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https://www.readbyqxmd.com/read/28092166/subchronic-metformin-pretreatment-enhances-novel-object-recognition-memory-task-in-forebrain-ischemia-behavioural-molecular-and-electrophysiological-studies
#1
Ghorbangol Ashabi, Alireza Sarkaki, Fariba Khodagholi, Shima Zareh Shahamati, Mahdi Goudarzvand, Yaghoob Farbood, Mohammad Badavi, Leila Khalaj
Metformin exerts its effect via AMP-activated protein kinase (AMPK), which is a key sensor for energy homeostasis that regulates different intracellular pathways. Metformin attenuates oxidative stress and cognitive impairment. In our experiment, rats were divided into 8 groups; some were pretreated with metformin (Met, 200 mg/kg) and (or) the AMPK inhibitor Compound C (CC) for 14 days. On day 14, rats underwent transient forebrain global ischemia. Data indicated that pretreatment of ischemic rats with metformin reduced working memory deficits in a novel object recognition test compared to group with ischemia-reperfusion (I-R) (P < 0...
November 4, 2016: Canadian Journal of Physiology and Pharmacology
https://www.readbyqxmd.com/read/28089566/metformin-inhibits-hepatic-mtorc1-signaling-via-dose-dependent-mechanisms-involving-ampk-and-the-tsc-complex
#2
Jessica J Howell, Kristina Hellberg, Marc Turner, George Talbott, Matthew J Kolar, Debbie S Ross, Gerta Hoxhaj, Alan Saghatelian, Reuben J Shaw, Brendan D Manning
Metformin is the most widely prescribed drug for the treatment of type 2 diabetes. However, knowledge of the full effects of metformin on biochemical pathways and processes in its primary target tissue, the liver, is limited. One established effect of metformin is to decrease cellular energy levels. The AMP-activated protein kinase (AMPK) and mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) are key regulators of metabolism that are respectively activated and inhibited in acute response to cellular energy depletion...
December 30, 2016: Cell Metabolism
https://www.readbyqxmd.com/read/28088959/-effect-of-exendin-4-on-lipid-deposition-in-skeletal-muscle-of-diet-induced-obese-mice-and-its-underlying-mechanism
#3
H Y Cao, F Xu, Z L Chen, B S Lin, X B Zheng, S H Yuan, H Liang, J P Weng
Objective: To investigate the effect of exendin-4, a glucagon-like peptide-1 (GLP-1) receptor agonist, on reducing lipid deposition and improving insulin resistance in skeletal muscle and the underlying mechanisms in high-fat diet (HFD)-induced obese mice. Methods: Twelve male C57BL/6J mice were challenged with HFD for 12 weeks to induce obesity and then randomly divided into two groups: exendin-4 group (intraperitoneal injection of 24 nmol·kg(-1)·d(-1) exendin-4 for 4 weeks) and HFD group (intraperitoneal injection of normal saline for 4 weeks), with 6 mice in each group...
January 10, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28088753/mitochondrial-redox-plays-a-critical-role-in-the-paradoxical-effects-of-napdh-oxidase-derived-ros-on-coronary-endothelium
#4
Ehtesham Shafique, Anali Torina, Karla Reichert, Bonnie Colantuono, Nasifa Nur, Khawaja Zeeshan, Vani Ravichandran, Yuhong Liu, Jun Feng, Khawaja Zeeshan, Laura E Benjamin, Kaikobad Irani, Elizabeth O Harrington, Frank W Sellke, Md Ruhul Abid
AIMS: There are conflicting reports on the role of reactive oxygen species (ROS) i.e. beneficial vs. harmful, in vascular endothelium. Here, we aim to examine whether duration of exposure to ROS and/or subcellular ROS levels are responsible for the apparently paradoxical effects of oxidants on endothelium. METHODS AND RESULTS: We have recently generated binary (Tet-ON/OFF) conditional transgenic mice (Tet-Nox2:VE-Cad-tTA) that can induce 1.8 ± 0.42-fold increase in NADPH oxidase (NOX)-derived ROS specifically in vascular endothelium upon withdrawal of tetracycline from the drinking water...
