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https://www.readbyqxmd.com/read/28911865/3-2-amino-ethyl-5-3-4-butoxyl-phenyl-propylidene-thiazolidine-2-4-dione-k145-ameliorated-dexamethasone-induced-hepatic-gluconeogenesis-through-activation-of-akt-foxo1-pathway
#1
Yanan Shi, Jiayun Qiao, Biao Mu, Bingfeng Zuo, Jihong Yuan
3-(2-amino-ethyl)-5-[3-(4-butoxyl-phenyl)-propylidene]-thiazolidine-2,4-dione (K145) is identified as a selective SphK2 inhibitor. It was previously reported as an anti-tumor agent, in this study we demonstrated that K145 was able to regulate hepatic gluconeogenesis and improve glucose intolerance in mice. C57BL/6 mice treated with dexamethasone injection were used as experimental animals, which exhibited impaired glucose tolerance and increased gluconeogenetic enzymes. After K145 treatment, we found that the impairment of glucose tolerance and gluconeogenetic genes mRNA expression were improved...
September 11, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28901442/the-uptake-exploration-of-68ga-labeled-ngr-in-well-differentiated-hepatocellular-carcinoma-xenografts-indication-for-the-new-clinical-translational-of-a-tracer-based-on-ngr
#2
Yongheng Gao, Zhengjie Wang, Xiaowei Ma, Wenhui Ma, Mingxuan Zhao, Tianming Fu, Guoquan Li, Shengjun Wang, Zhe Wang, Weidong Yang, Fei Kang, Jing Wang
18F-FDG has low uptake and poor diagnostic efficiency in hepatocellular carcinoma (HCC), particularly in well-differentiated HCC. The NGR peptide selectively targets CD13, which is overexpressed in many types of tumor cells as well as neovasculature cells. In the present study, we aimed to evaluate the feasibility of utilizing 68Ga-NGR to image CD13-positive well-differentiated HCC xenografts. The in vitro cellular uptake, in vivo micro-PET/CT imaging and biodistribution studies of 68Ga-NGR and 18F-FDG were quantitatively compared in SMMC-7721-based well‑differentiated HCC xenografts...
August 31, 2017: Oncology Reports
https://www.readbyqxmd.com/read/28900165/gcn5l1-modulates-cross-talk-between-mitochondria-and-cell-signaling-to-regulate-foxo1-stability-and-gluconeogenesis
#3
Lingdi Wang, Iain Scott, Lu Zhu, Kaiyuan Wu, Kim Han, Yong Chen, Marjan Gucek, Michael N Sack
The mitochondrial enriched GCN5-like 1 (GCN5L1) protein has been shown to modulate mitochondrial protein acetylation, mitochondrial content and mitochondrial retrograde signaling. Here we show that hepatic GCN5L1 ablation reduces fasting glucose levels and blunts hepatic gluconeogenesis without affecting systemic glucose tolerance. PEPCK and G6Pase transcript levels are downregulated in hepatocytes from GCN5L1 liver specific knockout mice and their upstream regulator, FoxO1 protein levels are decreased via proteasome-dependent degradation and via reactive oxygen species mediated ERK-1/2 phosphorylation...
September 12, 2017: Nature Communications
https://www.readbyqxmd.com/read/28832228/caffeic-acid-methyl-and-ethyl-esters-exert-potential-antidiabetic-effects-on-glucose-and-lipid-metabolism-in-cultured-murine-insulin-sensitive-cells-through-mechanisms-implicating-activation-of-ampk
#4
Hoda M Eid, Farah Thong, Abir Nachar, Pierre S Haddad
CONTEXT: Caffeic acid methyl (CAME) and ethyl (CAEE) esters stimulate glucose uptake and AMP-activated protein kinase (AMPK) in C2C12 myocytes (ATCC(®) CRL-1772(TM)). OBJECTIVE: Effects of CAME and CAEE were now assessed on myocyte glucose transporter GLUT4 activity and expression, on hepatic gluconeogenesis and on adipogenesis as well as major underlying signaling pathways. MATERIALS AND METHODS: GLUT4 protein translocation was studied in L6 GLUT4myc cells, glucose-6-phospatase (G6Pase) in H4IIE hepatocytes and adipogenesis in 3T3-L1 adipocytes...
