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https://www.readbyqxmd.com/read/28096054/glycogen-storage-disease-type-ia-mice-with-less-than-2-of-normal-hepatic-glucose-6-phosphatase-%C3%AE-activity-restored-are-at-risk-of-developing-hepatic-tumors
#1
Goo-Young Kim, Young Mok Lee, Joon Hyun Kwon, Jun-Ho Cho, Chi-Jiunn Pan, Matthew F Starost, Brian C Mansfield, Janice Y Chou
Glycogen storage disease type Ia (GSD-Ia), characterized by impaired glucose homeostasis and chronic risk of hepatocellular adenoma (HCA) and carcinoma (HCC), is caused by a deficiency in glucose-6-phosphatase-α (G6Pase-α or G6PC). We have previously shown that G6pc-/- mice receiving gene transfer mediated by rAAV-G6PC, a recombinant adeno-associated virus (rAAV) vector expressing G6Pase-α, and expressing 3-63% of normal hepatic G6Pase-α activity maintain glucose homeostasis and do not develop HCA/HCC. However, the threshold of hepatic G6Pase-α activity required to prevent tumor formation remained unknown...
January 10, 2017: Molecular Genetics and Metabolism
https://www.readbyqxmd.com/read/28076749/epigenetic-changes-of-hepatic-glucocorticoid-receptor-in-sheep-male-offspring-undernourished-in-utero
#2
Stella Chadio, Basiliki Kotsampasi, Stylliani Taka, Emmanouil Liandris, Nikolaos Papadopoulos, Elias Plakokefalos
The aim of this study was to characterise the effects of maternal undernutrition during gestation on hepatic gluconeogenic enzyme gene expression and to determine whether such effects are mediated through epigenetic changes in the glucocorticoid receptor (GR). Pregnant ewes were fed a 50% nutrient-restricted diet from Day 0 to 30 (R1) or from Day 31 to 100 of gestation (R2) or a 100% diet throughout gestation (Control). After parturition lambs were fed to appetite. At 10 months of age offspring were euthanised and livers were removed...
January 12, 2017: Reproduction, Fertility, and Development
https://www.readbyqxmd.com/read/28002512/pharmacotoxicological-screening-on-new-derivatives-of-beta-phenylethylamine-potential-agonists-of-beta3-adrenergic-receptors
#3
Simona Negreş, Anca Zanfirescu, Floriana Elvira Ionică, Elena Moroşan, Bruno Ştefan Velescu, Oana Cristina Şeremet, Cristina Elena Zbârcea, Emil Ştefănescu, Manuella Militaru, Andreea LetiŢia Arsene, Denisa Marilena Margină, Livia Uncu, Corina Scutari, Cornel ChiriŢă
BACKGROUND AND AIMS: Beta3-adrenergic receptors (beta3-ARs) have been initially characterized in 1989. Afterwards, their tissue distribution was established: white and brown adipose tissue, central nervous system, myocardium (atrial and ventricular), blood vessels, smooth gastrointestinal muscles (stomach, small intestine, colon), gallbladder, urinary bladder, prostate, skeletal muscles. Non-clinical trials have demonstrated the major implication of beta3-ARs in glucose metabolism, implicitly, in insulin release, and also in obesity...
2016: Romanian Journal of Morphology and Embryology, Revue Roumaine de Morphologie et Embryologie
https://www.readbyqxmd.com/read/27932985/pregnane-x-receptor-pxr-mediated-gene-repression-and-cross-talk-of-pxr-with-other-nuclear-receptors-via-coactivator-interactions
#4
REVIEW
Petr Pavek
Pregnane X receptor is a ligand-activated nuclear receptor (NR) that mainly controls inducible expression of xenobiotics handling genes including biotransformation enzymes and drug transporters. Nowadays it is clear that PXR is also involved in regulation of intermediate metabolism through trans-activation and trans-repression of genes controlling glucose, lipid, cholesterol, bile acid, and bilirubin homeostasis. In these processes PXR cross-talks with other NRs. Accumulating evidence suggests that the cross-talk is often mediated by competing for common coactivators or by disruption of coactivation and activity of other transcription factors by the ligand-activated PXR...
