory of Open Access Journals (Sweden)

Jukka S Alasaari

Full Text Available Shift-working nurses are exposed to a stressful work environment, which puts them at an increased risk for burnout and depression. We explored the effect of environmental stress on serotonin transporter gene (SLC6A4 promoter methylation among nurses from high and low work stress environments.Using bisulfite sequencing, we investigated the methylation status of five CpG residues of a CpG-rich region in the promoter of SLC6A4 by comparing female shift working nurses from a high work stress environment (n = 24 to low work stress environment (n = 25. We also analyzed the association of 5-HTTLPR polymorphism at 5' end of SLC6A4. Work stress was assessed by the Karasek's Model and possible signs of burnout or depression were measured by the Maslach Burnout Index General Survey and Beck Depression Index. Methylation levels were assessed by bisulfite sequencing of DNA extracted from peripheral blood leucocytes. Restriction enzyme treatment followed by standard PCR was used to identify 5-HTTLPR genotypes.We found that nurses in the high stress environment had significantly lower promoter methylation levels at all five CpG residues compared to nurses in the low stress environment (p<0.01. There was no significant interaction of 5-HTTLPR genotype and work stress with methylation (p = 0.58. In unadjusted (bivariate analysis, burnout was not significantly associated to methylation levels. However, when mutually adjusted for both, burnout and work stress were significant contributors (p = 0.038 and p<0.0001 respectively to methylation levels.Our findings show that environmental stress is concurrent with decreased methylation of the SLC6A4 promoter. This may lead to increased transcriptional activity of the gene, increased reuptake of serotonin from synaptic clefts, and termination of the activity of serotonin. This could present a possible coping mechanism for environmental stress in humans that could eventually increase risk for disturbed functional

Quercetin promotes proliferation and differentiation of oligodendrocyte precursor cells after oxygen/glucose deprivation-induced injury.

Science.gov (United States)

Wu, Xiuxiang; Qu, Xuebin; Zhang, Qiang; Dong, Fuxing; Yu, Hongli; Yan, Chen; Qi, Dashi; Wang, Meng; Liu, Xuan; Yao, Ruiqin

2014-04-01

The aim of this study was to investigate quercetin's (Qu) ability to promote proliferation and differentiation of oligodendrocyte precursor cells (OPCs) under oxygen/glucose deprivation (OGD)-induced injury in vitro. The results showed that after OGD, OPCs survival rate was significantly increased by Qu as measured by Cell Counting Kit-8. Furthermore, Qu treatment reduced apoptosis of OPCs surveyed by Hoechst 33258 nuclear staining. Qu at 9 and 27 μM promoted the proliferation of OPCs the most by Brdu and Olig2 immunocytochemical staining after OGD 3 days. Also, Qu treatment for 8 days after OGD, the differentiation of OPCs to oligodendrocyte was detected by immunofluorescence staining showing that O4, Olig2, and myelin basic protein (MBP) positive cells were significantly increased compared to control group. Additionally, the protein levels of Olig2 and MBP of OPCs were quantified using western blot and mRNA levels of Olig2 and Inhibitor of DNA binding 2 (Id2) were measured by RT-PCR. Western blot showed a significant increase in Olig2 and MBP expression levels compared with controls after OGD and Qu treatment with a linear does-response curve from 3 to 81 μM. After treatment with Qu compared to its control group, Olig2 mRNA level was significantly up-regulated, whereas Id2 mRNA level was down-regulated. In conclusion, Qu at 3-27 μM can promote the proliferation and differentiation of OPCs after OGD injury and may regulate the activity of Olig2 and Id2.

Protective Effects of Hesperidin (Citrus Flavonone on High Glucose Induced Oxidative Stress and Apoptosis in a Cellular Model for Diabetic Retinopathy

Directory of Open Access Journals (Sweden)

Wayne Young Liu

2017-12-01

Full Text Available The aim of this study was to investigate the protective effects and mechanisms of hesperidin, a plant based active flavanone found in citrus fruits, under the oxidative stress and apoptosis induced by high levels of glucose in retinal ganglial cells (RGCs. RGC-5 cells were pretreated with hesperidin (12.5, 25, or 50 μmol/L for 6 h followed by exposure to high (33.3 mmol/L d-glucose for 48 h. The 3-(4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide (MTT assay was adopted to evaluate cell viability. Mitochondrial function was estimated by measuring the mitochondrial membrane potential (ΔΨm. A fluorescent probe was employed to evaluate the intercellular production of reactive oxygen species (ROS. Colorimetric assay kits were used to evaluate lipid peroxidation, antioxidant enzyme activities, and protein carbonyls formation. The expression of apoptosis-related proteins and mitogen-activated protein kinase (MAPK were measured with Western blotting. Hesperidin inhibited high glucose-mediated cell loss and restored mitochondrial function including a reversion of ΔΨm loss and cytochrome c release. Treated with hesperidin, high glucose-induced increase in ROS, malondialdehyde, and protein carbonyl levels were blocked in RGC-5 cells. Hesperidin was found to elevate the activities of superoxide dismutase, catalase, glutathione peroxidase, and to recover glutathione levels. Hesperidin inhibited high glucose-induced cell apoptosis by attenuating the downregulation of caspase-9, caspase-3, and Bax/Bcl-2. Furthermore, the phosphorylation of c-Jun N-terminal kinases (JNK and p38 MAPK triggered by high glucose were attenuated in RGC-5 cells after their incubation with hesperdin. We concluded that hesperidin may protect RGC-5 cells from high glucose-induced injury since it owns the properties of antioxidant action and blocks mitochondria-mediated apoptosis.

Honokiol protects pancreatic β cell against high glucose and intermittent hypoxia-induced injury by activating Nrf2/ARE pathway in vitro and in vivo.

Science.gov (United States)

Li, Chen-Guang; Ni, Chang-Lin; Yang, Min; Tang, Yun-Zhao; Li, Zhu; Zhu, Yan-Juan; Jiang, Zhen-Huan; Sun, Bei; Li, Chun-Jun

2018-01-01

Obstructive sleep apnea hypopnea syndrome (OSAHS) is associated with glucose intolerance, insulin resistance and type 2 diabetes mellitus (T2DM). Although several studies have revealed that intermittent hypoxia (IH) in OSAHS may further aggravate pancreatic β cell damage and promote the evolution of type 2 diabetes (T2DM) by increasing oxidative stress, the underlying mechanisms are unclear. Honokiol, a potent radical scavenger, has been demonstrated to ameliorate oxidative stress in many cases. The present study aimed to explore the potential mechanism of IH and diabetes synergistically damage and destruct the pancreatic β cell, examine the effects of honokiol on ameliorating pancreatic β cell injury in this context and explore the mechanism of such effects. High glucose (HG) cultured INS-1 cells were exposed to 50 μM of honokiol for 24, 48 and 72 h with or without IH intervention. T2DM rats were treated with honokiol and exposed to 80 s of IH followed by 160 s of normoxia for 8 weeks. The cell proliferation, apoptosis and oxidative stress were measured. Blood glucose, insulin, glucagon and HOMA-IR (Homeostasis model assessment -insulin resistence) were also detected, and the expression of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1) were detected by immunofluorescence staining and western blotting. Honokiol can reduce oxidative stress, cytotoxicity and apoptosis in the INS-1 cells of rats receiving HG treatment or both HG and IH treatment. IH can further aggravate pancreas dysfunction, cause a marked elevation in fasting blood glucose, glucagon, HOMA-IR and oxidative stress levels in DM rats. In addition, honokiol can effectively activate the Nrf2/ARE pathway and reverse this pancreatic dysfunction in vivo and in vitro. These findings indicate that honokiol acts as a potent ROS scavenger via Nrf2/ARE pathway and effectively attenuates oxidative stress and improves pancreatic β cell function of DM rats under IH

Genetic disruption of SOD1 gene causes glucose intolerance and impairs β-cell function.

Science.gov (United States)

Muscogiuri, Giovanna; Salmon, Adam B; Aguayo-Mazzucato, Cristina; Li, Mengyao; Balas, Bogdan; Guardado-Mendoza, Rodolfo; Giaccari, Andrea; Reddick, Robert L; Reyna, Sara M; Weir, Gordon; Defronzo, Ralph A; Van Remmen, Holly; Musi, Nicolas

2013-12-01

Oxidative stress has been associated with insulin resistance and type 2 diabetes. However, it is not clear whether oxidative damage is a cause or a consequence of the metabolic abnormalities present in diabetic subjects. The goal of this study was to determine whether inducing oxidative damage through genetic ablation of superoxide dismutase 1 (SOD1) leads to abnormalities in glucose homeostasis. We studied SOD1-null mice and wild-type (WT) littermates. Glucose tolerance was evaluated with intraperitoneal glucose tolerance tests. Peripheral and hepatic insulin sensitivity was quantitated with the euglycemic-hyperinsulinemic clamp. β-Cell function was determined with the hyperglycemic clamp and morphometric analysis of pancreatic islets. Genetic ablation of SOD1 caused glucose intolerance, which was associated with reduced in vivo β-cell insulin secretion and decreased β-cell volume. Peripheral and hepatic insulin sensitivity were not significantly altered in SOD1-null mice. High-fat diet caused glucose intolerance in WT mice but did not further worsen the glucose intolerance observed in standard chow-fed SOD1-null mice. Our findings suggest that oxidative stress per se does not play a major role in the pathogenesis of insulin resistance and demonstrate that oxidative stress caused by SOD1 ablation leads to glucose intolerance secondary to β-cell dysfunction.

Neuroprotective effects of ginsenoside Rb1 on high glucose-induced neurotoxicity in primary cultured rat hippocampal neurons.

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Liu, Di; Zhang, Hong; Gu, Wenjuan; Liu, Yuqin; Zhang, Mengren

2013-01-01

Ginsenoside Rb1 is one of the main active principles in traditional herb ginseng and has been reported to have a wide variety of neuroprotective effects. Endoplasmic reticulum (ER) stress has been implicated in neurodegenerative diseases, so the present study aimed to observe the effects of ginsenoside Rb1 on ER stress signaling pathways in high glucose-treated hippocampal neurons. The results from MTT, TUNEL labeling and Annexin V-FITC/PI/Hoechst assays showed that incubating neurons with 50 mM high glucose for 72 h decreased cell viability and increased the number of apoptotic cells whereas treating neurons with 1 μM Rb1 for 72 h protected the neurons against high glucose-induced cell damage. Further molecular mechanism study demonstrated that Rb1 suppressed the activation of ER stress-associated proteins including protein kinase RNA (PKR)-like ER kinase (PERK) and C/EBP homology protein (CHOP) and downregulation of Bcl-2 induced by high glucose. Moreover, Rb1 inhibited both the elevation of intracellular reactive oxygen species (ROS) and the disruption of mitochondrial membrane potential induced by high glucose. In addition, the high glucose-induced cell apoptosis, activation of ER stress, ROS accumulation and mitochondrial dysfunction can also be attenuated by the inhibitor of ER stress 4-phenylbutyric acid (4-PBA) and anti-oxidant N-acetylcysteine(NAC). In conclusion, these results suggest that Rb1 may protect neurons against high glucose-induced cell injury through inhibiting CHOP signaling pathway as well as oxidative stress and mitochondrial dysfunction.

Glucose and lipid metabolism in rats supplemented with glycyrrhizic acid exposed to short- or long- term stress and fed on a high-calorie diet

OpenAIRE

Yaw, Hui Ping

2017-01-01

Stress and consumption of high-calorie diet are well-recognized as the primary contributor to various metabolic diseases such as the metabolic syndrome. Glycyrrhizic acid (GA), an active compound in the root extract of the licorice plant, Glycyrrhiza glabra has been shown to improve hyperglycaemia and dyslipidaemia in rats fed on a high- calorie diet. However, the effect of GA on glucose and lipid metabolism in rats under stress in combination with high- calorie diet has yet to be expl...

Institutional point-of-care glucometer identifies population trends in blood glucose associated with war.

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Boaz, Mona; Matas, Zipora; Chaimy, Tova; Landau, Zohar; Bar Dayan, Yosefa; Berlovitz, Yitzhak; Wainstein, Julio

2013-11-01

Acute physiological stress has been shown to impair glucose homeostasis. War is a period of acute psychological stress, and its effect on glucose control is unknown. In this study random point-of-care (POC) glucose levels were measured using an automated, institutional glucometer in hospitalized adult patients prior to versus during the Israeli Pillar of Defense campaign (November 7-10, 2012). Random POC glucose values measured with the institutional blood glucose monitoring system were obtained 1 week prior to the Pillar of Defense campaign (November 7-10, 2012) and compared with values to those obtained during the first 4 days of the war (November 14-17, 2012). In total, 3,573 POC glucose measures were included: 1,865 during the pre-war period and 1,708 during the campaign. POC glucose measures were significantly higher during the war compared with the week preceding the war: 9.7±4.7 versus 9.3±4.2 mmol/L (P=0.02). In a general linear model, period (pre-war vs. during war) persisted as a significant predictor of POC glucose even after controlling for age, sex, and department type (internal medicine vs. surgical). Acute stress, such as a wartime situation, is associated with a significant increase in random blood glucose values in a population of hospitalized adults. Long-term follow-up of the individuals hospitalized during these two periods can reveal differences in morbidity and mortality trends.

Nutrients and Oxidative Stress: Friend or Foe?

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Bee Ling Tan

2018-01-01

Full Text Available There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF-κB- mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD, and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs. Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.

Nutrients and Oxidative Stress: Friend or Foe?

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Tan, Bee Ling; Norhaizan, Mohd Esa; Liew, Winnie-Pui-Pui

2018-01-01

There are different types of nutritionally mediated oxidative stress sources that trigger inflammation. Much information indicates that high intakes of macronutrients can promote oxidative stress and subsequently contribute to inflammation via nuclear factor-kappa B- (NF- κ B-) mediated cell signaling pathways. Dietary carbohydrates, animal-based proteins, and fats are important to highlight here because they may contribute to the long-term consequences of nutritionally mediated inflammation. Oxidative stress is a central player of metabolic ailments associated with high-carbohydrate and animal-based protein diets and excessive fat consumption. Obesity has become an epidemic and represents the major risk factor for several chronic diseases, including diabetes, cardiovascular disease (CVD), and cancer. However, the molecular mechanisms of nutritionally mediated oxidative stress are complex and poorly understood. Therefore, this review aimed to explore how dietary choices exacerbate or dampen the oxidative stress and inflammation. We also discussed the implications of oxidative stress in the adipocyte and glucose metabolism and obesity-associated noncommunicable diseases (NCDs). Taken together, a better understanding of the role of oxidative stress in obesity and the development of obesity-related NCDs would provide a useful approach. This is because oxidative stress can be mediated by both extrinsic and intrinsic factors, hence providing a plausible means for the prevention of metabolic disorders.

DNA demethylases target promoter transposable elements to positively regulate stress responsive genes in Arabidopsis.

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Le, Tuan-Ngoc; Schumann, Ulrike; Smith, Neil A; Tiwari, Sameer; Au, Phil Chi Khang; Zhu, Qian-Hao; Taylor, Jennifer M; Kazan, Kemal; Llewellyn, Danny J; Zhang, Ren; Dennis, Elizabeth S; Wang, Ming-Bo

2014-09-17

DNA demethylases regulate DNA methylation levels in eukaryotes. Arabidopsis encodes four DNA demethylases, DEMETER (DME), REPRESSOR OF SILENCING 1 (ROS1), DEMETER-LIKE 2 (DML2), and DML3. While DME is involved in maternal specific gene expression during seed development, the biological function of the remaining DNA demethylases remains unclear. We show that ROS1, DML2, and DML3 play a role in fungal disease resistance in Arabidopsis. A triple DNA demethylase mutant, rdd (ros1 dml2 dml3), shows increased susceptibility to the fungal pathogen Fusarium oxysporum. We identify 348 genes differentially expressed in rdd relative to wild type, and a significant proportion of these genes are downregulated in rdd and have functions in stress response, suggesting that DNA demethylases maintain or positively regulate the expression of stress response genes required for F. oxysporum resistance. The rdd-downregulated stress response genes are enriched for short transposable element sequences in their promoters. Many of these transposable elements and their surrounding sequences show localized DNA methylation changes in rdd, and a general reduction in CHH methylation, suggesting that RNA-directed DNA methylation (RdDM), responsible for CHH methylation, may participate in DNA demethylase-mediated regulation of stress response genes. Many of the rdd-downregulated stress response genes are downregulated in the RdDM mutants nrpd1 and nrpe1, and the RdDM mutants nrpe1 and ago4 show enhanced susceptibility to F. oxysporum infection. Our results suggest that a primary function of DNA demethylases in plants is to regulate the expression of stress response genes by targeting promoter transposable element sequences.

Fasting plasma glucose levels and coronary artery calcification in subjects with impaired fasting glucose.

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Eun, Young-Mi; Kang, Sung-Goo; Song, Sang-Wook

2016-01-01

Prediabetes is associated with an increased risk of cardiovascular disease (CVD). While the association of impaired glucose tolerance with CVD has been shown in many studies, the relationship between impaired fasting glucose (IFG) and CVD remains unclear. The purpose of this study was to compare the coronary artery calcium (CAC) scores of participants with normal fasting glucose versus those with IFG, according to fasting plasma glucose (FPG) levels, and to assess whether differences in CAC scores were independent of important confounders. Retrospective study. Health Promotion Center of the University Hospital (Gyeonggi-do, South Korea), during the period 2010-2014. Participants were enrolled from the general population who visited for a medical check-up. CAC was assessed in asymptomatic individuals by multidetector computed tomography. Anthropometric parameters and metabolic profiles were also recorded. Subjects were divided into four fasting glucose groups. Participants with a history of CVD or diabetes mellitus were excluded. Correlation between FPG and CAC scores, CAC score categories, and association between CAC score and FPG categories. Of 1112 participants, 346 (34.2%) had a CAC score > 0. FPG values in the IFG patients were positively but weakly correlated with CAC scores (r=0.099, P=.001). The incidence of CAC differed according to FPG level (P =110 mg/dL had a significantly higher risk of CAC than did subjects with normal fasting glucose (110.

The role of health promotion behavior in controlling anxiety and stress in patients with hypertension

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Fatemeh Samiei Siboni

2012-12-01

Full Text Available    BACKGROUND: Hypertension is one of the most important, worldwide chronic diseases. In most cases the real cause of hypertension is not clear but recent studies have shown that unhealthy lifestyle may lead to stress, anxiety and hypertension.    METHODS: The study design of this article was written based on reviewing published articles in scientific database including ISI web of knowledge, Medline, pub med, Elsevier. The articles about healthy lifestyle, stress and anxiety in patients with hypertension was reviewed.    RESULTS: Hypertension was the major risk factor for developing cardiovascular and renal disease. In most cases the real cause of hypertension was not clear but recent studies have shown that unhealthy lifestyle may lead to stress, anxiety and hypertension. Lifestyle factors were critical determinants of blood pressure levels operating against a background of genetic susceptibility. An improving healthy lifestyle behavior was important in improving health and was a multidimensional pattern. Not all strategies would be effective for every individual, but to some extent all patients being treated for hypertension should incorporate elements of therapeutic lifestyle changes into their treatment regimen. Healthcare providers play an important role in teaching individuals with hypertension on health promotion program and healthy lifestyles. Not only healthcare providers, advice that controlling hypertension is integral, but also patients should follow that advice. Special attention must be paid to intervention programs aimed at modifying lifestyle and providing education on stress management techniques. Non pharmacologic interventions include methods to modify lifestyle and reduce or coping with stress and anxiety such as: stress management intervention (SMI, dietary sodium reduction, weight reduction, supplement regimens utilizing calcium, magnesium, fish oil, and potassium.    CONCLUSION: Several studies in the context of

Far infra-red therapy promotes ischemia-induced angiogenesis in diabetic mice and restores high glucose-suppressed endothelial progenitor cell functions

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Huang Po-Hsun

2012-08-01

Full Text Available Abstract Background Far infra-red (IFR therapy was shown to exert beneficial effects in cardiovascular system, but effects of IFR on endothelial progenitor cell (EPC and EPC-related vasculogenesis remain unclear. We hypothesized that IFR radiation can restore blood flow recovery in ischemic hindlimb in diabetic mice by enhancement of EPCs functions and homing process. Materials and methods Starting at 4 weeks after the onset of diabetes, unilateral hindlimb ischemia was induced in streptozotocine (STZ-induced diabetic mice, which were divided into control and IFR therapy groups (n = 6 per group. The latter mice were placed in an IFR dry sauna at 34°C for 30 min once per day for 5 weeks. Results Doppler perfusion imaging demonstrated that the ischemic limb/normal side blood perfusion ratio in the thermal therapy group was significantly increased beyond that in controls, and significantly greater capillary density was seen in the IFR therapy group. Flow cytometry analysis showed impaired EPCs (Sca-1+/Flk-1+ mobilization after ischemia surgery in diabetic mice with or without IFR therapy (n = 6 per group. However, as compared to those in the control group, bone marrow-derived EPCs differentiated into endothelial cells defined as GFP+/CD31+ double-positive cells were significantly increased in ischemic tissue around the vessels in diabetic mice that received IFR radiation. In in-vitro studies, cultured EPCs treated with IFR radiation markedly augmented high glucose-impaired EPC functions, inhibited high glucose-induced EPC senescence and reduced H2O2 production. Nude mice received human EPCs treated with IFR in high glucose medium showed a significant improvement in blood flow recovery in ischemic limb compared to those without IFR therapy. IFR therapy promoted blood flow recovery and new vessel formation in STZ-induced diabetic mice. Conclusions Administration of IFR therapy promoted collateral flow recovery and new vessel formation in STZ

Glucose Regulates the Expression of the Apolipoprotein A5 Gene

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Fruchart, Jamila; Nowak, Maxime; Helleboid-Chapman, Audrey; Jakel, Heidelinde; Moitrot, Emmanuelle; Rommens, Corinne; Pennacchio, Len A.; Fruchart-Najib, Jamila; Fruchart, Jean-Charles

2008-04-07

The apolipoprotein A5 gene (APOA5) is a key player in determining triglyceride concentrations in humans and mice. Since diabetes is often associated with hypertriglyceridemia, this study explores whether APOA5 gene expression is regulated by alteration in glucose homeostasis and the related pathways. D-glucose activates APOA5 gene expression in a time- and dose-dependent manner in hepatocytes, and the glycolytic pathway involved was determined using D-glucose analogs and metabolites. Together, transient transfections, electrophoretic mobility shift assays and chromatin immunoprecipitation assays show that this regulation occurs at the transcriptional level through an increase of USF1/2 binding to an E-box in the APOA5 promoter. We show that this phenomenon is not due to an increase of mRNA or protein expression levels of USF. Using protein phosphatases 1 and 2A inhibitor, we demonstrate that D-glucose regulates APOA5 gene via a dephosphorylation mechanism, thereby resulting in an enhanced USF1/2-promoter binding. Last, subsequent suppressions of USF1/2 and phosphatases mRNA through siRNA gene silencing abolished the regulation. We demonstrate that APOA5 gene is up regulated by D-glucose and USF through phosphatase activation. These findings may provide a new cross talk between glucose and lipid metabolism.

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

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Yong-Lim Kim

2012-06-01

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

DAF-16 employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity.

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Riedel, Christian G; Dowen, Robert H; Lourenco, Guinevere F; Kirienko, Natalia V; Heimbucher, Thomas; West, Jason A; Bowman, Sarah K; Kingston, Robert E; Dillin, Andrew; Asara, John M; Ruvkun, Gary

2013-05-01

Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The forkhead box O (FOXO) transcription factor DAF-16 (hereafter referred to as DAF-16/FOXO) is a central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO-binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally co-localize at DAF-16/FOXO target promoters. We show that specifically for gene activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role for SWI/SNF in DAF-16/FOXO-mediated processes, in particular dauer formation, stress resistance and the promotion of longevity. Thus, we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation.

Reproductive organ and vascular specific promoter of the rice plasma membrane Ca2+ATPase mediates environmental stress responses in plants.

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Huda, Kazi Md Kamrul; Banu, Mst Sufara Akhter; Pathi, Krishna Mohan; Tuteja, Narendra

2013-01-01

Plasma membrane Ca(2+)ATPase is a transport protein in the plasma membrane of cells and helps in removal of calcium (Ca(2+)) from the cell, hence regulating Ca(2+) level within cells. Though plant Ca(2+)ATPases have been shown to be involved in plant stress responses but their promoter regions have not been well studied. The 1478 bp promoter sequence of rice plasma membrane Ca(2+)ATPase contains cis-acting elements responsive to stresses and plant hormones. To identify the functional region, serial deletions of the promoter were fused with the GUS sequence and four constructs were obtained. These were differentially activated under NaCl, PEG cold, methyl viologen, abscisic acid and methyl jasmonate treatments. We demonstrated that the rice plasma membrane Ca(2+)ATPase promoter is responsible for vascular-specific and multiple stress-inducible gene expression. Only full-length promoter showed specific GUS expression under stress conditions in floral parts. High GUS activity was observed in roots with all the promoter constructs. The -1478 to -886 bp flanking region responded well upon treatment with salt and drought. Only the full-length promoter presented cold-induced GUS expression in leaves, while in shoots slight expression was observed for -1210 and -886 bp flanking region. The -1210 bp deletion significantly responded to exogenous methyl viologen and abscisic acid induction. The -1210 and -886 bp flanking region resulted in increased GUS activity in leaves under methyl jasmonate treatments, whereas in shoots the -886 bp and -519 bp deletion gave higher expression. Salicylic acid failed to induce GUS activities in leaves for all the constructs. The rice plasma membrane Ca(2+)ATPase promoter is a reproductive organ-specific as well as vascular-specific. This promoter contains drought, salt, cold, methyl viologen, abscisic acid and methyl jasmonate related cis-elements, which regulated gene expression. Overall, the tissue-specificity and inducible nature of this

Reproductive organ and vascular specific promoter of the rice plasma membrane Ca2+ATPase mediates environmental stress responses in plants.

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Kazi Md Kamrul Huda

Full Text Available Plasma membrane Ca(2+ATPase is a transport protein in the plasma membrane of cells and helps in removal of calcium (Ca(2+ from the cell, hence regulating Ca(2+ level within cells. Though plant Ca(2+ATPases have been shown to be involved in plant stress responses but their promoter regions have not been well studied.The 1478 bp promoter sequence of rice plasma membrane Ca(2+ATPase contains cis-acting elements responsive to stresses and plant hormones. To identify the functional region, serial deletions of the promoter were fused with the GUS sequence and four constructs were obtained. These were differentially activated under NaCl, PEG cold, methyl viologen, abscisic acid and methyl jasmonate treatments. We demonstrated that the rice plasma membrane Ca(2+ATPase promoter is responsible for vascular-specific and multiple stress-inducible gene expression. Only full-length promoter showed specific GUS expression under stress conditions in floral parts. High GUS activity was observed in roots with all the promoter constructs. The -1478 to -886 bp flanking region responded well upon treatment with salt and drought. Only the full-length promoter presented cold-induced GUS expression in leaves, while in shoots slight expression was observed for -1210 and -886 bp flanking region. The -1210 bp deletion significantly responded to exogenous methyl viologen and abscisic acid induction. The -1210 and -886 bp flanking region resulted in increased GUS activity in leaves under methyl jasmonate treatments, whereas in shoots the -886 bp and -519 bp deletion gave higher expression. Salicylic acid failed to induce GUS activities in leaves for all the constructs.The rice plasma membrane Ca(2+ATPase promoter is a reproductive organ-specific as well as vascular-specific. This promoter contains drought, salt, cold, methyl viologen, abscisic acid and methyl jasmonate related cis-elements, which regulated gene expression. Overall, the tissue-specificity and inducible

Plant Growth-Promoting Rhizobacteria Enhance Salinity Stress Tolerance in Okra through ROS-Scavenging Enzymes

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Sheikh Hasna Habib

2016-01-01

Full Text Available Salinity is a major environmental stress that limits crop production worldwide. In this study, we characterized plant growth-promoting rhizobacteria (PGPR containing 1-aminocyclopropane-1-carboxylate (ACC deaminase and examined their effect on salinity stress tolerance in okra through the induction of ROS-scavenging enzyme activity. PGPR inoculated okra plants exhibited higher germination percentage, growth parameters, and chlorophyll content than control plants. Increased antioxidant enzyme activities (SOD, APX, and CAT and upregulation of ROS pathway genes (CAT, APX, GR, and DHAR were observed in PGPR inoculated okra plants under salinity stress. With some exceptions, inoculation with Enterobacter sp. UPMR18 had a significant influence on all tested parameters under salt stress, as compared to other treatments. Thus, the ACC deaminase-containing PGPR isolate Enterobacter sp. UPMR18 could be an effective bioresource for enhancing salt tolerance and growth of okra plants under salinity stress.

Natto and viscous vegetables in a Japanese-style breakfast improved insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance.

