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Gluconeogenesis

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https://www.readbyqxmd.com/read/29152137/emodin-and-rhein-decrease-levels-of-hypoxia-inducible-factor-1%C3%AE-in-human-pancreatic-cancer-cells-and-attenuate-cancer-cachexia-in-athymic-mice-carrying-these-cells
#1
Lijuan Hu, Rui Cui, Hongyi Liu, Feng Wang
The transcription factor hypoxia-inducible factor-1 (HIF-1) consists of oxygen-sensitive HIF-1α and constitutive HIF-1β. HIF-1α is undetectable in normal cells, but cancer cells frequently express HIF-1α to support their growth, angiogenesis, and high glycolysis (also known as the Warburg effect). The Warburg effect in cancer cells increases energy expenditure and thus participates in cancer-induced metabolic disorder, cancer cachexia. In the present study, we investigated whether two components of Rheum palmatum, emodin and rhein, inhibited HIF-1α expression in human pancreatic cancer cells and whether the inhibiting effect, if any, attenuated cancer cachexia...
October 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/29134973/effect-of-cortisol-on-plasma-lactate-levels-following-cortisolinduced-hyperglycaemia-in-common-african-toad-bufo-regularis
#2
G O Isehunwa, O T Oladun, J E Akpan, A R A Alada
Previous studies in man have shown that cortisol induces hyperglycemia through gluconeogenesis. However,the metabolic substrates involved in cortisol-induced hyperglycemia and the role of adrenergic receptors in lactate productionin toads have not been well studied. This study investigated the effects of adrenergic receptor blockers in cortisol-inducedhyperglycemia and blood lactate levels in the common African toad (Bufo regularis). Each toad was fasted and anaesthetizedwith sodium thiopentone given intraperitoneally (50mg/kg/i...
June 30, 2017: Nigerian Journal of Physiological Sciences: Official Publication of the Physiological Society of Nigeria
https://www.readbyqxmd.com/read/29132537/nfil3-is-a-negative-regulator-of-hepatic-gluconeogenesis
#3
Geon Kang, Hye-Sook Han, Seung-Hoi Koo
OBJECTIVE: Nuclear factor interleukin-3 regulated (NFIL3) has been known as an important transcriptional regulator of the development and the differentiation of immune cells. Although expression of NFIL3 is regulated by nutritional cues in the liver, the role of NFIL3 in the glucose metabolism has not been extensively studied. Thus, we wanted to explore the potential role of NFIL3 in the control of hepatic glucose metabolism. MATERIALS/METHODS: Mouse primary hepatocytes were cultured to perform western blot analysis, Q-PCR and chromatin immunoprecipitation assay...
December 2017: Metabolism: Clinical and Experimental
https://www.readbyqxmd.com/read/29131453/mechanistic-insights-on-human-phosphoglucomutase-revealed-by-transition-path-sampling-and-molecular-dynamics-calculations
#4
Natercia Bras, Pedro Fernandes, Maria Ramos, Steven Schwartz
Human -phosphoglucomutase 1 (-PGM) catalyzes the isomerization of glucose-1-phosphate into glucose-6-phosphate (G6P) via two sequential phosphoryl transfer steps with a glucose-1,6-bisphosphate (G16P) intermediate. Given that the release of G6P in gluconeogenesis raises glucose output levels, -PGM represents a tempting pharmacological target for type 2 diabetes. Here, we provide the first theoretical study of the catalytic mechanism of human -PGM. We performed transition path sampling simulations to unveil the atomic details of the two catalytic chemical steps, which could be key for developing transition state (TS) analogue molecules with inhibitory properties...
November 12, 2017: Chemistry: a European Journal
https://www.readbyqxmd.com/read/29129786/mechanisms-by-which-a-very-low-calorie-diet-reverses-hyperglycemia-in-a-rat-model-of-type-2-diabetes
#5
Rachel J Perry, Liang Peng, Gary W Cline, Yongliang Wang, Aviva Rabin-Court, Joongyu D Song, Dongyan Zhang, Xian-Man Zhang, Yuichi Nozaki, Sylvie Dufour, Kitt Falk Petersen, Gerald I Shulman
Caloric restriction rapidly reverses type 2 diabetes (T2D), but the mechanism(s) of this reversal are poorly understood. Here we show that 3 days of a very-low-calorie diet (VLCD, one-quarter their typical intake) lowered plasma glucose and insulin concentrations in a rat model of T2D without altering body weight. The lower plasma glucose was associated with a 30% reduction in hepatic glucose production resulting from suppression of both gluconeogenesis from pyruvate carboxylase (VPC), explained by a reduction in hepatic acetyl-CoA content, and net hepatic glycogenolysis...