2016: Frontiers in Pharmacology
https://www.readbyqxmd.com/read/27914922/negative-regulation-of-hepatic-fat-mass-and-obesity-associated-fto-gene-expression-by-insulin
#5
Tooru M Mizuno, Pei San Lew, Yanming Luo, Arnold Leckstrom
AIMS: To investigate the role of glucose and insulin in the regulation of hepatic fat mass and obesity associated (Fto) gene expression and the role of hepatic Fto in the regulation of gluconeogenic gene expression. MAIN METHODS: To determine the effect of hyperglycemia on hepatic Fto expression, levels of Fto mRNA in liver were compared between normoglycemic/normoinsulinemic, hypereglycemic/hyperinsulinemic, and hyperglycemic/hypoinsulinemic mice. To determine the direct effect of insulin on Fto expression, levels of Fto, glucose-6-phosphatase (G6pase), and phosphoenolpyruvate carboxykinase (Pepck) mRNA levels were compared between control and insulin-treated mouse liver tissues cultured ex vivo and immortalized mouse hepatocytes AML12...
November 30, 2016: Life Sciences
https://www.readbyqxmd.com/read/27890887/royal-jelly-improves-hyperglycemia-in-obese-diabetic-kk-ay-mice
#6
Mei Yoshida, Kaori Hayashi, Risa Watadani, Yoshiyasu Okano, Keiya Tanimura, Jun Kotoh, Daiki Sasaki, Kozo Matsumoto, Akihiko Maeda
The study examined whether royal jelly (RJ) can prevent obesity and ameliorate hyperglycemia in type 2 diabetes. This study utilized obese/diabetic KK-Ay mice. RJ (10 mg/kg) was administered by oral gavage. Body weight, plasma glucose and insulin levels were measured. mRNA and protein levels were determined using quantitative reverse transcription polymerase chain reaction and western blotting, respectively. Four weeks of RJ administration improved hyperglycemia and partially suppressed body weight gain, although the latter effect did not reach statistical significance...
November 26, 2016: Journal of Veterinary Medical Science
https://www.readbyqxmd.com/read/27806092/effect-of-portal-glucose-sensing-on-systemic-glucose-levels-in-sd-and-zdf-rats
#7
Atanu Pal, David B Rhoads, Ali Tavakkoli
BACKGROUND: The global epidemic of Type-2-Diabetes (T2D) highlights the need for novel therapeutic targets and agents. Roux-en-Y-Gastric-Bypass (RYGB) is the most effective treatment. Studies investigating the mechanisms of RYGB suggest a role for post-operative changes in portal glucose levels. We investigate the impact of stimulating portal glucose sensors on systemic glucose levels in health and T2D, and evaluated the role of sodium-glucose-cotransporter-3 (SGLT3) as the possible sensor...
2016: PloS One
https://www.readbyqxmd.com/read/27803313/optimizing-human-hepatocyte-models-for-metabolic-phenotype-and-function-effects-of-treatment-with-dimethyl-sulfoxide-dmso
#8
Nikolaos Nikolaou, Charlotte J Green, Pippa J Gunn, Leanne Hodson, Jeremy W Tomlinson
Primary human hepatocytes are considered to be the "gold standard" cellular model for studying hepatic fatty acid and glucose metabolism; however, they come with limitations. Although the HepG2 cell line retains many of the primary hepatocyte metabolic functions they have a malignant origin and low rates of triglyceride secretion. The aim of this study was to investigate whether dimethyl sulfoxide supplementation in the media of HepG2 cells would enhance metabolic functionality leading to the development of an improved in vitro cell model that closely recapitulates primary human hepatocyte metabolism...
November 2016: Physiological Reports
https://www.readbyqxmd.com/read/27798359/transcriptional-coactivator-nt-pgc-1%C3%AE-promotes-gluconeogenic-gene-expression-and-enhances-hepatic-gluconeogenesis
#9
Ji Suk Chang, Hee-Jin Jun, Minsung Park
The transcriptional coactivator PGC-1α plays a central role in hepatic gluconeogenesis. We previously reported that alternative splicing of the PGC-1α gene produces an additional transcript encoding the truncated protein NT-PGC-1α NT-PGC-1α is co-expressed with PGC-1α and highly induced by fasting in the liver. NT-PGC-1α regulates tissue-specific metabolism, but its role in the liver has not been investigated. Thus, the objective of this study was to determine the role of hepatic NT-PGC-1α in the regulation of gluconeogenesis...
