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2 edition of Studies in vivo and in vitro on the development of rat hepatic glucokinase. found in the catalog.

Studies in vivo and in vitro on the development of rat hepatic glucokinase.

Michael Wakelam

Studies in vivo and in vitro on the development of rat hepatic glucokinase.

by Michael Wakelam

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  • 31 Currently reading

Published by University of Birmingham in Birmingham .
Written in English


Edition Notes

Thesis (Ph.D) - University of Birmingham, Dept of Biochemistry.

ID Numbers
Open LibraryOL13737822M

In vitro hepatocyte models represent very useful systems in both fundamental research and various application areas. Primary hepatocytes appear as the closest model for the liver in vivo. However.   Hepatic Oval Cell Isolation and in Vitro Cultures.. Activation of hepatic oval cells was achieved in vivo by using procedures as described by Petersen et al. with the 2-acetylamino-fluorene/hepatic injury ted oval cells were isolated from the intact treated rat livers by using the two-step collagenase perfusion protocol of Seglen (), then purified by cell sorting for the Thy

  Here, we describe the key studies in the TTP preclinical and clinical development program, including the design and results of the AGATA (Add Glucokinase Activator to Target A1c) trial, a phase 2b trial of TTP in patients with type 2 diabetes, and its impact on the physiological regulation of glucose metabolism. Title:Application of Model-Based Approaches to Evaluate Hepatic Transporter-Mediated Drug Clearance: In vitro, In vivo, and In vitro-In vivo Extrapolation VOLUME: 17 ISSUE: 5 Author(s):Zhihao Liu and Kexin Liu Affiliation:Department of Clinical Pharmacology, College of Pharmacy, Dalian Medical University, 9 West Section, Lvshun South Road, Lvshunkou District, Dalian , China.

In vitro experiments did not show stimulation of cultured CC cells by portal or systemic serum withdrawn 24 hours or 14 days after hepatectomy as compared with sera obtained after sham operation. Co‐cultures of CC cells and hepatocytes (in ratios of or ) demonstrated a higher 3 H‐thymidine incorporation than was the case in. Ball K, Bouzom F, Scherrmann JM et al () Development of a physiologically based pharmacokinetic model for the rat central nervous system and determination of an in vitro-in vivo scaling methodology for the blood-brain barrier permeability of two transporter substrates, morphine and oxycodone.


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Studies in vivo and in vitro on the development of rat hepatic glucokinase by Michael Wakelam Download PDF EPUB FB2

Clin Pharmacokinet. Oct;57(10) doi: /sz. Development of a Physiologically Based Pharmacokinetic Model for Sinogliatin, a First-in-Class Glucokinase Activator, by Integrating Allometric Scaling, In Vitro to In Vivo Exploration and Steady-State Concentration-Mean Residence Time Methods: Mechanistic Understanding of its by: 4.

Studies in vivo and in vitro on the development of rat hepatic glucokinase. (Thesis) Wakelam MJO. Publisher: University of Birmingham [] Metadata Source: The British Library Type: Thesis. Abstract. No abstract supplied. Menu. Formats. Abstract. EThOS. About. About Europe PMC Author: Wakelam Mjo.

Studies in vivo and in vitro on the development of rat hepatic glucokinase. By M Wakelam. Abstract. SIGLEAvailable from British Library Document Supply Centre- DSC:D/81 / BLDSC - British Library Document Supply CentreGBUnited KingdoAuthor: M Wakelam.

Studies in vivo and in vitro on the development of rat hepatic glucokinase Author: Wakelam, M. ISNI: Awarding Body: University of Birmingham Current Institution: University of Birmingham Date of Award: Availability of Full Text.

In vivo and in vitro studies are reported that demonstrate the use of liver and intestinal slices as an in vitro model to predict potential CYP induction in vivo. Rat liver slices and intestinal slices were incubated, for 24 h and 6 h, respectively, with β-naphthoflavone (βNF), phenobarbital (PB) or dexamethasone (DEX).Cited by: Performing early in vitro ADME screening and in vivo PK studies to better understand the Absorption, Distribution, Metabolism, Excretion (ADME) and Pharmacokinetics (PK) properties of your compounds is essential for selecting candidates with desirable profiles for later stages of drug development.

Specializing in nonclinical ADME and Toxicology Services for over 15 years, Eurofins Discovery. Hepatic glycogen synthesis plays a critical role in maintaining normal glucose homeostasis; however, the rate-controlling step regulating this process is unknown.

Applying metabolic control analysis in vivo, we show that the regulation of insulin-stimulated hepatic glycogen synthesis under both normal and pathophysiological conditions of fatty liver-associated hepatic insulin.