December 2017: Pharmaceutical Biology
https://www.readbyqxmd.com/read/28829278/glucose-6-phosphatase-%C3%AE-participates-in-dopaminergic-differentiation
#5
Jing Chen, Ting Wang, Xiao-Yan Zhou, Chuan-Xi Tang, Dian-Shuai Gao
OBJECTIVE:  Induction of dopaminergic (DA) differentiation is a cell-based therapy for Parkinson's disease (PD). Here, we explore the key factors of DA differentiation with a focus on glucose-6-phosphatase (G6Pase), a marker enzyme for the endoplasmic reticulum (ER) associated with cell differentiation. METHODS:  We cultured SH-SY5Y human neuroblastoma cells, a model system for PD research, and added glial cell-derived neurotrophic factor (GDNF; 25, 50, or 100 ng/ml) to stimulate differentiation...
August 22, 2017: Neurological Research
https://www.readbyqxmd.com/read/28827191/silver-nanoparticles-protect-acetaminophen-induced-acute-hepatotoxicity-a-biochemical-and-histopathological-approach
#6
Mohd Salim Reshi, Chhavi Uthra, Deepa Yadav, Samta Sharma, Asha Singh, Anjali Sharma, Amita Jaswal, Neelu Sinha, Sadhana Shrivastava, Sangeeta Shukla
The present study was premeditated to demonstrate the hepatoprotective effect of silver nanoparticles (AgNPs). Rats were treated with three different doses of AgNPs (50, 100 and 150 μg/kg, p.o.) after Acetaminophen (APAP; 2 g/kg, p.o. once only) intoxication. Treatment with AgNPs recouped the levels of serum aspartate amino transaminase (AST), alanine amino transaminase (ALT), lactate dehydrogenase (LDH), alkaline phosphatase (ALP), bilirubin, triglyceride (TG) and cholesterol in dose dependent manner. Significant reduction in lipid peroxidation (LPO) and restoration of reduced glutathione (GSH) was found in liver in AgNPs treated animals...
August 19, 2017: Regulatory Toxicology and Pharmacology: RTP
https://www.readbyqxmd.com/read/28817664/gold-nanoparticles-partition-to-and-increase-the-activity-of-glucose-6-phosphatase-in-a-synthetic-phospholipid-membrane-system
#7
Tyson J MacCormack, Amanda M Rundle, Michael Malek, Abhilash Raveendran, Maria-Victoria Meli
Engineered nanomaterials can alter the structure and/or function of biological membranes and membrane proteins but the underlying mechanisms remain unclear. We addressed this using a Langmuir phospholipid monolayer containing an active transmembrane protein, glucose-6-phosphatase (G6Pase). Gold nanoparticles (nAu) with varying ligand shell composition and hydrophobicity were synthesized, and their partitioning in the membrane and effects on protein activity characterized. nAu incorporation did not alter the macroscopic properties of the membrane...
2017: PloS One
https://www.readbyqxmd.com/read/28804981/lipopolysaccharide-inhibits-hepatic-gluconeogenesis-in-rats-the-role-of-immune-cells
#8
Hiroshi Tanaka, Yoshikazu Nishikawa, Toru Fukushima, Ataru Taniguchi, Yoshihito Fujita, Kinsuke Tsuda, Nobuya Inagaki, Masaya Hosokawa
AIMS/INTRODUCTION: Bacterial septicemia has diverse clinical symptoms including severe hypoglycemia. However, sepsis-induced hypoglycemia has not yet been examined in detail. The aim of the present study is to investigate the mechanisms underlying hypoglycemia in sepsis. MATERIALS AND METHODS: We induced endotoxin shock in rats using lipopolysaccharide (LPS). After an intraperitoneal injection of LPS, we measured gluconeogenesis using the pyruvate tolerance test (PTT)...