October 2016: Physiological Reports
https://www.readbyqxmd.com/read/27796348/metabolomics-reveals-the-protective-of-dihydromyricetin-on-glucose-homeostasis-by-enhancing-insulin-sensitivity
#10
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/27742409/entada-phaseoloides-extract-suppresses-hepatic-gluconeogenesis-via-activation-of-the-ampk-signaling-pathway
#11
Tao Zheng, Xincai Hao, Qibin Wang, Li Chen, Si Jin, Fang Bian
ETHNOPHARMACOLOGICAL RELEVANCE: The seed of Entada phaseoloides (L.) Merr. (Entada phaseoloides) has been long used as a folk medicine for the treatment of Diabetes mellitus by Chinese ethnic minorities. Recent reports have demonstrated that total saponins from Entada phaseoloides (TSEP) could reduce fasting blood glucose in type 2 diabetic rats. However, the mechanism has not been fully elucidated. The aim of this study was to explore the underlying mechanisms of TSEP on type 2 Diabetes mellitus (T2DM)...
December 4, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27704066/the-potential-beneficial-effects-of-phenolic-compounds-isolated-from-a-pilosa-ledeb-on-insulin-resistant-hepatic-hepg2-cells
#12
Hui Teng, Lei Chen, Hongbo Song
Agrimonia pilosa Ledeb (AP) has already been applied in practice for the treatment of different disorders and is available to access without the provision of a medical prescription. The present study aims at investigating the effect of bioactive compounds isolated from AP on the improvement of insulin resistance, figuring out the mechanism in insulin-responsive cell lines. Five compounds were isolated from AP using column chromatography, including agrimonolide (K1), desmethylagrimonolide (K2), tormentic acid (K3), ursolic acid (K4), and quercetin (K5)...
October 12, 2016: Food & Function
https://www.readbyqxmd.com/read/27686268/symplocos-cochinchinensis-enhances-insulin-sensitivity-via-the-down-regulation-of-lipogenesis-and-insulin-resistance-in-high-energy-diet-rat-model
#13
Kalathookunnel Antony Antu, Mariam Philip Riya, Anupama Nair, Arvind Mishra, Arvind K Srivastava, Kozhiparambil Gopalan Raghu
ETHNOPHARMACOLOGICAL RELEVANCE: This plant has been utilized in Indian system of medicine for treatment of diabetes. This is clearly evident from the composition of Ayurvedic preparation for diabetes 'Nisakathakadi Kashayam' where this is one of the main ingredients of this preparation AIM OF THE STUDY: The study aims in elucidating the molecular mechanisms underlying the insulin sensitizing effects of Symplocos cochinchinensis ethanol extract (SCE) using a high fructose and saturated fat (HFS) fed insulin resistant rat model...
December 4, 2016: Journal of Ethnopharmacology
https://www.readbyqxmd.com/read/27670086/dietary-supplementation-with-xylanase-expressing-b-%C3%A2-amyloliquefaciens-r8-improves-growth-performance-and-enhances-immunity-against-aeromonas-hydrophila-in-nile-tilapia-oreochromis-niloticus
#14
Febriyansyah Saputra, Ya-Li Shiu, Yo-Chia Chen, Asthervina Widyastami Puspitasari, Ridha Handriany Danata, Chun-Hung Liu, Shao-Yang Hu
Bacillus amyloliquefaciens has attracted attention as a probiotic in aquaculture due to its immunostimulatory activity against pathogenic infection. Xylanases are extensively used in animal feed to degrade plant ingredients, enhancing nutrient utilization and increasing the growth rate of various animals. In the present study, the effects of dietary supplementation with B. amyloliquefaciens and xylanase-expressing B. amyloliquefaciens R8 on the growth of Nile tilapia (Oreochromis niloticus) and immunity against Aeromonas hydrophila were evaluated...
