• These proteins regulate glucose and lipid metabolism in the liver but also in the skeletal muscle or the adipose tissue. (wikipedia.org)
  • Dr. Nadja Lehwald-Tywuschik from the University Hospital Düsseldorf with the project "Wnt / β-catenin signaling regulate lipid metabolism in the steatotic liver" for a research stay at Stanford University, Department of Surgery, Stanford, CA, USA. (uni-ulm.de)
  • Saltiel, A.R. & Kahn, C.R. Insulin signalling and the regulation of glucose and lipid metabolism. (nature.com)
  • It is generally accepted that dysregulated liver lipid metabolism and inflammation are two crucial mechanisms involved in NAFLD development, although the transcription network and the related epigenome remodeling events remain largely unclarified. (ki.se)
  • Body Composition and lipid metabolism are not inherently good nor bad, but rather an unstoppable force that must be comprehended and redirected for the treatment of various pathologies. (frontiersin.org)
  • MANNHEIM, Germany - A novel drug that targets production of a liver protein involved in lipid metabolism appears to markedly reduce low-density lipoprotein (LDL) cholesterol levels for patients with homozygous familial hypercholesterolemia (HoFH), suggest results from the phase 2 GATEWAY trial. (medscape.com)
  • Thank you for sharing this Drug Metabolism & Disposition article. (aspetjournals.org)
  • Message Body (Your Name) thought you would be interested in this article in Drug Metabolism & Disposition. (aspetjournals.org)
  • Species difference in drug metabolism and drug toxicity is a well-established phenomenon. (eurekaselect.com)
  • The ECCCS represents a powerful tool to anticipate the DDI potential of victim drugs based on in vitro drug metabolism and transport data. (degruyter.com)
  • The authors wish to acknowledge the many Novartis Drug Metabolism and Pharmacokinetic scientists of Basel, Switzerland, who have supported this work. (degruyter.com)
  • 6. Camenisch G, Umehara K. Predicting human hepatic clearance from in vitro drug metabolism and transport data: a scientific and pharmaceutical perspective for assessing drug-drug interactions. (degruyter.com)
  • The liver is the major site of drug metabolism and excretion. (helsinki.fi)
  • Successful cryopreservation of human hepatocytes to retain high viability, metabolic capacity, as well as the ability to be cultured allow routine application of this relevant experimental system. (eurekaselect.com)
  • This review summarizes the latest findings on human hepatocytes isolation, cryopreservation, culturing, as well as application in the evaluation of metabolic stability, metabolite profiling, hepatic uptake and efflux, metabolic drug-drug interactions, and drug toxicity. (eurekaselect.com)
  • Three iterations of bioreactor design and optimization produced a perfusion system that could enable direct oxygenation, accommodate high density hepatocyte seeding (8x10-7 to 1x10-8 cells), ensure adequate mass transfer and induce sustainable metabolic outputs for a least 7 days at a flow rate of 10 ml/min. (wayne.edu)
  • In total the results show that the experimental measures conducted in this study enhanced hepatocyte metabolic performance, viability and morphological appearance. (wayne.edu)
  • Hepatokines are hormone-like proteins secreted by hepatocytes, and many have been associated with extra-hepatic metabolic regulation. (wikipedia.org)
  • It has been stated that, "hepatocytes secrete more than 560 types of hepatokines, many of which regulate metabolic and inflammatory diseases in the liver or at distant organs through circulation delivery. (wikipedia.org)
  • In enterocyte microsomes, the CYP metabolic efficiency for metabolism to the oxon metabolites was approximately 28-fold greater for CPF than DZN. (cdc.gov)
  • Our research aims to understand how metabolic stress signals reprogram hepatocytes and immune cells to promote the progression of these diseases. (ki.se)
  • They are accompanied with a range of metabolic and endocrine abnormalities involved in the pathophysiology of pancreatic cancer, including fatty acid metabolism disorder, insulin resistance, inflammatory processes, and disorders in hormonal changes and pancreatic steatosis. (frontiersin.org)
  • While it is well-established that obesity generates cellular and molecular stress leading to abnormal functioning of many cellular processes, the mechanisms remain incompletely understood," said senior author Gökhan S. Hotamisligil , chair of the Department of Molecular Metabolism and the Sabri Ülker Center for Nutrient, Genetic, and Metabolic Research . (harvard.edu)
  • Hepatocytes (liver parenchymal cells) perform the liver's metabolic functions: Formation and excretion of bile as a component of bilirubin metabolism. (msdmanuals.com)
