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https://www.readbyqxmd.com/read/28439947/sirt1-hsf1-hsps-pathway-is-essential-for-exenatide-alleviated-lipid-induced-hepatic-endoplasmic-reticulum-stress
#1
Xiaobin Zheng, Fen Xu, Hua Liang, Huanyi Cao, Mengyin Cai, Wen Xu, Jianping Weng
Recent studies have indicated lipid-induced endoplasmic reticulum (ER) stress to be a major contributor to the progression of hepatic steatosis. Exenatide (Exendin-4), a glucagon-like peptide-1 receptor agonist, is known to improve hepatic steatosis with accumulating evidence. In this study, we investigated whether exenatide could alleviate lipid-induced hepatic ER stress through mammal sirtuin1 (SIRT1) and illustrated the detailed mechanisms. Male C57BL/6J mice challenged with a high-fat diet (HFD) were then treated with exenatide or normal saline by intraperitoneal injection for 4 weeks...
April 25, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28436464/glucose-dependent-regulation-of-pregnane-x-receptor-is-modulated-by-amp-activated-protein-kinase
#2
Peter O Oladimeji, Wenwei Lin, C Trent Brewer, Taosheng Chen
Pregnane X receptor (PXR) is a xenobiotic receptor that regulates the detoxification and clearance of drugs and foreign compounds from the liver. There has been mounting evidence of crosstalk between the drug metabolism pathway and the energy metabolism pathway, but little is known about this cross-regulation. To further delineate the energy metabolism and drug metabolism crosstalk in this study, we exposed HepG2 cells to varying glucose concentrations. We observed that PXR activity was induced under high-glucose conditions...
April 24, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28428480/exposure-to-high-glucose-concentration-decreases-cell-surface-abca1-and-hdl-biogenesis-in-hepatocytes
#3
Maki Tsujita, Mohammad Anwar Hossain, Rui Lu, Tomoe Tsuboi, Kuniko Okumura-Noji, Shinji Yokoyama
AIM: To study atherosclerosis risk in diabetes, we investigated ATP-binding cassette transporter A1 (ABCA1) expression and high-density lipoprotein (HDL) biogenesis in the liver and hepatocytes under hyperglycemic conditions. METHODS AND RESULTS: In streptozotocin-induced diabetic mice, plasma HDL decreased while ABCA1 protein increased without changing its mRNA in the liver, only in the animals that responded to the treatment to show hypoinsulinemia and fasting hyperglycemia but not in the poor responders not showing those...
April 19, 2017: Journal of Atherosclerosis and Thrombosis
https://www.readbyqxmd.com/read/28402540/the-hepatic-protection-effects-of-hepassocin-in-hyperglycemic-crisis
#4
Horng-Yih Ou, Hung-Tsung Wu, Ching-Han Lin, Ye-Fong Du, Che-Yuan Hu, Hao-Chang Hung, Pansee Wu, Hung-Yuan Li, Shu-Huei Wang, Chih-Jen Chang
CONTEXT: High glucose generates reactive oxygen species (ROS) and contributes to glucotoxicity in hepatocytes, and hyperglycemia causes structural and functional damage to the liver. However, only a mild hepatic dysfunction was observed in subjects with hyperglycemic crisis, implying a factor exists to exert a hepatic protective effect. Hepassocin is a hepatokine that modulates the proliferation and metabolism of hepatocytes, and also exerts protective activity in liver injury. However, its role in hyperglycemic crisis-induced hepatic dysfunction remains unknown...
April 11, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28393248/epigallocatechin-3-gallate-ameliorates-insulin-resistance-in-hepatocytes
#5
Shan-Bo Ma, Rui Zhang, Shan Miao, Bin Gao, Yang Lu, Sen Hui, Long Li, Xiao-Peng Shi, Ai-Dong Wen
Hyperglycemia is a typical pathogenic factor in a series of complications among patients with type II diabetes. Epigallocatechin-3-gallate (EGCG) is the major polyphenol extracted from green tea and is reported to be an antioxidant. The aim of the present study was to examine the effect of EGCG on insulin resistance in human HepG2 cells pretreated with high concentrations of glucose. The protein kinase B (AKT)/glycogen synthase kinase (GSK) pathways were analyzed using western blot analysis in HepG2 cells and primary mouse hepatocytes treated with high glucose and/or EGCG...
April 7, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28379184/the-effect-of-phloroglucinol-a-component-of-ecklonia-cava-extract-on-hepatic-glucose-production
#6
Ji-Young Yoon, Hojung Choi, Hee-Sook Jun
Phloroglucinol is a phenolic compound that is one of the major compounds in Ecklonia cava (brown alga). It has many pharmacological activities, but its anti-diabetic effect is not yet fully explored. In this study, we investigated the effect of phloroglucinol on the control of blood glucose levels and the regulation of hepatic glucose production. Phloroglucinol significantly improved glucose tolerance in male C57BL/6J mice fed a high fat diet (HFD) and inhibited glucose production in mouse primary hepatocytes...