January 14, 2017: Cardiovascular Research
https://www.readbyqxmd.com/read/28088385/flavonoid-derivative-fla-cn-inhibited-adipocyte-differentiation-via-activating-ampk-and-up-regulating-microrna-27-in-3t3-l1-cells
#5
Chun-Chun Gan, Tian-Wen Ni, Yang Yu, Nan Qin, Ying Chen, Mei-Na Jin, Hong-Quan Duan
Fla-CN (3-O-[(E)-4-(4-cyanophenyl)-2-oxobut-3-en-1-yl] kaempferol) is a semi-synthesized flavonoid derivative of tiliroside which exhibited anti-diabetic effect in vivo. Our previous study revealed the role of Fla-CN in anti-obesity and anti-diabetes in vivo, but the underlying mechanism remained to be addressed. The present study aimed to investigate the mechanism of anti-adipogenesis in vitro. Fla-CN markedly inhibited intracellular lipid accumulation in a dose-dependent manner, and the inhibitory effect was mainly limited to the early stage of adipocyte differentiation in vitro...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088384/the-signalling-mechanisms-of-a-novel-mitochondrial-complex-i-inhibitor-prevent-lipid-accumulation-and-attenuate-tnf-%C3%AE-induced-insulin-resistance-in-vitro
#6
Siobhán Leonard, Laura M Tobin, John B C Findlay
RTC-1 has recently been identified as a member of a new class of anti-diabetic compounds acting through the inhibition of complex I of the mitochondrial respiratory chain (NADH:ubiquinone oxidoreductase) to improve glucose handling and inhibit weight gain in mice fed a high-fat diet (HFD). The exact mechanism by which the reduced activity of NADH:ubiquinone oxidoreductase, in response to RTC-1, promotes these improved metabolic parameters remains to be established. Through extensive in vitro analysis, new molecular insights into these downstream signalling pathways have been obtained...
January 11, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28088331/eicosapentaenoic-acid-ameliorates-palmitate-induced-lipotoxicity-via-the-amp-kinase-dynamin-related-protein-1-signaling-pathway-in-differentiated-h9c2-myocytes
#7
Atsushi Sakamoto, Masao Saotome, Prottoy Hasan, Terumori Satoh, Hayato Ohtani, Tsuyoshi Urushida, Hideki Katoh, Hiroshi Satoh, Hideharu Hayashi
BACKGROUND: Emerging evidence suggested the preferable effects of eicosapentaenoic acid (EPA; n-3 polyunsaturated fatty acid) against cardiac lipotoxicity, which worsens cardiac function by means of excessive serum free fatty acids due to chronic adrenergic stimulation under heart failure. Nonetheless, the precise molecular mechanisms remain elusive. In this study, we focused on dynamin-related protein-1 (Drp1) as a possible modulator of the EPA-mediated cardiac protection against cardiac lipotoxicity, and investigated the causal relation between AMP-activated protein kinase (AMPK) and Drp1...
January 11, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28087886/d-chiro-inositol-ameliorates-endothelial-dysfunction-via-inhibition-of-oxidative-stress-and-mitochondrial-fission
#8
Bobo Zhang, Xudan Guo, Yunlong Li, Qiang Peng, Jinfeng Gao, Baolin Liu, Min Wang
SCOPE: D-chiro inositol (DCI), an isomer of inositol, possesses anti-oxidative and endothelial protective properties. The mechanism by which DCI prevents endothelial dysfunction was investigated, with emphasis on oxidative stress. METHODS AND RESULTS: DCI was found to inhibit NOX4 induction and enhance Nrf2 activity in palmitate (PA)-stimulated cells, showing that DCI prevents oxidative stress. DCI suppressed Ser616 phosphorylation and increased Ser637 phosphorylation of Drp1 and inhibited PA-induced mitochondrial fission...