  • However, it remained uncertain whether the effects on glucose production were due to direct effects on hepatocytes, involved central or portal vein-mediated actions, or were mediated by insulin secretion. (nih.gov)
  • These findings support direct insulinomimetic actions of the GLP-1 metabolite on gluconeogenesis in hepatocytes that are independent of insulin action and the GLP-1 receptor, and suggest that GLP-1 (9-36) amide-based peptides might present a novel therapy for the treatment of excessive hepatic glucose production in individuals with insulin-resistant diabetes. (nih.gov)
  • Insulin resistance (IR) in hepatocytes endangers human health, and frequently results in the development of non-alcoholic fatty liver disease (NAFLD). (biomedcentral.com)
  • Application of the METTL3 methyltransferase inhibitor, STM2457, increased the level of insulin sensitivity in hepatocytes. (biomedcentral.com)
  • These findings offer unique insights into the role that METTL3-mediated m 6 A modifications of CYP2B6 play in regulating insulin sensitivity in hepatocytes and provide key information for the development of strategies to induce m 6 A modifications for the clinical treatment of NAFLD. (biomedcentral.com)
  • These results are inconsistent with the canonical model of hepatic metabolism in which Akt is an obligate intermediate for proper insulin signaling. (nature.com)
  • Figure 6: Insulin-regulated expression of Foxo1 target genes was compromised in the Foxo1 −/− and TLKO primary hepatocytes. (nature.com)
  • Loss of insulin signaling in hepatocytes leads to severe insulin resistance and progressive hepatic dysfunction. (nature.com)
  • Because of its influence on carbohydrate metabolism and, at the same time, anti-catabolic effects, the misuse of the peptide hormone insulin and its synthetic analogs is prohibited in sports at all times according to the regulations of the World Anti-Doping Agency (WADA). (researchgate.net)
  • Inositol polyphosphate multikinase modulates free fatty acids-induced insulin resistance in primary mouse hepatocytes. (bvsalud.org)
  • This study aimed to determine whether inositol polyphosphate multikinase (IPMK), a regulator of insulin signaling, plays any role in FFA-induced insulin resistance in primary hepatocytes . (bvsalud.org)
  • SigmaPCBs was inversely associated with insulin resistance/production, leptin, and hepatocyte apoptosis, while other adipocytokines were increased. (cdc.gov)
  • The purpose of this study was to investigate the hepatic uptake mechanisms of [ 3 H]digoxin using sandwich-cultured human hepatocytes (SCHH) and transporter-expressing cells. (aspetjournals.org)
  • The latest advances include the use of human hepatocytes to evaluate hepatic uptake, metabolism, efflux and toxicity. (eurekaselect.com)
  • The use of the novel integrated discrete multiple organ coculture (IdMOC) system allows the evaluation of the role of hepatic metabolism on nonhepatic toxicity. (eurekaselect.com)
  • In vitro rat hepatic and intestinal metabolism of the organophosphate pesticides chlorpyrifos and diazinon. (cdc.gov)
  • This study evaluated the role intestinal and hepatic metabolism may play in both the activation and detoxification of CPF and DZN in Sprague-Dawley rats. (cdc.gov)
  • Through the cgeneration of novel conditional Hfe knock-out lines (for example in hematopoietic tissues) and respective cells, we will examine how impaired extra-hepatic Hfe functions cause cell/tissue/organ-specific iron imbalances and possibly identify novel, so far unrecognised, features of Hfe beyond the regulation of iron metabolism. (uni-ulm.de)
  • We applied a recently developed in vitro-in vivo extrapolation method, including hepatic metabolism and transport processes, herein referred to as the Extended Clearance Concept Classification System (ECCCS). (degruyter.com)
  • To circumvent the hepatic functional redundancy of the Foxa proteins, we used the T-77 transgenic (TG) mouse line in which the -3-kb transthyretin (TTR) promoter functioned to increase hepatocyte expression of the Foxa2 cDNA. (duke.edu)
  • One preclinical approach to evaluate human drug properties, especially ADMET (absorption, disposition, metabolism, elimination, and toxicity) properties, is to apply in vitro experimental systems with relevant human properties. (eurekaselect.com)
  • Hematopoietic Stem Cell and Leukaemic Stem Cell environmental stress responses (In vitro biomimicry of hypoxia, normoxia, hypothermia, hyperthermia, hypoglycemia and hyperglycemia): Effect on cellular growth, cell cycle distribution, apoptosis and cellular metabolism. (imperial.ac.uk)