April 5, 2017: Marine Drugs
https://www.readbyqxmd.com/read/28377317/dehydroascorbate-derivatized-chitosan-particles-for-targeting-antimalarial-agents-to-infected-erythrocytes
#7
Hasham Shafi, D V Siva Reddy, Tabassum Khan, Rajeev Ranjan, Ashish Srivastava, Suniti Vaishya, Tanuj Sharma, Mohammad Imran Siddiqui, Saman Habib, Amit Misra
The mammalian glucose transporter GLUT-1 and Plasmodium falciparum hexose transporter PfHT1 are overexpressed on human RBC infected with the parasite (iRBC), presumably for enhanced glucose uptake. Dehydroascorbic acid (DHA) competes out glucose in GLUT-1 binding. We prepared particles containing chloroquine phosphate using novel derivatives of chitosan (CSN). CSN was either pre-derivatized with DHA (PRE) or particles made of CSN were derivatized by surface-grafting DHA (POST). The optimized formulations were analyzed for size (170-200nm) drug content (about 40%) entrapment efficiency (50-57%), in vitro drug release (80% in 72h, Higuchi's model), hemolysis on exposure to whole blood or RBC at 5% hematocrit, cytotoxicity towards cultured HEK 293T (kidney) and HepG2 (hepatic) cells, targeting iRBC and in vitro efficacy against P...
April 2, 2017: International Journal of Pharmaceutics
https://www.readbyqxmd.com/read/28372462/polysaccharides-extraction-from-opuntia-stricta-and-their-protective-effect-against-hepg2-cell-death-and-hypolipidaemic-effects-on-hyperlipidaemia-rats-induced-by-high-fat-diet
#8
Bahira Harrabi, Khaled Athmouni, Latifa Hamdaoui, Lobna Ben Mahmoud, Ahmed Hakim, Abdelfattah El Feki, Khaled Zeghal, Hanéne Ghozzi
The aim of this study was to analyse cytoprotective effect of polysaccharides compound from Opuntia stricta (O. stricta) cladode (POS) in vitro including its radical scavenging activities and protective effects against hypercholesterolaemia. Our results showed that glucose was the dominant monosaccharides (30.35%). Arabinose, pyranose, fructose, galactose, glucose, sorbitol, S-inositol, M-inositol, trehalose and saccharose found in this species. O. stricta polysaccharides did not cause any cytotoxic effect on HepG2 cells within the range of concentrations tested (0-400 μgml(-1))...
April 3, 2017: Archives of Physiology and Biochemistry
https://www.readbyqxmd.com/read/28221022/quantitative-13-c-traces-of-glucose-fate-in-hepatitis-b-virus-infected-hepatocytes
#9
Qianfen Wan, Yulan Wang, Huiru Tang
Quantitative characterization of (13)C-labeled metabolites is an important part of the stable isotope tracing method widely used in metabolic flux analysis. Given the long relaxation time and low sensitivity of (13)C nuclei, direct measurement of (13)C-labeled metabolites using one-dimensional (13)C NMR often fails to meet the demand of metabolomics studies, especially with large numbers of samples and metabolites having low abundance. Although HSQC-based 2D NMR methods have improved sensitivity with inversion detection, they are time-consuming and thus unsuitable for high-throughput absolute quantification of (13)C-labeled metabolites...
March 6, 2017: Analytical Chemistry
https://www.readbyqxmd.com/read/28174122/role-of-salt-inducible-kinase-1-in-high-glucose-induced-lipid-accumulation-in-hepg2-cells-and-metformin-intervention
#10
Yue Zhang, Hiroshi Takemori, Chang Wang, JiaHui Fu, MingWang Xu, Liang Xiong, NingXu Li, XiuYing Wen
AIMS: To investigate the roles of salt inducible kinase (SIK1) in high glucose-induced triglyceride accumulation in human hepatoma HepG2 cells as well as in the molecular mechanism by which metformin, a drug to treat diabetes, suppresses high glucose-induced lipogenesis. MAIN METHODS: A cell model for high glucose-induced hepatic steatosis was prepared by exposing HepG2 cells to high glucose (25mmol) in the absence or presence of metformin (0.5mmol). Intracellular triglycerides were visualized by Oil Red O and measured using a triglyceride assay kit...