Science.gov (United States)

Taniguchi-Fukatsu, Akiko; Yamanaka-Okumura, Hisami; Naniwa-Kuroki, Yuko; Nishida, Yuka; Yamamoto, Hironori; Taketani, Yutaka; Takeda, Eiji

2012-04-01

We previously suggested that the consumption of natto and viscous vegetables as part of a Japanese-style meal based on white rice (WR) reduced postprandial glucose and insulin levels in healthy subjects. The aim of the present study was to assess whether a single breakfast of natto and viscous vegetables or the same breakfast consumed for 2 weeks could improve glucose control, insulin sensitivity, lipid metabolism and oxidative stress in overweight subjects with impaired glucose tolerance (IGT). A total of eleven free-living subjects with IGT followed a randomised, crossover breakfast intervention for 2 weeks. The test meal included boiled WR with natto (viscous fermented soyabeans), Japanese yam and okra. The control meal included WR with non-viscous boiled soyabeans, potatoes and broccoli. Both meals contained comparable amounts of carbohydrate, fat, protein and fibre. The test meal reduced acute glucose and insulin responses compared to the control meal in the study participants. Insulin sensitivity was assessed using the composite insulin sensitivity index (CISI) after both the test and control meal periods. The test meal resulted in improvements in CISI compared to the baseline, whereas no significant changes were observed after the control meal period. Serum levels of both total and LDL-cholesterol were assessed before and after the test meal period and found to decrease significantly. There was also a tendency towards reduced serum malondialdehyde-modified LDL and N(ɛ)-carboxymethyllysine. No differences were observed in the measures of chronic glycaemic control. Thus, we conclude that a breakfast of natto and viscous vegetables consumed for 2 weeks improves insulin sensitivity, serum lipid and oxidative stress.

DAF-16/FOXO employs the chromatin remodeller SWI/SNF to promote stress resistance and longevity

Science.gov (United States)

Riedel, Christian G.; Dowen, Robert H.; Lourenco, Guinevere F.; Kirienko, Natalia V.; Heimbucher, Thomas; West, Jason A.; Bowman, Sarah K.; Kingston, Robert E.; Dillin, Andrew; Asara, John M.; Ruvkun, Gary

2013-01-01

Organisms are constantly challenged by stresses and privations and require adaptive responses for their survival. The transcription factor DAF-16/FOXO is central nexus in these responses, but despite its importance little is known about how it regulates its target genes. Proteomic identification of DAF-16/FOXO binding partners in Caenorhabditis elegans and their subsequent functional evaluation by RNA interference (RNAi) revealed several candidate DAF-16/FOXO cofactors, most notably the chromatin remodeller SWI/SNF. DAF-16/FOXO and SWI/SNF form a complex and globally colocalize at DAF-16/FOXO target promoters. We show that specifically for gene-activation, DAF-16/FOXO depends on SWI/SNF, facilitating SWI/SNF recruitment to target promoters, in order to activate transcription by presumed remodelling of local chromatin. For the animal, this translates into an essential role of SWI/SNF for DAF-16/FOXO-mediated processes, i.e. dauer formation, stress resistance, and the promotion of longevity. Thus we give insight into the mechanisms of DAF-16/FOXO-mediated transcriptional regulation and establish a critical link between ATP-dependent chromatin remodelling and lifespan regulation. PMID:23604319

The Role of Leadership Support for Health Promotion in Employee Wellness Program Participation, Perceived Job Stress, and Health Behaviors.

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Hoert, Jennifer; Herd, Ann M; Hambrick, Marion

2018-05-01

The purpose of the study was to explore the relationship between leadership support for health promotion and job stress, wellness program participation, and health behaviors. A cross-sectional survey design was used. Four worksites with a range of wellness programs were selected for this study. Participants in this study were employees (n = 618) at 4 organizations (bank, private university, wholesale supplier, and public university) in the southeastern United States, each offering an employee wellness program. Response rates in each organization ranged from 3% to 34%. Leadership support for health promotion was measured with the Leading by Example instrument. Employee participation in wellness activities, job stress, and health behaviors were measured with multi-item scales. Correlation/regression analysis and descriptive statistics were used to analyze the relationships among the scaled variables. Employees reporting higher levels of leadership support for health promotion also reported higher levels of wellness activity participation, lower job stress, and greater levels of health behavior ( P = .001). To ascertain the amount of variance in health behaviors accounted for by the other variables in the study, a hierarchical regression analysis revealed a statistically significant model (model F 7,523 = 27.28; P = .001), with leadership support for health promotion (β = .19, t = 4.39, P = .001), wellness activity participation (β = .28, t = 6.95, P stress (β = -.27, t = -6.75, P ≤ .001) found to be significant predictors of health behaviors in the model. Exploratory regression analyses by organization revealed the focal variables as significant model predictors for only the 2 larger organizations with well-established wellness programs. Results from the study suggest that employees' perceptions of organizational leadership support for health promotion are related to their participation in wellness activities, perceived job stress levels, and health behaviors.

Proglucagon Promoter Cre-Mediated AMPK Deletion in Mice Increases Circulating GLP-1 Levels and Oral Glucose Tolerance.

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Sophie R Sayers

Full Text Available Enteroendocrine L-cells synthesise and release the gut hormone glucagon-like peptide-1 (GLP-1 in response to food transit. Deletion of the tumour suppressor kinase LKB1 from proglucagon-expressing cells leads to the generation of intestinal polyps but no change in circulating GLP-1 levels. Here, we explore the role of the downstream kinase AMP-activated protein kinase (AMPK in these cells.Loss of AMPK from proglucagon-expressing cells was achieved using a preproglucagon promoter-driven Cre (iGluCre to catalyse recombination of floxed alleles of AMPKα1 and α2. Oral and intraperitoneal glucose tolerance were measured using standard protocols. L-cell mass was measured by immunocytochemistry. Hormone and peptide levels were measured by electrochemical-based luminescence detection or radioimmunoassay.Recombination with iGluCre led to efficient deletion of AMPK from intestinal L- and pancreatic alpha-cells. In contrast to mice rendered null for LKB1 using the same strategy, mice deleted for AMPK displayed an increase (WT: 0.05 ± 0.01, KO: 0.09±0.02%, p<0.01 in L-cell mass and elevated plasma fasting (WT: 5.62 ± 0.800 pg/ml, KO: 14.5 ± 1.870, p<0.01 and fed (WT: 15.7 ± 1.48pg/ml, KO: 22.0 ± 6.62, p<0.01 GLP-1 levels. Oral, but not intraperitoneal, glucose tolerance was significantly improved by AMPK deletion, whilst insulin and glucagon levels were unchanged despite an increase in alpha to beta cell ratio (WT: 0.23 ± 0.02, KO: 0.33 ± 0.03, p<0.01.AMPK restricts L-cell growth and GLP-1 secretion to suppress glucose tolerance. Targeted inhibition of AMPK in L-cells may thus provide a new therapeutic strategy in some forms of type 2 diabetes.

Tandem-pore K+ channels mediate inhibition of orexin neurons by glucose

DEFF Research Database (Denmark)

Burdakov, Denis; Jensen, Lise T; Alexopoulos, Haris

2006-01-01

Glucose-inhibited neurons orchestrate behavior and metabolism according to body energy levels, but how glucose inhibits these cells is unknown. We studied glucose inhibition of orexin/hypocretin neurons, which promote wakefulness (their loss causes narcolepsy) and also regulate metabolism...... and reward. Here we demonstrate that their inhibition by glucose is mediated by ion channels not previously implicated in central or peripheral glucose sensing: tandem-pore K(+) (K(2P)) channels. Importantly, we show that this electrical mechanism is sufficiently sensitive to encode variations in glucose...... levels reflecting those occurring physiologically between normal meals. Moreover, we provide evidence that glucose acts at an extracellular site on orexin neurons, and this information is transmitted to the channels by an intracellular intermediary that is not ATP, Ca(2+), or glucose itself...

PGC-1α functions as a co-suppressor of XBP1s to regulate glucose metabolism

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Jaemin Lee

2018-01-01

Full Text Available Objective: Peroxisome proliferator-activated receptor γ (PPARγ coactivator-1α (PGC-1α promotes hepatic gluconeogenesis by activating HNF4α and FoxO1. PGC-1α expression in the liver is highly elevated in obese and diabetic conditions, leading to increased hepatic glucose production. We previously showed that the spliced form of X-box binding protein 1 (XBP1s suppresses FoxO1 activity and hepatic gluconeogenesis. The shared role of PGC-1α and XBP1s in regulating FoxO1 activity and gluconeogenesis led us to investigate the probable interaction between PGC-1α and XBP1s and its role in glucose metabolism. Methods: We investigated the biochemical interaction between PGC-1α and XBP1s and examined the role of their interaction in glucose homeostasis using animal models. Results: We show that PGC-1α interacts with XBP1s, which plays an anti-gluconeogenic role in the liver by suppressing FoxO1 activity. The physical interaction between PGC-1α and XBP1s leads to suppression of XBP1s activity rather than its activation. Upregulating PGC-1α expression in the liver of lean mice lessens XBP1s protein levels, and reducing PGC-1α levels in obese and diabetic mouse liver restores XBP1s protein induction. Conclusions: Our findings reveal a novel function of PGC-1α as a suppressor of XBP1s function, suggesting that hepatic PGC-1α promotes gluconeogenesis through multiple pathways as a co-activator for HNF4α and FoxO1 and also as a suppressor for anti-gluconeogenic transcription factor XBP1s. Keywords: PGC-1α, XBP1s, Glucose homeostasis, ER stress, UPR, Insulin resistance

Endoplasmic Reticulum Stress Sensor IRE1α Enhances IL-23 Expression by Human Dendritic Cells

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Saioa Márquez

2017-06-01

Full Text Available Human monocyte-derived dendritic cells (DCs exposed to pathogen-associated molecular patterns (PAMPs undergo bioenergetic changes that influence the immune response. We found that stimulation with PAMPs enhanced glycolysis in DCs, whereas oxidative phosphorylation remained unaltered. Glucose starvation and the hexokinase inhibitor 2-deoxy-d-glucose (2-DG modulated cytokine expression in stimulated DCs. Strikingly, IL23A was markedly induced upon 2-DG treatment, but not during glucose deprivation. Since 2-DG can also rapidly inhibit protein N-glycosylation, we postulated that this compound could induce IL-23 in DCs via activation of the endoplasmic reticulum (ER stress response. Indeed, stimulation of DCs with PAMPs in the presence of 2-DG robustly activated inositol-requiring protein 1α (IRE1α signaling and to a lesser extent the PERK arm of the unfolded protein response. Additional ER stressors such as tunicamycin and thapsigargin also promoted IL-23 expression by PAMP-stimulated DCs. Pharmacological, biochemical, and genetic analyses using conditional knockout mice revealed that IL-23 induction in ER stressed DCs stimulated with PAMPs was IRE1α/X-box binding protein 1-dependent upon zymosan stimulation. Interestingly, we further evidenced PERK-mediated and CAAT/enhancer-binding protein β-dependent trans-activation of IL23A upon lipopolysaccharide treatment. Our findings uncover that the ER stress response can potently modulate cytokine expression in PAMP-stimulated human DCs.

Hexachlorobenzene impairs glucose metabolism in a rat model of porphyria cutanea tarda: a mechanistic approach

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Mazzetti, Marta Blanca; Taira, Maria Cristina; Lelli, Sandra Marcela; Viale, Leonor Carmen San Martin de [Departamento de Quimica Biologica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, C1428BGA, Ciudad Autonoma Buenos Aires (Argentina); Dascal, Eduardo; Basabe, Juan Carlos [Centro de Investigaciones Endocrinologicas (CEDIE). Hospital de Ninos, Dr. Ricardo Gutierrez, C1425EDF, Ciudad Autonoma Buenos Aires (Argentina)

2004-01-01

Hexachlobenzene (HCB), one of the most persistent environmental pollutants, induces porphyria cutanea tarda (PCT). The aim of this work was to analyze the effect of HCB on some aspects of glucose metabolism, particularly those related to its neosynthesis in vivo. For this purpose, a time-course study on gluconeogenic enzymes, pyruvate carboxylase (PC), phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G-6-Pase) and on pyruvate kinase (PK), a glycolytic enzyme, was carried out. Plasma glucose and insulin levels, hepatic glycogen, tryptophan contents, and the pancreatic insulin secretion pattern stimulated by glucose were investigated. Oxidative stress and heme pathway parameters were also evaluated. HCB treatment decreased PC, PEPCK, and G-6-Pase activities. The effect was observed at an early time point and grew as the treatment progressed. Loss of 60, 56, and 37%, respectively, was noted at the end of the treatment when a considerable amount of porphyrins had accumulated in the liver as a result of drastic blockage of uroporphyrinogen decarboxylase (URO-D) (95% inhibition). The plasma glucose level was reduced (one-third loss), while storage of hepatic glucose was stimulated in a time-dependent way by HCB treatment. A decay in the normal plasma insulin level was observed as fungicide intoxication progressed (twice to four times lower). However, normal insulin secretion of perifused pancreatic Langerhans islets stimulated by glucose during the 3rd and 6th weeks of treatment did not prove to be significantly affected. HCB promoted a time-dependent increase in urinary chemiluminiscence (fourfold) and hepatic malondialdehide (MDA) content (fivefold), while the liver tryptophan level was only raised at the longest intoxication times. These results would suggest that HCB treatment does not cause a primary alteration in the mechanism of pancreatic insulin secretion and that the changes induced by the fungicide on insulin levels would be an adaptative

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

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

2009-01-01

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

The Lin28/let-7 axis regulates glucose metabolism

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Zhu, Hao; Shyh-Chang, Ng; Segrè, Ayellet V.; Shinoda, Gen; Shah, Samar P.; Einhorn, William S.; Takeuchi, Ayumu; Engreitz, Jesse M.; Hagan, John P.; Kharas, Michael G; Urbach, Achia; Thornton, James E.; Triboulet, Robinson; Gregory, Richard I.; Altshuler, David; Daley, George Q.

2012-01-01

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

Development of a Positive Youth Development Program: Promoting the Mental Health of Stressful Adolescents Using Principles of Problem Solving Therapy

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Daniel T.L. Shek

2006-01-01

Full Text Available This paper outlines the proposal for the development, implementation, and evaluation of a positive youth development program that attempts to promote the mental health of stressful Chinese adolescents using principles of Problem Solving Therapy (PST. There are two general aims of PST: to help clients identify life difficulties and resolve them, as well as to teach them skills on how to deal with future problems. The proposed project will utilize the principles of PST as the guiding framework to run two mental health promotion courses for adolescents who are experiencing disturbing stressful responses and students who want to improve their stress management style. Both objective and subjective outcome evaluation strategies will be carried out to assess the effectiveness of the intervention to promote the psychological well-being in adolescents who are experiencing stress. A related sample proposal is described that can give social workers some insight on how to prepare a proposal for developing the Tier 2 Program of the Project P.A.T.H.S. (Positive Adolescent Training through Holistic Social Programs.

Hypothalamic glucose sensing: making ends meet

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Vanessa eRouth

2014-12-01

Full Text Available The neuroendocrine system governs essential survival and homeostatic functions. For example, growth is needed for development. Thermoregulation maintains optimal core temperature in a changing environment. Reproduction ensures species survival. Stress and immune responses enable an organism to overcome external and internal threats. The circadian system regulates arousal and sleep such that vegetative and active functions do not overlap. All of these functions require a significant portion of the body’s energy. As the integrator of the neuroendocrine system, the hypothalamus carefully assesses the energy status of the body in order to appropriately partition resources to provide for each system without compromising the others. While doing so the hypothalamus must ensure that adequate glucose levels are preserved for brain function since glucose is the primary fuel of the brain. To this end, the hypothalamus contains specialized glucose sensing neurons which are scattered throughout the nuclei controlling distinct neuroendocrine functions. We hypothesize that these neurons play a key role in enabling the hypothalamus to partition energy to meet these peripheral survival needs without endangering the brain’s glucose supply. The goal of this review is to describe the varied mechanisms underlying glucose sensing in neurons within discrete hypothalamic nuclei. We will then evaluate the way in which peripheral energy status regulates glucose sensitivity. For example, during energy deficit such as fasting specific hypothalamic glucose sensing neurons become sensitized to decreased glucose. This increases the gain of the information relay when glucose availability is a greater concern for the brain. Finally, changes in glucose sensitivity under pathological conditions (e.g., recurrent insulin-hypoglycemia, diabetes will be addressed. The overall goal of this review is to place glucose sensing neurons within the context of hypothalamic control of

Inflammatory stress promotes the development of obesity-related chronic kidney disease via CD36 in mice.

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Yang, Ping; Xiao, Yayun; Luo, Xuan; Zhao, Yunfei; Zhao, Lei; Wang, Yan; Wu, Tingting; Wei, Li; Chen, Yaxi

2017-07-01

Ectopic fat located in the kidney has emerged as a novel cause of obesity-related chronic kidney disease (CKD). In this study, we aimed to investigate whether inflammatory stress promotes ectopic lipid deposition in the kidney and causes renal injury in obese mice and whether the pathological process is mediated by the fatty acid translocase, CD36. High-fat diet (HFD) feeding alone resulted in obesity, hyperlipidemia, and slight renal lipid accumulation in mice, which nevertheless had normal kidney function. HFD-fed mice with chronic inflammation had severe renal steatosis and obvious glomerular and tubular damage, which was accompanied by increased CD36 expression. Interestingly, CD36 deficiency in HFD-fed mice eliminated renal lipid accumulation and pathological changes induced by chronic inflammation. In both human mesangial cells (HMCs) and human kidney 2 (HK2) cells, inflammatory stress increased the efficiency of CD36 protein incorporation into membrane lipid rafts, promoting FFA uptake and intracellular lipid accumulation. Silencing of CD36 in vitro markedly attenuated FFA uptake, lipid accumulation, and cellular stress induced by inflammatory stress. We conclude that inflammatory stress aggravates renal injury by activation of the CD36 pathway, suggesting that this mechanism may operate in obese individuals with chronic inflammation, making them prone to CKD. Copyright © 2017 by the American Society for Biochemistry and Molecular Biology, Inc.

Calcium Homeostasis and ER Stress in Control of Autophagy in Cancer Cells

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Elżbieta Kania

2015-01-01

Full Text Available Autophagy is a basic catabolic process, serving as an internal engine during responses to various cellular stresses. As regards cancer, autophagy may play a tumor suppressive role by preserving cellular integrity during tumor development and by possible contribution to cell death. However, autophagy may also exert oncogenic effects by promoting tumor cell survival and preventing cell death, for example, upon anticancer treatment. The major factors influencing autophagy are Ca2+ homeostasis perturbation and starvation. Several Ca2+ channels like voltage-gated T- and L-type channels, IP3 receptors, or CRAC are involved in autophagy regulation. Glucose transporters, mainly from GLUT family, which are often upregulated in cancer, are also prominent targets for autophagy induction. Signals from both Ca2+ perturbations and glucose transport blockage might be integrated at UPR and ER stress activation. Molecular pathways such as IRE 1-JNK-Bcl-2, PERK-eIF2α-ATF4, or ATF6-XBP 1-ATG are related to autophagy induced through ER stress. Moreover ER molecular chaperones such as GRP78/BiP and transcription factors like CHOP participate in regulation of ER stress-mediated autophagy. Autophagy modulation might be promising in anticancer therapies; however, it is a context-dependent matter whether inhibition or activation of autophagy leads to tumor cell death.

Neighbourhood exposure to point-of-sale price promotions for cigarettes is associated with financial stress among smokers: results from a population-based study.

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Siahpush, Mohammad; Tibbits, Melissa; Soliman, Ghada A; Grimm, Brandon; Shaikh, Raees A; McCarthy, Molly; Wan, Neng; Ramos, Athena K; Correa, Antonia

2017-11-01

To examine the association between neighbourhood exposure to point-of-sale (POS) cigarette price promotions and financial stress among smokers in a Midwestern metropolitan area in the USA. Survey data from 888 smokers provided information on sociodemographic and smoking related variables. Financial stress was measured with the question: 'In the last six months, because of lack of money, was there a time when you were unable to buy food or pay any important bills on time, such as electricity, telephone, credit card, rent or your mortgage? (Yes/No).' Using audit data from 504 tobacco retailers, we estimated a score of POS price promotions for each respondent by summing the different types of promotion in each store in their neighbourhood, as defined by a 1-km roadway buffer. Adjusted results provided strong support for an association between higher scores of neighbourhood POS cigarette price promotions and a higher probability of financial stress (p=0.007). Exposure to POS cigarette price promotions is associated with financial stress. This finding, coupled with previous reports that smokers with financial stress are less likely to attempt to quit or succeed in quitting smoking, suggests that POS cigarette price promotions may act as an impediment to smoking cessation. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

Recommendations for Development of Botanical Polyphenols as "Natural Drugs" for Promotion of Resilience Against Stress-Induced Depression and Cognitive Impairment.

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Ward, Libby; Pasinetti, Giulio Maria

2016-09-01

Extensive evidence has demonstrated that psychological stress has detrimental effects on psychological health, cognitive function, and ultimately well-being. While stressful events are a significant cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The mechanisms underlying such resilience are poorly understood, and there is an urgent need to identify and target these mechanisms to promote resilience under stressful events. Botanicals have been used throughout history to treat various medical conditions; however, the development of botanical compounds into potential preventative and therapeutic agents in studies promoting brain health is hindered by the fact that most orally consumed botanicals are extensively metabolized during absorption and/or by post-absorptive xenobiotic metabolism. Therefore, the primary objective of this review article is to provide recommendations for developing natural compounds as novel therapeutic strategies to promote resilience in susceptible subjects. The development of botanical polyphenols to ultimately attenuate mood disorders and cognitive impairment will rely on understanding (1) the absorption and bioavailability of botanical polyphenols with emphasis on flavan-3-ols, (2) the characterization of tissue-specific accumulation of biologically available polyphenols and their mechanisms of action in the brain, and eventually (3) the characterization of biologically available polyphenol metabolites in mechanisms associated with the promotion of resilience against mood disorders and cognitive impairment in response to stress. We also summarize exciting new lines of investigation about the role of botanicals such as polyphenols in the promotion of cognitive and psychological resilience. This information will provide a strategical framework for the future development of botanicals as therapeutic agents to promote resilience, ultimately preventing and/or therapeutically treating

A CREB-Sirt1-Hes1 Circuitry Mediates Neural Stem Cell Response to Glucose Availability

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Salvatore Fusco

2016-02-01

Full Text Available Summary: Adult neurogenesis plays increasingly recognized roles in brain homeostasis and repair and is profoundly affected by energy balance and nutrients. We found that the expression of Hes-1 (hairy and enhancer of split 1 is modulated in neural stem and progenitor cells (NSCs by extracellular glucose through the coordinated action of CREB (cyclic AMP responsive element binding protein and Sirt-1 (Sirtuin 1, two cellular nutrient sensors. Excess glucose reduced CREB-activated Hes-1 expression and results in impaired cell proliferation. CREB-deficient NSCs expanded poorly in vitro and did not respond to glucose availability. Elevated glucose also promoted Sirt-1-dependent repression of the Hes-1 promoter. Conversely, in low glucose, CREB replaced Sirt-1 on the chromatin associated with the Hes-1 promoter enhancing Hes-1 expression and cell proliferation. Thus, the glucose-regulated antagonism between CREB and Sirt-1 for Hes-1 transcription participates in the metabolic regulation of neurogenesis. : Using a combination of in vitro and in vivo studies, Fusco et al. find that excess glucose impairs the self-renewal capacity of neural stem cells through a molecular circuit that involves the transcription factor CREB and Sirtuin 1. The authors suggest that this circuitry may link nutrient excess with neurodegeneration and brain aging. Keywords: neural stem cells, adult neurogenesis, CREB, Sirt-1, nutrients, metabolism, diabetes

Dynamic O-GlcNAc cycling at promoters of Caenorhabditis elegans genes regulating longevity, stress, and immunity.

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Love, Dona C; Ghosh, Salil; Mondoux, Michelle A; Fukushige, Tetsunari; Wang, Peng; Wilson, Mark A; Iser, Wendy B; Wolkow, Catherine A; Krause, Michael W; Hanover, John A

2010-04-20

Nutrient-driven O-GlcNAcylation of key components of the transcription machinery may epigenetically modulate gene expression in metazoans. The global effects of GlcNAcylation on transcription can be addressed directly in C. elegans because knockouts of the O-GlcNAc cycling enzymes are viable and fertile. Using anti-O-GlcNAc ChIP-on-chip whole-genome tiling arrays on wild-type and mutant strains, we detected over 800 promoters where O-GlcNAc cycling occurs, including microRNA loci and multigene operons. Intriguingly, O-GlcNAc-marked promoters are biased toward genes associated with PIP3 signaling, hexosamine biosynthesis, and lipid/carbohydrate metabolism. These marked genes are linked to insulin-like signaling, metabolism, aging, stress, and pathogen-response pathways in C. elegans. Whole-genome transcriptional profiling of the O-GlcNAc cycling mutants confirmed dramatic deregulation of genes in these key pathways. As predicted, the O-GlcNAc cycling mutants show altered lifespan and UV stress susceptibility phenotypes. We propose that O-GlcNAc cycling at promoters participates in a molecular program impacting nutrient-responsive pathways in C. elegans, including stress, pathogen response, and adult lifespan. The observed impact of O-GlcNAc cycling on both signaling and transcription in C. elegans has important implications for human diseases of aging, including diabetes and neurodegeneration.

Salinity stress effects on [14C-1]- and [14C-6]-glucose metabolism of a salt-tolerant and salt-susceptible variety of wheat

International Nuclear Information System (INIS)

Krishnaraj, S.; Thorpe, T.A.

1996-01-01

The effect of salt (sodium sulfate) on carbohydrate metabolism was studied in a salt-tolerant (Kharchia-65) variety and a salt-susceptible (Fielder) variety of wheat (Triticum aestivum L.) by comparing their responses under control and stress conditions. Leaf segments of Kharchia-65 showed increased activity through both the pentose phosphate pathway (PPP) and the glycolytic pathway of glucose oxidation, with the former being comparatively more active in response to salt. In Fielder, there was an increase in PPP activity at the expense of glycolytic pathway activity. Label from glucose was found in the lipid, neutral sugar, amino acid, organic acid, and phosphate ester fractions in all treatments. On the basis of the label distribution patterns, it appears that Fielder leaves incubated with [ 14 C-6]-glucose were not able to utilize glucose efficiently under saline conditions. This finding was further supported by decreased label incorporation into all the fractions, especially the amino acid and organic acid fractions. Adenosine phosphate and reduced pyridine nucleotide concentrations were consistent with these observations. We conclude therefore that the salt-tolerant variety had an enhanced metabolic activity compared with the salt-susceptible variety, which contributed to its ability to overcome the adverse effects of salt. (author)

Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

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Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio [University of Genoa and IRCCS San Martino-IST, Clinical Neurology, Department of Neuroscience (DINOGMI), Largo P. Daneo, 3, 16132, Genoa (Italy); Polidori, M.C. [University of Cologne, Institute of Geriatrics, Cologne (Germany); Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia [University of Perugia, Institute of Gerontology and Geriatrics, Department of Clinical and Experimental Medicine, Perugia (Italy); Morbelli, Silvia; Bossert, Irene [University of Genoa and IRCCS San Martino-IST, Nuclear Medicine, Department of Health Science (DISSAL), Genoa (Italy); Fiorucci, Giuliana; Dottorini, Massimo Eugenio [Nuclear Medicine, S. M. della Misericordia Hospital, Perugia (Italy)

2014-04-15

The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain{sup 18}F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

Plasma antioxidants and brain glucose metabolism in elderly subjects with cognitive complaints

International Nuclear Information System (INIS)

Picco, Agnese; Ferrara, Michela; Arnaldi, Dario; Brugnolo, Andrea; Nobili, Flavio; Polidori, M.C.; Cecchetti, Roberta; Baglioni, Mauro; Bastiani, Patrizia; Mecocci, Patrizia; Morbelli, Silvia; Bossert, Irene; Fiorucci, Giuliana; Dottorini, Massimo Eugenio

2014-01-01

The role of oxidative stress is increasingly recognized in cognitive disorders of the elderly, notably Alzheimer's disease (AD). In these subjects brain 18 F-FDG PET is regarded as a reliable biomarker of neurodegeneration. We hypothesized that oxidative stress could play a role in impairing brain glucose utilization in elderly subjects with increasing severity of cognitive disturbance. The study group comprised 85 subjects with cognitive disturbance of increasing degrees of severity including 23 subjects with subjective cognitive impairment (SCI), 28 patients with mild cognitive impairment and 34 patients with mild AD. In all subjects brain FDG PET was performed and plasma activities of extracellular superoxide dismutase (eSOD), catalase and glutathione peroxidase were measured. Voxel-based analysis (SPM8) was used to compare FDG PET between groups and to evaluate correlations between plasma antioxidants and glucose metabolism in the whole group of subjects, correcting for age and Mini-Mental State Examination score. Brain glucose metabolism progressively decreased in the bilateral posterior temporoparietal and cingulate cortices across the three groups, from SCI to mild AD. eSOD activity was positively correlated with glucose metabolism in a large area of the left temporal lobe including the superior, middle and inferior temporal gyri and the fusiform gyrus. These results suggest a role of oxidative stress in the impairment of glucose utilization in the left temporal lobe structures in elderly patients with cognitive abnormalities, including AD and conditions predisposing to AD. Further studies exploring the oxidative stress-energy metabolism axis are considered worthwhile in larger groups of these patients in order to identify pivotal pathophysiological mechanisms and innovative therapeutic opportunities. (orig.)