  • In vitro Modulation of the LPS-Induced Proinflammatory Profile of Hepatocytes and Macrophages- Approaches for Intervention in Obesity? (frontiersin.org)
  • Therefore, the aim of this study was to expose macrophages and hepatocytes to LPS and to gauge preventative or curative effects of Vitamin D 3 and docosahexaenoic acid (DHA) in vitro while quantifying a detrimental effect of FFA, a mixture of oleic acid and palmitic acid. (frontiersin.org)
  • Here we show that GLP-1 (9-36) amide directly suppresses glucose production in isolated mouse hepatocytes ex vivo independent of the GLP-1 receptor. (nih.gov)
  • Here, we show that excess FFA decreased IPMK expression, and blockade of IPMK decrease attenuated the FFA-induced suppression of protein kinase B (Akt) phosphorylation in primary mouse hepatocytes (PMH). (bvsalud.org)
  • The present study investigated whether streptozotocin-diabetes could be reversed in FRG mice in which chimeric mouse-human livers can readily be established and, in addition, whether pancreatic transdifferentiation occurred in the engrafted human hepatocytes. (nih.gov)
  • To study this hypothesis in more mechanistic detail, we have established a system of primary hepatocytes isolated from 90 day old mice fed one of 3 diets from weaning as a lipid-relevant perturbagen: high fat (65% kcal/fat), medium fat (45% kcal/fat) and normal chow (10% kcal/fat). (bmj.com)
  • Hepatocyte-specific loss of GPS2 in mice reduces non-alcoholic steatohepatitis via activation of PPARα. (ki.se)
  • The postnatal TG mice displayed significant reduction in serum glucose levels and in hepatocyte glycogen storage without increased serum levels of ketone bodies and free fatty acid suggesting that they are not undergoing a starvation response. (duke.edu)
  • In conclusion, our model proposes that in response to reduction in hepatocyte glycogen storage, the TTR-Foxa2 TG mice survive by maintaining sufficient serum levels of glucose through gluconeogenesis using deaminated amino acids with dicarboxylate products of peroxisomal lipid beta-oxidation shuttled through the tricarboxylic acid cycle. (duke.edu)
  • Under conditions of over-nutrition this balance is disrupted, which promotes lipid accumulation in the hepatocytes to form a pathological phenotype of steatosis. (ki.se)
  • This syndrome is characterized by steatosis in hepatocytes and elevated serum levels of free fatty acids (FFAs) ( 1 ). (spandidos-publications.com)
  • Steatosis is the accumulation of fat in hepatocytes which can lead to an overall increase in liver size, so-called hepatomegaly. (frontiersin.org)
  • Scholars@Duke publication: Elevated hepatocyte levels of the Forkhead box A2 (HNF-3beta) transcription factor cause postnatal steatosis and mitochondrial damage. (duke.edu)
  • The potent inhibition of TASO oxidation by TA, coupled with the back-reduction of TASO and its futile redox cycling with TA may help explain phenomena previously interpreted as "saturation toxicokinetics" in the in vivo metabolism and toxicity of TA and TASO. (ku.edu)
  • These data show that human hepatocytes can be induced to undergo partial pancreatic transdifferentiation in vivo, indicating that the technology holds promise for the treatment of type 1 diabetes. (nih.gov)
  • Hepatokines have been described to be involved in the regulation of energy and nutrient metabolism by acting directly on the liver or on distal target tissues. (wikipedia.org)
  • Here, we investigated the role of the methyltransferase METTL3 in exacerbating IR in hepatocytes, mainly focusing on the regulation of m 6 A modifications in CYP2B6 . (biomedcentral.com)
  • RNAs harboring m 6 A modifications are involved in the regulation of metabolism of liver triglycerides (TGs). (biomedcentral.com)
  • Together, these data suggest that curcumin protects hepatocytes from HFFA-induced lipoapoptosis and mitochondrial dysfunction, which partially occurs through the regulation of mitochondrial biogenesis. (spandidos-publications.com)
  • The study evaluated the effect of microencapsulated hepatocytes after intraperitoneal transplantation of heptolenticular degeneration (HLD) of serum copper and copper metabolism in the liver. (uwi.edu)
  • This indicates that in microencapsulated hepatocytes intraperitoneal transplantation can significantly reduce the liver copper deposition of HLD rats. (uwi.edu)
  • Hepatocytes derived from iPS cells are suitable for transplantation into patients with liver insufficiency and for use in toxicity tests ( 2 ). (spandidos-publications.com)
  • To generate a suite of liver proteins adducted by TA metabolites for proteomic analysis, and to reduce the need for both animals and labeled compounds, we treated isolated hepatocytes directly with TA. (ku.edu)