January 14, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28087344/up-regulation-of-the-active-form-of-small-gtpase-rab13-promotes-macroautophagy-in-vascular-endothelial-cells
#9
Lu Zhang, Fang Dai, LiuQing Cui, Bo Zhou, YuQi Guo
The importance of macroautophagy (hereafter referred to as autophagy) in vascular endothelial cell (VEC) biology and dysfunction is increasingly recognized, but the molecular mechanisms of autophagy in VECs in the presence of serum are still poorly understood. Previously, we identified pterostilbene as a potent autophagy inducer of VECs in the presence of serum. In this study, we used pterostilbene as a tool to induce VEC autophagy and identified the differentially expressed genes using high-throughput DAN microarray...
January 10, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28087254/anti-diabetic-drug-metformin-dilates-retinal-blood-vessels-through-activation-of-amp-activated-protein-kinase-in-rats
#10
Asami Mori, Eriko Ishikawa, Tomoyo Amano, Kenji Sakamoto, Tsutomu Nakahara
The aim of this study was to examine whether metformin, a biguanide anti-hyperglycemic drug, dilates retinal blood vessels in rats. Ocular fundus images were captured with an original high-resolution digital fundus camera in vivo and diameters of retinal blood vessels were measured. Both systemic blood pressure and heart rate were continuously recorded. Metformin (0.01-0.3mg/kg/min) increased diameters of retinal blood vessels in a dose-dependent manner. This retinal vasodilator effect of metformin was abolished by compound C, an inhibitor of AMP-activated protein kinase (AMPK), and N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide (NO) synthase...
January 10, 2017: European Journal of Pharmacology
https://www.readbyqxmd.com/read/28079150/sustained-kidney-biochemical-derangement-in-treated-experimental-diabetes-a-clue-to-metabolic-memory
#11
Antonio Anax F de Oliveira, Tiago F de Oliveira, Larissa L Bobadilla, Camila C M Garcia, Carolina Maria Berra, Nadja C de Souza-Pinto, Marisa H G Medeiros, Paolo Di Mascio, Roberto Zatz, Ana Paula de M Loureiro
The occurrence of biochemical alterations that last for a long period of time in diabetic individuals even after adequate handling of glycemia is an intriguing phenomenon named metabolic memory. In this study, we show that a kidney pathway is gradually altered during the course of diabetes and remains persistently changed after late glycemic control in streptozotocin-induced diabetic rats. This pathway comprises an early decline of uric acid clearance and pAMPK expression followed by fumarate accumulation, increased TGF-β expression, reduced PGC-1α expression, and downregulation of methylation and hydroxymethylation of mitochondrial DNA...
January 12, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28077576/specific-inhibition-of-acyl-coa-oxidase-1-by-an-acetylenic-acid-improves-hepatic-lipid-and-reactive-oxygen-species-ros-metabolism-in-rats-fed-a-high-fat-diet
#12
Jia Zeng, Senwen Deng, Yiping Wang, Ping Li, Lian Tang, Yefeng Pang
Chronic high-fat diet (HFD) results in hepatic mitochondrial dysfunction and induction of peroxisomal fatty acid oxidation (FAO), whether specific inhibition of peroxisomal FAO benefits mitochondrial FAO and reactive oxygen species (ROS) metabolism remains unclear. In this study, a specific inhibitor for the rate-limiting enzyme involved in peroxisomal FAO, acyl-CoA oxidase-1 (ACOX1) was developed and used for the investigation of peroxisomal FAO inhibition upon mitochondrial FAO and ROS metabolism. Specific inhibition of ACOX1 by 10,12 -tricosadiynoic acid increased hepatic mitochondrial FAO via activation of the SIRT1-AMPK pathway and PPARα and reduced hydrogen peroxide accumulation in high-fat diet fed rats, which significantly decreased hepatic lipid and ROS contents, reduced body weight gain and decreased serum triglyceride and insulin levels...