Homeobox gene Dlx-2 is implicated in metabolic stress-induced necrosis

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Lim Sung-Chul

2011-09-01

Full Text Available Abstract Background In contrast to tumor-suppressive apoptosis and autophagic cell death, necrosis promotes tumor progression by releasing the pro-inflammatory and tumor-promoting cytokine high mobility group box 1 (HMGB1, and its presence in tumor patients is associated with poor prognosis. Thus, necrosis has important clinical implications in tumor development; however, its molecular mechanism remains poorly understood. Results In the present study, we show that Distal-less 2 (Dlx-2, a homeobox gene of the Dlx family that is involved in embryonic development, is induced in cancer cell lines dependently of reactive oxygen species (ROS in response to glucose deprivation (GD, one of the metabolic stresses occurring in solid tumors. Increased Dlx-2 expression was also detected in the inner regions, which experience metabolic stress, of human tumors and of a multicellular tumor spheroid, an in vitro model of solid tumors. Dlx-2 short hairpin RNA (shRNA inhibited metabolic stress-induced increase in propidium iodide-positive cell population and HMGB1 and lactate dehydrogenase (LDH release, indicating the important role(s of Dlx-2 in metabolic stress-induced necrosis. Dlx-2 shRNA appeared to exert its anti-necrotic effects by preventing metabolic stress-induced increases in mitochondrial ROS, which are responsible for triggering necrosis. Conclusions These results suggest that Dlx-2 may be involved in tumor progression via the regulation of metabolic stress-induced necrosis.

Influence of Regularity of Exposure to Chronic Stress on the Pattern of Habituation of Pituitary-Adrenal Hormones, Prolactin and Glucose.

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Martí; Armario

1997-05-01

The effect of regularity of exposure to two different chronic stressors (noise or immobilization (IMO)) on the pattern of habituation of pituitary-adrenal (PA) hormones, prolactin and glucose was evaluated in adult male rats. Animals were chronically subjected to either regular or irregular time schedule of noise (30 min/day) or IMO (2 h/day) for two weeks. The day after the last stress session the rats were killed without stress or after having been subjected to 30 min of the homotypic stressor. Whereas regular noise did not affect food intake, body weight gain or adrenal weight, irregular noise decreased body weight gain and induced a moderate adrenal hypertrophy. In addition, previous daily exposure to regular but not to irregular noise reduced both prolactin and corticosterone responses to acute noise. In contrast, glucose response to acute noise was reduced after both regular and irregular exposure to chronic noise. Either regular or irregular exposure to chronic IMO decreased food intake and body weight and increased adrenal weight to the same extent. Likewise, no influence of regularity of exposure to chronic IMO on corticosterone and prolactin responses to acute IMO was observed. However, habituation of the ACTH response to acute IMO was observed in rats subjected to chronic regular IMO, but not in rats subjected to chronic irregular IMO. Finally, acute IMO-induced hyperglycemia diminished to the same extent after regular and irregular IMO. From these results we can conclude that: first, the process of habituation of the PA axis to chronic stress is greatly dependent upon factors such as regularity of exposure to the stressor and stressor intensity, and second, the influence of regularity on the pattern of habituation to a repeated stressor is dependent on the physiological variable we are dealing with.

Astroglial Pentose Phosphate Pathway Rates in Response to High-Glucose Environments

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Shinichi Takahashi

2012-02-01

Full Text Available ROS (reactive oxygen species play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain parenchymal cells remain unclear. The PPP (pentose phosphate pathway and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of 14CO2 production from [1-14C]glucose and [6-14C]glucose. ROS production, mainly H2O2, and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum stress (presumably through increased hexosamine biosynthetic pathway flux. Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2, which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke.

Astroglial pentose phosphate pathway rates in response to high-glucose environments

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Takahashi, Shinichi; Izawa, Yoshikane; Suzuki, Norihiro

2012-01-01

ROS (reactive oxygen species) play an essential role in the pathophysiology of diabetes, stroke and neurodegenerative disorders. Hyperglycaemia associated with diabetes enhances ROS production and causes oxidative stress in vascular endothelial cells, but adverse effects of either acute or chronic high-glucose environments on brain parenchymal cells remain unclear. The PPP (pentose phosphate pathway) and GSH participate in a major defence mechanism against ROS in brain, and we explored the role and regulation of the astroglial PPP in response to acute and chronic high-glucose environments. PPP activity was measured in cultured neurons and astroglia by determining the difference in rate of 14CO2 production from [1-14C]glucose and [6-14C]glucose. ROS production, mainly H2O2, and GSH were also assessed. Acutely elevated glucose concentrations in the culture media increased PPP activity and GSH level in astroglia, decreasing ROS production. Chronically elevated glucose environments also induced PPP activation. Immunohistochemical analyses revealed that chronic high-glucose environments induced ER (endoplasmic reticulum) stress (presumably through increased hexosamine biosynthetic pathway flux). Nuclear translocation of Nrf2 (nuclear factor-erythroid 2 p45 subunit-related factor 2), which regulates G6PDH (glyceraldehyde-6-phosphate dehydrogenase) by enhancing transcription, was also observed in association with BiP (immunoglobulin heavy-chain-binding protein) expression. Acute and chronic high-glucose environments activated the PPP in astroglia, preventing ROS elevation. Therefore a rapid decrease in glucose level seems to enhance ROS toxicity, perhaps contributing to neural damage when insulin levels given to diabetic patients are not properly calibrated and plasma glucose levels are not adequately maintained. These findings may also explain the lack of evidence for clinical benefits from strict glycaemic control during the acute phase of stroke. PMID:22300409

Long-term treatment with the sodium glucose cotransporter 2 inhibitor, dapagliflozin, ameliorates glucose homeostasis and diabetic nephropathy in db/db mice.

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Naoto Terami

Full Text Available Inhibition of sodium glucose cotransporter 2 (SGLT2 has been reported as a new therapeutic strategy for treating diabetes. However, the effect of SGLT2 inhibitors on the kidney is unknown. In addition, whether SGLT2 inhibitors have an anti-inflammatory or antioxidative stress effect is still unclear. In this study, to resolve these issues, we evaluated the effects of the SGLT2 inhibitor, dapagliflozin, using a mouse model of type 2 diabetes and cultured proximal tubular epithelial (mProx24 cells. Male db/db mice were administered 0.1 or 1.0 mg/kg of dapagliflozin for 12 weeks. Body weight, blood pressure, blood glucose, hemoglobin A1c, albuminuria and creatinine clearance were measured. Mesangial matrix accumulation and interstitial fibrosis in the kidney and pancreatic β-cell mass were evaluated by histological analysis. Furthermore, gene expression of inflammatory mediators, such as osteopontin, monocyte chemoattractant protein-1 and transforming growth factor-β, was evaluated by quantitative reverse transcriptase-PCR. In addition, oxidative stress was evaluated by dihydroethidium and NADPH oxidase 4 staining. Administration of 0.1 or 1.0 mg/kg of dapagliflozin ameliorated hyperglycemia, β-cell damage and albuminuria in db/db mice. Serum creatinine, creatinine clearance and blood pressure were not affected by administration of dapagliflozin, but glomerular mesangial expansion and interstitial fibrosis were suppressed in a dose-dependent manner. Dapagliflozin treatment markedly decreased macrophage infiltration and the gene expression of inflammation and oxidative stress in the kidney of db/db mice. Moreover, dapagliflozin suppressed the high-glucose-induced gene expression of inflammatory cytokines and oxidative stress in cultured mProx24 cells. These data suggest that dapagliflozin ameliorates diabetic nephropathy by improving hyperglycemia along with inhibiting inflammation and oxidative stress.

Intermittent hypoxia impairs glucose homeostasis in C57BL6/J mice: partial improvement with cessation of the exposure.

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Polak, Jan; Shimoda, Larissa A; Drager, Luciano F; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y; Punjabi, Naresh M

2013-10-01

Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism.

Glucose-6-phosphate dehydrogenase is required for hpa1xoo (harpin protein fragment)-mediated salt stress tolerance in transgenic arabidopsis thaliana

International Nuclear Information System (INIS)

Sang, S.L.; Xie, L.L.; Cui, X.W.; Wang, Z.Y.

2018-01-01

Harpin induces salicylic acid and abscisic acid signaling in plants under biotic and abiotic stress, respectively. Our previous report showed that the effective harpin fragment Hpa1xoo enhanced H2O2 production and pathogen resistance in a transgenic Arabidopsis mutant. In this study, we examined contents of thiobarbituric acid reactive substance (TBARS), H2O2 and glutathione, and glucose-6-phosphate dehydrogenase (G6PDH), glutathione reductase (GR) and glutathione peroxidase (GPX) enzyme activity in Hpa1xoo-expressing Arabidopsis under salt stress. The results revealed increased amounts of TBARS and H2O2 in wild-type (WT) compared to mutant plants under salt stress conditions. In contrast, increased levels were observed in the mutant under stress-free conditions. Moreover, a higher reduced glutathione (GSH) content and ratio of GSH/oxidized glutathione (GSSG) was observed in mutant compared to WT plants under both stress-free and salt stress conditions. In addition, mutant plants exhibited significantly higher G6PDH, GR and GPX activity than WT plants under salt stress. Suppression of G6PDH activity via 6-aminonicotinamide (6-AN, a specific inhibitor of G6PDH) was partly reversed by L-buthionine-sulfoximine (BSO, a specific inhibitor of GSH regeneration) and aggravated by GSH. Combined with previous reports, these findings suggest that the G6PDH enzyme plays a key role in harpin fragment (Hpa1xoo)-mediated salt stress tolerance in transgenic Arabidopsis. (author)

Ribosomal elongation factor 4 promotes cell death associated with lethal stress.

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Li, Liping; Hong, Yuzhi; Luan, Gan; Mosel, Michael; Malik, Muhammad; Drlica, Karl; Zhao, Xilin

2014-12-09

Ribosomal elongation factor 4 (EF4) is highly conserved among bacteria, mitochondria, and chloroplasts. However, the EF4-encoding gene, lepA, is nonessential and its deficiency shows no growth or fitness defect. In purified systems, EF4 back-translocates stalled, posttranslational ribosomes for efficient protein synthesis; consequently, EF4 has a protective role during moderate stress. We were surprised to find that EF4 also has a detrimental role during severe stress: deletion of lepA increased Escherichia coli survival following treatment with several antimicrobials. EF4 contributed to stress-mediated lethality through reactive oxygen species (ROS) because (i) the protective effect of a ΔlepA mutation against lethal antimicrobials was eliminated by anaerobic growth or by agents that block hydroxyl radical accumulation and (ii) the ΔlepA mutation decreased ROS levels stimulated by antimicrobial stress. Epistasis experiments showed that EF4 functions in the same genetic pathway as the MazF toxin, a stress response factor implicated in ROS-mediated cell death. The detrimental action of EF4 required transfer-messenger RNA (tmRNA, which tags truncated proteins for degradation and is known to be inhibited by EF4) and the ClpP protease. Inhibition of a protective, tmRNA/ClpP-mediated degradative activity would allow truncated proteins to indirectly perturb the respiratory chain and thereby provide a potential link between EF4 and ROS. The connection among EF4, MazF, tmRNA, and ROS expands a pathway leading from harsh stress to bacterial self-destruction. The destructive aspect of EF4 plus the protective properties described previously make EF4 a bifunctional factor in a stress response that promotes survival or death, depending on the severity of stress. Translation elongation factor 4 (EF4) is one of the most conserved proteins in nature, but it is dispensable. Lack of strong phenotypes for its genetic knockout has made EF4 an enigma. Recent biochemical work has

Fabrication of Mediatorless/Membraneless Glucose/Oxygen Based Biofuel Cell using Biocatalysts Including Glucose Oxidase and Laccase Enzymes

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Christwardana, Marcelinus; Kim, Ki Jae; Kwon, Yongchai

2016-07-01

Mediatorless and membraneless enzymatic biofuel cells (EBCs) employing new catalytic structure are fabricated. Regarding anodic catalyst, structure consisting of glucose oxidase (GOx), poly(ethylenimine) (PEI) and carbon nanotube (CNT) is considered, while three cathodic catalysts consist of glutaraldehyde (GA), laccase (Lac), PEI and CNT that are stacked together in different ways. Catalytic activities of the catalysts for glucose oxidation and oxygen reduction reactions (GOR and ORR) are evaluated. As a result, it is confirmed that the catalysts work well for promotion of GOR and ORR. In EBC tests, performances of EBCs including 150 μm-thick membrane are measured as references, while those of membraneless EBCs are measured depending on parameters like glucose flow rate, glucose concentration, distance between two electrodes and electrolyte pH. With the measurements, how the parameters affect EBC performance and their optimal conditions are determined. Based on that, best maximum power density (MPD) of membraneless EBC is 102 ± 5.1 μW · cm-2 with values of 0.5 cc · min-1 (glucose flow rate), 40 mM (glucose concentration), 1 mm (distance between electrodes) and pH 3. When membrane and membraneless EBCs are compared, MPD of the membraneless EBC that is run at the similar operating condition to EBC including membrane is speculated as about 134 μW · cm-2.

Recommendations for Development of Botanical Polyphenols as “Natural Drugs” for Promotion of Resilience Against Stress-Induced Depression and Cognitive Impairment

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Ward, Libby; Pasinetti, Giulio Maria

2016-01-01

Extensive evidence has demonstrated that psychological stress has detrimental effects on psychological health, cognitive function, and ultimately well-being. While stressful events are a significant cause of psychopathology, most individuals exposed to adversity maintain normal psychological functioning. The mechanisms underlying such resilience are poorly understood, and there is an urgent need to identify and target these mechanisms to promote resilience under stressful events. Botanicals have been used throughout history to treat various medical conditions; however, the development of botanical compounds into potential preventative and therapeutic agents in studies promoting brain health is hindered by the fact that most orally consumed botanicals are extensively metabolized during absorption and/or by post-absorptive xenobiotic metabolism. Therefore, the primary objective of this review article is to provide recommendations for developing natural compounds as novel therapeutic strategies to promote resilience in susceptible subjects. The development of botanical polyphenols to ultimately attenuate mood disorders and cognitive impairment will rely on understanding (1) the absorption and bioavailability of botanical polyphenols with emphasis on flavan-3-ols, (2) the characterization of tissue specific accumulation of biologically available polyphenols and their mechanisms of action in the brain, and eventually (3) the characterization of biologically available polyphenol metabolites in mechanisms associated with the promotion of resilience against mood disorders and cognitive impairment in response to stress. We also summarize exciting new lines of investigation about the role of botanicals such as polyphenols in the promotion of cognitive and psychological resilience. This information will provide a strategical framework for the future development of botanicals as therapeutic agents to promote resilience, ultimately preventing and/or therapeutically treating

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

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

2014-12-01

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

Individual differences in the peripheral immune system promote resilience versus susceptibility to social stress.

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Hodes, Georgia E; Pfau, Madeline L; Leboeuf, Marylene; Golden, Sam A; Christoffel, Daniel J; Bregman, Dana; Rebusi, Nicole; Heshmati, Mitra; Aleyasin, Hossein; Warren, Brandon L; Lebonté, Benoit; Horn, Sarah; Lapidus, Kyle A; Stelzhammer, Viktoria; Wong, Erik H F; Bahn, Sabine; Krishnan, Vaishnav; Bolaños-Guzman, Carlos A; Murrough, James W; Merad, Miriam; Russo, Scott J

2014-11-11

Depression and anxiety disorders are associated with increased release of peripheral cytokines; however, their functional relevance remains unknown. Using a social stress model in mice, we find preexisting individual differences in the sensitivity of the peripheral immune system that predict and promote vulnerability to social stress. Cytokine profiles were obtained 20 min after the first social stress exposure. Of the cytokines regulated by stress, IL-6 was most highly up-regulated only in mice that ultimately developed a susceptible behavioral phenotype following a subsequent chronic stress, and levels remained elevated for at least 1 mo. We confirmed a similar elevation of serum IL-6 in two separate cohorts of patients with treatment-resistant major depressive disorder. Before any physical contact in mice, we observed individual differences in IL-6 levels from ex vivo stimulated leukocytes that predict susceptibility versus resilience to a subsequent stressor. To shift the sensitivity of the peripheral immune system to a pro- or antidepressant state, bone marrow (BM) chimeras were generated by transplanting hematopoietic progenitor cells from stress-susceptible mice releasing high IL-6 or from IL-6 knockout (IL-6(-/-)) mice. Stress-susceptible BM chimeras exhibited increased social avoidance behavior after exposure to either subthreshold repeated social defeat stress (RSDS) or a purely emotional stressor termed witness defeat. IL-6(-/-) BM chimeric and IL-6(-/-) mice, as well as those treated with a systemic IL-6 monoclonal antibody, were resilient to social stress. These data establish that preexisting differences in stress-responsive IL-6 release from BM-derived leukocytes functionally contribute to social stress-induced behavioral abnormalities.

Exercising Tactically for Taming Postmeal Glucose Surges

Directory of Open Access Journals (Sweden)

Elsamma Chacko

2016-01-01

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

Exercising Tactically for Taming Postmeal Glucose Surges.

Science.gov (United States)

Chacko, Elsamma

2016-01-01

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

High Glucose-Induced Oxidative Stress Increases the Copy Number of Mitochondrial DNA in Human Mesangial Cells

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Ghada Al-Kafaji

2013-01-01

Full Text Available Oxidative damage to mitochondrial DNA (mtDNA has been linked to the pathogenicity of diabetic nephropathy. We tested the hypothesis that mtDNA copy number may be increased in human mesangial cells in response to high glucose-induced reactive oxygen species (ROS to compensate for damaged mtDNA. The effect of manganese superoxide dismutase mimetic (MnTBAP on glucose-induced mtDNA copy number was also examined. The copy number of mtDNA was determined by real-time PCR in human mesangial cells cultured in 5 mM glucose, 25 mM glucose, and mannitol (osmotic control, as well as in cells cultured in 25 mM glucose in the presence and absence of 200 μM MnTBAP. Intracellular ROS was assessed by confocal microscopy and flow cytometry in human mesangial cells. The copy number of mtDNA was significantly increased when human mesangial cells were incubated with 25 mM glucose compared to 5 mM glucose and mannitol. In addition, 25 mM glucose rapidly generated ROS in the cells, which was not detected in 5 mM glucose. Furthermore, mtDNA copy number was significantly decreased and maintained to normal following treatment of cells with 25 mM glucose and MnTBAP compared to 25 mM glucose alone. Inclusion of MnTBAP during 25 mM glucose incubation inhibited mitochondrial superoxide in human mesangial cells. Increased mtDNA copy number in human mesangial cells by high glucose could contribute to increased mitochondrial superoxide, and prevention of mtDNA copy number could have potential in retarding the development of diabetic nephropathy.

Mechanocatalytic Production of Lactic Acid from Glucose by Ball Milling

Directory of Open Access Journals (Sweden)

Luyang Li

2017-06-01

Full Text Available A solvent-free process was developed for the direct production of lactic acid from glucose in a mechanocatalytic process in the presence of Ba(OH2, and a moderate lactic acid yield of 35.6% was obtained. Glucose conversion and lactic acid formation were favorable at higher catalyst/glucose mass ratios. However, at relatively lower catalyst/glucose mass ratios, they were greatly inhibited, and the promotion of fructose formation was observed. The mechanocatalytic process was applicable for various carbohydrates such as C5 sugars, C6 sugars, and disaccharides with 20–36% lactic acid yields achieved. This work provides a new pathway for the production of value-added chemicals from biomass resources.

Activation of ERK2 in basolateral amygdala underlies the promoting influence of stress on fear memory and anxiety: influence of midazolam pretreatment.

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Maldonado, N M; Espejo, P J; Martijena, I D; Molina, V A

2014-02-01

Exposure to emotionally arousing experiences elicits a robust and persistent memory and enhances anxiety. The amygdala complex plays a key role in stress-induced emotional processing and in the fear memory formation. It is well known that ERK activation in the amygdala is a prerequisite for fear memory consolidation. Moreover, stress elevates p-ERK2 levels in several areas of the brain stress circuitry. Therefore, given that the ERK1/2 cascade is activated following stress and that the role of this cascade is critical in the formation of fear memory, the present study investigated the potential involvement of p-ERK2 in amygdala subnuclei in the promoting influence of stress on fear memory formation and on anxiety-like behavior. A robust and persistent ERK2 activation was noted in the Basolateral amygdala (BLA), which was evident at 5min after restraint and lasted at least one day after the stressful experience. Midazolam, a short-acting benzodiazepine ligand, administered prior to stress prevented the increase in the p-ERK2 level in the BLA. Pretreatment with intra-BLA infusion of U0126 (MEK inhibitor), but not into the adjacent central nucleus of the amygdala, attenuated the stress-induced promoting influence on fear memory formation. Finally, U0126 intra-BLA infusion prevented the enhancement of anxiety-like behavior in stressed animals. These findings suggest that the selective ERK2 activation in BLA following stress exposure is an important mechanism for the occurrence of the promoting influence of stress on fear memory and on anxiety-like behavior. © 2013 Published by Elsevier B.V. and ECNP.

The effectiveness of stress management training on blood glucose control in patients with type 2 diabetes.

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Zamani-Alavijeh, Fereshteh; Araban, Marzieh; Koohestani, Hamid Reza; Karimy, Mahmood

2018-01-01

Type 2 diabetes is a chronic disease that is expanding at an alarming rate in the world. Research on individuals with type 2 diabetes showed that stressful life events cause problems in the effective management and control of diabetes. This study aimed at investigating the effect of a stress management intervention on blood glucose control in individuals with type 2 diabetes referred to Zarandeh clinic, Iran. In this experimental study, 230 individuals with type 2 diabetes (179 female and 51 male) were enrolled and assigned to experimental (n = 115) and control (n = 115) groups. A valid and reliable multi-part questionnaire including demographics, Perceived Stress Scale, Coping Inventory for Stressful Situations, Coping Self-Efficacy Scale, and multidimensional scale of perceived social support was used to for data collection. The experimental group received a training program, developed based on the social cognitive theory and with an emphasis on improving self-efficacy and perceived social support, during eight sessions of one and a half hours. Control group received only standard care. Data were analyzed using SPSS 15 applying the t test, paired t-tests, Pearson correlation coefficient, and Chi square analysis. The significance level was considered at 0.05. Before the intervention, the mean perceived stress scores of the experimental and control groups were 33.9 ± 4.6 and 35 ± 6.5, respectively, and no significant difference was observed (p > 0.05). However, after the intervention, the mean perceived stress score of the experimental group (26.7 ± 4.7) was significantly less than that of the control group (34.5 ± 7) (p = 0.001). Before the intervention, the mean scores of HbA1c in the experimental and control groups were 8.52 ± 1 and 8.42 ± 1.2, respectively, and there was no significant difference between the two groups. However, after the intervention, the results showed a significant decrease in glycosylated

Gibberellic Acid-Stimulated Arabidopsis6 Serves as an Integrator of Gibberellin, Abscisic Acid, and Glucose Signaling during Seed Germination in Arabidopsis.

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Zhong, Chunmei; Xu, Hao; Ye, Siting; Wang, Shiyi; Li, Lingfei; Zhang, Shengchun; Wang, Xiaojing

2015-11-01

The DELLA protein REPRESSOR OF ga1-3-LIKE2 (RGL2) plays an important role in seed germination under different conditions through a number of transcription factors. However, the functions of the structural genes associated with RGL2-regulated germination are less defined. Here, we report the role of an Arabidopsis (Arabidopsis thaliana) cell wall-localized protein, Gibberellic Acid-Stimulated Arabidopsis6 (AtGASA6), in functionally linking RGL2 and a cell wall loosening expansin protein (Arabidopsis expansin A1 [AtEXPA1]), resulting in the control of embryonic axis elongation and seed germination. AtGASA6-overexpressing seeds showed precocious germination, whereas transfer DNA and RNA interference mutant seeds displayed delayed seed germination under abscisic acid, paclobutrazol, and glucose (Glc) stress conditions. The differences in germination rates resulted from corresponding variation in cell elongation in the hypocotyl-radicle transition region of the embryonic axis. AtGASA6 was down-regulated by RGL2, GLUCOSE INSENSITIVE2, and ABSCISIC ACID-INSENSITIVE5 genes, and loss of AtGASA6 expression in the gasa6 mutant reversed the insensitivity shown by the rgl2 mutant to paclobutrazol and the gin2 mutant to Glc-induced stress, suggesting that it is involved in regulating both the gibberellin and Glc signaling pathways. Furthermore, it was found that the promotion of seed germination and length of embryonic axis by AtGASA6 resulted from a promotion of cell elongation at the embryonic axis mediated by AtEXPA1. Taken together, the data indicate that AtGASA6 links RGL2 and AtEXPA1 functions and plays a role as an integrator of gibberellin, abscisic acid, and Glc signaling, resulting in the regulation of seed germination through a promotion of cell elongation. © 2015 American Society of Plant Biologists. All Rights Reserved.

Maternal high-fat diet intensifies the metabolic response to stress in male rat offspring.

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Karbaschi, Roxana; Zardooz, Homeira; Khodagholi, Fariba; Dargahi, Leila; Salimi, Mina; Rashidi, FatemehSadat

2017-01-01

The mother's consumption of high-fat food can affect glucose metabolism and the hypothalamic-pituitary-adrenal axis responsiveness in the offspring and potentially affect the metabolic responses to stress as well. This study examines the effect of maternal high-fat diet on the expression of pancreatic glucose transporter 2 and the secretion of insulin in response to stress in offspring. Female rats were randomly divided into normal and high-fat diet groups and were fed in accordance with their given diets from pre-pregnancy to the end of lactation. The offspring were divided into control (NC and HFC) and stress (NS and HFS) groups based on their mothers' diet and exposure to stress in adulthood. After the two-week stress induction period was over, an intraperitoneal glucose tolerance test (IPGTT) was performed and plasma glucose and insulin levels were assessed. The pancreas was then removed for measuring insulin secretion from the isolated islets as well as glucose transporter 2 mRNA expression and protein levels. According to the results obtained, plasma corticosterone concentrations increased significantly on days 1 and 14 of the stress induction period and were lower on the last day compared to on the first day. In both the NS and HFS groups, stress reduced plasma insulin concentration in the IPGTT without changing the plasma glucose concentration, suggesting an increased insulin sensitivity in the NS and HFS groups, although more markedly in the latter. Stress reduced insulin secretion (at high glucose concentrations) and increased glucose transporter 2 mRNA and protein expression, especially in the HFS group. Mothers' high-fat diet appears to intensify the stress response by changing the programming of the neuroendocrine system in the offspring.

BRCA1-regulated RRM2 expression protects glioblastoma cells from endogenous replication stress and promotes tumorigenicity

DEFF Research Database (Denmark)

Rasmussen, Rikke D.; Gajjar, Madhavsai K.; Tuckova, Lucie

2016-01-01

Oncogene-evoked replication stress (RS) fuels genomic instability in diverse cancer types. Here we report that BRCA1, traditionally regarded a tumour suppressor, plays an unexpected tumour-promoting role in glioblastoma (GBM), safeguarding a protective response to supraphysiological RS levels. Hi...

14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis

International Nuclear Information System (INIS)

Wang, Lai; Chen, Man; Yuan, Lin; Xiang, Yuting; Zheng, Ruimao; Zhu, Shigong

2014-01-01

Highlights: • 14,15-EET inhibits OGD-induced apoptosis in cortical neurons. • Mitochondrial biogenesis of cortical neurons is promoted by 14,15-EET. • 14,15-EET preserves mitochondrial function of cortical neurons under OGD. • CREB mediates effect of 14,15-EET on mitochondrial biogenesis and function. - Abstract: 14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen–glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1

14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis

Energy Technology Data Exchange (ETDEWEB)

Wang, Lai; Chen, Man; Yuan, Lin; Xiang, Yuting [Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China); Zheng, Ruimao, E-mail: rmzheng@pku.edu.cn [Department of Anatomy, Histology and Embryology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China); Zhu, Shigong, E-mail: sgzhu@bjmu.edu.cn [Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Peking University Health Science Center, Beijing (China)

2014-07-18

Highlights: • 14,15-EET inhibits OGD-induced apoptosis in cortical neurons. • Mitochondrial biogenesis of cortical neurons is promoted by 14,15-EET. • 14,15-EET preserves mitochondrial function of cortical neurons under OGD. • CREB mediates effect of 14,15-EET on mitochondrial biogenesis and function. - Abstract: 14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen–glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1.

Orbital fluid shear stress promotes osteoblast metabolism, proliferation and alkaline phosphates activity in vitro

Energy Technology Data Exchange (ETDEWEB)

Aisha, M.D. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); Nor-Ashikin, M.N.K. [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Sharaniza, A.B.R. [DDH, Universiti Teknologi MARA, ShahAlam 40450, Selangor (Malaysia); Nawawi, H. [Center for Pathology Diagnostic and Research Laboratories, Clinical Training Center, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia); Froemming, G.R.A., E-mail: gabriele@salam.uitm.edu.my [Institute of Medical Molecular Biotechnology and Faculty of Medicine, Universiti Teknologi MARA, Sungai Buloh 47000, Selangor (Malaysia); I-PPerForM, Universiti Teknologi MARA, Selayang 47000 Selangor (Malaysia)

2015-09-10

Prolonged disuse of the musculoskeletal system is associated with reduced mechanical loading and lack of anabolic stimulus. As a form of mechanical signal, the multidirectional orbital fluid shear stress transmits anabolic signal to bone forming cells in promoting cell differentiation, metabolism and proliferation. Signals are channeled through the cytoskeleton framework, directly modifying gene and protein expression. For that reason, we aimed to study the organization of Normal Human Osteoblast (NHOst) cytoskeleton with regards to orbital fluid shear (OFS) stress. Of special interest were the consequences of cytoskeletal reorganization on NHOst metabolism, proliferation, and osteogenic functional markers. Cells stimulated at 250 RPM in a shaking incubator resulted in the rearrangement of actin and tubulin fibers after 72 h. Orbital shear stress increased NHOst mitochondrial metabolism and proliferation, simultaneously preventing apoptosis. The ratio of RANKL/OPG was reduced, suggesting that orbital shear stress has the potential to inhibit osteoclastogenesis and osteoclast activity. Increase in ALP activity and OCN protein production suggests that stimulation retained osteoblast function. Shear stress possibly generated through actin seemed to hold an anabolic response as osteoblast metabolism and functional markers were enhanced. We hypothesize that by applying orbital shear stress with suitable magnitude and duration as a non-drug anabolic treatment can help improve bone regeneration in prolonged disuse cases. - Highlights: • OFS stress transmits anabolic signals to osteoblasts. • Actin and tubulin fibers are rearranged under OFS stress. • OFS stress increases mitochondrial metabolism and proliferation. • Reduced RANKL/OPG ratio in response to OFS inhibits osteoclastogenesis. • OFS stress prevents apoptosis and stimulates ALP and OCN.