August 14, 2017: Journal of Diabetes Investigation
https://www.readbyqxmd.com/read/28802581/pkm2-aggravates-palmitate-induced-insulin-resistance-in-hepg2-cells-via-stat3-pathway
#9
Ling Chen, Zhuqi Tang, Xiaohua Wang, Hong Ma, Dandan Shan, Shiwei Cui
Studies have identified that PKM2 is related to the development of glucose intolerance and insulin resistance in rodents and humans. However, the underlying mechanism remains largely unknown. In the present study, we found that PKM2 expression was significantly elevated in insulin-resistant hepatic tissues and hepatocytes, implicating an association between PKM2 expression and hepatic insulin resistance (IR). In vitro study revealed that overexpression of PKM2 impaired the insulin signaling pathway by decreasing the phosphorylation of protein kinase B (Akt) and glycogen synthase kinase-3β (GSK3β)...
August 9, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28799756/caffeic-acid-phenethyl-ester-propolis-extract-ameliorates-insulin-resistance-by-inhibiting-jnk-and-nf-%C3%AE%C2%BAb-inflammatory-pathways-in-diabetic-mice-and-hepg2-cells-models
#10
Jia-Rui Nie, Ya-Ning Chang, Yujia Li, Yingjun Zhou, Jiawen Qin, Zhen Sun, Haibin Li
Caffeic acid phenethyl ester (CAPE), extracted from propolis, was evaluated the ameliorative effects on insulin resistance and identified the mechanisms, using noninsulin-dependent diabetes mellitus (NIDDM) model mice and insulin resistance (IR) model cells. After 5-week of CAPE supplementation, insulin sensitivity, hyperlipidemia, and peroxisome proliferator-activated receptor-α (PPAR-α) levels were improved in mice. Pro-inflammatory cytokines in serum and the expressions of tumour necrosis factor- alpha (TNF-α) mRNA in tissues were markedly down-regulated from CAPE-treated mice...
August 11, 2017: Journal of Agricultural and Food Chemistry
https://www.readbyqxmd.com/read/28751144/interplay-between-h6pdh-and-11%C3%AE-hsd1-implicated-in-the-pathogenesis-of-type-2-diabetes-mellitus
#11
Fan Yao, Li Chen, Zheng Fan, Fei Teng, Yali Zhao, Fengying Guan, Ming Zhang, Yanjun Liu
Extensive studies have been performed on the role of 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) in metabolic diseases. Our previous study reported glucose could directly regulate hexose-6-phosphate dehydrogenase (H6PDH) and 11β-HSD1. Recently, we further investigated the interplay of H6PDH and 11β-HSD1 and their roles in hepatic gluconeogenesis and insulin resistance to elucidate the importance of H6PDH and 11β-HSD1 in pathogenesis of type 2 diabetes mellitus (T2DM). T2DM rats model and H6PDH or 11β-HSD1 siRNA transfected in CBRH-7919 cells were used to explore the effect of H6PDH and 11β-HSD1 in T2DM...
September 1, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28727166/hepatocytes-contribute-to-residual-glucose-production-in-a-mouse-model-for-glycogen-storage-disease-type-ia
#12
Brenda S Hijmans, Andreas Boss, Theo H van Dijk, Maud Soty, Henk Wolters, Elodie Mutel, Albert K Groen, Terry G J Derks, Gilles Mithieux, Arend Heerschap, Dirk-Jan Reijngoud, Fabienne Rajas, Maaike H Oosterveer
It is a longstanding enigma how glycogen storage disease (GSD) type I patients retain a limited capacity for endogenous glucose production (EGP) despite the loss of glucose-6-phosphatase (G6Pase) activity. Insight into the source of residual EGP is of clinical importance given the risk of sudden death in these patients, but so far contradictory mechanisms have been proposed. We investigated G6Pase-independent EGP in hepatocytes isolated from a liver-specific GSD Ia mouse model (L-G6pc(-/-) mice), and performed real-time analysis of hepatic glucose fluxes and glycogen metabolism in L-G6pc(-/-) mice using state-of-the-art stable isotope methodologies...