Aim: The objective of this study was to develop a physiologically based pharmacokinetic (PBPK) model for sinogliatin (HMS, dorzagliatin) by integrating allometric scaling (AS), in vitro to in vivo exploration (IVIVE), and steady-state concentration-mean residence time (C ss-MRT) methods and to provide mechanistic insight into its pharmacokinetic properties in humans.

An In vivo pharmacokinetic study in db/db mice treated with BBR was performed. The mean serum and liver concentration-time curves are shown in Fig. 4A,B.

The maximum concentration (C max) of serum BBR was ngmL −1, the time to reach C max (T max) was 2 h and the area under the concentration-time curve (AUC 0-t) was ngh. Several recommendations have been made to compare the in vitro and in vivo studies, which need to be considered while developing and validating any in vitro platform ().

Several design parameters, such as stability, CYP activity, metabolite formation and reaction velocities should be validated for any in vitro platform (40, 43).

The role of insulin, glucocorticoids, and hepatic cyclic AMP in the regulation of the activity of rat liver glucokinase was investigated in following results were found: (i) Refeeding of starved rats with glucose or injection of diabetic animals with insulin resulted in a dramatic increase in the concentration of serum insulin and a decrease in the concentration of hepatic cyclic AMP.

Clearly, improvement of in vitro hepatic differentiation protocols and a better understanding of the molecular mechanisms underlying liver development are needed. Therefore, it can be speculated that there are certain specific TFs, or a combination of TFs, that can facilitate the differentiation of ESCs.

It is also important to ensure that the formulations used are discussed with Pharmaceutical Development (see Chapter 16), and are appropriate for safety and early clinical development studies. If in vitro and in vivo (rat and dog) assessments of f a do not agree, the risk of an inaccurate estimate of absorption in man will increase.

RESEARCH. AND. DISCOVERY. CLINICAL DEVELOPMENT. PRE. CLINICAL. DEVELOPMENT. P h a s e 1. P h a s e 2. P h a s e 3. POST. APPROVAL. PHASE. Initial IND (first in human) NDA/BLA. Rat hepatoma FaO cells treated with a mixture of free fatty acids (FFAs) (O/P) were used as an in vitro model of hepatic steatosis.

In parallel, a high-fat diet (HFD) animal model was also established. In vitro and in vivo studies revealed that both chickpea accessions showed a significant antioxidant ability. Bontemps F, Hue L, Hers HG. Phosphorylation of glucose in isolated rat hepatocytes. Sigmoidal kinetics explained by the activity of glucokinase alone.

Biochem J. Aug 15; (2)– [PMC free article] [Google Scholar] Walker DG, Holland G. The development of hepatic glucokinase in the neonatal rat. Biochem J. Dec; 97 (3)– A group of enzymes that catalyzes the conversion of ATP and D-glucose to ADP and D-glucose 6-phosphate.

They are found in invertebrates and | Explore the latest full-text research PDFs. Yeoh GC, Edkins E, Mackenzi K, Fuller S, Mercer JF, Dahl HH The development of phenylalanine hydroxylase in rat liver; in vivo, and in vitro studies utilizing fetal hepatocyte cultures.

Case studies are also provided to illustrate how the in vitro assays can help to derisk preclinical in vivo toxicity findings and to better predict clinical human liver toxicity outcomes. The objective of this study was to evaluate the ability of anthocyanins (ANC) present in purple corn to enhance insulin secretion and hepatic glucose uptake in pancreatic cells and hepatocytes, through activation of the free fatty acid receptor-1 (FFAR1) and glucokinase (GK), respectively.

Using a dual-layer cell culture with Caco-2 cells, INS-1E or HepG2 cells were treated with an anthocyanin. The enzyme glucokinase (GK) plays a central role in glucose homeostasis. Hepatic GK activity is acutely controlled by the action of the GK regulatory protein (GKRP).

In vitro evidence suggests that GKRP reversibly binds to GK and inhibits its activity; however, less is known about the in vivo function of GKRP. To further explore the physiological role of GKRP in vivo, we used an E1/E2a/E3.The mutagenic potential of Cyprodinil was investigated in five independent studies that covered different endpoints in eukaryotes and prokaryotes in vivo and in vitro.

No induction of back mutations was noted in four strains of Salmonella typhimurium (TA 98, TATA .Thermoresponsive Poly(glycidyl ether) Brush Coatings on Various Tissue Culture Substrates—How Block Copolymer Design and Substrate Material Govern Self-Assembly and Phase Transition.