Intermittent Hypoxia Impairs Glucose Homeostasis in C57BL6/J Mice: Partial Improvement with Cessation of the Exposure

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Polak, Jan; Shimoda, Larissa A.; Drager, Luciano F.; Undem, Clark; McHugh, Holly; Polotsky, Vsevolod Y.; Punjabi, Naresh M.

2013-01-01

Objectives: Obstructive sleep apnea is associated with insulin resistance, glucose intolerance, and type 2 diabetes mellitus. Although several studies have suggested that intermittent hypoxia in obstructive sleep apnea may induce abnormalities in glucose homeostasis, it remains to be determined whether these abnormalities improve after discontinuation of the exposure. The objective of this study was to delineate the effects of intermittent hypoxia on glucose homeostasis, beta cell function, and liver glucose metabolism and to investigate whether the impairments improve after the hypoxic exposure is discontinued. Interventions: C57BL6/J mice were exposed to 14 days of intermittent hypoxia, 14 days of intermittent air, or 7 days of intermittent hypoxia followed by 7 days of intermittent air (recovery paradigm). Glucose and insulin tolerance tests were performed to estimate whole-body insulin sensitivity and calculate measures of beta cell function. Oxidative stress in pancreatic tissue and glucose output from isolated hepatocytes were also assessed. Results: Intermittent hypoxia increased fasting glucose levels and worsened glucose tolerance by 67% and 27%, respectively. Furthermore, intermittent hypoxia exposure was associated with impairments in insulin sensitivity and beta cell function, an increase in liver glycogen, higher hepatocyte glucose output, and an increase in oxidative stress in the pancreas. While fasting glucose levels and hepatic glucose output normalized after discontinuation of the hypoxic exposure, glucose intolerance, insulin resistance, and impairments in beta cell function persisted. Conclusions: Intermittent hypoxia induces insulin resistance, impairs beta cell function, enhances hepatocyte glucose output, and increases oxidative stress in the pancreas. Cessation of the hypoxic exposure does not fully reverse the observed changes in glucose metabolism. Citation: Polak J; Shimoda LA; Drager LF; Undem C; McHugh H; Polotsky VY; Punjabi NM

Chronic restraint stress promotes learning and memory impairment due to enhanced neuronal endoplasmic reticulum stress in the frontal cortex and hippocampus in male mice.

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Huang, Rong-Rong; Hu, Wen; Yin, Yan-Yan; Wang, Yu-Chan; Li, Wei-Ping; Li, Wei-Zu

2015-02-01

Chronic stress has been implicated in many types of neurodegenerative diseases, such as Alzheimer's disease (AD). In our previous study, we demonstrated that chronic restraint stress (CRS) induced reactive oxygen species (ROS) overproduction and oxidative damage in the frontal cortex and hippocampus in mice. In the present study, we investigated the effects of CRS (over a period of 8 weeks) on learning and memory impairment and endoplasmic reticulum (ER) stress in the frontal cortex and hippocampus in male mice. The Morris water maze was used to investigate the effects of CRS on learning and memory impairment. Immunohistochemistry and immunoblot analysis were also used to determine the expression levels of protein kinase C α (PKCα), 78 kDa glucose-regulated protein (GRP78), C/EBP-homologous protein (CHOP) and mesencephalic astrocyte-derived neurotrophic factor (MANF). The results revealed that CRS significantly accelerated learning and memory impairment, and induced neuronal damage in the frontal cortex and hippocampus CA1 region. Moreover, CRS significantly increased the expression of PKCα, CHOP and MANF, and decreased that of GRP78 in the frontal cortex and hippocampus. Our data suggest that exposure to CRS (for 8 weeks) significantly accelerates learning and memory impairment, and the mechanisms involved may be related to ER stress in the frontal cortex and hippocampus.

Hypothalamic glucose-sensing: role of Glia-to-neuron signaling.

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Tonon, M C; Lanfray, D; Castel, H; Vaudry, H; Morin, F

2013-12-01

The hypothalamus senses hormones and nutrients in order to regulate energy balance. In particular, detection of hypothalamic glucose levels has been shown to regulate both feeding behavior and peripheral glucose homeostasis, and impairment of this regulatory system is believed to be involved in the development of obesity and diabetes. Several data clearly demonstrate that glial cells are key elements in the perception of glucose, constituting with neurons a "glucose-sensing unit". Characterization of this interplay between glia and neurons represents an exciting challenge, and will undoubtedly contribute to identify new candidates for therapeutic intervention. The purpose of this review is to summarize the current data that stress the importance of glia in central glucose-sensing. The nature of the glia-to-neuron signaling is discussed, with a special focus on the endozepine ODN, a potent anorexigenic peptide that is highly expressed in hypothalamic glia. © Georg Thieme Verlag KG Stuttgart · New York.

Glucose Sensor MdHXK1 Phosphorylates and Stabilizes MdbHLH3 to Promote Anthocyanin Biosynthesis in Apple

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Hu, Da-Gang; Zhang, Quan-Yan; An, Jian-Ping; You, Chun-Xiang; Hao, Yu-Jin

2016-01-01

Glucose induces anthocyanin accumulation in many plant species; however, the molecular mechanism involved in this process remains largely unknown. Here, we found that apple hexokinase MdHXK1, a glucose sensor, was involved in sensing exogenous glucose and regulating anthocyanin biosynthesis. In vitro and in vivo assays suggested that MdHXK1 interacted directly with and phosphorylated an anthocyanin-associated bHLH transcription factor (TF) MdbHLH3 at its Ser361 site in response to glucose. Furthermore, both the hexokinase_2 domain and signal peptide are crucial for the MdHXK1-mediated phosphorylation of MdbHLH3. Moreover, phosphorylation modification stabilized MdbHLH3 protein and enhanced its transcription of the anthocyanin biosynthesis genes, thereby increasing anthocyanin biosynthesis. Finally, a series of transgenic analyses in apple calli and fruits demonstrated that MdHXK1 controlled glucose-induced anthocyanin accumulation at least partially, if not completely, via regulating MdbHLH3. Overall, our findings provide new insights into the mechanism of the glucose sensor HXK1 modulation of anthocyanin accumulation, which occur by directly regulating the anthocyanin-related bHLH TFs in response to a glucose signal in plants. PMID:27560976

Glucose Sensor MdHXK1 Phosphorylates and Stabilizes MdbHLH3 to Promote Anthocyanin Biosynthesis in Apple.

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Da-Gang Hu

2016-08-01

Full Text Available Glucose induces anthocyanin accumulation in many plant species; however, the molecular mechanism involved in this process remains largely unknown. Here, we found that apple hexokinase MdHXK1, a glucose sensor, was involved in sensing exogenous glucose and regulating anthocyanin biosynthesis. In vitro and in vivo assays suggested that MdHXK1 interacted directly with and phosphorylated an anthocyanin-associated bHLH transcription factor (TF MdbHLH3 at its Ser361 site in response to glucose. Furthermore, both the hexokinase_2 domain and signal peptide are crucial for the MdHXK1-mediated phosphorylation of MdbHLH3. Moreover, phosphorylation modification stabilized MdbHLH3 protein and enhanced its transcription of the anthocyanin biosynthesis genes, thereby increasing anthocyanin biosynthesis. Finally, a series of transgenic analyses in apple calli and fruits demonstrated that MdHXK1 controlled glucose-induced anthocyanin accumulation at least partially, if not completely, via regulating MdbHLH3. Overall, our findings provide new insights into the mechanism of the glucose sensor HXK1 modulation of anthocyanin accumulation, which occur by directly regulating the anthocyanin-related bHLH TFs in response to a glucose signal in plants.

Reactive oxygen species as a signal in glucose-stimulated insulin secretion.

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Pi, Jingbo; Bai, Yushi; Zhang, Qiang; Wong, Victoria; Floering, Lisa M; Daniel, Kiefer; Reece, Jeffrey M; Deeney, Jude T; Andersen, Melvin E; Corkey, Barbara E; Collins, Sheila

2007-07-01

One of the unique features of beta-cells is their relatively low expression of many antioxidant enzymes. This could render beta-cells susceptible to oxidative damage but may also provide a system that is sensitive to reactive oxygen species as signals. In isolated mouse islets and INS-1(832/13) cells, glucose increases intracellular accumulation of H2O2. In both models, insulin secretion could be stimulated by provision of either exogenous H2O2 or diethyl maleate, which raises intracellular H2O2 levels. Provision of exogenous H2O2 scavengers, including cell permeable catalase and N-acetyl-L-cysteine, inhibited glucose-stimulated H2O2 accumulation and insulin secretion (GSIS). In contrast, cell permeable superoxide dismutase, which metabolizes superoxide into H2O2, had no effect on GSIS. Because oxidative stress is an important risk factor for beta-cell dysfunction in diabetes, the relationship between glucose-induced H2O2 generation and GSIS was investigated under various oxidative stress conditions. Acute exposure of isolated mouse islets or INS-1(832/13) cells to oxidative stressors, including arsenite, 4-hydroxynonenal, and methylglyoxal, led to decreased GSIS. This impaired GSIS was associated with increases in a battery of endogenous antioxidant enzymes. Taken together, these findings suggest that H2O2 derived from glucose metabolism is one of the metabolic signals for insulin secretion, whereas oxidative stress may disturb its signaling function.

Does workplace health promotion contribute to job stress reduction? Three-year findings from Partnering Healthy@Work.

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Jarman, Lisa; Martin, Angela; Venn, Alison; Otahal, Petr; Sanderson, Kristy

2015-12-24

Workplace health promotion (WHP) has been proposed as a preventive intervention for job stress, possibly operating by promoting positive organizational culture or via programs promoting healthy lifestyles. The aim of this study was to investigate whether job stress changed over time in association with the availability of, and/or participation in a comprehensive WHP program (Healthy@Work). This observational study was conducted in a diverse public sector organization (~28,000 employees). Using a repeated cross-sectional design with models corroborated using a cohort of repeat responders, self-report survey data were collected via a 40 % employee population random sample in 2010 (N = 3406) and 2013 (N = 3228). Outcomes assessed were effort and reward (self-esteem) components of the effort-reward imbalance (ERI) measure of job stress. Exposures were availability of, and participation in, comprehensive WHP. Linear mixed models and Poisson regression were used, with analyses stratified by sex and weighted for non-response. Higher WHP availability was positively associated with higher perceived self-esteem among women. Women's mean reward scores increased over time but were not statistically different (p > 0.05) after 3 years. For men, higher WHP participation was associated with lower perceived effort. Men's mean ERI increased over time. Results were supported in the cohort group. For women, comprehensive WHP availability contributed to a sense of organizational support, potentially impacting the esteem component of reward. Men with higher WHP participation also benefitted but gains were modest over time and may have been hindered by other work environment factors.

LKB1 promotes metabolic flexibility in response to energy stress.

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Parker, Seth J; Svensson, Robert U; Divakaruni, Ajit S; Lefebvre, Austin E; Murphy, Anne N; Shaw, Reuben J; Metallo, Christian M

2017-09-01

The Liver Kinase B1 (LKB1) tumor suppressor acts as a metabolic energy sensor to regulate AMP-activated protein kinase (AMPK) signaling and is commonly mutated in various cancers, including non-small cell lung cancer (NSCLC). Tumor cells deficient in LKB1 may be uniquely sensitized to metabolic stresses, which may offer a therapeutic window in oncology. To address this question we have explored how functional LKB1 impacts the metabolism of NSCLC cells using 13 C metabolic flux analysis. Isogenic NSCLC cells expressing functional LKB1 exhibited higher flux through oxidative mitochondrial pathways compared to those deficient in LKB1. Re-expression of LKB1 also increased the capacity of cells to oxidize major mitochondrial substrates, including pyruvate, fatty acids, and glutamine. Furthermore, LKB1 expression promoted an adaptive response to energy stress induced by anchorage-independent growth. Finally, this diminished adaptability sensitized LKB1-deficient cells to combinatorial inhibition of mitochondrial complex I and glutaminase. Together, our data implicate LKB1 as a major regulator of adaptive metabolic reprogramming and suggest synergistic pharmacological strategies for mitigating LKB1-deficient NSCLC tumor growth. Copyright © 2016. Published by Elsevier Inc.

Phorbol ester tumor promoter induced the synthesis of two major cytoplasmic proteins: identity with two proteins induced under heat-shocked and glucose-starved conditions

International Nuclear Information System (INIS)

Zhang, H.; Chen, K.Y.; Liu, A.Y.C.

1987-01-01

The regulation of specific protein synthesis by the phorbol ester tumor promoter, 12-O-tetradecanoyl-phorbol-13-acetate (TPA), was evaluated using the L-8 and C-2 myoblast and the 3T3-L1 fibroblast cell cultures. TPA increased, by 2-4 fold, the synthesis rates of two cytoplasmic proteins with apparent molecular weights of 89,000 and 74,000 as determined by SDS-polyacrylamide gel electrophoresis and autoradiography. The concentration of TPA and the time of incubation needed to elicit this induction was determined to be 10 μg/ml and 20 hrs, respectively. Increasing the concentration of TPA to 100, 200, and 500 ng/ml did not result in a greater magnitude of induction. The possibility that these two TPA-induced proteins may be identical to proteins with similar molecular weights induced under heat-shocked or glucose-starved conditions was evaluated by 1-D and 2-D gel electrophoresis and autoradiography. Results provided evidence that the TPA-induced 89,000- and 74,000-dalton proteins were identical to hsp 89 and hsp 74, 2 out of a set of 8-9 proteins induced under heat shocked conditions. Furthermore, they are identical to two of the set of glucose-regulated proteins induced under a glucose-starved condition

Isoamyl alcohol odor promotes longevity and stress tolerance via DAF-16 in Caenorhabditis elegans.

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Kurino, Chiho; Furuhashi, Tsubasa; Sudoh, Kaori; Sakamoto, Kazuichi

2017-04-01

The possibility that odor plays a role in lifespan regulation through effects on the nervous system is indicated by research on Caenorhabditis elegans. In fact, ablation of AWA and AWC, which are suggested as olfactory neurons, has been shown to extend lifespan via DAF-16, a homolog of FoxO. However, the effects of odor stimuli on the lifespan still remain unclear. Thus, we here aimed to clarify the effect of attractive and repulsive odors on longevity and stress tolerance in C. elegans and to analyze the pathways thereof. We used isoamyl alcohol as an attractive odor, and acetic acid as a repellent component, as identified by chemotaxis assay. We found that isoamyl alcohol stimulus promoted longevity in a DAF-16-dependent manner. On the other hand, acetic acid stimulus promoted thermotolerance through mechanisms independent of DAF-16. Above all, our results indicate that odor stimuli affect the lifespan and stress tolerance of C. elegans, with attractive and repulsive odors exerting their effects through different mechanisms, and that longevity is induced by both activation and inactivation of olfactory neurons. Copyright © 2017 Elsevier Inc. All rights reserved.

The GATA transcription factor egl-27 delays aging by promoting stress resistance in Caenorhabditis elegans.

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Xiao Xu

Full Text Available Stress is a fundamental aspect of aging, as accumulated damage from a lifetime of stress can limit lifespan and protective responses to stress can extend lifespan. In this study, we identify a conserved Caenorhabditis elegans GATA transcription factor, egl-27, that is involved in several stress responses and aging. We found that overexpression of egl-27 extends the lifespan of wild-type animals. Furthermore, egl-27 is required for the pro-longevity effects from impaired insulin/IGF-1 like signaling (IIS, as reduced egl-27 activity fully suppresses the longevity of worms that are mutant for the IIS receptor, daf-2. egl-27 expression is inhibited by daf-2 and activated by pro-longevity factors daf-16/FOXO and elt-3/GATA, suggesting that egl-27 acts at the intersection of IIS and GATA pathways to extend lifespan. Consistent with its role in IIS signaling, we found that egl-27 is involved in stress response pathways. egl-27 expression is induced in the presence of multiple stresses, its targets are significantly enriched for many types of stress genes, and altering levels of egl-27 itself affects survival to heat and oxidative stress. Finally, we found that egl-27 expression increases between young and old animals, suggesting that increased levels of egl-27 in aged animals may act to promote stress resistance. These results identify egl-27 as a novel factor that links stress and aging pathways.

N-Acetyl-Cysteine Alleviates Gut Dysbiosis and Glucose Metabolic Disorder in High-Fat Diet-Induced Mice.

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Zheng, Junping; Yuan, Xubing; Zhang, Chen; Jia, Peiyuan; Jiao, Siming; Zhao, Xiaoming; Yin, Heng; Du, Yuguang; Liu, Hongtao

2018-05-30

N-acetyl cysteine (NAC), an anti-oxidative reagent for clinical diseases, shows potential application to diabetes and other metabolic diseases. However, it is unknown how NAC modulates the gut microbiota of mice with metabolic syndrome. In present study, we aim to demonstrate the preventive effect of NAC on intestinal dysbiosis and glucose metabolic disorder. C57BL/6J mice were fed with normal chow diet (NCD), NCD plus NAC, high-fat diet (HFD) or HFD plus NAC for five months. After the treatment, the glucose level, circulating endotoxin and metabolism-related key proteins were determined. The fecal samples were analyzed by 16S rRNA sequencing. A novel analysis was carried out to predict the functional changes of gut microbiota. In addition, Spearman's correlation between metabolic biomarkers and bacterial abundance was also assayed. The results show that NAC treatment significantly reversed the glucose intolerance, fasting glucose level, body weight and plasma endotoxin in HFD-fed mice. Further, NAC upregulated the levels of Occludin protein and mucin glycoproteins in proximal colons of HFD-treated mice. Noticeably, NAC promoted the growth of beneficial bacteria such as Akkermansia, Bifidobacterium, Lactobacillus and Allobaculum, and hampered the population of diabetes-related genera including Desulfovibrio and Blautia. Also, NAC may influence the metabolic pathways of intestinal bacteria including lipopolysaccharide biosynthesis, oxidative stress and bacterial motility. Finally, the modified gut microbiota showed close association with the metabolic changes of the NAC treated HFD-fed mice. In summary, NAC may be a potential drug to prevent glucose metabolic disturbance by reshaping the structure of gut microbiota. This article is protected by copyright. All rights reserved. This article is protected by copyright. All rights reserved.

Do Health Promotion Behaviors Affect Levels of Job Satisfaction and Job Stress for Nurses in an Acute Care Hospital?

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Williams, Heather L; Costley, Teresa; Bellury, Lanell M; Moobed, Jasmine

2018-06-01

The aim of this study was to explore the relationships between nurse-reported health-promoting behaviors (HPBs), job stress, and job satisfaction in a hospital setting. Job stress and satisfaction are key components of the nursing work environment; however, evidence of the relationship between HPB and job stress and satisfaction is lacking. A cross-sectional, 144-item survey was administered to nurses working in an acute care, community hospital in the southeastern United States. Higher levels of HPB were associated with lower job stress and higher job satisfaction. Total HPB was associated with the competence subscale of job stress. Lower job stress was significantly associated with HPB subscales: spiritual growth, interpersonal relations, and stress management. Nursing organizations can implement interventions that support HPB for nurses to reduce job stress and improve satisfaction.

Health promotion in the workplace: assessing stress and lifestyle with an intranet tool.

Science.gov (United States)

Lucini, Daniela; Solaro, Nadia; Lesma, Alessandro; Gillet, Veronique Bernadette; Pagani, Massimo

2011-11-08

Chronic noncommunicable conditions, particularly cardiovascular and metabolic diseases, are the major causes of death and morbidity in both industrialized and low- to middle-income countries. Recent epidemiological investigations suggest that management of lifestyle factors, such as stress and lack of physical activity, could have an important value in cardiometabolic conditions, while information technology tools could play a significant facilitatory role. The objective of our study was to verify the feasibility of using a private website, directed to the workers of a major Italian company, to describe their health profile and lifestyle and work habits using an ad hoc self-administered questionnaire. We administered anonymous multiple choice Web-based questionnaires to 945 participants (683 completed the task) as part of an ongoing health promotion program in a multinational company. Qualitative and quantitative data were synthesized with nonlinear principal component analysis to construct indicators (ie, variables) for stress, control, and lifestyle domains. Considering in addition absenteeism, the Calinski-Harabasz statistic and cluster analysis jointly differentiated seven clusters, which displayed different distributions of standardized classification variables. The final step consisted in assessing the relationship of the resulting seven subject typologies with personal data, illnesses, and metabolic syndrome status, carried out for the most part with descriptive methods. Statistical analyses singled out two not-overlapping domains of stress and control, as well as three not-overlapping domains of physical activity, smoking, and alcohol habits. The centroids of the seven clusters generated by the procedure were significantly (P stress group than in the overall studied population; preclinical metabolic syndrome status was more prevalent in the group with higher alcohol consumption. Absentees reported more illness. The present Intranet-based study shows the

Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

OpenAIRE

Fonville, Susanne; Hertog, Heleen; Zandbergen, Adrienne; Koudstaal, Peter Jan; Lingsma, Hester

2014-01-01

textabstractBackground Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing undiagnosed impaired glucose metabolism possibly requiring treatment. We aimed to assess the occurrence of persistent impaired glucose tolerance after a stroke or TIA and to develop a prediction model to...

Autophagy fails to prevent glucose deprivation/glucose reintroduction-induced neuronal death due to calpain-mediated lysosomal dysfunction in cortical neurons.

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Gerónimo-Olvera, Cristian; Montiel, Teresa; Rincon-Heredia, Ruth; Castro-Obregón, Susana; Massieu, Lourdes

2017-06-29

Autophagy is triggered during nutrient and energy deprivation in a variety of cells as a homeostatic response to metabolic stress. In the CNS, deficient autophagy has been implicated in neurodegenerative diseases and ischemic brain injury. However, its role in hypoglycemic damage is poorly understood and the dynamics of autophagy during the hypoglycemic and the glucose reperfusion periods, has not been fully described. In the present study, we analyzed the changes in the content of the autophagy proteins BECN1, LC3-II and p62/SQSTM1 by western blot, and autophagosome formation was followed through time-lapse experiments, during glucose deprivation (GD) and glucose reintroduction (GR) in cortical cultures. According to the results, autophagosome formation rapidly increased during GD, and was followed by an active autophagic flux early after glucose replenishment. However, cells progressively died during GR and autophagy inhibition reduced neuronal death. Neurons undergoing apoptosis during GR did not form autophagosomes, while those surviving up to late GR showed autophagosomes. Calpain activity strongly increased during GR and remained elevated during progressive neuronal death. Its activation led to the cleavage of LAMP2 resulting in lysosome membrane permeabilization (LMP) and release of cathepsin B to the cytosol. Calpain inhibition prevented LMP and increased the number of neurons containing lysosomes and autophagosomes increasing cell viability. Taken together, the present results suggest that calpain-mediated lysosome dysfunction during GR turns an adaptive autophagy response to energy stress into a defective autophagy pathway, which contributes to neuronal death. In these conditions, autophagy inhibition results in the improvement of cell survival.

Effects of Parental Stress, Optimism, and Health-Promoting Behaviors on the Quality of Life of Primiparous and Multiparous Mothers.

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Loh, Jennifer; Harms, Craig; Harman, Bronwyn

Parental stress, optimism, and health-promoting behaviors (HPBs) are important predictors of the quality of life (QoL) of mothers. However, it is unclear how strongly these predictors affect the QoL of mothers. It is also unclear if the impact of these predictors on QoL differs between primiparous and multiparous mothers. In this study, we defined primiparous as "bearing young for the first time" and multiparous as "having experienced one or more previous childbirths." The first objective of this study was to examine the relative effect of parental stress, optimism, and HPBs on the QoL of mothers. The second objective was to investigate if the effect of these predictors differed between primiparous and multiparous mothers. One hundred ninety-four Australian mothers (n = 87, 44.8% primiparous mothers) participated in an online survey that included the Parental Stress Scale, the Health-Promoting Lifestyle Profile II, the Revised Life Orientation Test, and the Quality of Life Enjoyment and Satisfaction Questionnaire. All predictors (parental stress, optimism, and HPBs) significantly affected the QoL of mothers; higher levels of optimism, greater use of HPBs, and lower parental stress were associated with higher levels of QoL for all mothers. Parity did not affect the relationships. This study sheds light on the nature and unique effect of parental stress, optimism, and HPBs on the QoL of mothers.

Blood glucose lowering effect of ophiopogonis tuber extract and mechanism of anti-insulin-resistance

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Meng NING

2013-01-01

Full Text Available Objective 　To study the hypoglycemic effect and insulin sensitization mechanism of ophiopogonis tuber extracts on the 3T3-L1-induced adipocytes, and also in rats with reproduction of type 2 diabetes mellitus (T2DM. Methods 　3T3-L1 cells were induced and differentiated into adipocytes. After the intervention with ophiopogonpolysaccharide (OPSR and ophiopogonin (OPG, glucose consuming rate was detected for screening the extracts which may have effective hypoglycemic effects. The insulin resistance (IR adipocyte model was established by dexamethasone induction, and then it was treated with OPSR. The protein expression levels of leptin, adiponectin and resistin were detected by Western blotting. The T2DM rat model was reproduced and then treated with OPSR for 4 weeks. Body weight (BW, triglyeride (TG, fasting blood glucose (FBG and fasting insulin (FINs of the rats were measured respectively. Results 　OPSR in dosage of 0.5-50mg/L promoted glucose consumption of adipocytes in a dose-dependent manner, the glucose consumption ratios were 32.27%, 75.14% and 90.47% respectively. OPG of 50mg/L showed very weak activity with glucose consumption ratio of only 8.49%. OPSR could significantly promote the protein expression of leptin and adiponectin, and showed an inhibitory effect on the protein expression of resistin (P<0.05. After treatment with OPSR for 4 weeks, the BW of rats increased obviously, while TG, FBG and HOMA-IR decreased significantly (P<0.05 or P<0.01. Conclusions 　OPSR may promote glucose transport and utilization of adipocytes, decrease the level of FBG and TG, and improve the condition of IR in T2DM rats. The mechanism of blood glucose lowering effect may be attributed to secretion of adipokines, such as leptin, adiponectin and resistin by IR adipocytes.

The glucose oxidase-peroxidase assay for glucose

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

Stable-label intravenous glucose tolerance test minimal model

International Nuclear Information System (INIS)

Avogaro, A.; Bristow, J.D.; Bier, D.M.; Cobelli, C.; Toffolo, G.

1989-01-01

The minimal model approach to estimating insulin sensitivity (Sl) and glucose effectiveness in promoting its own disposition at basal insulin (SG) is a powerful tool that has been underutilized given its potential applications. In part, this has been due to its inability to separate insulin and glucose effects on peripheral uptake from their effects on hepatic glucose inflow. Prior enhancements, with radiotracer labeling of the dosage, permit this separation but are unsuitable for use in pregnancy and childhood. In this study, we labeled the intravenous glucose tolerance test (IVGTT) dosage with [6,6- 2 H 2 ]glucose, [2- 2 H]glucose, or both stable isotopically labeled glucose tracers and modeled glucose kinetics in six postabsorptive, nonobese adults. As previously found with the radiotracer model, the tracer-estimated S*l derived from the stable-label IVGTT was greater than Sl in each case except one, and the tracer-estimated SG* was less than SG in each instance. More importantly, however, the stable-label IVGTT estimated each parameter with an average precision of +/- 5% (range 3-9%) compared to average precisions of +/- 74% (range 7-309%) for SG and +/- 22% (range 3-72%) for Sl. In addition, because of the different metabolic fates of the two deuterated tracers, there were minor differences in basal insulin-derived measures of glucose effectiveness, but these differences were negligible for parameters describing insulin-stimulated processes. In conclusion, the stable-label IVGTT is a simple, highly precise means of assessing insulin sensitivity and glucose effectiveness at basal insulin that can be used to measure these parameters in individuals of all ages, including children and pregnant women

IL-23 Promotes Myocardial I/R Injury by Increasing the Inflammatory Responses and Oxidative Stress Reactions

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Xiaorong Hu

2016-05-01

Full Text Available Background/Aims: Inflammation and oxidative stress play an important role in myocardial ischemia and reperfusion (I/R injury. We hypothesized that IL-23, a pro-inflammatory cytokine, could promote myocardial I/R injury by increasing the inflammatory response and oxidative stress. Methods: Male Sprague-Dawley rats were randomly assigned into sham operated control (SO group, ischemia and reperfusion (I/R group, (IL-23 + I/R group and (anti-IL-23 + I/R group. At 4 h after reperfusion, the serum concentration of lactate dehydrogenase (LDH, creatine kinase (CK and the tissue MDA concentration and SOD activity were measured. The infarcte size was measured by TTC staining. Apoptosis in heart sections were measured by TUNEL staining. The expression of HMGB1 and IL-17A were detected by Western Blotting and the expression of TNF-α and IL-6 were detected by Elisa. Results: After 4 h reperfusion, compared with the I/R group, IL-23 significantly increased the infarct size, the apoptosis of cardiomyocytes and the levels of LDH and CK (all P 0.05. All these effects were abolished by anti-IL-23 administration. Conclusion: The present study suggested that IL-23 may promote myocardial I/R injury by increasing the inflammatory responses and oxidative stress reaction.

