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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
#1
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...
November 22, 2016: 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
#2
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
#3
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...
October 31, 2016: Archives of Pharmacal Research
https://www.readbyqxmd.com/read/27796348/metabolomics-reveals-the-protective-of-dihydromyricetin-on-glucose-homeostasis-by-enhancing-insulin-sensitivity
#4
Liang Le, Baoping Jiang, Wenting Wan, Wei Zhai, Lijia Xu, Keping Hu, Peigen Xiao
Dihydromyricetin (DMY), an important flavanone found in Ampelopsis grossedentata, possesses antioxidative properties that ameliorate skeletal muscle insulin sensitivity and exert a hepatoprotective effect. However, little is known about the effects of DMY in the context of high-fat diet (HFD)-induced hepatic insulin resistance. Male Sprague-Dawley(SD) rats were fed a HFD(60% fat) supplemented with DMY for 8 weeks. The administration of DMY to the rats with HFD-induced insulin resistance reduces hyperglycemia, plasma levels of insulin, and steatosis in the liver...
October 31, 2016: Scientific Reports
https://www.readbyqxmd.com/read/27765569/%C3%AE-1%C3%A2-3-1%C3%A2-6-d-glucans-produced-by-diaporthe-sp-endophytes-purification-chemical-characterization-and-antiproliferative-activity-against-mcf-7-and-hepg2-c3a-cells
#5
Ravely Casarotti Orlandelli, Maria de Lourdes Corradi da Silva, Ana Flora Dalberto Vasconcelos, Igor Vivian Almeida, Veronica Elisa Pimenta Vicentini, Alicia Prieto, Maria Dolores Diaz Hernandez, João Lúcio Azevedo, João Alencar Pamphile
This study reports the characterization and antiproliferative activity of exopolysaccharides (EPS) produced by submerged cultures of the endophytes Diaporthe sp. JF766998 and Diaporthe sp. JF767007 isolated from the medicinal plant Piper hispidum Sw. Both strains secreted a crude EPS that, upon size exclusion chromatography, showed to contain a heteropolysaccharide (galactose, glucose and mannose) and a high-molecular weight glucan. Data from methylation analysis, FTIR and NMR spectroscopy ((1)H, COSY, TOCSY and HSQC-DEPT) indicated that the purified glucan consisted of a main chain of glucopyranosyl β-(1→3) linkages substituted at O-6 by glucosyl residues...
October 17, 2016: International Journal of Biological Macromolecules
https://www.readbyqxmd.com/read/27695899/sequential-cleavage-of-insulin-receptor-by-calpain-2-and-%C3%AE-secretase-impairs-insulin-signalling
#6
Tomoyuki Yuasa, Kikuko Amo-Shiinoki, Shuhei Ishikura, Mitsuyoshi Takahara, Takaaki Matsuoka, Hideaki Kaneto, Akio Kuroda, Munehide Matsuhisa, Seiichi Hashida
AIMS/HYPOTHESIS: Soluble insulin receptor (sIR), the ectodomain of the insulin receptor (IR), has been detected in human plasma and its concentration paralleled that of blood glucose. We have previously developed an in vitro model using HepG2 liver-derived cells, which mimics changes in sIR levels in plasma from diabetic patients and shows that calcium-dependent proteases cleave IR extracellularly (a process known as shedding). The present study aimed to reveal the mechanisms of IR cleavage...
September 30, 2016: Diabetologia
https://www.readbyqxmd.com/read/27658743/thioredoxin-mimetic-peptides-txm-inhibit-inflammatory-pathways-associated-with-high-glucose-and-oxidative-stress
#7
Katia Lejnev, Lena Khomsky, Krister Bokvist, Shani Mistriel-Zerbib, Tahel Naveh, Thomas Bradley Farb, Jorge Alsina-Fernandez, Daphne Atlas
Impaired insulin signaling and the associated insulin-resistance in liver, adipose tissue, and skeletal muscle, represents a hallmark of the pathogenesis of type 2-diabetes-mellitus. Here we show that in the liver of db/db mice, a murine model of obesity, type 2 diabetes, and dyslipidemia, the elevated activities of mitogen-activated protein kinases (MAPK; ERK1/2 and p38(MAPK)), and Akt/PKB are abolished by rosiglitazone-treatment, which normalizes blood glucose in db/db mice. This is unequivocal evidence of a functional link between the activation of the MAPK specific inflammatory-pathway and high-blood sugar...