March 15, 2017: Life Sciences
https://www.readbyqxmd.com/read/28119530/decreased-lipid-metabolism-but-increased-fa-biosynthesis-are-coupled-with-changes-in-liver-micrornas-in-obese-subjects-with-nafld
#11
J Latorre, J M Moreno-Navarrete, J M Mercader, M Sabater, Ò Rovira, J Gironès, W Ricart, J M Fernández-Real, F J Ortega
BACKGROUND/OBJECTIVE: Many controversies regarding the association of liver miRNAs with obesity and nonalcoholic fatty liver diseases (NAFLD) call for additional validations. This study sought to investigate variations in genes and hepatic miRNAs in a sample of obese patients with or without NAFLD and human hepatocytes (HH). SUBJECTS/METHODS: A total of 60 non-consecutive obese women following bariatric surgery were recruited. Subjects were classified as NAFLD (n=17), borderline (n=24) and controls (n=19) with normal enzymatic profile, liver histology and ultrasound assessments...
April 2017: International Journal of Obesity: Journal of the International Association for the Study of Obesity
https://www.readbyqxmd.com/read/28067838/effect-of-phenolic-compounds-from-elderflowers-on-glucose-and-fatty-acid-uptake-in-human-myotubes-and-hepg2-cells
#12
Giang Thanh Thi Ho, Eili Tranheim Kase, Helle Wangensteen, Hilde Barsett
Type 2 diabetes (T2D) is manifested by progressive metabolic impairments in tissues such as skeletal muscle and liver, and these tissues become less responsive to insulin, leading to hyperglycemia. In the present study, stimulation of glucose and oleic acid uptake by elderflower extracts, constituents and metabolites were tested in vitro using the HepG2 hepatocellular liver carcinoma cell line and human skeletal muscle cells. Among the crude extracts, the 96% EtOH extract showed the highest increase in glucose and oleic acid uptake in human skeletal muscle cells and HepG2-cells...
January 6, 2017: Molecules: a Journal of Synthetic Chemistry and Natural Product Chemistry
https://www.readbyqxmd.com/read/28024794/does-resveratrol-improve-insulin-signalling-in-hepg2-cells
#13
Marjan Norouzzadeh, Fatemehsadat Amiri, Ali Akbar Saboor-Yaraghi, Farnoosh Shemirani, Yas Kalikias, Loghman Sharifi, Monireh Sadat Seyyedsalehi, Maryam Mahmoudi
OBJECTIVES: Diabetes mellitus is a common metabolic disorder with high global prevalence. It is characterized by a decrease in insulin secretion or a decrease in insulin sensitivity or both. The aim of the present study was to investigate the effects of resveratrol treatment on the expression of the genes involved in insulin signalling cascade, such as Forkhead box protein O1 (FoxO1), 3-phosphoinositide-dependent protein kinase 1 (PDPK1) and mammalian target of rapamycin (mTOR). METHODS: HepG2 cells were cultured in serum-free medium with high concentrations of glucose and insulin and then were treated with resveratrol (5, 10 and 20 µM) for 24 and 48 hours...
December 23, 2016: Canadian Journal of Diabetes
https://www.readbyqxmd.com/read/28012395/regulatory-mechanism-of-mineral-balanced-deep-sea-water-on-hypocholesterolemic-effects-in-hepg2-hepatic-cells
#14
Kyu-Shik Lee, Yun-Suk Kwon, Soyoung Kim, Deok-Soo Moon, Hyeon Ju Kim, Kyung-Soo Nam
Several previous studies have shown the benefits of deep sea water (DSW) in lipid metabolism. However, the effects of DSW on cellular cholesterol accumulation and synthesis induced by high glucose or free fatty acid plus high glucose [4.5g/L] (FFA/glucose) have not been fully elucidated to date. Herein, we showed the effects of mineral-balanced DSW [magnesium (Mg):calcium (Ca)=3:1] (MB-DSW) on cholesterol metabolism induced by high glucose or FFA/glucose in HepG2 hepatic cells. Moreover, the effects of high ratio Mg DSW [Mg:Ca=40:1] (Mg40) were also investigated...
February 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28011762/idh1-deficiency-attenuates-gluconeogenesis-in-mouse-liver-by-impairing-amino-acid-utilization
#15
Jing Ye, Yu Gu, Feng Zhang, Yuanlin Zhao, Yuan Yuan, Zhenyue Hao, Yi Sheng, Wanda Y Li, Andrew Wakeham, Rob A Cairns, Tak W Mak
Although the enzymatic activity of isocitrate dehydrogenase 1 (IDH1) was defined decades ago, its functions in vivo are not yet fully understood. Cytosolic IDH1 converts isocitrate to α-ketoglutarate (α-KG), a key metabolite regulating nitrogen homeostasis in catabolic pathways. It was thought that IDH1 might enhance lipid biosynthesis in liver or adipose tissue by generating NADPH, but we show here that lipid contents are relatively unchanged in both IDH1-null mouse liver and IDH1-deficient HepG2 cells generated using the CRISPR-Cas9 system...