Adaptation of the hypothalamic-pituitary-adrenal axis and glucose to repeated immobilization or restraint stress is not influenced by associative signals.

Science.gov (United States)

Rabasa, Cristina; Delgado-Morales, Raúl; Muñoz-Abellán, Cristina; Nadal, Roser; Armario, Antonio

2011-02-02

Repeated exposure to the same stressor very often results in a reduction of some prototypical stress responses, namely those related to the hypothalamic-pituitary-adrenal (HPA) and sympatho-medullo-adrenal (SMA) axes. This reduced response to repeated exposure to the same (homotypic) stressor (adaptation) is usually considered as a habituation-like process, and therefore, a non-associative type of learning. However, there is some evidence that contextual cues and therefore associative processes could contribute to adaptation. In the present study we demonstrated in two experiments using adult male rats that repeated daily exposure to restraint (REST) or immobilization on boards (IMO) reduced the HPA (plasma levels of ACTH and corticosterone) and glucose responses to the homotypic stressor and such reduced responses remained intact when all putative cues associated to the procedure (experimenter, way of transporting to the stress room, stress boxes, stress room and colour of the restrainer in the case of REST) were modified on the next day. Therefore, the present results do not favour the view that adaptation after repeated exposure to a stressor may involve associative processes related to signals predicting the imminence of the stressors, but more studies are needed on this issue. Copyright © 2010 Elsevier B.V. All rights reserved.

Plasma Glucose Levels for Red Drum Sciaenops Ocellatus in a Florida Estuarine Fisheries Reserve

Science.gov (United States)

Bourtis, Carla M.; Francis-Floyd, Ruth; Boggs, Ashley S P.; Reyier, Eric A.; Stolen, Eric D.; Yanong, Roy P.; Guillette, Louis J., Jr.

2015-01-01

Despite the significant value of the southeastern United States' red drum (Sciaenops ocellatus) fishery, there is a lack of clinical blood chemistry data. This was the first study to assess plasma glucose values as an indicator of stress response to evaluate variation and the effect of reproductive activity for wild adult red drum in Florida. Red drum (n=126) were collected from NASA's Kennedy Space Center waters during three reproductive periods in 2011. Samples were obtained from the branchial vessels of the gill arch. Plasma glucose levels were significantly different among reproductive periods, with the highest mean values recorded during the spawning period, September- October (38.23 mg / dL +/- 10.0). The glucose range was 17 - 69 mg / dL. Glucose values were lower during all three periods than previous values recorded for cultured or captive red drum studies. This may indicate that fish from this population were under less stress than other populations previously sampled.

[PROGNOSTIC SIGNIFICANCE OF CHANGES OF BLOOD GLUCOSE LEVEL IN PATIENTS WITH THORACOABDOMINAL INJURIES.

Science.gov (United States)

Sorokin, E P; Ponomarev, S V; Shilyaeva, Ye V; Bel'skih, Ye A; Gritsan, A I

2016-07-01

Background Currently, one of the causes of high morbidity and mortality is injuries. Predict the outcome of injuries - it is an important task of the treating physician. Trauma is a stress factor so to predict the outcome, you can use markers of stress, the most accessible ofwhich is blood glucose. to reveal the dynamics of the relationship between blood glucose levels and the outlook for the life ofpatients with thoracoabdominal injuries. A retrospective analysis of medical records of hospitalized patients were divided into two groups, depending on the outlook for the life of (favorable or unfavorable), and each of the groups - into two subgroups according to the presence or absence of signs of intoxication at admission. The subgroups were calculated and compared the mean blood glucose levels at different hours of hospital treatment. It was found that the average blood glucose levels at various hours of hospital stay were significantly higher in patients with poor outcome. The most noticeable was the difference in the first days of hospital treatment. Signs of intoxication was associated with lower values of glucose and a tendency to hypoglycaemia. In addition, among patients with high blood glucose ( 8 mg / dL) was observed over deaths in the first day of hospital stay. High blood glucose levels ( 8,0 mmol / L) in the first day of hospital treatment is a predictor ofpoor outcome in patients with thoracoabdominal injuries.

The Role of PAS Kinase in PASsing the Glucose Signal

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Julianne H. Grose

2010-06-01

Full Text Available PAS kinase is an evolutionarily conserved nutrient responsive protein kinase that regulates glucose homeostasis. Mammalian PAS kinase is activated by glucose in pancreatic beta cells, and knockout mice are protected from obesity, liver triglyceride accumulation, and insulin resistance when fed a high-fat diet. Yeast PAS kinase is regulated by both carbon source and cell integrity stress and stimulates the partitioning of glucose toward structural carbohydrate biosynthesis. In our current model for PAS kinase regulation, a small molecule metabolite binds the sensory PAS domain and activates the enzyme. Although bona fide PAS kinase substrates are scarce, in vitro substrate searches provide putative targets for exploration.

Chronic stress, cortisol dysfunction, and pain: a psychoneuroendocrine rationale for stress management in pain rehabilitation.

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Hannibal, Kara E; Bishop, Mark D

2014-12-01

Pain is a primary symptom driving patients to seek physical therapy, and its attenuation commonly defines a successful outcome. A large body of evidence is dedicated to elucidating the relationship between chronic stress and pain; however, stress is rarely addressed in pain rehabilitation. A physiologic stress response may be evoked by fear or perceived threat to safety, status, or well-being and elicits the secretion of sympathetic catecholamines (epinephrine and norepinepherine) and neuroendocrine hormones (cortisol) to promote survival and motivate success. Cortisol is a potent anti-inflammatory that functions to mobilize glucose reserves for energy and modulate inflammation. Cortisol also may facilitate the consolidation of fear-based memories for future survival and avoidance of danger. Although short-term stress may be adaptive, maladaptive responses (eg, magnification, rumination, helplessness) to pain or non-pain-related stressors may intensify cortisol secretion and condition a sensitized physiologic stress response that is readily recruited. Ultimately, a prolonged or exaggerated stress response may perpetuate cortisol dysfunction, widespread inflammation, and pain. Stress may be unavoidable in life, and challenges are inherent to success; however, humans have the capability to modify what they perceive as stressful and how they respond to it. Exaggerated psychological responses (eg, catastrophizing) following maladaptive cognitive appraisals of potential stressors as threatening may exacerbate cortisol secretion and facilitate the consolidation of fear-based memories of pain or non-pain-related stressors; however, coping, cognitive reappraisal, or confrontation of stressors may minimize cortisol secretion and prevent chronic, recurrent pain. Given the parallel mechanisms underlying the physiologic effects of a maladaptive response to pain and non-pain-related stressors, physical therapists should consider screening for non-pain-related stress to

Impact of plant growth promoting bacillus subtilis on growth and physiological parameters of bassia indica (indian bassia) grown udder salt stress

International Nuclear Information System (INIS)

Abeer, H.; Asma, A. H.; Allah, A.; Qarawi, A.; Shalawi, A.; Dilfuza, E.

2015-01-01

In this study, the role of a salt-tolerant plant growth-promoting bacterium (PGPR), Bacillus subtilis, in the alleviation of salinity stress during the growth of Indian bassia (Bassia indica (Wight) A.J. Scott), was studied under ccontrolled growth chamber conditions following seed inoculation. Physiological parameters such as neutral and phospholipids, fatty acid composition as well as photosynthetic pigments, were investigated. Salinity inhibited shoot and root length by 16 and 42 percentage, dry weight by 37 and 23 percentage respectively and negatively affected physiological parameters. Inoculation of unstressed and salt-stressed Indian bassia with B. subtilis significantly improved root and shoot growth, total lipid content, the phospholipid fraction, photosynthetic pigments (chlorophyll a and b and carotenoid contents) and also increased oleic (C 18:1 ), linoleic (C 18:2 ) and linolenic (C 18:3 ) acids in plant leaves compared to uninoculated plants. The salt-tolerant PGPR, B. subtilis could act synergistically to promote the growth and fitness of Indian bassia plants under salt stress by providing an additional supply of an auxin (IAA) and induce salt stress resistance by reducing stress ethylene levels. (author)

Validation of 123I-6-deoxy-6-iodo-D-glucose (6-DIC) as tracer for the in-vivo glucose transport

International Nuclear Information System (INIS)

Perret, P.; Ghezzi, C.; Mathieu, J.P.; Morin, C.; Vidal, M.; Comet, M.; Fagret, D.

1997-01-01

The evaluation of the glucose transport is very important clinically because alterations of this transport were described in numerous pathologies, in neurology, oncology and endocrinology. A new analog of the 123 I-labelled has been synthesized: 123 I-6-deoxy-6-iodo-D-glucose (6-DIG). Its in-vitro biological behaviour is similar to that of 3-O-methyl-D-glucose (3-OMG), the reference tracer of glucose transport. The aim of the study was to determine if it is possible to make evident by 6-DIG a variations of in-vivo glucose transport. The studies were effected on a model of homozygote mice (db/db), genetically diabetic (NIDDM), presenting a severe insulin-resistance, characterized by deficient glucose transport in response to insulin. The studies of 6-DIG biodistribution (5 nmol/mouse) with (1.5 UI/Kg) or without exogenous insulin, were conducted in diabetic mice (db/db) and in non-diabetic (db/+) control mice. The results show that the capture of 6-DIG, as well as that of glucose, increases (by 30%) in response to insulin in most of insulin-sensitive tissues in control mice. In the insulin-resistant and hyperglycemic db/db mouse, the capture of 6-DIG is not modified, no matter whether the exogenous insulin is present. In conclusion, the 6-DIG is able to make evident a lack of glucose transport in heart, diaphragm and skeletal muscle in diabetic mouse and a physiological variation of this transport in response to insulin, in the control mouse. This result should be stressed because for the first time it is possible to evidence in-vivo variations into glucose transport with a iodated molecule

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

Energy Technology Data Exchange (ETDEWEB)

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

2012-01-15

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

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

International Nuclear Information System (INIS)

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

2012-01-01

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

Stress-induced cell death is mediated by ceramide synthesis in Neurospora crassa

DEFF Research Database (Denmark)

Plesofsky, Nora S; Levery, Steven B; Castle, Sherry A

2008-01-01

The combined stresses of moderate heat shock (45 degrees C) and analog-induced glucose deprivation constitute a lethal stress for Neurospora crassa. We found that this cell death requires fatty acid synthesis and the cofactor biotin. In the absence of the cofactor, the stressed cells are particul......The combined stresses of moderate heat shock (45 degrees C) and analog-induced glucose deprivation constitute a lethal stress for Neurospora crassa. We found that this cell death requires fatty acid synthesis and the cofactor biotin. In the absence of the cofactor, the stressed cells...

Self-compassion and physical health: Exploring the roles of perceived stress and health-promoting behaviors

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Kristin J Homan

2017-09-01

Full Text Available Growing evidence indicates that self-compassion is associated with better physical health, but the pathways that mediate this relationship are not well understood. This study tested a serial mediation model that linked self-compassion, perceived stress, health behaviors, and a comprehensive index of physical health. A sample of 176 individuals completed an online survey posted on Amazon’s Mechanical Turk. Self-compassion had an indirect effect on physical health via both mediators and through the sequential pathway, suggesting that taking a kind, accepting and mindful stance toward one’s flaws and failures may have benefits for reducing stress and promoting health behaviors.

Glucose tolerance during pulmonary exacerbations in children with cystic fibrosis.

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John Widger

Full Text Available BACKGROUND: Patients with Cystic Fibrosis (CF are relatively insulinopenic and are at risk of diabetes, especially during times of stress. There is a paucity of data in the literature describing glucose tolerance during CF pulmonary exacerbations. We hypothesised that glucose tolerance would be worse during pulmonary exacerbations in children with CF than during clinical stability. METHODS: Patients with CF, 10 years or older, admitted with a pulmonary exacerbation underwent an OGTT within 48 hours of admission. A repeat OGTT was performed 4 to 6 weeks post discharge when the patients were well. RESULTS: Nine patients completed the study. Four patients were found to have normal glucose tolerance, 3 with impaired and 2 with CF related diabetes during the exacerbation. Mean change in 2-hour glucose was 1.1 mmol (SD = 0.77. At the follow up OGTT, 8 of 9 (89% remained within their respective glucose tolerance status groupings. CONCLUSION: The findings of this study show that there is little difference in glucose tolerance during CF exacerbations compared to clinical stability in the majority of patients.

Rapamycin and Glucose-Target of Rapamycin (TOR) Protein Signaling in Plants*

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Xiong, Yan; Sheen, Jen

2012-01-01

Target of rapamycin (TOR) kinase is an evolutionarily conserved master regulator that integrates energy, nutrients, growth factors, and stress signals to promote survival and growth in all eukaryotes. The reported land plant resistance to rapamycin and the embryo lethality of the Arabidopsis tor mutants have hindered functional dissection of TOR signaling in plants. We developed sensitive cellular and seedling assays to monitor endogenous Arabidopsis TOR activity based on its conserved S6 kinase (S6K) phosphorylation. Surprisingly, rapamycin effectively inhibits Arabidopsis TOR-S6K1 signaling and retards glucose-mediated root and leaf growth, mimicking estradiol-inducible tor mutants. Rapamycin inhibition is relieved in transgenic plants deficient in Arabidopsis FK506-binding protein 12 (FKP12), whereas FKP12 overexpression dramatically enhances rapamycin sensitivity. The role of Arabidopsis FKP12 is highly specific as overexpression of seven closely related FKP proteins fails to increase rapamycin sensitivity. Rapamycin exerts TOR inhibition by inducing direct interaction between the TOR-FRB (FKP-rapamycin binding) domain and FKP12 in plant cells. We suggest that variable endogenous FKP12 protein levels may underlie the molecular explanation for longstanding enigmatic observations on inconsistent rapamycin resistance in plants and in various mammalian cell lines or diverse animal cell types. Integrative analyses with rapamycin and conditional tor and fkp12 mutants also reveal a central role of glucose-TOR signaling in root hair formation. Our studies demonstrate the power of chemical genetic approaches in the discovery of previously unknown and pivotal functions of glucose-TOR signaling in governing the growth of cotyledons, true leaves, petioles, and primary and secondary roots and root hairs. PMID:22134914

14,15-EET promotes mitochondrial biogenesis and protects cortical neurons against oxygen/glucose deprivation-induced apoptosis.

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Wang, Lai; Chen, Man; Yuan, Lin; Xiang, Yuting; Zheng, Ruimao; Zhu, Shigong

2014-07-18

14,15-Epoxyeicosatrienoic acid (14,15-EET), a metabolite of arachidonic acid, is enriched in the brain cortex and exerts protective effect against neuronal apoptosis induced by ischemia/reperfusion. Although apoptosis has been well recognized to be closely associated with mitochondrial biogenesis and function, it is still unclear whether the neuroprotective effect of 14,15-EET is mediated by promotion of mitochondrial biogenesis and function in cortical neurons under the condition of oxygen-glucose deprivation (OGD). In this study, we found that 14,15-EET improved cell viability and inhibited apoptosis of cortical neurons. 14,15-EET significantly increased the mitochondrial mass and the ratio of mitochondrial DNA to nuclear DNA. Key makers of mitochondrial biogenesis, peroxisome proliferator activator receptor gamma-coactivator 1 alpha (PGC-1α), nuclear respiratory factor 1 (NRF-1) and mitochondrial transcription factor A (TFAM), were elevated at both mRNA and protein levels in the cortical neurons treated with 14,15-EET. Moreover, 14,15-EET markedly attenuated the decline of mitochondrial membrane potential, reduced ROS, while increased ATP synthesis. Knockdown of cAMP-response element binding protein (CREB) by siRNA blunted the up-regulation of PGC-1α and NRF-1 stimulated by 14,15-EET, and consequently abolished the neuroprotective effect of 14,15-EET. Our results indicate that 14,15-EET protects neurons from OGD-induced apoptosis by promoting mitochondrial biogenesis and function through CREB mediated activation of PGC-1α and NRF-1. Copyright © 2014 Elsevier Inc. All rights reserved.

Fermented Moringa oleifera Decreases Hepatic Adiposity and Ameliorates Glucose Intolerance in High-Fat Diet-Induced Obese Mice.

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Joung, Hyunchae; Kim, Bobae; Park, Hyunjoon; Lee, Kyuyeon; Kim, Hee-Hoon; Sim, Ho-Cheol; Do, Hyun-Jin; Hyun, Chang-Kee; Do, Myoung-Sool

2017-05-01

Metabolic diseases, such as glucose intolerance and nonalcoholic fatty-liver disease (NAFLD), are primary risk factors for life-threatening conditions such as diabetes, heart attack, stroke, and hepatic cancer. Extracts from the tropical tree Moringa oleifera show antidiabetic, antioxidant, anti-inflammatory, and anticancer effects. Fermentation can further improve the safety and nutritional value of certain foods. We investigated the efficacy of fermented M. oleifera extract (FM) against high-fat diet (HFD)-induced glucose intolerance and hepatic lipid accumulation and investigated the underlying mechanisms by analyzing expression of proteins and genes involved in glucose and lipid regulation. C57BL/6 mice were fed with normal chow diet (ND) or HFD supplemented with distilled water (DW, control), nonfermented M. oleifera extract (NFM), or FM for 10 weeks. Although body weights were similar among HFD-fed treatment groups, liver weight was decreased, and glucose tolerance test (GTT) results improved in the FM group compared with DW and NFM groups. Hepatic lipid accumulation was also lower in the FM group, and expressions of genes involved in liver lipid metabolism were upregulated. In addition, HFD-induced endoplasmic reticulum (ER) stress, oxidative stress, and lipotoxicity in quadriceps muscles were decreased by FM. Finally, proinflammatory cytokine mRNA expression was decreased by FM in the liver, epididymal adipose tissue, and quadriceps of HFD-fed mice. FMs may decrease glucose intolerance and NAFLD under HFD-induced obesity by decreasing ER stress, oxidative stress, and inflammation.

Neurotrophin Signaling Is Required for Glucose-Induced Insulin Secretion.

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Houtz, Jessica; Borden, Philip; Ceasrine, Alexis; Minichiello, Liliana; Kuruvilla, Rejji

2016-11-07

Insulin secretion by pancreatic islet β cells is critical for glucose homeostasis, and a blunted β cell secretory response is an early deficit in type 2 diabetes. Here, we uncover a regulatory mechanism by which glucose recruits vascular-derived neurotrophins to control insulin secretion. Nerve growth factor (NGF), a classical trophic factor for nerve cells, is expressed in pancreatic vasculature while its TrkA receptor is localized to islet β cells. High glucose rapidly enhances NGF secretion and increases TrkA phosphorylation in mouse and human islets. Tissue-specific deletion of NGF or TrkA, or acute disruption of TrkA signaling, impairs glucose tolerance and insulin secretion in mice. We show that internalized TrkA receptors promote insulin granule exocytosis via F-actin reorganization. Furthermore, NGF treatment augments glucose-induced insulin secretion in human islets. These findings reveal a non-neuronal role for neurotrophins and identify a new regulatory pathway in insulin secretion that can be targeted to ameliorate β cell dysfunction. Copyright © 2016 Elsevier Inc. All rights reserved.

In vitro degradation of pure Mg in response to glucose

Science.gov (United States)

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

2015-08-01

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

Combat Stress Decreases Memory of Warfighters in Action.

Science.gov (United States)

Delgado-Moreno, Rosa; Robles-Pérez, José Juan; Clemente-Suárez, Vicente Javier

2017-08-01

The present research aimed to analyze the effect of combat stress in the psychophysiological response and attention and memory of warfighters in a simulated combat situation. Variables of blood oxygen saturation, heart rate, blood glucose, blood lactate, body temperature, lower body muscular strength manifestation, cortical arousal, autonomic modulation, state anxiety and memory and attention through a postmission questionnaire were analyzed before and after a combat simulation in 20 male professional Spanish Army warfighters. The combat simulation produces a significant increase (p body temperature post, HF post/correct sound, body temperature post/glucose post, CFFTpre/lactate post, CFFT post/wrong sound, glucose post/AC pre, AC post/wrong fusil, AS post/SC post and SC post/wrong olfactory; and negative correlations: LF post/correct sound, body temperature post/lactate post and glucose post/lactate post. This data suggest that combat stress actives fight-flight system of soldiers. As conclusion, Combat stress produces an increased psychophysiological response that cause a selective decrease of memory, depending on the nature, dangerous or harmless of the objects.

Vitamin E and Vitamin C supplementation does not prevent glucose intolerance in obese-prone rats

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Obesity-induced glucose intolerance affects over 70 million Americans. Elevated oxidative stress is associated with development of glucose intolerance. In this work, we tested the hypothesis that supplementation with the anti-oxidants vitamin E (d-alpha-tocopherol acetate; 0.4 g/kg diet) and vitamin...

A late embryogenesis abundant protein HVA1 regulated by an inducible promoter enhances root growth and abiotic stress tolerance in rice without yield penalty.

Science.gov (United States)

Chen, Yi-Shih; Lo, Shuen-Fang; Sun, Peng-Kai; Lu, Chung-An; Ho, Tuan-Hua D; Yu, Su-May

2015-01-01

Regulation of root architecture is essential for maintaining plant growth under adverse environment. A synthetic abscisic acid (ABA)/stress-inducible promoter was designed to control the expression of a late embryogenesis abundant protein (HVA1) in transgenic rice. The background of HVA1 is low but highly inducible by ABA, salt, dehydration and cold. HVA1 was highly accumulated in root apical meristem (RAM) and lateral root primordia (LRP) after ABA/stress treatments, leading to enhanced root system expansion. Water-use efficiency (WUE) and biomass also increased in transgenic rice, likely due to the maintenance of normal cell functions and metabolic activities conferred by HVA1 which is capable of stabilizing proteins, under osmotic stress. HVA1 promotes lateral root (LR) initiation, elongation and emergence and primary root (PR) elongation via an auxin-dependent process, particularly by intensifying asymmetrical accumulation of auxin in LRP founder cells and RAM, even under ABA/stress-suppressive conditions. We demonstrate a successful application of an inducible promoter in regulating the spatial and temporal expression of HVA1 for improving root architecture and multiple stress tolerance without yield penalty. © 2014 Society for Experimental Biology, Association of Applied Biologists and John Wiley & Sons Ltd.

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

DEFF Research Database (Denmark)

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

2007-01-01

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

Cytokinin-producing, plant growth-promoting rhizobacteria that confer resistance to drought stress in Platycladus orientalis container seedlings.

Science.gov (United States)

Liu, Fangchun; Xing, Shangjun; Ma, Hailin; Du, Zhenyu; Ma, Bingyao

2013-10-01

One of the proposed mechanisms through which plant growth-promoting rhizobacteria (PGPR) enhance plant growth is the production of plant growth regulators, especially cytokinin. However, little information is available regarding cytokinin-producing PGPR inoculation on growth and water stress consistence of forest container seedlings under drought condition. This study determined the effects of Bacillus subtilis on hormone concentration, drought resistance, and plant growth under water-stressed conditions. Although no significant difference was observed under well-watered conditions, leaves of inoculated Platycladus orientalis (oriental thuja) seedlings under drought stress had higher relative water content and leaf water potential compared with those of noninoculated ones. Regardless of water supply levels, the root exudates, namely sugars, amino acids and organic acids, significantly increased because of B. subtilis inoculation. Water stress reduced shoot cytokinins by 39.14 %. However, inoculation decreased this deficit to only 10.22 %. The elevated levels of cytokinins in P. orientalis shoot were associated with higher concentration of abscisic acid (ABA). Stomatal conductance was significantly increased by B. subtilis inoculation in well-watered seedlings. However, the promoting effect of cytokinins on stomatal conductance was hampered, possibly by the combined action of elevated cytokinins and ABA. B. subtilis inoculation increased the shoot dry weight of well-watered and drought seedlings by 34.85 and 19.23 %, as well as the root by 15.445 and 13.99 %, respectively. Consequently, the root/shoot ratio significantly decreased, indicative of the greater benefits of PGPR on shoot growth than root. Thus, inoculation of cytokinin-producing PGPR in container seedlings can alleviate the drought stress and interfere with the suppression of shoot growth, showing a real potential to perform as a drought stress inhibitor in arid environments.

Occurrence and predictors of persistent impaired glucose tolerance after acute ischemic stroke or transient ischemic attack

NARCIS (Netherlands)

S. Fonville (Susanne); H.M. den Hertog (Heleen); A.A.M. Zandbergen (Adrienne); P.J. Koudstaal (Peter Jan); H.F. Lingsma (Hester)

2014-01-01

textabstractBackground Impaired glucose tolerance is often present in patients with a transient ischemic attack (TIA) or ischemic stroke and doubles the risk of recurrent stroke. This impaired glucose tolerance can be transient, reflecting an acute stress response, or persistent, representing

Mitochondrial Stress Signaling Promotes Cellular Adaptations

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Jayne Alexandra Barbour

2014-01-01

Full Text Available Mitochondrial dysfunction has been implicated in the aetiology of many complex diseases, as well as the ageing process. Much of the research on mitochondrial dysfunction has focused on how mitochondrial damage may potentiate pathological phenotypes. The purpose of this review is to draw attention to the less well-studied mechanisms by which the cell adapts to mitochondrial perturbations. This involves communication of stress to the cell and successful induction of quality control responses, which include mitophagy, unfolded protein response, upregulation of antioxidant and DNA repair enzymes, morphological changes, and if all else fails apoptosis. The mitochondrion is an inherently stressful environment and we speculate that dysregulation of stress signaling or an inability to switch on these adaptations during times of mitochondrial stress may underpin mitochondrial dysfunction and hence amount to pathological states over time.

Early life diets with prebiotics and bioactive milk fractions attenuate the impact of stress on learned helplessness behaviours and alter gene expression within neural circuits important for stress resistance.

Science.gov (United States)

Mika, Agnieszka; Day, Heidi E W; Martinez, Alexander; Rumian, Nicole L; Greenwood, Benjamin N; Chichlowski, Maciej; Berg, Brian M; Fleshner, Monika

2017-02-01

Manipulating gut microbes may improve mental health. Prebiotics are indigestible compounds that increase the growth and activity of health-promoting microorganisms, yet few studies have examined how prebiotics affect CNS function. Using an acute inescapable stressor known to produce learned helplessness behaviours such as failure to escape and exaggerated fear, we tested whether early life supplementation of a blend of two prebiotics, galactooligosaccharide (GOS) and polydextrose (PDX), and the glycoprotein lactoferrin (LAC) would attenuate behavioural and biological responses to stress later in life. Juvenile, male F344 rats were fed diets containing either GOS and PDX alone, LAC alone, or GOS, PDX and LAC. All diets altered gut bacteria, while diets containing GOS and PDX increased Lactobacillus spp. After 4 weeks, rats were exposed to inescapable stress, and either immediately killed for blood and tissues, or assessed for learned helplessness 24 h later. Diets did not attenuate stress effects on spleen weight, corticosterone and blood glucose; however, all diets differentially attenuated stress-induced learned helplessness. Notably, in situ hybridization revealed that all diets reduced stress-evoked cfos mRNA in the dorsal raphe nucleus (DRN), a structure important for learned helplessness behaviours. In addition, GOS, PDX and LAC diet attenuated stress-evoked decreases in mRNA for the 5-HT 1A autoreceptor in the DRN and increased basal BDNF mRNA within the prefrontal cortex. These data suggest early life diets containing prebiotics and/or LAC promote behavioural stress resistance and uniquely modulate gene expression in corresponding circuits. © 2016 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Positioning of sodium-glucose cotransporter-2 inhibitors in national and international guidelines.

Science.gov (United States)

Morillas, Carlos

2016-11-01

Sodium-glucose cotransporter-2 inhibitors (SGLT2-i) selectively and reversibly inhibit sodium-glucose cotransporter-2 (SGLT2), promoting renal glucose excretion and reducing plasma glycaemia. By increasing renal glucose excretion, these drugs favour a negative energy balance, leading to weight loss. Their glucoselowering effect is independent of insulin. Although these drugs have only recently been developed, they have been included in all the main national and international guidelines since 2014. The present review summarises the most important recommendations on the use of SGLT2 in patients with DM2 contained in the most recently published guidelines and consensus statements. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

Comparison of the changes in blood glucose level during sedation with midazolam and propofol in implant surgery: a prospective randomized clinical trial.

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Kaviani, Nasser; Koosha, Farzad; Shahtusi, Mina

2014-09-01

Reducing the patients' stress can prevent, or at least, limit the increase in blood glucose level. The study compares the effect of propofol and midazolam on blood glucose level in the patients undergoing dental implant surgery. The effect of pre-operational stress on blood glucose level during the surgery is also evaluated. This prospective randomized clinical trial recruited 33 patients undergoing dental implant surgery and divided into two groups. Conscious sedation was performed by midazolam in one group and with propofol in another group. The pre-operational stress was scored and the blood glucose level was measured in 4 different stages; before the operation, two minutes after the local anesthetic injection; thirty minutes after the onset of operation and at the end of the operation. The results were analyzed by employing ANOVA and Pearson test. The p Value was adopted 0.05 and the confidence coefficient was assumed 95%. The average levels of the blood glucose in midazolam and propofol group were 93.82 mg/dl and 94 mg/dl before the operation which displayed a meaningful increase of blood glucose level in both groups as the operation went on. The values were 103.76 mg/dl for midazolam and 108.56 mg/dl for the propofol group (pblood glucose level between two groups in the different stages of the operation (p= 0.466). The Pearson correlation coefficient test revealed a higher increase in the blood glucose level in the patients with a higher pre-operational stress score (r= 0.756, pblood glucose level while undergoing an operation. No statistically significant difference was detected between midazolam and propofol.