January 11, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28076367/a-chemogenomic-screen-reveals-novel-snf1p-ampk-independent-regulators-of-acetyl-coa-carboxylase
#13
Bruno L Bozaquel-Morais, Juliana B Madeira, Thiago M Venâncio, Thiago Pacheco-Rosa, Claudio A Masuda, Monica Montero-Lomeli
Acetyl-CoA carboxylase (Acc1p) is a key enzyme in fatty acid biosynthesis and is essential for cell viability. To discover new regulators of its activity, we screened a Saccharomyces cerevisiae deletion library for increased sensitivity to soraphen A, a potent Acc1p inhibitor. The hits identified in the screen (118 hits) were filtered using a chemical-phenotype map to exclude those associated with pleiotropic drug resistance. This enabled the identification of 82 ORFs that are genetic interactors of Acc1p. The main functional clusters represented by these hits were "transcriptional regulation", "protein post-translational modifications" and "lipid metabolism"...
2017: PloS One
https://www.readbyqxmd.com/read/28074608/aged-garlic-extract-suppresses-the-increase-of-plasma-glycated-albumin-level-and-enhances-the-amp-activated-protein-kinase-in-adipose-tissue-in-tsod-mice
#14
Satomi Miki, Ken-Ichi Inokuma, Miyuki Takashima, Mitsuho Nishida, Yoko Sasaki, Mitsuyasu Ushijima, Jun-Ichiro Suzuki, Naoaki Morihara
SCOPE: In this study, we investigated the effect of aged garlic extract (AGE) on the high level of blood glucose in Tsumura Suzuki Obese-Diabetes (TSOD) mice. METHODS AND RESULTS: TSOD mice were fed standard diet with or without 2% AGE for 19 weeks. AGE treatment lowered the blood glucose level and significantly reduced the plasma level of glycated albumin in TSOD mice as compared with those without AGE treatment. In addition, AGE treatment increased the level of phosphorylated AMP-activated protein kinase (AMPK) in the adipose tissue, liver and muscle that played an important role in the maintenance of insulin sensitivity...
January 11, 2017: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/28074493/ampk-does-not-play-a-requisite-role-in-regulation-of-ppargc1a-gene-expression-via-the-alternative-promoter-in-endurance-trained-human-skeletal-muscle
#15
Daniil V Popov, Evgeny A Lysenko, Alexey D Butkov, Tatiana F Vepkhvadze, Dmitriy V Perfilov, Olga L Vinogradova
In human skeletal muscle, PGC-1α is constitutively expressed via the canonical promoter. By contrast, the expression of PGC-1α mRNA via the alternative promoter was found to be highly dependent on the intensity of exercise and to contribute largely to the post-exercise increase of total PGC-1α mRNA. This study investigated the role of AMPK in regulating PGC-1α gene expression via the alternative promoter through a cAMP responsive element-binding protein-1 (CREB1)-dependent mechanism in human skeletal muscle...
January 10, 2017: Experimental Physiology
https://www.readbyqxmd.com/read/28073046/olanzapine-and-aripiprazole-differentially-affect-glucose-uptake-and-energy-metabolism-in-human-mononuclear-blood-cells
#16
Britta Stapel, Alexandra Kotsiari, Michaela Scherr, Denise Hilfiker-Kleiner, Stefan Bleich, Helge Frieling, Kai G Kahl
The use of antipsychotics carries the risk of metabolic side effects, such as weight gain and new onset type-2 diabetes mellitus. The mechanisms of the observed metabolic alterations are not fully understood. We compared the effects of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (aripiprazole), on glucose metabolism. Primary human peripheral blood mononuclear cells (PBMC) were isolated and stimulated with olanzapine or aripiprazole for 72 h. Cellular glucose uptake was analyzed in vitro by 18F-FDG uptake...