  • The metabolism of MeIQx is composed of metabolites involved in the detoxification pathways (printed in green) and components of the bioactivation pathway (printed in orange and red). (peerj.com)
  • Transporters in the canalicular domain (apical) of the hepatocyte faclitate removal of drugs or metabolites from the cell interior. (helsinki.fi)
  • Metabolism and Toxicity of Thioacetamide and Thioacetamide S-Oxide in Rat Hepatocytes. (ku.edu)
  • The use of hepatocyte to evaluate the role of metabolism in drug toxicity represents a major advance in drug toxicity evaluation. (eurekaselect.com)
  • their toxicity is mediated through CYP metabolism to CPF-oxon and DZN-oxon, respectively. (cdc.gov)
  • Adiponutrin Variant M148 Causes Resistance to Starvation-Mediated Lipid Droplet Autophagy in Hepatocytes. (lu.se)
  • While the human liver microsomal system demonstrated rapid clearance by CYP enzymes, the hepatocyte incubations showed much slower clearance, possibly providing some insight into the long duration of carfentanils effects. (diva-portal.org)
  • Important products and enzymes in ornithine metabolism (see text for pathway detail). (medscape.com)
  • Transporters in the basolateral membrane of the hepatocyte facilitate drug entry and access to drug metabolizing enzymes. (helsinki.fi)
  • In this study, macrophages (J774) and hepatocytes (HepG2) were stimulated with lipopolysaccharide (LPS) from E. coli 0111: B4 and analyzed for modulation of this response when preconditioned or stimulated subsequent to LPS, with different doses of Vitamin D 3 or docosahexaenoic acid (DHA) over a time period of 1 and 5 days. (frontiersin.org)
  • The four CYP2C mRNAs were expressed in human livers and cultured primary hepatocytes, but only the CYP2C18 protein was not detected. (aspetjournals.org)
  • The expression and inducibility of four CYP2C genes, including CYP2C8 , - 2C9 , - 2C18 , and - 2C19 , was investigated in primary cultures of human hepatocytes. (aspetjournals.org)
  • In the current study, the role of CYP3A5 was quantified in the metabolism of vincristine with human cryopreserved hepatocytes. (aspetjournals.org)
  • Whereas human hepatocytes with predicted low CYP3A5 expression did not detectably metabolize vincristine, human hepatocytes with predicted high CYP3A5 expression metabolized vincristine to one primary metabolite, M1. (aspetjournals.org)
  • We conclude that genetically determined CYP3A5 expression in human cryopreserved hepatocytes plays a major role in vincristine metabolism. (aspetjournals.org)
  • No human carfentanil metabolism data are available. (diva-portal.org)
  • We incubated carfentanil with human hepatocytes for up to 1 h and analyzed samples on a Sciex 3200 QTRAP mass spectrometer to measure parent compound depletion and extrapolated that to represent intrinsic clearance. (diva-portal.org)
  • Pooled primary human hepatocytes were then incubated with carfentanil up to 6 h and analyzed for metabolite identification on a Sciex 5600+ TripleTOF (QTOF) high-resolution mass spectrometer. (diva-portal.org)
  • Engraftment of human hepatocytes was confirmed by measuring human albumin levels. (nih.gov)
  • Quantitative RT-PCR showed expression of human and mouse endocrine hormones and β-cell transcription factors, indicating partial pancreatic transdifferentiation of mouse and human hepatocytes. (nih.gov)
  • Nonfasting human C-peptide levels were significantly higher than mouse levels, suggesting that transdifferentiated human hepatocytes made a significant contribution to the reversal of diabetes. (nih.gov)
  • Human liver organoids are formed from the assembly of hepatocyte-like cells differentiated from iPS cells, human umbilical vascular endothelial cells and mesenchymal stem cells ( 9 ). (spandidos-publications.com)
  • Protocols for hepatocyte differentiation from iPS cells have been studied. (spandidos-publications.com)
  • After two days of culture in HSM, the expression levels of α-fetoprotein (AFP) and albumin, which are hepatocyte markers, were upregulated, suggesting that hepatocyte differentiation was initiated ( 19 ). (spandidos-publications.com)
  • The HSM was modified into a hepatocyte differentiation inducer (HDI). (spandidos-publications.com)
  • The improved understanding of the metabolism and covalent binding of TA and TASO facilitates the use of hepatocytes to prepare protein adducts for target protein identification. (ku.edu)
  • The drug, ARO-ANG3 (Arrowhead Pharmaceuticals), is a hepatocyte-targeted small interfering ribonucleic acid (siRNA) designed to silence expression of the angiopoietin-like protein 3 (ANGPTL3) gene. (medscape.com)