October 2016: Free Radical Biology & Medicine
https://www.readbyqxmd.com/read/27622707/benzylglucosinolate-derived-isothiocyanate-from-tropaeolum-majus-reduces-gluconeogenic-gene-and-protein-expression-in-human-cells
#8
Valentina Guzmán-Pérez, Christiane Bumke-Vogt, Monika Schreiner, Inga Mewis, Andrea Borchert, Andreas F H Pfeiffer
Nasturtium (Tropaeolum majus L.) contains high concentrations of benzylglcosinolate. We found that a hydrolysis product of benzyl glucosinolate-the benzyl isothiocyanate (BITC)-modulates the intracellular localization of the transcription factor Forkhead box O 1 (FOXO1). FoxO transcription factors can antagonize insulin effects and trigger a variety of cellular processes involved in tumor suppression, longevity, development and metabolism. The current study evaluated the ability of BITC-extracted as intact glucosinolate from nasturtium and hydrolyzed with myrosinase-to modulate i) the insulin-signaling pathway, ii) the intracellular localization of FOXO1 and, iii) the expression of proteins involved in gluconeogenesis, antioxidant response and detoxification...
2016: PloS One
https://www.readbyqxmd.com/read/27614433/hdac5-inhibits-hepatic-lipogenic-genes-expression-by-attenuating-the-transcriptional-activity-of-liver-x-receptor
#9
Hai-Yan Jia, Quan-Zhong Li, Li-Fang Lv
BACKGROUND/AIMS: Liver X receptor (LXR), a member of the nuclear receptor superfamily, is known to induce the expression of SREBP-1c and ChREBP, two master regulators of hepatic lipogenesis. Histone deacyetylases (HDACs) have been shown to play critical roles in glucose and lipids metabolism. However, the exact role of HDAC5 in lipogenesis remains elusive. METHODS: mRNA and protein levels of HDAC5 were analyzed by quantitative real-time PCR and Western blots in high-fat-diet-induced and leptin receptor deficiency-induced obese mice...
2016: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/27580020/mulberry-anthocyanin-extract-ameliorates-insulin-resistance-by-regulating-pi3k-akt-pathway-in-hepg2-cells-and-db-db-mice
#10
Fujie Yan, Guanhai Dai, Xiaodong Zheng
This study evaluated the capacity of mulberry anthocyanin extract (MAE) on insulin resistance amelioration in HepG2 cells induced by high glucose and palmitic acid and diabetes-related metabolic changes in type 2 diabetic mice. In vitro, MAE alleviated insulin resistance in HepG2 cells and increased glucose consumption, glucose uptake and glycogen content. Enzyme activities of phosphoenolpyruvate carboxykinase (PEPCK) and glucose-6-phosphatase (G6Pase) were decreased due to PPARγ coactivator 1α (PGC-1α) and forkhead box protein O1 (FOXO1) inhibition...
October 2016: Journal of Nutritional Biochemistry
https://www.readbyqxmd.com/read/27576594/effect-of-bi-1-on-insulin-resistance-through-regulation-of-cyp2e1
#11
Geum-Hwa Lee, Kyoung-Jin Oh, Hyung-Ryong Kim, Hye-Sook Han, Hwa-Young Lee, Keun-Gyu Park, Ki-Hoan Nam, Seung-Hoi Koo, Han-Jung Chae
Diet-induced obesity is a major contributing factor to the progression of hepatic insulin resistance. Increased free fatty acids in liver enhances endoplasmic reticulum (ER) stress and production of reactive oxygen species (ROS), both are directly responsible for dysregulation of hepatic insulin signaling. BI-1, a recently studied ER stress regulator, was examined to investigate its association with ER stress and ROS in insulin resistance models. To induce obesity and insulin resistance, BI-1 wild type and BI-1 knock-out mice were fed a high-fat diet for 8 weeks...