November 2016: Fish & Shellfish Immunology
https://www.readbyqxmd.com/read/27630021/modulation-of-appetite-lipid-and-glucose-metabolism-of-juvenile-grass-carp-ctenopharyngodon-idellus-by-different-dietary-protein-levels
#15
Jiao Li, Liwei Liu, Xu-Fang Liang, Xiaochen Yuan, Jie Li, Bin Li, Qingchao Wang, Jinguang Fang, Min Xue, Jia Wang
This study was undertaken to explore the systemic metabolic strategies of juvenile grass carp (Ctenopharyngodon idellus) to maintain growth when fed with different dietary protein levels. The optimal growth group and two growing discomfort groups were selected through the basic data, to explain the growth difference from appetite regulation and lipid and glucose metabolism perspective. Three experimental diets were formulated with three dietary protein levels at 200.3, 296.1 and 442.9 g kg(-1), named P1, P2 and P3, respectively...
September 14, 2016: Fish Physiology and Biochemistry
https://www.readbyqxmd.com/read/27592052/hnf-4%C3%AE-regulated-mir-122-contributes-to-development-of-gluconeogenesis-and-lipid-metabolism-disorders-in-type-2-diabetic-mice-and-in-palmitate-treated-hepg2-cells
#16
Shengnan Wei, Ming Zhang, Yang Yu, Huan Xue, Xiaoxin Lan, Shuping Liu, Grant Hatch, Li Chen
Hepatocyte Nuclear Factor-4α (HNF-4α) is a key nuclear receptor protein required for liver development. miR-122 is a predominant microRNA expressed in liver and is involved in the regulation of cholesterol and fatty acid metabolism. HNF-4α is know to regulate expression of miR-122 in liver. We examined how HNF-4α regulated gluconeogenesis and lipid metabolism through miR-122 in vivo and in vitro. Expression of miR-122, HNF-4α, phosphoenolpyruvate carboxykinase (PEPCK), glucose-6-phosphatase (G6Pase), sterol response elementary binding protein-1 (SREBP-1), fatty acid synthase-1 (FAS-1), carnitine palmitoyltransferase-1 (CPT-1) and acetyl Coenzyme A carboxylase alpha (ACCα) were determined in livers of Type 2 diabetic mice and in insulin resistant palmitate-treated HepG2 cells...
November 15, 2016: European Journal of Pharmacology
https://www.readbyqxmd.com/read/27580020/mulberry-anthocyanin-extract-ameliorates-insulin-resistance-by-regulating-pi3k-akt-pathway-in-hepg2-cells-and-db-db-mice
#17
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/27506476/casein-glycomacropeptide-derived-peptide-ippkknqdkte-ameliorates-high-glucose-induced-insulin-resistance-in-hepg2-cells-via-activation-of-ampk-signaling
#18
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/27495223/microrna-451-negatively-regulates-hepatic-glucose-production-and-glucose-homeostasis-by-targeting-glycerol-kinase-mediated-gluconeogenesis
#19
Shu Zhuo, Mengmei Yang, Yanan Zhao, Xiaofang Chen, Feifei Zhang, Na Li, Pengle Yao, Tengfei Zhu, Hong Mei, Shanshan Wang, Yu Li, Shiting Chen, Yingying Le
MicroRNAs (miRNAs) are a new class of regulatory molecules implicated in type 2 diabetes, which is characterized by insulin resistance and hepatic glucose overproduction. We show that miRNA-451 (miR-451) is elevated in the liver tissues of dietary and genetic mouse models of diabetes. Through an adenovirus-mediated gain- and loss-of-function study, we found that miR-451 negatively regulates hepatic gluconeogenesis and blood glucose levels in normal mice and identified glycerol kinase (Gyk) as a direct target of miR-451...
November 2016: Diabetes
https://www.readbyqxmd.com/read/27495220/renal-denervation-reverses-hepatic-insulin-resistance-induced-by-high-fat-diet
#20
Malini S Iyer, Richard N Bergman, Jeremy E Korman, Orison O Woolcott, Morvarid Kabir, Ronald G Victor, Deborah J Clegg, Cathryn Kolka
Activation of the sympathetic nervous system (SNS) constitutes a putative mechanism of obesity-induced insulin resistance. Thus, we hypothesized that inhibiting the SNS by using renal denervation (RDN) will improve insulin sensitivity (SI) in a nonhypertensive obese canine model. SI was measured using euglycemic-hyperinsulinemic clamp (EGC), before (week 0 [w0]) and after 6 weeks of high-fat diet (w6-HFD) feeding and after either RDN (HFD + RDN) or sham surgery (HFD + sham). As expected, HFD induced insulin resistance in the liver (sham 2...
November 2016: Diabetes
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