July 20, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28724379/regulation-of-glucose-uptake-in-lymphoma-cell-lines-by-c-myc-and-pi3k-dependent-signaling-pathways-and-impact-of-glycolytic-pathways-on-cell-viability
#13
Martina Broecker-Preuss, Nina Becher-Boveleth, Andreas Bockisch, Ulrich Dührsen, Stefan Müller
BACKGROUND: Changes in glucose and energy metabolism contribute to the altered phenotype of cancer cells and are the basis for positron emission tomography with (18)F-fluoro-2-deoxy-D-glucose (FDG) to visualize tumors in vivo. The molecular background of the enhanced glucose uptake and its regulation in lymphoma cells is not fully clarified and may provide new possibilities to reverse the altered metabolism. Thus in this study we investigated regulation of glucose uptake by different signaling pathways...
July 19, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28678435/molecular-mechanisms-of-action-of-styrene-toxicity-in-blood-plasma-and-liver
#14
Kamal Niaz, Faheem Mabqool, Fazlullah Khan, Fatima Ismail Hassan, Maryam Baeeri, Mona Navaei-Nigjeh, Shokoufeh Hassani, Mahdi Gholami, Mohammad Abdollahi
Styrene is an aromatic colorless hydrocarbon available in liquid form and highly volatile. In its pure form, it gives a sweet smell. The primary source of exposure in the environment is from plastic materials, rubber industries, packaging materials, insulations, and fiber glass and carpet industry. Natural sources of styrene include: few metabolites in plants which are transferred through food chain. The current study was designed to evaluate styrene toxicity, including: superoxide dismutase (SOD) and protein carbonyl, oxidative stress, glucose-6-phosphatase (G6Pase), glycogen phosphorylase (GP), and phosphoenolpyruvate carboxykinase (PEPCK) activities, adenosine triphosphate (ATP) to adenosine diphosphate (ADP) ratio, and changes in gene expressions such as glutamate dehydrogenase 1 (GLUD1), glucose transporter 2 (GLUT2), and glucokinase (GCK) in the rat liver tissue...
July 5, 2017: Environmental Toxicology
https://www.readbyqxmd.com/read/28627440/microrna-21-regulates-hepatic-glucose-metabolism-by-targeting-foxo1
#15
Ailing Luo, Haibo Yan, Jichao Liang, Chunyuan Du, Xuemei Zhao, Lijuan Sun, Yong Chen
Abnormal activation of hepatic gluconeogenesis is a major contributor to fasting hyperglycemia in type 2 diabetes; however, the potential role of microRNAs in gluconeogenesis remains unclear. Here, we showed that hepatic expression levels of microRNA-21 (miR-21) were decreased in db/db and high-fat diet (HFD)-induced diabetic mice. Adenovirus-mediated overexpression of miR-21 decreased the expression of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) and inhibited glucose production in primary mouse hepatocytes...
September 5, 2017: Gene
https://www.readbyqxmd.com/read/28622511/metabolic-adaptation-establishes-disease-tolerance-to-sepsis
#16
Sebastian Weis, Ana Rita Carlos, Maria Raquel Moita, Sumnima Singh, Birte Blankenhaus, Silvia Cardoso, Rasmus Larsen, Sofia Rebelo, Sascha Schäuble, Laura Del Barrio, Gilles Mithieux, Fabienne Rajas, Sandro Lindig, Michael Bauer, Miguel P Soares
Sepsis is an often lethal syndrome resulting from maladaptive immune and metabolic responses to infection, compromising host homeostasis. Disease tolerance is a defense strategy against infection that preserves host homeostasis without exerting a direct negative impact on pathogens. Here, we demonstrate that induction of the iron-sequestering ferritin H chain (FTH) in response to polymicrobial infections is critical to establish disease tolerance to sepsis. The protective effect of FTH is exerted via a mechanism that counters iron-driven oxidative inhibition of the liver glucose-6-phosphatase (G6Pase), and in doing so, sustains endogenous glucose production via liver gluconeogenesis...