2016: Scientific Reports
https://www.readbyqxmd.com/read/27506476/casein-glycomacropeptide-derived-peptide-ippkknqdkte-ameliorates-high-glucose-induced-insulin-resistance-in-hepg2-cells-via-activation-of-ampk-signaling
#12
Jia-Jia Song, Qian Wang, Min Du, Tian-Ge Li, Bin Chen, Xue-Ying Mao
SCOPE: Recently, casein glycomacropeptide (GMP)-derived peptide was found to possess potent antioxidant and anti-inflammatory activities. In the current study, the improvement effects and underlying molecular mechanisms of GMP-derived peptide on hepatic insulin resistance were investigated. METHODS AND RESULTS: The peptide IPPKKNQDKTE was identified from GMP papain hydrolysates by LC-ESI-MS/MS. Effects of IPPKKNQDKTE on glucose metabolism and expression levels of the hepatic insulin signaling proteins in high glucose-induced insulin-resistant HepG2 cells were evaluated...
August 9, 2016: Molecular Nutrition & Food Research
https://www.readbyqxmd.com/read/27456392/activation-of-the-ampk-sirt1-pathway-by-a-leucine-metformin-combination-increases-insulin-sensitivity-in-skeletal-muscle-and-stimulates-glucose-and-lipid-metabolism-and-increases-life-span-in-caenorhabditis-elegans
#13
Jheelam Banerjee, Antje Bruckbauer, Michael B Zemel
BACKGROUND: We have previously shown leucine (Leu) to activate Sirt1 by lowering its KM for NAD(+), thereby amplifying the effects of other sirtuin activators and improving insulin sensitivity. Metformin (Met) converges on this pathway both indirectly (via AMPK) and by direct activation of Sirt1, and we recently found Leu to synergize with Met to improve insulin sensitivity and glycemic control while achieving ~80% dose-reduction in diet-induced obese mice. Accordingly, we sought here to define the mechanism of this interaction...
November 2016: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/27452313/irisin-ameliorates-hepatic-glucose-lipid-metabolism-and-enhances-cell-survival-in-insulin-resistant-human-hepg2-cells-through-adenosine-monophosphate-activated-protein-kinase-signaling
#14
Wing Yan So, Po Sing Leung
Irisin is a newly identified myokine that promotes the browning of white adipose tissue, enhances glucose uptake in skeletal muscle and modulates hepatic metabolism. However, the signaling pathways involved in the effects on hepatic glucose and lipid metabolism have not been resolved. This study aimed to examine the role of irisin in the regulation of hepatic glucose/lipid metabolism and cell survival, and whether adenosine monophosphate-activated protein kinase (AMPK), a master metabolic regulator in the liver, is involved in irisin's actions...
September 2016: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/27426490/dimethylesculetin-ameliorates-maternal-glucose-intolerance-and-fetal-overgrowth-in-high-fat-diet-fed-pregnant-mice-via-constitutive-androstane-receptor
#15
Hisashi Masuyama, Takashi Mitsui, Jota Maki, Kazumasa Tani, Keiichiro Nakamura, Yuji Hiramatsu
The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance along with obesity. 6,7-dimethylesculetin (DE) is an active component of Yin Zhi Huang which is a traditional Asian medicine used to treat neonatal jaundice via CAR. In this study, we examined whether DE could affect the expression of gluconeogenic and lipogenic genes via human CAR pathway using human HepG2 cells in vitro. We also studied whether DE treatment during pregnancy could prevent maternal hypertension, glucose intolerance and hyperlipidemia, and fetal overgrowth in high-fat diet (HFD)-induced obese pregnant mice...
August 2016: Molecular and Cellular Biochemistry
https://www.readbyqxmd.com/read/27423393/pink1-alleviates-palmitate-induced-insulin-resistance-in-hepg2-cells-by-suppressing-ros-mediated-mapk-pathways
#16
Xiaomin Cang, Xiaohua Wang, Pingli Liu, Xue Wu, Jin Yan, Jinfeng Chen, Gang Wu, Yan Jin, Feng Xu, Jianbin Su, Chunhua Wan, Xueqin Wang
Oxidative stress is an important pathogenesis of insulin resistance (IR) and Type 2 diabetes mellitus (T2DM). Studies have shown that knockdown of PTEN-induced putative kinase 1 (PINK1) causes oxidative stress and mitophagy. In db/db mice, PINK1 protein level is down-regulated. However, little is known regarding the mechanism by which PINK1 modulates IR in response to reactive oxygen species (ROS) induced stress. In our study, PINK1 expression decreased during palmitate (PA) induced IR in HepG2 cells and the hepatic tissues of high fat diet (HFD) fed mice...