  • These effects on lipoprotein metabolism may be exerted through specific modulation of the expression of the LDL receptor and apolipoprotein B genes. (cambridge.org)
  • ANGPTL3 regulates lipoprotein metabolism by inhibiting lipoprotein and endothelial lipases. (medscape.com)
  • Curcumin treatment inhibited the lipoapoptosis, ROS production and ATP depletion elicited by HFFA in primary hepatocytes. (spandidos-publications.com)
  • A primary hepatocyte from an obese mouse, showing close interaction between the endoplasmic reticulum (red) and the mitochondria (green). (harvard.edu)
  • Our results demonstrate that (1) the detoxification pathway predominates, (2) the ratio between detoxification and bioactivation pathways is not linear and shows a maximum at 10 µM of MeIQx in hepatocyte cell models, and (3) CYP1A2 is a key enzyme in the system that regulates the balance between bioactivation and detoxification. (peerj.com)
  • Hepatokines, sometimes referred to as hepatocytes-derived cytokines have been shown to relate to non-alcoholic fatty liver disease. (wikipedia.org)
  • Our recent studies classified Hfe-hemochromatosis as a liver disease since the lack of Hfe in hepatocytes associated with impaired production of the liver iron hormone hepcidin, as observed in constitutive Hfe deficiency. (uni-ulm.de)
  • In this study we investigated the effects that convective and direct oxygenation had on hepatocyte functionality, morphology and viability while cultured in bulk 3D chitosan scaffolds and perfusion bioreactor systems. (wayne.edu)
  • On the other hand, TASO was highly toxic to isolated hepatocytes as indicated by LDH release, cellular morphology and vital staining with Hoechst 33342/propidium iodide. (ku.edu)
  • Before cellular metabolism can occur, a drug must first enter the hepatocyte. (helsinki.fi)
  • For each hepatocyte preparation, the rates of vincristine depletion and metabolite formation were quantified. (aspetjournals.org)
  • Significantly, we found that hepatocytes produce TA from TASO relatively efficiently by back-reduction. (ku.edu)
  • Non-transferrin-bound circulating iron is readily taken up by hepatocytes, where it promotes the formation of free radical oxygen species that cause cell injury. (medscape.com)
  • Not only did curcumin treatment increase mitochondrial DNA (mtDNA) copy number in hepatocytes, but it also increased levels of transcriptional factors that regulate mitochondrial biogenesis, including peroxisome proliferator-activated receptor-γ coactivator 1α (PGC1α), nuclear respiratory factor 1 (NRF1) and mitochondrial transcription factor A (Tfam). (spandidos-publications.com)
  • The Forkhead box (Fox) transcription factor Foxa2 (HNF-3beta) and related family members Foxa1 (HNF-3alpha) and Foxa3 (HNF-3gamma) act in concert with other hepatocyte nuclear factors (HNF) to coordinately regulate liver-specific gene expression. (duke.edu)
  • In addition, innovations pertaining to the Sustainable Development Goals and potential impacts of fatty acid metabolism subtypes are of specific importance, so long as they highlight general or distinct efforts and identify current gaps in the health impacts of various diseases such as pancreatic cancer and obesity, as well as strategies for addressing them. (frontiersin.org)
  • A macrophage-hepatocyte glucocroticoid receptor axis coordinates fasting ketogenesis. (uni-ulm.de)
  • Mbanu, Chijioke, "Oxygen Transport, Shear Stress, And Metabolism In Perfused Hepatocyte-Seeded Scaffolds With Radial Pore Architecture: Experimental And Computational Analyses" (2016). (wayne.edu)
  • The hepatocytes were genotyped for common CYP3A5 allelic variants ( CYP3A5 * 3 , CYP3A5 * 6 , and CYP3A5 * 7 ) to predict CYP3A5 expression. (aspetjournals.org)
  • Using a computational approach, we developed a numerical model for MeIQx metabolism in the liver that predicts the MeIQx biotransformation into detoxification or bioactivation pathways according to the concentration of MeIQx. (peerj.com)
  • 1998).Linkage and molecular scaning analysis of MODY 3/hepatocyte nuclear factor 1-alpha gene in typical familial type 2 diabetes: Evidence for novel mutation in exon 8 and 10. (scirp.org)
  • Analysis using dot blot and epitranscriptomic chips revealed that the m 6 A modification pattern of the transcriptome in high-fat diet (HFD)-induced fatty liver and free fatty acid (FFA)-induced fatty hepatocytes showed significant changes. (biomedcentral.com)
  • Reactive oxygen species (ROS) are produced as a result of aerobic metabolism and as by-products through numerous physiological and biochemical processes. (hindawi.com)
  • Therefore, this topic encourages novel research on the many facets of fatty acid metabolism and their effects on pancreatic cancer and other associated ailments. (frontiersin.org)