November 8, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29129613/pgc-1%C3%AE-functions-as-a-co-suppressor-of-xbp1s-to-regulate-glucose-metabolism
#6
Jaemin Lee, Mario Andrés Salazar Hernández, Thomas Auen, Patrick Mucka, Justin Lee, Umut Ozcan
OBJECTIVE: Peroxisome proliferator-activated receptor γ (PPARγ) coactivator-1α (PGC-1α) promotes hepatic gluconeogenesis by activating HNF4α and FoxO1. PGC-1α expression in the liver is highly elevated in obese and diabetic conditions, leading to increased hepatic glucose production. We previously showed that the spliced form of X-box binding protein 1 (XBP1s) suppresses FoxO1 activity and hepatic gluconeogenesis. The shared role of PGC-1α and XBP1s in regulating FoxO1 activity and gluconeogenesis led us to investigate the probable interaction between PGC-1α and XBP1s and its role in glucose metabolism...
October 28, 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29128353/pyruvate-dehydrogenase-kinase-4-mediates-lipogenesis-and-contributes-to-the-pathogenesis-of-nonalcoholic-steatohepatitis
#7
Ming Zhang, Yujie Zhao, Zhen Li, Congying Wang
Nonalcoholic steatohepatitis (NASH) is a progressive disease and poses a high risk of severe liver damage. However, the pathogenesis of NASH is still unclear. Accumulation of lipid droplets and insulin resistance is the hallmark of NASH. Pyruvate dehydrogenase kinase isoenzyme 4 (PDK4) plays key role in glucose metabolism via regulating the activity of pyruvate dehydrogenase complex (PDC). Here, we demonstrated a novel of PDK4 in NASH by regulating hepatic steatosis and insulin signaling pathway in methionine and choline deficient (MCD) diet induced NASH model...
November 8, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29123026/the-klf14-transcription-factor-regulates-hepatic-gluconeogenesis-in-mice
#8
Lu Wang, Xin Tong, Fang Gu, Lei Zhang, Wei Chen, Xiaowen Cheng, Liwei Xie, Yongsheng Chang, Huabing Zhang
Krüppel-like factor 14 (KLF14) is a member of the Cys2/His2 zinc-finger DNA-binding proteins. Despite strong evidence showing that a polymorphism in the Klf14 gene is closely linked to the development of type 2 diabetes (T2D), the physiological and metabolic functions of KLF14 still remain unclear. In the present study, we investigated the role of KLF14 in the regulation of hepatic gluconeogenesis. Adenoviruses expressing KLF14 (Ad-Klf14) or KLF14-specific shRNAs (Ad-shKlf14) were injected into normal C57BL/6J, db/db diabetic or high-fat diet-induced obese (DIO) mice...
November 9, 2017: Journal of Biological Chemistry
https://www.readbyqxmd.com/read/29118282/the-role-of-bile-acids-in-glucose-metabolism-and-their-relation-with-diabetes
#9
José Alberto González-Regueiro, Lidia Moreno-Castañeda, Misael Uribe, Norberto C Chávez-Tapia
Bile acids (BAs), the end products of cholesterol catabolism, are essential for the absorption of lipids and fat-soluble vitamins; but they have also emerged as novel signaling molecules that act as metabolic regulators. It has been well described that the enterohepatic circulation, a nuclear (FXR) and a cytoplasmic (TGR5/M-BAR) receptor aid in controlling hepatic bile acid synthesis. Modulating bile acid synthesis greatly impacts in metabolism, because these receptors also are implicated in glucose, lipid, and energy expenditure...
October 4, 2017: Annals of Hepatology
https://www.readbyqxmd.com/read/29117552/circulating-glucagon-1-61-regulates-blood-glucose-by-increasing-insulin-secretion-and-hepatic-glucose-production
#10
Nicolai J Wewer Albrechtsen, Rune E Kuhre, Daniel Hornburg, Christian Z Jensen, Mads Hornum, Carsten Dirksen, Maria Svane, Lærke S Gasbjerg, Nils B Jørgensen, Maria N Gabe, Emilie Balk-Møller, Reidar Albrechtsen, Marie Winther-Sørensen, Katrine D Galsgaard, Felix Meissner, Tina Jorsal, Asger Lund, Tina Vilsbøll, Rasmus Eliasen, Kirstine N Bojsen-Møller, Thomas Idorn, Carolyn F Deacon, Filip K Knop, Mette M Rosenkilde, Bolette Hartmann, Bo Feldt-Rasmussen, Matthias Mann, Sten Madsbad, Jens J Holst
Glucagon is secreted from pancreatic α cells, and hypersecretion (hyperglucagonemia) contributes to diabetic hyperglycemia. Molecular heterogeneity in hyperglucagonemia is poorly investigated. By screening human plasma using high-resolution-proteomics, we identified several glucagon variants, among which proglucagon 1-61 (PG 1-61) appears to be the most abundant form. PG 1-61 is secreted in subjects with obesity, both before and after gastric bypass surgery, with protein and fat as the main drivers for secretion before surgery, but glucose after...