September 9, 2016: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/27417255/impairment-of-oxidative-phosphorylation-increases-the-toxicity-of-syd-1-on-hepatocarcinoma-cells-hepg2
#17
Anna Paula Brandt, Gustavo Jabor Gozzi, Amanda do Rocio Andrade Pires, Glaucia Regina Martinez, André Vinícius Dos Santos Canuto, Aurea Echevarria, Attilio Di Pietro, Sílvia Maria Suter Correia Cadena
Toxicity of the SYD-1 mesoionic compound (3-[4-chloro-3-nitrophenyl]-1,2,3-oxadiazolium-5-olate) was evaluated on human liver cancer cells (HepG2) grown in either high glucose (HG) or galactose (GAL) medium, and also on suspended cells kept in HG medium. SYD-1 was able to decrease the viability of cultured HepG2 cells in a dose-dependent manner, as assessed by MTT, LDH release and dye with crystal violet assays, but no effect was observed on suspended cells after 1-40 min of treatment. Respiration analysis was performed after 2 min (suspended cells) or 24 h (cultured cells) of treatment: no change was observed in suspended cells, whereas SYD-1 inhibited as well basal, leak and uncoupled states of the respiration in cultured cells with HG medium...
August 25, 2016: Chemico-biological Interactions
https://www.readbyqxmd.com/read/27405739/partial-characterization-and-antioxidant-and-antiproliferative-activities-of-the-aqueous-extracellular-polysaccharides-from-the-thermophilic-microalgae-graesiella-sp
#18
Lamia Trabelsi, Olfa Chaieb, Amira Mnari, Salwa Abid-Essafi, Lotfi Aleya
BACKGROUND: For thousands of years, Tunisian geothermal water has been used in bathing. Indeed, thermal baths "Hammam" were recommended in the treatment of different type of illnesses as, for instance, for relaxing joints and soothing. The ability of microalgae to sustain at the high temperature makes them potential producers of high value thermostable bio-products. This study aimed to explore the therapeutic potential of the aqueous extracellular polysaccharides (AEPS) of the Tunisian thermophilic microalgae Graesiella sp...
2016: BMC Complementary and Alternative Medicine
https://www.readbyqxmd.com/read/27404023/insulin-mediated-downregulation-of-apolipoprotein-a-i-gene-in-human-hepatoma-cell-line-hepg2-the-role-of-interaction-between-foxo1-and-lxr%C3%AE-transcription-factors
#19
Vladimir S Shavva, Alexandra M Bogomolova, Artemy A Nikitin, Ella B Dizhe, Dmitry A Tanyanskiy, Alexander M Efremov, Galina N Oleinikova, Andrej P Perevozchikov, Sergey V Orlov
Apolipoprotein A-I (ApoA-I) is a key component of High Density Lipoproteins which possess anti-atherosclerotic and anti-inflammatory properties. Insulin is a crucial mediator of the glucose and lipid metabolism that has been implicated in atherosclerotic and inflammatory processes. Important mediators of insulin signaling such as Liver X Receptors (LXRs) and Forkhead Box A2 (FOXA2) are known to regulate apoA-I expression in liver. Forkhead Box O1 (FOXO1) is a well-known target of insulin signaling and a key mediator of oxidative stress response...
July 12, 2016: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/27387397/protective-effects-of-marein-on-high-glucose-induced-glucose-metabolic-disorder-in-hepg2-cells
#20
Baoping Jiang, Liang Le, Wei Zhai, Wenting Wan, Keping Hu, Peng Yong, Chunnian He, Lijia Xu, Peigen Xiao
BACKGROUND: Our previous study has shown that Coreopsis tinctoria increases insulin sensitivity and regulates hepatic metabolism in high-fat diet (HFD)-induced insulin resistance rats. However, it is unclear whether or not marein, a major compound of C. tinctoria, could improve insulin resistance. Here we investigate the effect and mechanism of action of marein on improving insulin resistance in HepG2 cells. METHODS: We investigated the protective effects of marein in high glucose-induced human liver carcinoma cell HepG2...
August 15, 2016: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
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