June 15, 2017: Cell
https://www.readbyqxmd.com/read/28611150/effects-of-stress-during-pregnancy-on-hepatic-glucogenic-capacity-in-rat-dams-and-their-fetuses
#17
Kathryn L Franko, Alison J Forhead, Abigail L Fowden
Stress during pregnancy is associated with metabolic dysfunction in the adult offspring in human and other animals. However, little is known about the metabolic effects of pregnancy stress on the mothers and fetuses during pregnancy itself. This study aimed to determine the consequences of the common experimental procedures of injection and single housing in pregnant rats on fetal and maternal hepatic glucogenic capacities. On day (D) 20 of pregnancy, feto-placental weights and the glycogen content and activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) of fetal and maternal liver were measured in rats pair or single housed from D1 with or without saline injection from D15 to D19...
June 2017: Physiological Reports
https://www.readbyqxmd.com/read/28589315/effect-of-blood-glucose-level-on-acute-stress-response-of-grass-carp-ctenopharyngodon-idella
#18
Danli Jiang, Yubo Wu, Di Huang, Xing Ren, Yan Wang
Stress has a considerable impact on welfare and productivity of fish, and blood glucose level of fish may be a factor modulating stress response. This study evaluated the effect of blood glucose level and handling on acute stress response of grass carp Ctenopharyngodon idella. Fish were intraperitoneally injected with glucose at 0, 0.2, 0.5, and 1.0 mg g(-1) body mass (BM) and then were exposed to handling for 5 min. Glucose injection resulted in increase of plasma glucose level and liver glycogen content and decrease of plasma lactate level...
June 6, 2017: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/28565878/ginsenoside-rb3-strengthens-the-hypoglycemic-effect-through-ampk-for-inhibition-of-hepatic-gluconeogenesis
#19
Fanli Meng, Xiaotian Su, Wei Li, Yinan Zheng
Ginsenoside Rb3 is one of the major active components in protopanaxdiol type ginsenosides, and has demonstrated anti-diabetic activity. However, the mechanism of this action has yet to be elucidated. The present study investigated the effects of ginsenoside Rb3 on the AMP-activated protein kinase (AMPK) gluconeogenesis pathway. The present study involved the use of HepG2 cells and western blot analysis to systematically evaluate the effect of ginsenoside Rb3 on AMPK signaling proteins and key factors of gluconeogenesis [phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase, forkhead transcription factor 1 (FOXO1) and hepatic nuclear receptor 4α (HNF4α)]...
May 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28564652/roux-en-y-gastric-bypass-improves-hepatic-glucose-metabolism-involving-down-regulation-of-protein-tyrosine-phosphatase-1b-in-obese-rats
#20
Song Mu, Jiayu Liu, Wei Guo, Shuping Zhang, Xiaoqiu Xiao, Zhihong Wang, Jun Zhang
OBJECTIVE: This study was initiated to investigate the effects of Roux-en-Y gastric bypass (RYGB) surgery on hepatic glucose metabolism and hepatic expression of protein tyrosine phosphatase 1B (PTP1B) in obese rats. METHODS: Body weight, glucose, intraperitoneal glucose, insulin, and pyruvate tolerance tests were performed pre- and postoperatively, and plasma lipid, insulin and glucagon-like peptide 1 (GLP-1) were measured. The mRNA levels of G6Pase, Pepck, Gsk-3β and Gys-2, and the expression levels of PTP1B mRNA, protein, and other components of the insulin signaling pathway were measured by using RT-PCR and western blotting...
2017: Obesity Facts
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