Human Peritoneal Mesothelial Cell Death Induced by High-Glucose Hypertonic Solution Involves Ca2+ and Na+ Ions and Oxidative Stress with the Participation of PKC/NOX2 and PI3K/Akt Pathways

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Felipe Simon

2017-06-01

Full Text Available Chronic peritoneal dialysis (PD therapy is equally efficient as hemodialysis while providing greater patient comfort and mobility. Therefore, PD is the treatment of choice for several types of renal patients. During PD, a high-glucose hyperosmotic (HGH solution is administered into the peritoneal cavity to generate an osmotic gradient that promotes water and solutes transport from peritoneal blood to the dialysis solution. Unfortunately, PD has been associated with a loss of peritoneal viability and function through the generation of a severe inflammatory state that induces human peritoneal mesothelial cell (HPMC death. Despite this deleterious effect, the precise molecular mechanism of HPMC death as induced by HGH solutions is far from being understood. Therefore, the aim of this study was to explore the pathways involved in HGH solution-induced HPMC death. HGH-induced HPMC death included influxes of intracellular Ca2+ and Na+. Furthermore, HGH-induced HPMC death was inhibited by antioxidant and reducing agents. In line with this, HPMC death was induced solely by increased oxidative stress. In addition to this, the cPKC/NOX2 and PI3K/Akt intracellular signaling pathways also participated in HGH-induced HPMC death. The participation of PI3K/Akt intracellular is in agreement with previously shown in rat PMC apoptosis. These findings contribute toward fully elucidating the underlying molecular mechanism mediating peritoneal mesothelial cell death induced by high-glucose solutions during peritoneal dialysis.

[Effects of blood glucose control on glucose variability and clinical outcomes in patients with severe acute pancreatitis in intensive care unit].

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Wu, Jing; Sun, Qiuhong; Yang, Hua

2015-05-19

To explore the effects of blood glucose control on glucose variability and clinical outcomes in patients with severe acute pancreatitis in intensive care unit (ICU). A total of 72 ICU patients with severe acute pancreatitis were recruited and divided randomly into observation and control groups (n = 36 each). Both groups were treated conventionally. And the observation group achieved stable blood glucose at 6.1-8.3 mmol/L with intensive glucose control. The length of ICU and hospital stays, ICU mortality rate, transit operative rate, concurrent infection rate, admission blood glucose, glycosylated hemoglobin, mean insulin dose, mean blood glucose, blood glucose value standard deviation (GLUSD), glycemic liability index (GLUGLI) and mean amplitude of glycemic excursion (GLUMAGE) of two groups were compared. At the same time, the relationship between blood glucose variability, ICU mortality rate and its predictive value were analyzed by correlation analysis and receiver operating characteristic curve (ROC). The lengths of ICU and hospital stays of observation group were all significantly less than those of the control group [(11.7 ± 9.9) vs (15.9 ± 8.02) days, (21.8 ± 10.8) vs (28.2 ± 12.7) days, P blood glucose value and GLUSD of observation group were significantly lower than those of control group [(7.4 ± 1.1) vs (9.6 ± 1.2), (1.8 ± 1.0) vs (2.5 ± 1.3) mmol/L]. The differences were statistically significant (P curve analysis showed that, AUC of GLUGLI was 0.748 and 95% CI 0.551-0.965 (P glucose control in patients with severe acute pancreatitis helps reduce the blood sugar fluctuations, lower the risks of infectious complications and promote the patient rehabilitation. And GLUGLI is positively correlated with ICU mortality rate. It has good predictive values.

Parasite stress promotes homicide and child maltreatment

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Thornhill, Randy; Fincher, Corey L.

2011-01-01

Researchers using the parasite-stress theory of human values have discovered many cross-cultural behavioural patterns that inform a range of scholarly disciplines. Here, we apply the theory to major categories of interpersonal violence, and the empirical findings are supportive. We hypothesize that the collectivism evoked by high parasite stress is a cause of adult-on-adult interpersonal violence. Across the US states, parasite stress and collectivism each positively predicts rates of men's and women's slaying of a romantic partner, as well as the rate of male-honour homicide and of the motivationally similar felony-related homicide. Of these four types of homicide, wealth inequality has an independent effect only on rates of male-honour and felony-related homicide. Parasite stress and collectivism also positively predict cross-national homicide rates. Child maltreatment by caretakers is caused, in part, by divestment in offspring of low phenotypic quality, and high parasite stress produces more such offspring than low parasite stress. Rates of each of two categories of the child maltreatment—lethal and non-lethal—across the US states are predicted positively by parasite stress, with wealth inequality and collectivism having limited effects. Parasite stress may be the strongest predictor of interpersonal violence to date. PMID:22042922

Early Life Stress Increases Metabolic Risk, HPA Axis Reactivity, and Depressive-Like Behavior When Combined with Postweaning Social Isolation in Rats.

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Vargas, Javier; Junco, Mariana; Gomez, Carlos; Lajud, Naima

2016-01-01

Early-life stress is associated with depression and metabolic abnormalities that increase the risk of cardiovascular disease and diabetes. Such associations could be due to increased glucocorticoid levels. Periodic maternal separation in the neonate and rearing in social isolation are potent stressors that increase hypothalamus-pituitary-adrenal axis activity. Moreover, social isolation promotes feed intake and body weight gain in rats subjected to periodic maternal separation; however, its effects on metabolic risks have not been described. In the present study, we evaluated whether periodic maternal separation, social isolation rearing, and a combination of these two stressors (periodic maternal separation + social isolation rearing) impair glucose homeostasis and its relation to the hypothalamus-pituitary-adrenal axis and depressive-like behavior. Periodic maternal separation increased basal corticosterone levels, induced a passive coping strategy in the forced swimming test, and was associated with a mild (24%) increase in fasting glucose, insulin resistance, and dyslipidemia. Rearing in social isolation increased stress reactivity in comparison to both controls and in combination with periodic maternal separation, without affecting the coping strategy associated with the forced swimming test. However, social isolation also increased body weight gain, fasting glucose (120%), and insulin levels in rats subjected to periodic maternal separation. Correlation analyses showed that stress-induced effects on coping strategy on the forced swimming test (but not on metabolic risk markers) are associated with basal corticosterone levels. These findings suggest that maternal separation and postweaning social isolation affect stress and metabolic vulnerability differentially and that early-life stress-related effects on metabolism are not directly dependent on glucocorticoid levels. In conclusion, our study supports the cumulative stress hypothesis, which suggests that

Engineering of synthetic, stress-responsive yeast promoters

DEFF Research Database (Denmark)

Rajkumar, Arun Stephen; Liu, Guodong; Bergenholm, David

2016-01-01

Advances in synthetic biology and our understanding of the rules of promoter architecture have led to the development of diverse synthetic constitutive and inducible promoters in eukaryotes and prokaryotes. However, the design of promoters inducibleby specific endogenous or environmental conditions...

A stressful microenvironment: opposing effects of the endoplasmic reticulum stress response in the suppression and enhancement of adaptive tumor immunity.

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Rausch, Matthew P; Sertil, Aparna Ranganathan

2015-03-01

The recent clinical success of immunotherapy in the treatment of certain types of cancer has demonstrated the powerful ability of the immune system to control tumor growth, leading to significantly improved patient survival. However, despite these promising results current immunotherapeutic strategies are still limited and have not yet achieved broad acceptance outside the context of metastatic melanoma. The limitations of current immunotherapeutic approaches can be attributed in part to suppressive mechanisms present in the tumor microenvironment that hamper the generation of robust antitumor immune responses thus allowing tumor cells to escape immune-mediated destruction. The endoplasmic reticulum (ER) stress response has recently emerged as a potent regulator of tumor immunity. The ER stress response is an adaptive mechanism that allows tumor cells to survive in the harsh growth conditions inherent to the tumor milieu such as low oxygen (hypoxia), low pH and low levels of glucose. Activation of ER stress can also alter the cancer cell response to therapies. In addition, the ER stress response promotes tumor immune evasion by inducing the production of protumorigenic inflammatory cytokines and impairing tumor antigen presentation. However, the ER stress response can boost antitumor immunity in some situations by enhancing the processing and presentation of tumor antigens and by inducing the release of immunogenic factors from stressed tumor cells. Here, we discuss the dualistic role of the ER stress response in the modulation of tumor immunity and highlight how strategies to either induce or block ER stress can be employed to improve the clinical efficacy of tumor immunotherapy.

Glucose enhancement of memory is modulated by trait anxiety in healthy adolescent males.

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Smith, Michael A; Hii, Hilary L; Foster, Jonathan K; van Eekelen, J A M

2011-01-01

Glucose administration is associated with memory enhancement in healthy young individuals under conditions of divided attention at encoding. While the specific neurocognitive mechanisms underlying this 'glucose memory facilitation effect' are currently uncertain, it is thought that individual differences in glucoregulatory efficiency may alter an individual's sensitivity to the glucose memory facilitation effect. In the present study, we sought to investigate whether basal hypothalamic-pituitary-adrenal axis function (itself a modulator of glucoregulatory efficiency), baseline self-reported stress and trait anxiety influence the glucose memory facilitation effect. Adolescent males (age range = 14-17 years) were administered glucose and placebo prior to completing a verbal episodic memory task on two separate testing days in a counter-balanced, within-subjects design. Glucose ingestion improved verbal episodic memory performance when memory recall was tested (i) within an hour of glucose ingestion and encoding, and (ii) one week subsequent to glucose ingestion and encoding. Basal hypothalamic-pituitary-adrenal axis function did not appear to influence the glucose memory facilitation effect; however, glucose ingestion only improved memory in participants reporting relatively higher trait anxiety. These findings suggest that the glucose memory facilitation effect may be mediated by biological mechanisms associated with trait anxiety.

Integrative Genomic and Proteomic Analysis of the Response of Lactobacillus casei Zhang to Glucose Restriction.

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Yu, Jie; Hui, Wenyan; Cao, Chenxia; Pan, Lin; Zhang, Heping; Zhang, Wenyi

2018-03-02

Nutrient starvation is an important survival challenge for bacteria during industrial production of functional foods. As next-generation sequencing technology has greatly advanced, we performed proteomic and genomic analysis to investigate the response of Lactobacillus casei Zhang to a glucose-restricted environment. L. casei Zhang strains were permitted to evolve in glucose-restricted or normal medium from a common ancestor over a 3 year period, and they were sampled at 1000, 2000, 3000, 4000, 5000, 6000, 7000, and 8000 generations and subjected to proteomic and genomic analyses. Genomic resequencing data revealed different point mutations and other mutational events in each selected generation of L. casei Zhang under glucose restriction stress. The differentially expressed proteins induced by glucose restriction were mostly related to fructose and mannose metabolism, carbohydrate metabolic processes, lyase activity, and amino-acid-transporting ATPase activity. Integrative proteomic and genomic analysis revealed that the mutations protected L. casei Zhang against glucose starvation by regulating other cellular carbohydrate, fatty acid, and amino acid catabolism; phosphoenolpyruvate system pathway activation; glycogen synthesis; ATP consumption; pyruvate metabolism; and general stress-response protein expression. The results help reveal the mechanisms of adapting to glucose starvation and provide new strategies for enhancing the industrial utility of L. casei Zhang.

The Grape VlWRKY3 Gene Promotes Abiotic and Biotic Stress Tolerance in Transgenic Arabidopsis thaliana

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Rongrong Guo

2018-04-01

Full Text Available WRKY transcription factors are known to play important roles in plant responses to various abiotic and biotic stresses. The grape WRKY gene, WRKY3 was previously reported to respond to salt and drought stress, as well as methyl jasmonate and ethylene treatments in Vitis labrusca × V. vinifera cv. ‘Kyoho.’ In the current study, WRKY3 from the ‘Kyoho’ grape cultivar was constitutively expressed in Arabidopsis thaliana under control of the cauliflower mosaic virus 35S promoter. The 35S::VlWRKY3 transgenic A. thaliana plants showed improved salt and drought stress tolerance during the germination, seedling and the mature plant stages. Various physiological traits related to abiotic stress responses were evaluated to gain further insight into the role of VlWRKY3, and it was found that abiotic stress caused less damage to the transgenic seedlings than to the wild-type (WT plants. VlWRKY3 over-expression also resulted in altered expression levels of abiotic stress-responsive genes. Moreover, the 35S::VlWRKY3 transgenic A. thaliana lines showed improved resistance to Golovinomyces cichoracearum, but increased susceptibility to Botrytis cinerea, compared with the WT plants. Collectively, these results indicate that VlWRKY3 plays important roles in responses to both abiotic and biotic stress, and modification of its expression may represent a strategy to enhance stress tolerance in crops.

Endoplasmic Reticulum Stress-Mediated Hippocampal Neuron Apoptosis Involved in Diabetic Cognitive Impairment

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Xiaoming Zhang

2013-01-01

Full Text Available Poor management of DM causes cognitive impairment while the mechanism is still unconfirmed. The aim of the present study was to investigate the activation of C/EBP Homology Protein (CHOP, the prominent mediator of the endoplasmic reticulum (ER stress-induced apoptosis under hyperglycemia. We employed streptozotocin- (STZ- induced diabetic rats to explore the ability of learning and memory by the Morris water maze test. The ultrastructure of hippocampus in diabetic rats and cultured neurons in high glucose medium were observed by transmission electron microscopy and scanning electron microscopy. TUNEL staining was also performed to assess apoptotic cells while the expression of CHOP was assayed by immunohistochemistry and Western blot assay in these hippocampal neurons. Six weeks after diabetes induction, the escape latency increased and the average frequency in finding the platform decreased in diabetic rats (P<0.05. The morphology of neuron and synaptic structure was impaired; the number of TUNEL-positive cells and the expression of CHOP in hippocampus of diabetic rats and high glucose medium cultured neurons were markedly altered (P<0.05. The present results suggested that the CHOP-dependent endoplasmic reticulum (ER stress-mediated apoptosis may be involved in hyperglycemia-induced hippocampal synapses and neurons impairment and promote the diabetic cognitive impairment.

Tolerance of transgenic canola plants (Brassica napus) amended with plant growth-promoting bacteria to flooding stress at a metal-contaminated field site

International Nuclear Information System (INIS)

Farwell, Andrea J.; Vesely, Susanne; Nero, Vincent; Rodriguez, Hilda; McCormack, Kimberley; Shah, Saleh; Dixon, D. George; Glick, Bernard R.

2007-01-01

The growth of transgenic canola (Brassica napus) expressing a gene for the enzyme 1-aminocyclopropane-1-carboxylate (ACC) deaminase was compared to non-transformed canola exposed to flooding and elevated soil Ni concentration, in situ. In addition, the ability of the plant growth-promoting bacterium Pseudomonas putida UW4, which also expresses ACC deaminase, to facilitate the growth of non-transformed and transgenic canola under the above mentioned conditions was examined. Transgenic canola and/or canola treated with P. putida UW4 had greater shoot biomass compared to non-transformed canola under low flood-stress conditions. Under high flood-stress conditions, shoot biomass was reduced and Ni accumulation was increased in all instances relative to low flood-stress conditions. This is the first field study to document the increase in plant tolerance utilizing transgenic plants and plant growth-promoting bacteria exposed to multiple stressors. - Using transgenic plants and plant growth-promoting bacteria as phytoremediation methods increased plant tolerance at a metal-contaminated field site under low flood conditions

Bacillus aryabhattai SRB02 tolerates oxidative and nitrosative stress and promotes the growth of soybean by modulating the production of phytohormones

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Kang, Sang-Mo; Shahzad, Raheem; Seo, Chang-Woo; Kim, Ah-Yeong; Lee, Sang-Uk; Oh, Kyeong Yeol; Lee, Dong Yeol; Lee, In-Jung; Yun, Byung-Wook

2017-01-01

Plant growth promoting rhizobacteria (PGPR) are diverse, naturally occurring bacteria that establish a close association with plant roots and promote the growth and immunity of plants. Established mechanisms involved in PGPR-mediated plant growth promotion include regulation of phytohormones, improved nutrient availability, and antagonistic effects on plant pathogens. In this study, we isolated a bacterium from the rhizospheric soil of a soybean field in Chungcheong buk-do, South Korea. Using 16S rRNA sequencing, the bacterium was identified as Bacillus aryabhattai strain SRB02. Here we show that this strain significantly promotes the growth of soybean. Gas chromatography—mass spectrometry analysis showed that SRB02 produced significant amounts of abscisic acid, indole acetic acid, cytokinin and different gibberellic acids in culture. SRB02-treated soybean plants showed significantly better heat stress tolerance than did untreated plants. These plants also produced consistent levels of ABA under heat stress and exhibited ABA-mediated stomatal closure. High levels of IAA, JA, GA12, GA4, and GA7, were recorded in SRB02-treated plants. These plants produced longer roots and shoots than those of control plants. B. aryabhattai SRB02 was found to be highly tolerant to oxidative stress induced by H2O2 and MV potentiated by high catalase (CAT) and superoxide dismutase (SOD) activities. SRB02 also tolerated high nitrosative stress induced by the nitric oxide donors GSNO and CysNO. Because of these attributes, B. aryabhattai SRB02 may prove to be a valuable resource for incorporation in biofertilizers and other soil amendments that seek to improve crop productivity. PMID:28282395

Functional Characterization of the Tau Class Glutathione-S-Transferases Gene (SbGSTU) Promoter of Salicornia brachiata under Salinity and Osmotic Stress.

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Tiwari, Vivekanand; Patel, Manish Kumar; Chaturvedi, Amit Kumar; Mishra, Avinash; Jha, Bhavanath

2016-01-01

Reactive oxygen or nitrogen species are generated in the plant cell during the extreme stress condition, which produces toxic compounds after reacting with the organic molecules. The glutathione-S-transferase (GST) enzymes play a significant role to detoxify these toxins and help in excretion or sequestration of them. In the present study, we have cloned 1023 bp long promoter region of tau class GST from an extreme halophyte Salicornia brachiata and functionally characterized using the transgenic approach in tobacco. Computational analysis revealed the presence of abiotic stress responsive cis-elements like ABRE, MYB, MYC, GATA, GT1 etc., phytohormones, pathogen and wound responsive motifs. Three 5'-deletion constructs of 730 (GP2), 509 (GP3) and 348 bp (GP4) were made from 1023 (GP1) promoter fragment and used for tobacco transformation. The single event transgenic plants showed notable GUS reporter protein expression in the leaf tissues of control as well as treated plants. The expression level of the GUS gradually decreases from GP1 to GP4 in leaf tissues, whereas the highest level of expression was detected with the GP2 construct in root and stem under control condition. The GUS expression was found higher in leaves and stems of salinity or osmotic stress treated transgenic plants than that of the control plants, but, lower in roots. An efficient expression level of GUS in transgenic plants suggests that this promoter can be used for both constitutive as well as stress inducible expression of gene(s). And this property, make it as a potential candidate to be used as an alternative promoter for crop genetic engineering.

Bacillus aryabhattai SRB02 tolerates oxidative and nitrosative stress and promotes the growth of soybean by modulating the production of phytohormones.

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Yeon-Gyeong Park

Full Text Available Plant growth promoting rhizobacteria (PGPR are diverse, naturally occurring bacteria that establish a close association with plant roots and promote the growth and immunity of plants. Established mechanisms involved in PGPR-mediated plant growth promotion include regulation of phytohormones, improved nutrient availability, and antagonistic effects on plant pathogens. In this study, we isolated a bacterium from the rhizospheric soil of a soybean field in Chungcheong buk-do, South Korea. Using 16S rRNA sequencing, the bacterium was identified as Bacillus aryabhattai strain SRB02. Here we show that this strain significantly promotes the growth of soybean. Gas chromatography-mass spectrometry analysis showed that SRB02 produced significant amounts of abscisic acid, indole acetic acid, cytokinin and different gibberellic acids in culture. SRB02-treated soybean plants showed significantly better heat stress tolerance than did untreated plants. These plants also produced consistent levels of ABA under heat stress and exhibited ABA-mediated stomatal closure. High levels of IAA, JA, GA12, GA4, and GA7, were recorded in SRB02-treated plants. These plants produced longer roots and shoots than those of control plants. B. aryabhattai SRB02 was found to be highly tolerant to oxidative stress induced by H2O2 and MV potentiated by high catalase (CAT and superoxide dismutase (SOD activities. SRB02 also tolerated high nitrosative stress induced by the nitric oxide donors GSNO and CysNO. Because of these attributes, B. aryabhattai SRB02 may prove to be a valuable resource for incorporation in biofertilizers and other soil amendments that seek to improve crop productivity.

High Glucose Increases Metallothionein Expression in Renal Proximal Tubular Epithelial Cells

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Daisuke Ogawa

2011-01-01

Full Text Available Metallothionein (MT is an intracellular metal-binding, cysteine-rich protein, and is a potent antioxidant that protects cells and tissues from oxidative stress. Although the major isoforms MT-1 and -2 (MT-1/-2 are highly inducible in many tissues, the distribution and role of MT-1/-2 in diabetic nephropathy are poorly understood. In this study, diabetes was induced in adult male rats by streptozotocin, and renal tissues were stained with antibodies for MT-1/-2. MT-1/-2 expression was also evaluated in mProx24 cells, a mouse renal proximal tubular epithelial cell line, stimulated with high glucose medium and pretreated with the antioxidant vitamin E. MT-1/-2 expression was gradually and dramatically increased, mainly in the proximal tubular epithelial cells and to a lesser extent in the podocytes in diabetic rats, but was hardly observed in control rats. MT-1/-2 expression was also increased by high glucose stimulation in mProx24 cells. Because the induction of MT was suppressed by pretreatment with vitamin E, the expression of MT-1/-2 is induced, at least in part, by high glucose-induced oxidative stress. These observations suggest that MT-1/-2 is induced in renal proximal tubular epithelial cells as an antioxidant to protect the kidney from oxidative stress, and may offer a novel therapeutic target against diabetic nephropathy.

Association between Blood Levels of Glucose and Urea and the ...

African Journals Online (AJOL)

osman

2017-08-05

Aug 5, 2017 ... Normal blood glucose and urea levels in dairy cows vary within breeds, ..... prolapse, and postpartum uterine haemorrhage, the effect of metabolic stress, ... and the effect of efficiency of heat detection on the average days to.

Effect of leptin gene methylation on glucose metabolism in pregnant rats

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Zhen LI

2011-11-01

Full Text Available Objective To examine the dynamic level of progesterone,insulin,and leptin,as well as the change in the features of leptin gene methylation in the promoter region of pregnant rats during different gestation stages and to analyze the correlation and effect of these conditions on glucose metabolism during gestation.Methods C57BL/6J pregnant rats are divided to four different groups,namely,early,mid-,and late gestation,as well as seven days postpartum(five rats for each group.Five C57BL/6J non-pregnant rats are taken as the control group.The change in glucose metabolism during gestation was determined by measuring the glucose tolerance of rats in different groups and by testing the level of progesterone,insulin,and leptin in the sera and the level of the methylation of leptin gene promoters during different stages of gestation.Results The levels of insulin [(13.70±0.70,14.78±0.91,and 16.07±0.55mU/L],progesterone [(10.10±0.37,11.41±0.50,and 15.34±0.65μg/L],and leptin [(1356.73±100.41,1628.02±53.03,and 1954.12±39.71ng/L] in pregnant rats in the three groups(early,mid-,and late gestation are apparently higher than that of the non-pregnant rats [(12.25±1.62mU/L,(7.14±0.38μg/L,and(934.38±62.29ng/L] and the postpartum group [(12.46±0.93mU/L,(9.74±0.82μg/L,and(1259.19±105.74ng/L].The difference among the different stages of gestation has statistical significance(P < 0.01,but the difference between the non-pregnant and postpartum groups is statistically insignificant.Fasting blood glucose during gestation is low.The level of blood glucose in mid-gestation and late-gestation rats after being injected with glucose is apparently higher than that of the non-pregnant group(P < 0.01.The level of methylation in the leptin gene promoter zone of the placenta drops along with gestation.Conclusions High levels of progesterone,insulin,and leptin contribute to physiological insulin resistance during gestation,resulting in reduced fasting blood glucose

Clinical Implications of Glucose Variability: Chronic Complications of Diabetes

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Hye Seung Jung

2015-06-01

Full Text Available Glucose variability has been identified as a potential risk factor for diabetic complications; oxidative stress is widely regarded as the mechanism by which glycemic variability induces diabetic complications. However, there remains no generally accepted gold standard for assessing glucose variability. Representative indices for measuring intraday variability include calculation of the standard deviation along with the mean amplitude of glycemic excursions (MAGE. MAGE is used to measure major intraday excursions and is easily measured using continuous glucose monitoring systems. Despite a lack of randomized controlled trials, recent clinical data suggest that long-term glycemic variability, as determined by variability in hemoglobin A1c, may contribute to the development of microvascular complications. Intraday glycemic variability is also suggested to accelerate coronary artery disease in high-risk patients.

LncRNAs H19 and HULC, activated by oxidative stress, promote cell migration and invasion in cholangiocarcinoma through a ceRNA manner

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Wen-Tao Wang

2016-11-01

Full Text Available Abstract Background Long non-coding RNAs (lncRNAs are known to play important roles in different cell contexts, including cancers. However, little is known about lncRNAs in cholangiocarcinoma (CCA, a cholangiocyte malignancy with poor prognosis, associated with chronic inflammation and damage to the biliary epithelium. The aim of the study is to identify if any lncRNA might associate with inflammation or oxidative stress in CCA and regulate the disease progression. Methods In this study, RNA-seqs datasets were used to identify aberrantly expressed lncRNAs. Small interfering RNA and overexpressed plasmids were used to modulate the expression of lncRNAs, and luciferase target assay RNA immunoprecipitation (RIP was performed to explore the mechanism of miRNA-lncRNA sponging. Results We firstly analyzed five available RNA-seqs datasets to investigate aberrantly expressed lncRNAs which might associate with inflammation or oxidative stress. We identified that two lncRNAs, H19 and HULC, were differentially expressed among all the samples under the treatment of hypoxic or inflammatory factors, and they were shown to be stimulated by short-term oxidative stress responses to H2O2 and glucose oxidase in CCA cell lines. Further studies revealed that these two lncRNAs promoted cholangiocyte migration and invasion via the inflammation pathway. H19 and HULC functioned as competing endogenous RNAs (ceRNAs by sponging let-7a/let-7b and miR-372/miR-373, respectively, which activate pivotal inflammation cytokine IL-6 and chemokine receptor CXCR4. Conclusions Our study revealed that H19 and HULC, up-regulated by oxidative stress, regulate CCA cell migration and invasion by targeting IL-6 and CXCR4 via ceRNA patterns of sponging let-7a/let-7b and miR-372/miR-373, respectively. The results suggest that these lncRNAs might be the chief culprits of CCA pathogenesis and progression. The study provides new insight into the mechanism linking lncRNA function with CCA and

Light and abiotic stresses regulate the expression of GDP-L-galactose phosphorylase and levels of ascorbic acid in two kiwifruit genotypes via light-responsive and stress-inducible cis-elements in their promoters.

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Li, Juan; Liang, Dong; Li, Mingjun; Ma, Fengwang

2013-09-01

Ascorbic acid (AsA) plays an essential role in plants by protecting cells against oxidative damage. GDP-L-galactose phosphorylase (GGP) is the first committed gene for AsA synthesis. Our research examined AsA levels, regulation of GGP gene expression, and how these are related to abiotic stresses in two species of Actinidia (kiwifruit). When leaves were subjected to continuous darkness or light, ABA or MeJA, heat, or a hypoxic environment, we found some correlation between the relative levels of GGP mRNA and AsA concentrations. In transformed tobacco plants, activity of the GGP promoter was induced by all of these treatments. However, the degree of inducibility in the two kiwifruit species differed among the GGP promoter deletions. We deduced that the G-box motif, a light-responsive element, may have an important function in regulating GGP transcripts under various light conditions in both A. deliciosa and A. eriantha. Other elements such as ABRE, the CGTCA motif, and HSE might also control the promoter activities of GGP in kiwifruit. Altogether, these data suggest that GGP expression in the two kiwifruit species is regulated by light or abiotic stress via the relative cis-elements in their promoters. Furthermore, GGP has a critical role in modulating AsA concentrations in kiwifruit species under abiotic stresses.

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

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

1990-05-01

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

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

International Nuclear Information System (INIS)

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

1990-01-01

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

Cooperation between brain and islet in glucose homeostasis and diabetes

Science.gov (United States)

Schwartz, Michael W.; Seeley, Randy J.; Tschöp, Matthias H.; Woods, Stephen C.; Morton, Gregory J.; Myers, Martin G.; D'Alessio, David

2014-01-01

Although a prominent role for the brain in glucose homeostasis was proposed by scientists in the nineteenth century, research throughout most of the twentieth century focused on evidence that the function of pancreatic islets is both necessary and sufficient to explain glucose homeostasis, and that diabetes results from defects of insulin secretion, action or both. However, insulin-independent mechanisms, referred to as ‘glucose effectiveness’, account for roughly 50% of overall glucose disposal, and reduced glucose effectiveness also contributes importantly to diabetes pathogenesis. Although mechanisms underlying glucose effectiveness are poorly understood, growing evidence suggests that the brain can dynamically regulate this process in ways that improve or even normalize glycaemia in rodent models of diabetes. Here we present evidence of a brain-centred glucoregulatory system (BCGS) that can lower blood glucose levels via both insulin-dependent and -independent mechanisms, and propose a model in which complex and highly coordinated interactions between the BCGS and pancreatic islets promote normal glucose homeostasis. Because activation of either regulatory system can compensate for failure of the other, defects in both may be required for diabetes to develop. Consequently, therapies that target the BCGS in addition to conventional approaches based on enhancing insulin effects may have the potential to induce diabetes remission, whereas targeting just one typically does not. PMID:24201279

Glucose-induced metabolic memory in Schwann cells: prevention by PPAR agonists.