November 7, 2017: Cell Reports
https://www.readbyqxmd.com/read/29115403/expression-profile-analysis-of-long-non-coding-rnas-involved-in-the-metformin-inhibited-gluconeogenesis-of-primary-mouse-hepatocytes
#11
Yao Wang, Hongju Tang, Xueying Ji, Yuqing Zhang, Wan Xu, Xue Yang, Ruyuan Deng, Yun Liu, Fengying Li, Xiao Wang, Libin Zhou
Long non-coding RNAs (lncRNAs) have been demonstrated to regulate metabolic tissue development and function, including adipogenesis, hepatic lipid metabolism, islet function and energy balance. However, the role of lncRNAs in gluconeogenesis remains completely unknown. Metformin reduces glucose output mainly via the inhibition of gluconeogenesis. In the present study, the lncRNA expression profile of primary mouse hepatocytes exposed to cyclic adenosine monophosphate (cAMP), a gluconeogenic stimulus, with or without metformin was analyzed by microarray...
November 7, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/29114996/impaired-p53-cep-1-is-associated-with-lifespan-extension-through-an-age-related-imbalance-in-the-energy-metabolism-of-c-%C3%A2-elegans
#12
Sumino Yanase, Hitoshi Suda, Kayo Yasuda, Naoaki Ishii
In the nematode Caenorhabditis elegans, the mammalian tumor suppressor p53 ortholog CEP-1 mediates the stress response, activates germ line apoptosis and regulates meiotic chromosome segregation. A reduction in its expression, which frequently occurs in mammalian cancer cells, extends lifespan and induces an adaptive response in C. elegans. However, these effects do not involve an increase in oxidative stress resistance. Here, we showed that intermittent exposure to hyperoxia, which induces oxidative stress resistance and lowers the production of ROS derived from mitochondrial respiration in C...
November 8, 2017: Genes to Cells: Devoted to Molecular & Cellular Mechanisms
https://www.readbyqxmd.com/read/29114912/silencing-pyruvate-kinase-nlpyk-leads-to-reduced-fecundity-in-brown-planthoppers-nilaparvata-lugens-st%C3%A3-l-hemiptera-delphacidae
#13
Lin-Quan Ge, Bo Huang, Xin Li, Hao-Tian Gu, Sui Zheng, Ze Zhou, Hong Miao, Jin-Cai Wu
Pyruvate kinase (PYK) operates in the glycolytic pathway, responsible for regulating the balance between glycolysis and gluconeogenesis. The previous work indicates PYK acts in development of Drosophila embryos and in embryonic muscle growth, from which it may be inferred that PYK acts in insect fecundity. More to the point, as a central enzyme in the glycolytic pathway, PYK acts in many energy-spending functions in most organisms. On the background findings that triazophos (TZP) stimulates fecundity via increase activities of several genes in brown planthoppers, Nilaparvata lugens, we investigated the combined influence of TZP and silencing a N...
November 7, 2017: Archives of Insect Biochemistry and Physiology
https://www.readbyqxmd.com/read/29111188/food-intake-regulation-by-leptin-mechanisms-mediating-gluconeogenesis-and-energy-expenditure
#14
REVIEW
Zulfia Hussain, Junaid Ali Khan
Regulation of blood glucose levels and body fat is critical for survival. Leptin circulates freely in blood and controls body weight and food intake mainly through hypothalamic receptors and regulates glucose metabolism in the liver both directly through leptin receptors and indirectly via the hypothalamic receptors of central nervous system. Leptin affects food intake regulation and eventually glucose metabolism, lipometabolism, endocrine and immune functions, reproductive function, adipose tissue metabolism and energy expenditure...
October 2017: Asian Pacific Journal of Tropical Medicine
https://www.readbyqxmd.com/read/29109794/ginsenoside-rg1-inhibits-glucagon-induced-hepatic-gluconeogenesis-through-akt-foxo1-interaction
#15
Qun Liu, Fei-Ge Zhang, Wen-Song Zhang, An Pan, Yi-Lin Yang, Jin-Feng Liu, Ping Li, Bao-Lin Liu, Lian-Wen Qi
Rationale: Glucagon is involved in hepatic gluconeogenesis, playing a key role in type 2 diabetes. Ginsenosides are reported to have antidiabetic activities. Ginsenoside Rg1 is a major propanaxatriol-type saponin in ginseng. This study aims to investigate the regulatory effects of Rg1 on glucagon-induced hepatic glucose production. Methods: The effects of Rg1 were investigated in high-fat-diet (HFD)-fed mice and glucagon-challenged C57BL/6J mice. Glucose metabolism was evaluated by oral glucose tolerance test and pyruvate tolerance test...