January 10, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/27926473/growth-differentiation-factor-15-increases-following-oral-glucose-ingestion-effect-of-meal-composition-and-obesity
#16
RANDOMIZED CONTROLLED TRIAL
Marie Helene Schernthaner-Reiter, Dominik Kasses, Christina Tugendsam, Michaela Riedl, Slobodan Peric, Gerhard Prager, Michael Krebs, Miriam Promintzer-Schifferl, Martin Clodi, Anton Luger, Greisa Vila
OBJECTIVE: Growth differentiation factor 15 (GDF15) is a cardiovascular biomarker belonging to the transforming growth factor-β superfamily. Increased GDF15 concentrations are associated with insulin resistance, diabetes and obesity. We investigated the physiological effects of meal composition and obesity on the regulation of systemic GDF15 levels. DESIGN: Lean (n = 8) and obese (n = 8) individuals received a carbohydrate- or fat-rich meal, a 75 g oral glucose load (OGTT) or short-term fasting...
December 2016: European Journal of Endocrinology
https://www.readbyqxmd.com/read/27921399/antioxidant-and-antidiabetic-properties-of-tartary-buckwheat-rice-flavonoids-after-in-vitro-digestion
#17
Tao Bao, Ye Wang, Yu-Ting Li, Vemana Gowd, Xin-He Niu, Hai-Ying Yang, Li-Shui Chen, Wei Chen, Chong-de Sun
Oxidative stress and diabetes have a tendency to alter protein, lipid, and DNA moieties. One of the strategic methods used to reduce diabetes-associated oxidative stress is to inhibit the carbohydrate-digesting enzymes, thereby decreasing gastrointestinal glucose production. Plant-derived natural antioxidant molecules are considered a therapeutic tool in the treatment of oxidative stress and diabetes. The objective of this study was to identify tartary buckwheat rice flavonoids and evaluate the effect of in vitro digestion on their antioxidant and antidiabetic properties...
2016: Journal of Zhejiang University. Science. B
https://www.readbyqxmd.com/read/27888103/luteolin-improves-non-alcoholic-fatty-liver-disease-in-db-db-mice-by-inhibition-of-liver-x-receptor-activation-to-down-regulate-expression-of-sterol-regulatory-element-binding-protein-1c
#18
Ye Yin, Lu Gao, Haiyan Lin, Yue Wu, Xiao Han, Yunxia Zhu, Jie Li
In this study, we report that daily administration of luteolin for 8 weeks improved hepatic steatosis by repressing hepatic TG accumulation and increasing glycogen storage. Luteolin inhibited hepatic de novo lipid synthesis by regulating the LXR-SREBP-1c signaling pathway, which is over-activated in the livers of db/db mice. Further in vitro studies revealed that luteolin can competitively bind to the ligand binding domain to suppress the LXR activation induced by an LXR agonist and high glucose, thereby decreasing TG accumulation in HepG2 cells and primary hepatocytes...
January 22, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27853282/novel-podophyllotoxin-derivatives-as-partial-ppar%C3%AE-agonists-and-their-effects-on-insulin-resistance-and-type-2-diabetes
#19
Xiangming Zhang, Huijuan Liu, Bo Sun, Yan Sun, Weilong Zhong, Yanrong Liu, Shuang Chen, Honglei Ling, Lei Zhou, Xiangyan Jing, Yuan Qin, Ting Xiao, Tao Sun, Honggang Zhou, Cheng Yang
Peroxisome proliferator-activated receptor γ (PPARγ) is recognized as a key regulator of insulin resistance. In this study, we searched for novel PPARγ agonists in a library of structurally diverse organic compounds and determined that podophyllotoxin exhibits partial agonist activity toward PPARγ. Eight novel podophyllotoxin-like derivatives were synthesized and assayed for toxicity and functional activity toward PPARγ to reduce the possible systemic toxic effects of podophyllotoxin and to maintain partial agonist activity toward PPARγ...
November 17, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27798765/prunin-is-a-highly-potent-flavonoid-from-prunus-davidiana-stems-that-inhibits-protein-tyrosine-phosphatase-1b-and-stimulates-glucose-uptake-in-insulin-resistant-hepg2-cells
#20
Hyun Ah Jung, Md Yousof Ali, Himanshu Kumar Bhakta, Byung-Sun Min, Jae Sue Choi
Prunin is the main flavonoid in Prunus davidiana stems and improves hyperglycemia and hyperlipidemia in streptozotocin-induced diabetic rats. The aim of this study was to investigate the in vitro anti-diabetic potential of prunin via the inhibition of protein tyrosine phosphatase 1B (PTP1B), α-glucosidase, peroxynitrite (ONOO(-))-mediated tyrosine nitration, and stimulation of glucose uptake in insulin-resistant hepatocytes. In addition, a molecular docking simulation was performed to predict specific prunin binding modes during PTP1B inhibition...
January 2017: Archives of Pharmacal Research
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