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Kim, Esther S; Isoda, Fumiko; Kurland, Irwin; Mobbs, Charles V

2013-09-01

A major barrier in reversing diabetic complications is that molecular and pathologic effects of elevated glucose persist despite normalization of glucose, a phenomenon referred to as metabolic memory. In the present studies we have investigated the effects of elevated glucose on Schwann cells, which are implicated in diabetic neuropathy. Using quantitative PCR arrays for glucose and fatty acid metabolism, we have found that chronic (>8 wk) 25 mM high glucose induces a persistent increase in genes that promote glycolysis, while inhibiting those that oppose glycolysis and alternate metabolic pathways such as fatty acid metabolism, the pentose phosphate pathway, and trichloroacetic acid cycle. These sustained effects were associated with decreased peroxisome proliferator-activated receptor (PPAR)γ binding and persistently increased reactive oxygen species, cellular NADH, and altered DNA methylation. Agonists of PPARγ and PPARα prevented select effects of glucose-induced gene expression. These observations suggest that Schwann cells exhibit features of metabolic memory that may be regulated at the transcriptional level. Furthermore, targeting PPAR may prevent metabolic memory and the development of diabetic complications.

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

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

2018-03-01

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

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

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

2017-09-01

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

Ultraviolet (UV and Hydrogen Peroxide Activate Ceramide-ER Stress-AMPK Signaling Axis to Promote Retinal Pigment Epithelium (RPE Cell Apoptosis

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Jin Yao

2013-05-01

Full Text Available Ultraviolet (UV radiation and reactive oxygen species (ROS impair the physiological functions of retinal pigment epithelium (RPE cells by inducing cell apoptosis, which is the main cause of age-related macular degeneration (AMD. The mechanism by which UV/ROS induces RPE cell death is not fully addressed. Here, we observed the activation of a ceramide-endoplasmic reticulum (ER stress-AMP activated protein kinase (AMPK signaling axis in UV and hydrogen peroxide (H2O2-treated RPE cells. UV and H2O2 induced an early ceramide production, profound ER stress and AMPK activation. Pharmacological inhibitors against ER stress (salubrinal, ceramide production (fumonisin B1 and AMPK activation (compound C suppressed UV- and H2O2-induced RPE cell apoptosis. Conversely, cell permeable short-chain C6 ceramide and AMPK activator AICAR (5-amino-1-β-D-ribofuranosyl-imidazole-4-carboxamide mimicked UV and H2O2’s effects and promoted RPE cell apoptosis. Together, these results suggest that UV/H2O2 activates the ceramide-ER stress-AMPK signaling axis to promote RPE cell apoptosis.

Low glucose availability stimulates progesterone production by mouse ovaries in vitro.

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Wilsterman, Kathryn; Pepper, Aimee; Bentley, George E

2017-12-15

Steroid production by the ovary is primarily stimulated by gonadotropins but can also be affected by biological cues that provide information about energy status and environmental stress. To further understand which metabolic cues the ovary can respond to, we exposed gonadotropin-stimulated mouse ovaries in vitro to glucose metabolism inhibitors and measured steroid accumulation in media. Gonadotropin-stimulated ovaries exposed to 2-deoxy-d-glucose increased progesterone production and steroidogenic acute regulatory protein mRNA levels. However, oocytes and granulosa cells in antral follicles do not independently mediate this response because targeted treatment of these cell types with a different inhibitor of glucose metabolism (bromopyruvic acid) did not affect progesterone production. Elevated progesterone production is consistent with the homeostatic role of progesterone in glucose regulation in mammals. It also may regulate follicle growth and/or atresia within the ovary. These results suggest that ovaries can regulate glucose homeostasis in addition to their primary role in reproductive activity. © 2017. Published by The Company of Biologists Ltd.

Oxidative stress specifically downregulates survivin to promote breast tumour formation.

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Pervin, S; Tran, L; Urman, R; Braga, M; Parveen, M; Li, S A; Chaudhuri, G; Singh, R

2013-03-05

Breast cancer, a heterogeneous disease has been broadly classified into oestrogen receptor positive (ER+) or oestrogen receptor negative (ER-) tumour types. Each of these tumours is dependent on specific signalling pathways for their progression. While high levels of survivin, an anti-apoptotic protein, increases aggressive behaviour in ER- breast tumours, oxidative stress (OS) promotes the progression of ER+ breast tumours. Mechanisms and molecular targets by which OS promotes tumourigenesis remain poorly understood. DETA-NONOate, a nitric oxide (NO)-donor induces OS in breast cancer cell lines by early re-localisation and downregulation of cellular survivin. Using in vivo models of HMLE(HRAS) xenografts and E2-induced breast tumours in ACI rats, we demonstrate that high OS downregulates survivin during initiation of tumourigenesis. Overexpression of survivin in HMLE(HRAS) cells led to a significant delay in tumour initiation and tumour volume in nude mice. This inverse relationship between survivin and OS was also observed in ER+ human breast tumours. We also demonstrate an upregulation of NADPH oxidase-1 (NOX1) and its activating protein p67, which are novel markers of OS in E2-induced tumours in ACI rats and as well as in ER+ human breast tumours. Our data, therefore, suggest that downregulation of survivin could be an important early event by which OS initiates breast tumour formation.

Region-specific vulnerability to endoplasmic reticulum stress ...

Indian Academy of Sciences (India)

2013-11-06

Nov 6, 2013 ... glucose-regulated protein (GRP) 78, a good marker of ER stress, were assessed by Western ..... calcium homeostasis is disturbed, because ATP is needed to ... lum stress and insulin signalling proteins in diabetes-induced.

VvVHP1; 2 Is Transcriptionally Activated by VvMYBA1 and Promotes Anthocyanin Accumulation of Grape Berry Skins via Glucose Signal.

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Sun, Tianyu; Xu, Lili; Sun, Hong; Yue, Qianyu; Zhai, Heng; Yao, Yuxin

2017-01-01

In this work, four vacuolar H + -PPase ( VHP ) genes were identified in the grape genome. Among them, VvVHP1; 2 was strongly expressed in berry skin and its expression exhibited high correlations to anthocyanin content of berry skin during berry ripening and under ABA and UVB treatments. VvVHP1; 2 was transcriptionally activated directly by VvMYBA1, and VvVHP1; 2 overexpression promoted anthocyanin accumulation in berry skins and Arabidopsis leaves; therefore, VvVHP1; 2 mediated VvMYBA1-regulated berry pigmentation. On the other hand, RNA-Seq analysis of WT and transgenic berry skins revealed that carbohydrate metabolism, flavonoid metabolism and regulation and solute carrier family expression were the most clearly altered biological processes. Further experiments elucidated that VvVHP1; 2 overexpression up-regulated the expression of the genes related to anthocyanin biosynthesis and transport via hexokinase-mediated glucose signal and thereby promoted anthocyanin accumulation in berry skins and Arabidopsis leaves. Additionally, modifications of sugar status caused by enhanced hexokinase activities likely play a key role in VvVHP1; 2- induced sugar signaling.

Effect of Ganoderma lucidum spores intervention on glucose and lipid metabolism gene expression profiles in type 2 diabetic rats.

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Wang, Fang; Zhou, Zhongkai; Ren, Xiaochong; Wang, Yuyang; Yang, Rui; Luo, Jinhua; Strappe, Padraig

2015-05-22

The fruiting body of Ganoderma lucidum has been used as a traditional herbal medicine for many years. However, to the date, there is no detailed study for describing the effect of G. lucidum spores on oxidative stress, blood glucose level and lipid compositions in animal models of type 2 diabetic rats, in particular the effect on the gene expression profiles associated with glucose and lipid metabolisms. G. lucidum spores powder (GLSP) with a shell-broken rate >99.9 % was used. Adult male Sprague-Dawley rats were randomly divided into three groups (n = 8/group). Group 1: Normal control, normal rats with ordinary feed; Group 2: Model control, diabetic rats with ordinary feed without intervention; Group 3: GLSP, diabetic rats with ordinary feed, an intervention group utilizing GLSP of 1 g per day by oral gavages for 4 consecutive weeks. Type 2 diabetic rats were obtained by streptozocin (STZ) injection. The changes in the levels of glucose, triglycerides, total cholesterol and HDL-cholesterol in blood samples were analyzed after GLSP intervention. Meanwhile, gene expressions associated with the possible molecular mechanism of GLSP regulation were also investigated using a quantitative RT-PCR. The reduction of blood glucose level occurred within the first 2 weeks of GLSP intervention and the lipid synthesis in the diabetic rats of GLSP group was significantly decreased at 4 weeks compared to the model control group. Furthermore, it was also found that GLSP intervention greatly attenuated the level of oxidative stress in the diabetic rats. Quantitative RT-PCR analysis showed up-regulation of lipid metabolism related genes (Acox1, ACC, Insig-1 and Insig-2) and glycogen synthesis related genes (GS2 and GYG1) in GLSP group compared to model control group. Additionally, there were no significant changes in the expression of other genes, such as SREBP-1, Acly, Fas, Fads1, Gpam, Dgat1, PEPCK and G6PC1. This study might indicate that GLSP consumption could provide a

Expression of genes involved in energy mobilization and osmoprotectant synthesis during thermal and dehydration stress in the Antarctic midge, Belgica antarctica.

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Teets, Nicholas M; Kawarasaki, Yuta; Lee, Richard E; Denlinger, David L

2013-02-01

The Antarctic midge, Belgica antarctica, experiences sub-zero temperatures and desiccating conditions for much of the year, and in response to these environmental insults, larvae undergo rapid shifts in metabolism, mobilizing carbohydrate energy reserves to promote synthesis of low-molecular-mass osmoprotectants. In this study, we measured the expression of 11 metabolic genes in response to thermal and dehydration stress. During both heat and cold stress, we observed upregulation of phosphoenolpyruvate carboxykinase (pepck) and glycogen phosphorylase (gp) to support rapid glucose mobilization. In contrast, there was a general downregulation of pathways related to polyol, trehalose, and proline synthesis during both high- and low-temperature stress. Pepck was likewise upregulated in response to different types of dehydration stress; however, for many of the other genes, expression patterns depended on the nature of dehydration stress. Following fast dehydration, expression patterns were similar to those observed during thermal stress, i.e., upregulation of gp accompanied by downregulation of trehalose and proline synthetic genes. In contrast, gradual, prolonged dehydration (both at a constant temperature and in conjunction with chilling) promoted marked upregulation of genes responsible for trehalose and proline synthesis. On the whole, our data agree with known metabolic adaptations to stress in B. antarctica, although a few discrepancies between gene expression patterns and downstream metabolite contents point to fluxes that are not controlled at the level of transcription.

TLQP-21 protects human umbilical vein endothelial cells against high-glucose-induced apoptosis by increasing G6PD expression.

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Wei Zhang

Full Text Available Hyperglycemia causes oxidative stress that could damage vascular endothelial cells, leading to cardiovascular complications. The Vgf gene was identified as a nerve growth factor-responsive gene, and its protein product, VGF, is characterized by the presence of partially cleaved products. One of the VGF-derived peptides is TLQP-21, which is composed of 21 amino acids (residues 556-576. Past studies have reported that TLQP-21 could stimulate insulin secretion in pancreatic cells and protect these cells from apoptosis, which suggests that TLQP-21 has a potential function in diabetes therapy. Here, we explore the protective role of TLQP-21 against the high glucose-mediated injury of vascular endothelial cells. Using human umbilical vascular endothelial cells (HUVECs, we demonstrated that TLQP-21 (10 or 50 nM dose-dependently prevented apoptosis under high-glucose (30 mmol/L conditions (the normal glucose concentration is 5.6 mmol/L. TLQP-21 enhanced the expression of NAPDH, resulting in upregulation of glutathione (GSH and a reduction in the levels of reactive oxygen species (ROS. TLQP-21 also upregulated the expression of glucose-6-phosphate dehydrogenase (G6PD, which is known as the main source of NADPH. Knockdown of G6PD almost completely blocked the increase of NADPH induced by TLQP-21, indicating that TLQP-21 functions mainly through G6PD to promote NADPH generation. In conclusion, TLQP-21 could increase G6PD expression, which in turn may increase the synthesis of NADPH and GSH, thereby partially restoring the redox status of vascular endothelial cells under high glucose injury. We propose that TLQP-21 is a promising drug for diabetes therapy.

Edaravone protects against oxygen-glucose-serum deprivation/restoration-induced apoptosis in spinal cord astrocytes by inhibiting integrated stress response

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Bin Dai

2017-01-01

Full Text Available We previously found that oxygen-glucose-serum deprivation/restoration (OGSD/R induces apoptosis of spinal cord astrocytes, possibly via caspase-12 and the integrated stress response, which involves protein kinase R-like endoplasmic reticulum kinase (PERK, eukaryotic initiation factor 2-alpha (eIF2α and activating transcription factor 4 (ATF4. We hypothesized that edaravone, a low molecular weight, lipophilic free radical scavenger, would reduce OGSD/R-induced apoptosis of spinal cord astrocytes. To test this, we established primary cultures of rat astrocytes, and exposed them to 8 hours/6 hours of OGSD/R with or without edaravone (0.1, 1, 10, 100 μM treatment. We found that 100 μM of edaravone significantly suppressed astrocyte apoptosis and inhibited the release of reactive oxygen species. It also inhibited the activation of caspase-12 and caspase-3, and reduced the expression of homologous CCAAT/enhancer binding protein, phosphorylated (p-PERK, p-eIF2α, and ATF4. These results point to a new use of an established drug in the prevention of OGSD/R-mediated spinal cord astrocyte apoptosis via the integrated stress response.

 Oxidative stress modulates the organization of erythrocyte membrane cytoskeleton

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Maria Olszewska

2012-07-01

Full Text Available  Background:Apart from their main role in transporting oxygen and carbon dioxide, erythrocytes play also an important role in organism antioxidative defence. Direct exposure to reactive oxygen species (ROS results in shortening of their half-life, even by 50�20The presence of glucose, being the substrate in pentose phosphate pathway (PPP cycle, is one of the factors that can have influence on the level of oxidative stress. The activity of PPP increases during oxidative stress. Glucose guarantees normal PPP functioning with the production of reductive equivalents in the amounts necessary to reproduction of glutathione – nonenzymatic free radical scavenger. In available literature there are no reports regarding the changes in protein contents of erythrocyte cytoskeleton exposed to t-butyl hydroperoxide in relation to glucose presence in incubation medium.Material/methods:Erythrocytes taken from 10 healthy subjects were used to assess the influence of generated free radicals on erythrocyte proteins and chosen parameters of oxidative stress. Erythrocytes were incubated in the solutions containing deferent concentrations of t-butyl hydroperoxide and glucose. Electrophoresis was performed on polyacrylamide gel in denaturating conditions. The contents of tryptophan in membranes was evaluated spectrofluorometrically.Results/conclusions:In vitro conditions oxidative stress leads to protein damage in erythrocyte cytoskeleton, both in proteins inside the cell as well as having contact with extracellular environment. In consequence, the amount of low-molecular proteins – mainly globin, which bind to cytoskeleton, increases. This process takes place independently of glucose presence in incubation medium. One of the element of protein cytoskeleton, tryptophan, also undergoes degradation. The decrease of its contents is higher during erythrocyte exposure to t-BOOH in environment containing glucose, what can suggest prooxidative influence of glucose in

Reduced α-MSH Underlies Hypothalamic ER-Stress-Induced Hepatic Gluconeogenesis.

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Schneeberger, Marc; Gómez-Valadés, Alicia G; Altirriba, Jordi; Sebastián, David; Ramírez, Sara; Garcia, Ainhoa; Esteban, Yaiza; Drougard, Anne; Ferrés-Coy, Albert; Bortolozzi, Analía; Garcia-Roves, Pablo M; Jones, John G; Manadas, Bruno; Zorzano, Antonio; Gomis, Ramon; Claret, Marc

2015-07-21

Alterations in ER homeostasis have been implicated in the pathophysiology of obesity and type-2 diabetes (T2D). Acute ER stress induction in the hypothalamus produces glucose metabolism perturbations. However, the neurobiological basis linking hypothalamic ER stress with abnormal glucose metabolism remains unknown. Here, we report that genetic and induced models of hypothalamic ER stress are associated with alterations in systemic glucose homeostasis due to increased gluconeogenesis (GNG) independent of body weight changes. Defective alpha melanocyte-stimulating hormone (α-MSH) production underlies this metabolic phenotype, as pharmacological strategies aimed at rescuing hypothalamic α-MSH content reversed this phenotype at metabolic and molecular level. Collectively, our results posit defective α-MSH processing as a fundamental mediator of enhanced GNG in the context of hypothalamic ER stress and establish α-MSH deficiency in proopiomelanocortin (POMC) neurons as a potential contributor to the pathophysiology of T2D. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

GRASP55 Senses Glucose Deprivation through O-GlcNAcylation to Promote Autophagosome-Lysosome Fusion.

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Zhang, Xiaoyan; Wang, Leibin; Lak, Behnam; Li, Jie; Jokitalo, Eija; Wang, Yanzhuang

2018-04-23

The Golgi apparatus is the central hub for protein trafficking and glycosylation in the secretory pathway. However, how the Golgi responds to glucose deprivation is so far unknown. Here, we report that GRASP55, the Golgi stacking protein located in medial- and trans-Golgi cisternae, is O-GlcNAcylated by the O-GlcNAc transferase OGT under growth conditions. Glucose deprivation reduces GRASP55 O-GlcNAcylation. De-O-GlcNAcylated GRASP55 forms puncta outside of the Golgi area, which co-localize with autophagosomes and late endosomes/lysosomes. GRASP55 depletion reduces autophagic flux and results in autophagosome accumulation, while expression of an O-GlcNAcylation-deficient mutant of GRASP55 accelerates autophagic flux. Biochemically, GRASP55 interacts with LC3-II on the autophagosomes and LAMP2 on late endosomes/lysosomes and functions as a bridge between LC3-II and LAMP2 for autophagosome and lysosome fusion; this function is negatively regulated by GRASP55 O-GlcNAcylation. Therefore, GRASP55 senses glucose levels through O-GlcNAcylation and acts as a tether to facilitate autophagosome maturation. Copyright © 2018 Elsevier Inc. All rights reserved.

Glucose Sensing

CERN Document Server

Geddes, Chris D

2006-01-01

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

The Arabidopsis Transcription Factor MYB112 Promotes Anthocyanin Formation during Salinity and under High Light Stress.

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Lotkowska, Magda E; Tohge, Takayuki; Fernie, Alisdair R; Xue, Gang-Ping; Balazadeh, Salma; Mueller-Roeber, Bernd

2015-11-01

MYB transcription factors (TFs) are important regulators of flavonoid biosynthesis in plants. Here, we report MYB112 as a formerly unknown regulator of anthocyanin accumulation in Arabidopsis (Arabidopsis thaliana). Expression profiling after chemically induced overexpression of MYB112 identified 28 up- and 28 down-regulated genes 5 h after inducer treatment, including MYB7 and MYB32, which are both induced. In addition, upon extended induction, MYB112 also positively affects the expression of PRODUCTION OF ANTHOCYANIN PIGMENT1, a key TF of anthocyanin biosynthesis, but acts negatively toward MYB12 and MYB111, which both control flavonol biosynthesis. MYB112 binds to an 8-bp DNA fragment containing the core sequence (A/T/G)(A/C)CC(A/T)(A/G/T)(A/C)(T/C). By electrophoretic mobility shift assay and chromatin immunoprecipitation coupled to quantitative polymerase chain reaction, we show that MYB112 binds in vitro and in vivo to MYB7 and MYB32 promoters, revealing them as direct downstream target genes. We further show that MYB112 expression is up-regulated by salinity and high light stress, environmental parameters that both require the MYB112 TF for anthocyanin accumulation under these stresses. In contrast to several other MYB TFs affecting anthocyanin biosynthesis, MYB112 expression is not controlled by nitrogen limitation or an excess of carbon. Thus, MYB112 constitutes a regulator that promotes anthocyanin accumulation under abiotic stress conditions. © 2015 American Society of Plant Biologists. All Rights Reserved.

Citricoccus zhacaiensis B-4 (MTCC 12119) a novel osmotolerant plant growth promoting actinobacterium enhances onion (Allium cepa L.) seed germination under osmotic stress conditions.

Science.gov (United States)

Selvakumar, Govindan; Bhatt, Ravindra M; Upreti, Kaushal K; Bindu, Gurupadam Hema; Shweta, Kademani

2015-05-01

The water potential of rhizospheric soil is a key parameter that determines the availability of water, oxygen, and nutrients to plants and microbes. Recent global warming trends and erratic precipitation patterns have resulted in the emergence of drought as a major constraint of agricultural productivity. Though several strategies are being evaluated to address this issue, a novel approach is the utilization of microbes for alleviation of drought stress effects in crops. Citricoccus zhacaiensis B-4 is an osmotolerant actinobacterium isolated from banana rhizosphere on mannitol supplemented medium (-2.92 MPa osmotic potential). This isolate expressed plant growth promotion traits viz, IAA, GA3 production, phosphate, zinc solubilization, ACC deaminase activity and ammonia production under PEG induced osmotic stress and non-stress conditions. Under in vitro osmotic conditions, biopriming with the actinobacterium improved the percent germination, seedling vigour and germination rate of onion seeds (cv. Arka Kalyan) at osmotic potentials up to -0.8 MPa. Considering its novelty, osmotolerance and plant growth promoting traits, biopriming with C. zhacaiensis is suggested as a viable option for the promotion of onion seed germination under drought stressed environments.

A Dual-Promoter Gene Orchestrates the Sucrose-Coordinated Synthesis of Starch and Fructan in Barley

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Jin, Yunkai; Fei, Mingliang; Rosenquist, Sara; Jin, Lu; Gohil, Suresh; Sandström, Corine; Olsson, Helena; Persson, Cecilia; Höglund, Anna-Stina; Fransson, Gunnel; Ruan, Ying; Åman, Per; Jansson, Christer; Liu, Chunlin; Andersson, Roger; Sun, Chuanxin

2017-12-01

Starch and fructan are two important carbohydrates in many flowering plants and in human diets. Understanding how plants allocate photosynthates and how they prioritize synthesis of different carbohydrates during development is essential in efforts to improve cereals for increased stress tolerance and for desirable carbohydrate compositions in food and feed. We report the coordinated synthesis of starch and fructan in barley, orchestrated by two functionally opposing transcription factors encoded from two alternative promoters, one intronic/exonic, harbored on a single gene. . This dual-transcription factor system employs an autoregulatory, antagonsitic mechanism in sensing sucrose at one promoter, potentially via sucrose/glucose/fructose/trehalose 6-phosphate signaling, and conduct a coordinated synthesis of starch and fructan synthesis by competitive transcription factor binding to the second promoter The finding of an intron/exon-spanning promoter in a hosting gene, resulting in proteins with distinct functions, contributes to our appreciation of the complexity of the plant genome As a case in point for the physiological role of the antagonistic transcription factor system, we have demonstrated that it can be exploited in breeding barley with tailored amounts of fructan for production of specialty food ingredients.

Preparation of some D-glucofuranosides from unprotected D-glucose

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M. POLÁKOVÁ

2001-02-01

Full Text Available O-Glycosidation of 3-(4-methoxyphenyl propyl alcohol, benzyl alcohol and vanillin with totally unprotected D-glucose, performed in a heterogeneous media and promoted by anhydrous ferric chloride, afforded competent D-glucofuranosides as the major and D-glucopyranosides as the minor products of the reaction.

The Small Protein SgrT Controls Transport Activity of the Glucose-Specific Phosphotransferase System.

Science.gov (United States)

Lloyd, Chelsea R; Park, Seongjin; Fei, Jingyi; Vanderpool, Carin K

2017-06-01

The bacterial small RNA (sRNA) SgrS has been a fruitful model for discovery of novel RNA-based regulatory mechanisms and new facets of bacterial physiology and metabolism. SgrS is one of only a few characterized dual-function sRNAs. SgrS can control gene expression posttranscriptionally via sRNA-mRNA base-pairing interactions. Its second function is coding for the small protein SgrT. Previous work demonstrated that both functions contribute to relief of growth inhibition caused by glucose-phosphate stress, a condition characterized by disrupted glycolytic flux and accumulation of sugar phosphates. The base-pairing activity of SgrS has been the subject of numerous studies, but the activity of SgrT is less well characterized. Here, we provide evidence that SgrT acts to specifically inhibit the transport activity of the major glucose permease PtsG. Superresolution microscopy demonstrated that SgrT localizes to the cell membrane in a PtsG-dependent manner. Mutational analysis determined that residues in the N-terminal domain of PtsG are important for conferring sensitivity to SgrT-mediated inhibition of transport activity. Growth assays support a model in which SgrT-mediated inhibition of PtsG transport activity reduces accumulation of nonmetabolizable sugar phosphates and promotes utilization of alternative carbon sources by modulating carbon catabolite repression. The results of this study expand our understanding of a basic and well-studied biological problem, namely, how cells coordinate carbohydrate transport and metabolism. Further, this work highlights the complex activities that can be carried out by sRNAs and small proteins in bacteria. IMPORTANCE Sequencing, annotation and investigation of hundreds of bacterial genomes have identified vast numbers of small RNAs and small proteins, the majority of which have no known function. In this study, we explore the function of a small protein that acts in tandem with a well-characterized small RNA during metabolic

IL-10 Promotes Neurite Outgrowth and Synapse Formation in Cultured Cortical Neurons after the Oxygen-Glucose Deprivation via JAK1/STAT3 Pathway.

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Chen, Hongbin; Lin, Wei; Zhang, Yixian; Lin, Longzai; Chen, Jianhao; Zeng, Yongping; Zheng, Mouwei; Zhuang, Zezhong; Du, Houwei; Chen, Ronghua; Liu, Nan

2016-07-26

As a classic immunoregulatory and anti-inflammatory cytokine, interleukin-10 (IL-10) provides neuroprotection in cerebral ischemia in vivo or oxygen-glucose deprivation (OGD)-induced injury in vitro. However, it remains blurred whether IL-10 promotes neurite outgrowth and synapse formation in cultured primary cortical neurons after OGD injury. In order to evaluate its effect on neuronal apoptosis, neurite outgrowth and synapse formation, we administered IL-10 or IL-10 neutralizing antibody (IL-10NA) to cultured rat primary cortical neurons after OGD injury. We found that IL-10 treatment activated the Janus kinase 1 (JAK1)/signal transducers and activators of transcription 3 (STAT3) signaling pathway. Moreover, IL-10 attenuated OGD-induced neuronal apoptosis by down-regulating the Bax expression and up-regulating the Bcl-2 expression, facilitated neurite outgrowth by increasing the expression of Netrin-1, and promoted synapse formation in cultured primary cortical neurons after OGD injury. These effects were partly abolished by JAK1 inhibitor GLPG0634. Contrarily, IL-10NA produced opposite effects on the cultured cortical neurons after OGD injury. Taken together, our findings suggest that IL-10 not only attenuates neuronal apoptosis, but also promotes neurite outgrowth and synapse formation via the JAK1/STAT3 signaling pathway in cultured primary cortical neurons after OGD injury.

Aluminium resistant, plant growth promoting bacteria induce overexpression of Aluminium stress related genes in Arabidopsis thaliana and increase the ginseng tolerance against Aluminium stress.

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Farh, Mohamed El-Agamy; Kim, Yeon-Ju; Sukweenadhi, Johan; Singh, Priyanka; Yang, Deok-Chun

2017-07-01

Panax ginseng is an important cash crop in the Asian countries due to its pharmaceutical effects, however the plant is exposed to various abiotic stresses, lead to reduction of its quality. One of them is the Aluminum (Al) accumulation. Plant growth promoting bacteria which able to tolerate heavy metals has been considered as a new trend for supporting the growth of many crops in heavy metal occupied areas. In this study, twelve bacteria strains were isolated from rhizosphere of diseased Korean ginseng roots located in Gochang province, Republic of Korea and tested for their ability to grow in Al-embedded broth media. Out of them, four strains (Pseudomonas simiae N3, Pseudomonas fragi N8, Chryseobacterium polytrichastri N10, and Burkholderia ginsengiterrae N11-2) were able to grow. The strains could also show other plant growth promoting activities e.g. auxins and siderophores production and phosphate solubilization. P. simiae N3, C. polytrichastri N10, and B. ginsengiterrae N11-2 strains were able to support the growth of Arabidopsis thaliana stressed by Al while P. fragi N8 could not. Plants inoculated with P. simiae N3, C. polytrichastri N10, and B. ginsengiterrae N11-2 showed higher expression level of Al-stress related genes, AtAIP, AtALS3 and AtALMT1, compared to non-bacterized plants. Expression profiles of the genes reveal the induction of external mechanism of Al resistance by P. simiae N3 and B. ginsengiterrae N11-2 and internal mechanism by C. polytrichastri N10. Korean ginseng seedlings treated with these strains showed higher biomass, particularly the foliar part, higher chlorophyll content than non-bacterized Al-stressed seedlings. According to the present results, these strains can be used in the future for the cultivation of ginseng in Al-persisted locations. Copyright © 2017 Elsevier GmbH. All rights reserved.

Glucose availability controls adipogenesis in mouse 3T3-L1 adipocytes via up-regulation of nicotinamide metabolism.