December 22, 2016: Journal of Psychiatric Research
https://www.readbyqxmd.com/read/28072841/a-small-insulinomimetic-molecule-also-improves-insulin-sensitivity-in-diabetic-mice
#17
Sandip Mukherjee, Mrittika Chattopadhyay, Sushmita Bhattacharya, Suman Dasgupta, Sahid Hussain, Saitanya K Bharadwaj, Dhrubajyoti Talukdar, Abul Usmani, Bhola S Pradhan, Subeer S Majumdar, Pronobesh Chattopadhyay, Satinath Mukhopadhyay, Tushar K Maity, Mihir K Chaudhuri, Samir Bhattacharya
Dramatic increase of diabetes over the globe is in tandem with the increase in insulin requirement. This is because destruction and dysfunction of pancreatic β-cells are of common occurrence in both Type1 diabetes and Type2 diabetes, and insulin injection becomes a compulsion. Because of several problems associated with insulin injection, orally active insulin mimetic compounds would be ideal substitute. Here we report a small molecule, a peroxyvanadate compound i.e. DmpzH[VO(O2)2(dmpz)], henceforth referred as dmp, which specifically binds to insulin receptor with considerable affinity (KD-1...
2017: PloS One
https://www.readbyqxmd.com/read/28070105/%C3%AE-lipoic-acid-potentially-targets-amp-activated-protein-kinase-and-energy-production-in-the-fetal-brain-to-ameliorate-dioxin-produced-attenuation-in-fetal-steroidogenesis
#18
Tomoki Takeda, Yuki Matsuo, Kyoko Nishida, Akihisa Fujiki, Yukiko Hattori, Takayuki Koga, Yuji Ishii, Hideyuki Yamada
Our previous studies demonstrated that treating pregnant rats with dioxins, including 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), targets the pituitary expression of luteinizing hormone (LH) to attenuate testicular steroidogenesis in fetuses, resulting in the imprinting of sexual immaturity of the offspring after reaching maturity. Furthermore, we found that although TCDD disturbs the tricarboxylic acid (TCA) cycle in the fetal hypothalamus, maternal co-treatment with α-lipoic acid (α-LA), a cofactor of the TCA cycle, restores a TCDD-produced reduction in the LH-evoked steroidogenesis as well as the TCA cycle activity in fetuses...
2017: Journal of Toxicological Sciences
https://www.readbyqxmd.com/read/28069811/tgf-%C3%AE-1-smad3-pathway-targets-pp2a-ampk-foxo1-to-regulate-hepatic-gluconeogenesis
#19
Hariom Yadav, Samir Devalaraja, Stephanie Chung, Sushil G Rane
Maintenance of glucose homeostasis is essential for normal physiology. Deviation from normal glucose levels, in either direction, increases susceptibility to serious medical complications such as hypoglycemia or diabetes. Maintenance of glucose homeostasis is achieved via functional interactions amongst various organs, liver, skeletal muscle, adipose tissue, brain and the endocrine pancreas. The liver is the primary site for endogenous glucose production, especially during states of prolonged fasting. However, enhanced gluconeogenesis is also a signature feature of type 2 diabetes (T2D)...
January 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/28069379/ndrg2-overexpression-suppresses-hepatoma-cells-survival-during-metabolic-stress-through-disturbing-the-activation-of-fatty-acid-oxidation
#20
Tao Pan, Mei Zhang, Fang Zhang, Guang Yan, Yi Ru, Qinhao Wang, Yao Zhang, Xuehui Wei, Xinyuan Xu, Lan Shen, Jian Zhang, Kaichun Wu, Libo Yao, Xia Li
Because of the high nutrient consumption and inadequate vascularization, solid tumor constantly undergoes metabolic stress during tumor development. Oncogenes and tumor suppressor genes participated in cancer cells' metabolic reprogramming. N-Myc downstream regulated gene 2 (NDRG2) is a recently identified tumor suppressor gene, but its function in cancer metabolism, particularly during metabolic stress, remains unclear. In this study, we found that NDRG2 overexpression significantly reduced hepatoma cell proliferation and enhanced cell apoptosis under glucose limitation...
January 6, 2017: Biochemical and Biophysical Research Communications
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