2017: Theranostics
https://www.readbyqxmd.com/read/29107687/mir-150-deficiency-ameliorated-hepatosteatosis-and-insulin-resistance-in-nonalcoholic-fatty-liver-disease-via-targeting-casp8-and-fadd-like-apoptosis-regulator
#16
Baozhong Zhuge, Guohong Li
The prevalence of Non-alcoholic fatty liver diseases (NAFLD) increased rapidly in the world. However, the pathogenesis of is still unclear. Hepatic steatosis and insulin resistance are considered to be central to the pathophysiology of NAFLD. MicroRNAs are short non-coding RNAs and has been reported to be involved in pathogenesis of NAFLD and related metabolic diseases. Here, we investigated the mechanisms by which miR-150 regulate hepatic steatosis and insulin resistance in high fat diet (HFD) induced NAFLD model...
October 28, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/29107505/system-wide-benefits-of-intermeal-fasting-by-autophagy
#17
Nuria Martinez-Lopez, Elena Tarabra, Miriam Toledo, Marina Garcia-Macia, Srabani Sahu, Luisa Coletto, Ana Batista-Gonzalez, Nir Barzilai, Jeffrey E Pessin, Gary J Schwartz, Sander Kersten, Rajat Singh
Autophagy failure is associated with metabolic insufficiency. Although caloric restriction (CR) extends healthspan, its adherence in humans is poor. We established an isocaloric twice-a-day (ITAD) feeding model wherein ITAD-fed mice consume the same food amount as ad libitum controls but at two short windows early and late in the diurnal cycle. We hypothesized that ITAD feeding will provide two intervals of intermeal fasting per circadian period and induce autophagy. We show that ITAD feeding modifies circadian autophagy and glucose/lipid metabolism that correlate with feeding-driven changes in circulating insulin...
October 24, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/29107293/the-mitochondrial-pyruvate-carrier-mediates-high-fat-diet-induced-increases-in-hepatic-tca-cycle-capacity
#18
Adam J Rauckhorst, Lawrence R Gray, Ryan D Sheldon, Xiaorong Fu, Alvin D Pewa, Charlotte R Feddersen, Adam J Dupuy, Katherine N Gibson-Corley, James E Cox, Shawn C Burgess, Eric B Taylor
OBJECTIVE: Excessive hepatic gluconeogenesis is a defining feature of type 2 diabetes (T2D). Most gluconeogenic flux is routed through mitochondria. The mitochondrial pyruvate carrier (MPC) transports pyruvate from the cytosol into the mitochondrial matrix, thereby gating pyruvate-driven gluconeogenesis. Disruption of the hepatocyte MPC attenuates hyperglycemia in mice during high fat diet (HFD)-induced obesity but exerts minimal effects on glycemia in normal chow diet (NCD)-fed conditions...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29107283/acute-activation-of-glp-1-expressing-neurons-promotes-glucose-homeostasis-and-insulin-sensitivity
#19
Xuemei Shi, Shaji Chacko, Feng Li, Depei Li, Douglas Burrin, Lawrence Chan, Xinfu Guan
OBJECTIVE: Glucagon-like peptides are co-released from enteroendocrine L cells in the gut and preproglucagon (PPG) neurons in the brainstem. PPG-derived GLP-1/2 are probably key neuroendocrine signals for the control of energy balance and glucose homeostasis. The objective of this study was to determine whether activation of PPG neurons per se modulates glucose homeostasis and insulin sensitivity in vivo. METHODS: We generated glucagon (Gcg) promoter-driven Cre transgenic mice and injected excitatory hM3Dq-mCherry AAV into their brainstem NTS...
November 2017: Molecular Metabolism
https://www.readbyqxmd.com/read/29106945/activation-of-the-sting-irf3-pathway-promotes-hepatocyte-inflammation-apoptosis-and-induces-metabolic-disorders-in-nonalcoholic-fatty-liver-disease
#20
J T Qiao, C Cui, L Qing, L S Wang, T Y He, F Yan, F Q Liu, Y H Shen, X G Hou, L Chen
BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a common result of obesity and metabolic syndrome. Hepatocyte injury and metabolic disorders are hallmarks of NAFLD. Stimulator of interferon genes (STING) and its downstream factor interferon regulatory factor 3 (IRF3) trigger inflammatory reaction in response to the presence of cytosolic DNA. STING has recently been shown to play an important role in early alcoholic liver disease. However, little is known about the role of STING-IRF3 pathway in hepatocyte injury...
October 26, 2017: Metabolism: Clinical and Experimental
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