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Jackson, Robert M; Griesel, Beth A; Gurley, Jami M; Szweda, Luke I; Olson, Ann Louise

2017-11-10

Expansion of adipose tissue in response to a positive energy balance underlies obesity and occurs through both hypertrophy of existing cells and increased differentiation of adipocyte precursors (hyperplasia). To better understand the nutrient signals that promote adipocyte differentiation, we investigated the role of glucose availability in regulating adipocyte differentiation and maturation. 3T3-L1 preadipocytes were grown and differentiated in medium containing a standard differentiation hormone mixture and either 4 or 25 mm glucose. Adipocyte maturation at day 9 post-differentiation was determined by key adipocyte markers, including glucose transporter 4 (GLUT4) and adiponectin expression and Oil Red O staining of neutral lipids. We found that adipocyte differentiation and maturation required a pulse of 25 mm glucose only during the first 3 days of differentiation. Importantly, fatty acids were unable to substitute for the 25 mm glucose pulse during this period. The 25 mm glucose pulse increased adiponectin and GLUT4 expression and accumulation of neutral lipids via distinct mechanisms. Adiponectin expression and other early markers of differentiation required an increase in the intracellular pool of total NAD/P. In contrast, GLUT4 protein expression was only partially restored by increased NAD/P levels. Furthermore, GLUT4 mRNA expression was mediated by glucose-dependent activation of GLUT4 gene transcription through the cis-acting GLUT4-liver X receptor element (LXRE) promoter element. In summary, this study supports the conclusion that high glucose promotes adipocyte differentiation via distinct metabolic pathways and independently of fatty acids. This may partly explain the mechanism underlying adipocyte hyperplasia that occurs much later than adipocyte hypertrophy in the development of obesity. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

Effects of Watermelon ( Citrullus lanatus ) Seed on Blood Glucose ...

African Journals Online (AJOL)

Given the prevalence of diabetes worldwide, with its associated complications, this study is aimed at investigating the effect of citrullus lanatus seed extract on blood glucose concentration and electrolyte parameters. Citrullus lanatus is an antioxidant and has been shown to reduce oxidative stress (Khaki et al., 2013). Effects ...

Exon expression in lymphoblastoid cell lines from subjects with schizophrenia before and after glucose deprivation

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Martin Maureen V

2009-09-01

Full Text Available Abstract Background The purpose of this study was to examine the effects of glucose reduction stress on lymphoblastic cell line (LCL gene expression in subjects with schizophrenia compared to non-psychotic relatives. Methods LCLs were grown under two glucose conditions to measure the effects of glucose reduction stress on exon expression in subjects with schizophrenia compared to unaffected family member controls. A second aim of this project was to identify cis-regulated transcripts associated with diagnosis. Results There were a total of 122 transcripts with significant diagnosis by probeset interaction effects and 328 transcripts with glucose deprivation by probeset interaction probeset effects after corrections for multiple comparisons. There were 8 transcripts with expression significantly affected by the interaction between diagnosis and glucose deprivation and probeset after correction for multiple comparisons. The overall validation rate by qPCR of 13 diagnosis effect genes identified through microarray was 62%, and all genes tested by qPCR showed concordant up- or down-regulation by qPCR and microarray. We assessed brain gene expression of five genes found to be altered by diagnosis and glucose deprivation in LCLs and found a significant decrease in expression of one gene, glutaminase, in the dorsolateral prefrontal cortex (DLPFC. One SNP with previously identified regulation by a 3' UTR SNP was found to influence IRF5 expression in both brain and lymphocytes. The relationship between the 3' UTR rs10954213 genotype and IRF5 expression was significant in LCLs (p = 0.0001, DLPFC (p = 0.007, and anterior cingulate cortex (p = 0.002. Conclusion Experimental manipulation of cells lines from subjects with schizophrenia may be a useful approach to explore stress related gene expression alterations in schizophrenia and to identify SNP variants associated with gene expression.

Decreased serum glucose and glycosylated hemoglobin levels in patients with Chuvash polycythemia: a role for HIF in glucose metabolism

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McClain, Donald A.; Abuelgasim, Khadega A.; Nouraie, Mehdi; Salomon-Andonie, Juan; Niu, Xiaomei; Miasnikova, Galina; Polyakova, Lydia A.; Sergueeva, Adelina; Okhotin, Daniel J.; Cherqaoui, Rabia; Okhotin, David; Cox, James E.; Swierczek, Sabina; Song, Jihyun; Simon, M.Celeste; Huang, Jingyu; Simcox, Judith A.; Yoon, Donghoon; Prchal, Josef T.; Gordeuk, Victor R.

2012-01-01

In Chuvash polycythemia, a homozygous 598C>T mutation in the von Hippel-Lindau gene (VHL) leads to an R200W substitution in VHL protein, impaired degradation of α-subunits of hypoxia inducible factor (HIF)-1 and HIF-2, and augmented hypoxic responses during normoxia. Chronic hypoxia of high altitude is associated with decreased serum glucose and insulin concentrations. Other investigators reported that HIF-1 promotes cellular glucose uptake by increased expression of GLUT1 and increased glycolysis by increased expression of enzymes such as PDK. On the other hand, inactivation of Vhl in murine liver leads to hypoglycemia associated with a HIF-2-related decrease in the expression of the gluconeogenic enzymes genes Pepck, G6pc, and Glut2. We therefore hypothesized that glucose concentrations are decreased in individuals with Chuvash polycythemia. We found that 88 Chuvash VHLR200W homozygotes had lower random glucose and glycosylated hemoglobin A1c levels than 52 Chuvash subjects with wildtype VHL alleles. Serum metabolomics revealed higher glycerol and citrate levels in the VHLR200W homozygotes. We expanded these observations in VHLR200W homozygote mice and found that they had lower fasting glucose values and lower glucose excursions than wild-type control mice but no change in fasting insulin concentrations. Hepatic expression of Glut2 and G6pc but not Pdk2 was decreased and skeletal muscle expression of Glut1, Pdk1 and Pdk4 was increased. These results suggest that both decreased hepatic gluconeogenesis and increased skeletal uptake and glycolysis contribute to the decreased glucose concentrations. Further study is needed to determine whether pharmacologically manipulating HIF expression might be beneficial for treatment of diabetic patients. PMID:23015148

Relationship between occupational stress and cardiovascular diseases risk factors in drivers.

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Biglari, Hamed; Ebrahimi, Mohammad Hossein; Salehi, Maryam; Poursadeghiyan, Mohsen; Ahmadnezhad, Iman; Abbasi, Milad

2016-11-18

Of all work stressors, occupational stress is the leading cause of many disorders among workers. Drivers are classified as a high risk group for work related stress. This study set out to determine the relationship between risk factors of cardiovascular diseases and occupational stress among drivers. Two hundred and twenty two Ilam's intercity drivers were selected for the study. For measuring work stress, the Osipow work stress questionnaire was used. After a 10-h fasting period, systolic and diastolic blood pressure was recorded. Intravenous blood samples were taken to determine cholesterol, triglyceride and blood glucose levels. The independent samples t-test and Pearson's correlation test were used to assess the relationship between variables and occupational stress. Seventy-one percent of the intercity drivers suffered from average to acute stress, and 3.1% of them suffered from acute stress. There was no significant relationship between occupational stress and diastolic blood pressure (p = 0.254) among the drivers. Nevertheless, the Pearson's correlation test demonstrated a strong relationship between work stress and blood glucose (p stress were observed in the Ilam's intercity drivers. Occupational stress may have effect on blood glucose levels but the results did not suggest a considerable relationship between risk factors of cardiovascular diseases and occupational stress among intercity drivers. Int J Occup Med Environ Health 2016;29(6):895-901. This work is available in Open Access model and licensed under a CC BY-NC 3.0 PL license.

Characterization of a Lactococcus lactis promoter for heterologous protein production

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Christian E. Ogaugwu

2018-03-01

Full Text Available Constitutively active promoter elements for heterologous protein production in Lactococcus lactis are scarce. Here, the promoter of the PTS-IIC gene cluster from L. lactis NZ3900 is described. This promoter was cloned upstream of an enhanced green fluorescent protein, GFPmut3a, and transformed into L. lactis. Transformants produced up to 13.5 μg of GFPmut3a per milliliter of log phase cells. Addition of cellobiose further increased the production of GFPmut3a by up to two-fold when compared to glucose. Analysis of mutations at two specific positions in the PTS-IIC promoter showed that a ‘T’ to ‘G’ mutation within the −35 element resulted in constitutive expression in glucose, while a ‘C’ at nucleotide 7 in the putative cre site enhanced promoter activity in cellobiose. Finally, this PTS-IIC promoter is capable of mediating protein expression in Bacillus subtilis and Escherichia coli Nissle 1917, suggesting the potential for future biotechnological applications of this element and its derivatives.

Prior stress promotes the generalization of contextual fear memories: Involvement of the gabaergic signaling within the basolateral amygdala complex.

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Bender, C L; Otamendi, A; Calfa, G D; Molina, V A

2018-04-20

Fear generalization occurs when a response, previously acquired with a threatening stimulus, is transferred to a similar one. However, it could be maladaptive when stimuli that do not represent a real threat are appraised as dangerous, which is a hallmark of several anxiety disorders. Stress exposure is a major risk factor for the occurrence of anxiety disorders and it is well established that it influences different phases of fear memory; nevertheless, its impact on the generalization of contextual fear memories has been less studied. In the present work, we have characterized the impact of acute restraint stress prior to contextual fear conditioning on the generalization of this fear memory, and the role of the GABAergic signaling within the basolateral amygdala complex (BLA) on the stress modulatory effects. We have found that a single stress exposure promoted the generalization of this memory trace to a different context that was well discriminated in unstressed conditioned animals. Moreover, this effect was dependent on the formation of a contextual associative memory and on the testing order (i.e., conditioning context first vs generalization context first). Furthermore, we observed that increasing GABA-A signaling by intra-BLA midazolam administration prior to the stressful session exposure prevented the generalization of fear memory, whereas intra-BLA administration of the GABA-A antagonist (Bicuculline), prior to fear conditioning, induced the generalization of fear memory in unstressed rats. We concluded that stress exposure, prior to contextual fear conditioning, promotes the generalization of fear memory and that the GABAergic transmission within the BLA has a critical role in this phenomenon. Copyright © 2017 Elsevier Inc. All rights reserved.

Association of Androgen Excess with Glucose Intolerance in Women with Polycystic Ovary Syndrome.

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Zhang, Bingjie; Wang, Jing; Shen, Shanmei; Liu, Jiayi; Sun, Jie; Gu, Tianwei; Ye, Xiao; Zhu, Dalong; Bi, Yan

2018-01-01

Women with polycystic ovary syndrome (PCOS) show high prevalence of glucose intolerance. This study aimed to investigate the association of androgen excess with glucose intolerance in PCOS. A total of 378 women with PCOS participated in the study. Free androgen index (FAI) was selected as indicator of hyperandrogenism. Insulin sensitivity was assessed by 1/homeostasis model assessment of insulin resistance (1/HOMA-IR) and Matsuda insulin sensitivity index (ISI M ); β -cell function was assessed by disposition index (DI). We found that women with glucose intolerance had higher FAI levels compared to women with normal glucose tolerance (NGT) (prediabetes 6.2, T2DM 7.9 versus NGT 5.0, resp.; p androgen excess indicated by high FAI levels might serve as indicator of glucose intolerance, as it might promote insulin resistance and β -cell dysfunction in women with PCOS.

Impact of diabetes on gingival wound healing via oxidative stress.

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Daisuke Kido

Full Text Available The aim of this study is to investigate the mechanisms linking high glucose to gingival wound healing. Bilateral wounds were created in the palatal gingiva adjacent to maxillary molars of control rats and rats with streptozotocin-induced diabetes. After evaluating postsurgical wound closure by digital imaging, the maxillae including wounds were resected for histological examinations. mRNA expressions of angiogenesis, inflammation, and oxidative stress markers in the surgical sites were quantified by real-time polymerase chain reaction. Primary fibroblast culture from the gingiva of both rats was performed in high glucose and normal medium. In vitro wound healing and cell proliferation assays were performed. Oxidative stress marker mRNA expressions and reactive oxygen species production were measured. Insulin resistance was evaluated via PI3K/Akt and MAPK/Erk signaling following insulin stimulation using Western blotting. To clarify oxidative stress involvement in high glucose culture and cells of diabetic rats, cells underwent N-acetyl-L-cysteine treatment; subsequent Akt activity was measured. Wound healing in diabetic rats was significantly delayed compared with that in control rats. Nox1, Nox2, Nox4, p-47, and tumor necrosis factor-α mRNA levels were significantly higher at baseline in diabetic rats than in control rats. In vitro study showed that cell proliferation and migration significantly decreased in diabetic and high glucose culture groups compared with control groups. Nox1, Nox2, Nox4, and p47 expressions and reactive oxygen species production were significantly higher in diabetic and high glucose culture groups than in control groups. Akt phosphorylation decreased in the high glucose groups compared with the control groups. Erk1/2 phosphorylation increased in the high glucose groups, with or without insulin treatment, compared with the control groups. Impaired Akt phosphorylation partially normalized after antioxidant N

Early Glucose Derangement Detected by Continuous Glucose Monitoring and Progression of Liver Fibrosis in Nonalcoholic Fatty Liver Disease: An Independent Predictive Factor?

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Schiaffini, Riccardo; Liccardo, Daniela; Alisi, Anna; Benevento, Danila; Cappa, Marco; Cianfarani, Stefano; Nobili, Valerio

2016-01-01

Glucose derangement has been reported to increase oxidative stress, one of the most important factors underlying the progression of hepatic fibrosis in adults with nonalcoholic fatty liver disease (NAFLD). To date, careful evaluation of the glucose profile in pediatric NAFLD has not been performed. A total of 30 severely obese children (15 males; mean age 12.87 ± 2.19 years) with biopsy-proven NAFLD were enrolled in this study from September to December 2013. All patients underwent anthropometric and laboratory evaluation, including the oral glucose tolerance test (OGTT) and continuous glucose monitoring (CGM). Our study reveals some differences between OGTT and CGM in detecting NAFLD children with impaired fasting glucose (IFG) and impaired glucose tolerance (IGT). OGTT showed 2 (6.67%) patients with IFG and 1 (3.34%) with IGT, while CGM showed 5 (16.67%) patients with IFG and 6 (20%) with IGT. The daily blood glucose profile positively correlated with the baseline blood glucose (r = 0.39, p = 0.04) and the homeostatic model assessment (r = 0.56, p = 0.05). A positive correlation between hyperglycemia and liver fibrosis was found (r = 0.65, p < 0.05). Mean glucose values (F3-F4 group: 163.2 ± 35.92 mg/dl vs. F1 group: 136.58 ± 46.83 mg/dl and F2 group: 154.12 ± 22.51 mg/dl) and the difference between the minimum and maximum blood glucose levels (F3-F4 group: 110.21 ± 25.26 mg/dl vs. F1 group: 91.67 ± 15.97 mg/dl and F2 group: 92 ± 15.48 mg/dl) were significantly (p < 0.05) higher in the F3-F4 group compared to the F1 and F2 groups. Glucose profile derangement as detected by CGM is associated with the severity of hepatic fibrosis in children with NAFLD. © 2015 S. Karger AG, Basel.

Impaired brain energy gain upon a glucose load in obesity.

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Wardzinski, Ewelina K; Kistenmacher, Alina; Melchert, Uwe H; Jauch-Chara, Kamila; Oltmanns, Kerstin M

2018-03-06

There is evidence that the brain's energy status is lowered in obesity despite of chronic hypercaloric nutrition. The underlying mechanisms are unknown. We hypothesized that the brain of obese people does not appropriately generate energy in response to a hypercaloric supply. Glucose was intravenously infused in 17 normal weights and 13 obese participants until blood glucose concentrations reached the postprandial levels of 7 mmol/L and 10 mmol/L. Changes in cerebral adenosine triphosphate (ATP) and phosphocreatine (PCr) content were measured by 31 phosphorus magnetic resonance spectroscopy and stress hormonal measures regulating glucose homeostasis were monitored. Because vitamin C is crucial for a proper neuronal energy synthesis we determined circulating concentrations during the experimental testing. Cerebral high-energy phosphates were increased at blood glucose levels of 7 mmol/L in normal weights, which was completely missing in the obese. Brain energy content moderately raised only at blood glucose levels of 10 mmol/L in obese participants. Vitamin C concentrations generally correlated with the brain energy content at blood glucose concentrations of 7 mmol/L. Our data demonstrate an inefficient cerebral energy gain upon a glucose load in obese men, which may result from a dysfunctional glucose transport across the blood-brain barrier or a downregulated energy synthesis in mitochondrial oxidation processes. Our finding offers an explanation for the chronic neuroenergetic deficiency and respectively missing satiety perception in obesity. Copyright © 2018. Published by Elsevier Inc.

Teacher Wellness: Too Stressed for Stress Management?

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Kipps-Vaughan, Debi; Ponsart, Tyler; Gilligan, Tammy

2012-01-01

Healthier, happier teachers promote healthier, happier, and more effective learning environments. Yet, many teachers experience considerable stress. Studies have found that between one fifth and one fourth of teachers frequently experience a great deal of stress (Kyriacou, 1998). Stress in teaching appears to be universal across nations and…

Isolation of Endophytic Plant Growth-Promoting Bacteria Associated with the Halophyte Salicornia europaea and Evaluation of their Promoting Activity Under Salt Stress.

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Zhao, Shuai; Zhou, Na; Zhao, Zheng-Yong; Zhang, Ke; Wu, Guo-Hua; Tian, Chang-Yan

2016-10-01

Several reports have highlighted that many plant growth-promoting endophytic bacteria (PGPE) can assist their host plants in coping with various biotic and abiotic stresses. However, information about the PGPE colonizing in the halophytes is still scarce. This study was designed to isolate and characterize PGPE from salt-accumulating halophyte Salicornia europaea grown under extreme salinity and to evaluate in vitro the bacterial mechanisms related to plant growth promotion. A total of 105 isolates were obtained from the surface-sterilized roots, stems, and assimilation twigs of S. europaea. Thirty-two isolates were initially selected for their ability to produce 1-aminocyclopropane-1-carboxylate deaminase as well as other properties such as production of indole-3-acetic acid and phosphate-solubilizing activities. The 16S rRNA gene-sequencing analysis revealed that these isolates belong to 13 different genera and 19 bacterial species. For these 32 strains, seed germination and seedling growth in axenically grown S. europaea seedlings at different NaCl concentrations (50-500 mM) were quantified. Five isolates possessing significant stimulation of the host plant growth were obtained. The five isolates were identified as Bacillus endophyticus, Bacillus tequilensis, Planococcus rifietoensis, Variovorax paradoxus, and Arthrobacter agilis. All the five strains could colonize and can be reisolated from the host plant interior tissues. These results demonstrate that habitat-adapted PGPE isolated from halophyte could enhance plant growth under saline stress conditions.

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

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

2015-09-01

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

Tracing Fasting Glucose Fluxes with Unstressed Catheter Approach in Streptozotocin Induced Diabetic Rats

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Shichun Du

2014-01-01

Full Text Available Objective. Blood glucose concentrations of type 1 diabetic rats are vulnerable, especially to stress and trauma. The present study aimed to investigate the fasting endogenous glucose production and skeletal muscle glucose uptake of Streptozotocin induced type 1 diabetic rats using an unstressed vein and artery implantation of catheters at the tails of the rats as a platform. Research Design and Methods. Streptozotocin (65 mg·kg−1 was administered to induce type 1 diabetic state. The unstressed approach of catheters of vein and artery at the tails of the rats was established before the isotope tracer injection. Dynamic measurement of fasting endogenous glucose production was assessed by continuously infusing stable isotope [6, 6-2H2] glucose, while skeletal muscle glucose uptake by bolus injecting radioactively labeled [1-14C]-2-deoxy-glucose. Results. Streptozotocin induced type 1 diabetic rats displayed polydipsia, polyphagia, and polyuria along with overt hyperglycemia and hypoinsulinemia. They also had enhanced fasting endogenous glucose production and reduced glucose uptake in skeletal muscle compared to nondiabetic rats. Conclusions. The dual catheters implantation at the tails of the rats together with isotope tracers injection is a save time, unstressed, and feasible approach to explore the glucose metabolism in animal models in vivo.

Stress as a common risk factor for obesity and addiction.

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Sinha, Rajita; Jastreboff, Ania M

2013-05-01

Stress is associated with obesity, and the neurobiology of stress overlaps significantly with that of appetite and energy regulation. This review will discuss stress, allostasis, the neurobiology of stress and its overlap with neural regulation of appetite, and energy homeostasis. Stress is a key risk factor in the development of addiction and in addiction relapse. High levels of stress changes eating patterns and augments consumption of highly palatable (HP) foods, which in turn increases incentive salience of HP foods and allostatic load. The neurobiological mechanisms by which stress affects reward pathways to potentiate motivation and consumption of HP foods as well as addictive drugs is discussed. With enhanced incentive salience of HP foods and overconsumption of these foods, there are adaptations in stress and reward circuits that promote stress-related and HP food-related motivation as well as concomitant metabolic adaptations, including alterations in glucose metabolism, insulin sensitivity, and other hormones related to energy homeostasis. These metabolic changes in turn might also affect dopaminergic activity to influence food motivation and intake of HP foods. An integrative heuristic model is proposed, wherein repeated high levels of stress alter the biology of stress and appetite/energy regulation, with both components directly affecting neural mechanisms contributing to stress-induced and food cue-induced HP food motivation and engagement in overeating of such foods to enhance risk of weight gain and obesity. Future directions in research are identified to increase understanding of the mechanisms by which stress might increase risk of weight gain and obesity. Copyright © 2013 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.

Lipopolysaccharide (LPS) and tumor necrosis factor alpha (TNFα) blunt the response of Neuropeptide Y/Agouti-related peptide (NPY/AgRP) glucose inhibited (GI) neurons to decreased glucose.

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Hao, Lihong; Sheng, Zhenyu; Potian, Joseph; Deak, Adam; Rohowsky-Kochan, Christine; Routh, Vanessa H

2016-10-01

A population of Neuropeptide Y (NPY) neurons which co-express Agouti-related peptide (AgRP) in the arcuate nucleus of the hypothalamus (ARC) are inhibited at physiological levels of brain glucose and activated when glucose levels decline (e.g. glucose-inhibited or GI neurons). Fasting enhances the activation of NPY/AgRP-GI neurons by low glucose. In the present study we tested the hypothesis that lipopolysaccharide (LPS) inhibits the enhanced activation of NPY/AgRP-GI neurons by low glucose following a fast. Mice which express green fluorescent protein (GFP) on their NPY promoter were used to identify NPY/AgRP neurons. Fasting for 24h and LPS injection decreased blood glucose levels. As we have found previously, fasting increased c-fos expression in NPY/AgRP neurons and increased the activation of NPY/AgRP-GI neurons by decreased glucose. As we predicted, LPS blunted these effects of fasting at the 24h time point. Moreover, the inflammatory cytokine tumor necrosis factor alpha (TNFα) blocked the activation of NPY/AgRP-GI neurons by decreased glucose. These data suggest that LPS and TNFα may alter glucose and energy homeostasis, in part, due to changes in the glucose sensitivity of NPY/AgRP neurons. Interestingly, our findings also suggest that NPY/AgRP-GI neurons use a distinct mechanism to sense changes in extracellular glucose as compared to our previous studies of GI neurons in the adjacent ventromedial hypothalamic nucleus. Copyright © 2016 Elsevier B.V. All rights reserved.

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

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

2017-12-12

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

Mechanism of glucose electrochemical oxidation on gold surface

KAUST Repository

Pasta, Mauro; La Mantia, Fabio; Cui, Yi

2010-01-01

The complex oxidation of glucose at the surface of gold electrodes was studied in detail in different conditions of pH, buffer and halide concentration. As observed in previous studies, an oxidative current peak occurs during the cathodic sweep showing a highly linear dependence on glucose concentration, when other electrolyte conditions are unchanged. The effect of the different conditions on the intensity of this peak has stressed the limitations of the previously proposed mechanisms. A mechanism able to explain the presence of this oxidative peak was proposed. The mechanism takes into account ion-sorption and electrochemical adsorption of OH-, buffer species (K2HPO4/KH2PO4) and halides. © 2010 Elsevier Ltd. All rights reserved.

Mechanism of glucose electrochemical oxidation on gold surface

KAUST Repository

Pasta, Mauro

2010-08-01

The complex oxidation of glucose at the surface of gold electrodes was studied in detail in different conditions of pH, buffer and halide concentration. As observed in previous studies, an oxidative current peak occurs during the cathodic sweep showing a highly linear dependence on glucose concentration, when other electrolyte conditions are unchanged. The effect of the different conditions on the intensity of this peak has stressed the limitations of the previously proposed mechanisms. A mechanism able to explain the presence of this oxidative peak was proposed. The mechanism takes into account ion-sorption and electrochemical adsorption of OH-, buffer species (K2HPO4/KH2PO4) and halides. © 2010 Elsevier Ltd. All rights reserved.

A prescribed Chinese herbal medicine improves glucose profile and ameliorates oxidative stress in Goto-Kakisaki rats fed with high fat diet.

Directory of Open Access Journals (Sweden)

Lin Wu

Full Text Available Oxidative stress (OS plays a role in hyperglycemia induced islet β cell dysfunction, however, studies on classic anti-oxidants didn't show positive results in treating diabetes. We previously demonstrated that the prescribed Chinese herbal medicine preparation "Qing Huo Yi Hao" (QHYH improved endothelial function in type 2 diabetic patients. QHYH protected endothelial cells from high glucose-induced damages by scavenging superoxide anion and reducing production of reactive oxygen species. Its active component protected C2C12 myotubes against palmitate-induced oxidative damage and mitochondrial dysfunction. In the present study, we investigated whether QHYH protected islet β cell function exacerbated by high fat diet (HFD in hyperglycemic GK rats. 4-week-old male rats were randomly divided into high HFD feeding group (n = 20 and chow diet feeding group (n = 10. Each gram of HFD contained 4.8 kcal of energy, 52% of which from fat. Rats on HFD were further divided into 2 groups given either QHYH (3 ml/Kg/d or saline through gastric tube. After intervention, serum glucose concentrations were monitored; IPGTTs were performed without anesthesia on 5 fasting rats randomly chosen from each group on week 4 and 16. Serum malondialdehyde (MDA concentrations and activities of serum antioxidant enzymes were measured on week 4 and 16. Islet β cell mass and OS marker staining was done by immunohistochemistry on week 16. QHYH prevented the exacerbation of hyperglycemia in HFD feeding GK rats for 12 weeks. On week 16, it improved the exacerbated glucose tolerance and prevented the further loss of islet β cell mass induced by HFD. QHYH markedly decreased serum MDA concentration, increased serum catalase (CAT and SOD activities on week 4. However, no differences of serum glucose concentration or OS were observed on week 16. We concluded that QHYH decreased hyperglycemia exacerbated by HFD in GK rats by improving β cell function partly via its

Anti-stress effect of ethyl acetate soluble fraction of Morus alba in chronic restraint stress.

Science.gov (United States)

Nade, Vandana S; Yadav, Adhikrao V

2010-09-01

Restraint stress is a well-known method to induce chronic stress which leads to alterations in various behavioral and biochemical parameters. The present work was designed to study anti-stress effects of Morus alba in chronic restraint stress (RS)-induced perturbations in behavioral, biochemical and brain oxidative stress status. The stress was produced by restraining the animals inside an adjustable cylindrical plastic tube for 3 h once daily for ten consecutive days. The ethyl acetate soluble fraction of Morus alba (EASF) 25, 50, 100 mg/kg and diazepam (1 mg/kg) per day was administered 60 min prior to the stress procedure. The behavioral and biochemical parameters such as open field, cognitive dysfunction; leucocytes count; blood glucose and corticosteroid levels were determined. On day 10, the rats were sacrificed and biochemical assessment of superoxide dismutase (SOD), lipid peroxidation (LPO), catalase (CAT), and glutathione reductase (GSH) in whole rat brain were performed. Chronic restraint stress produced cognitive dysfunction, altered behavioral parameters, increased leucocytes count, SOD, LPO, glucose and corticosterone levels, with concomitant decrease in CAT and GSH activities. Gastric ulceration, adrenal gland and spleen weights were also used as the stress indices. All these RS induced perturbations were attenuated by EASF of Morus alba. The results of the study suggest that in addition to its classically established pharmacological activities, the plant also has immense potential as an anti-stress agent of great therapeutic relevance. This study indicates the beneficial role of Morus alba for the treatment of oxidative stress-induced disorders.

Molecular mechanisms of glucose uptake in skeletal muscle at rest and in response to exercise

Directory of Open Access Journals (Sweden)

Rodrigo Martins Pereira

2017-05-01

Full Text Available Abstract Glucose uptake is an important phenomenon for cell homeostasis and for organism health. Under resting conditions, skeletal muscle is dependent on insulin to promote glucose uptake.Insulin, after binding to its membrane receptor, triggers a cascade of intracellular reactions culminating in activation of the glucose transporter 4, GLUT4, among other outcomes.This transporter migrates to the plasma membrane and assists in glucose internalization.However, under special conditions such as physical exercise, alterations in the levels of intracellular molecules such as ATP and calcium actto regulate GLUT4 translocation and glucose uptake in skeletal muscle, regardless of insulinlevels.Regular physical exercise, due to stimulating pathways related to glucose uptake, is an important non-pharmacological intervention for improving glycemic control in obese and diabetic patients. In this mini-review the main mechanisms involved in glucose uptake in skeletal muscle in response to muscle contraction will be investigated.

Implication of snail in metabolic stress-induced necrosis.