Probing Hepatic Glucose Metabolism via 13C NMR Spectroscopy in Perfused Livers-Applications to Drug Development

被引:1
|
作者
Miller, Corin O. [1 ]
Cao, Jin [1 ]
机构
[1] Merck & Co Inc, Dept Translat Imaging, Kenilworth, NJ 07033 USA
关键词
perfused liver; nuclear magnetic resonance spectroscopy; NMR; MRS; stable isotope; C-13 (carbon-13); glucose metabolism; glycogen metabolism; gluconeogenesis; lipid metabolism; de novo lipogenesis; fatty acid oxidation; FATTY-ACID OXIDATION; GLUCAGON RECEPTOR; INSULIN; GLUCONEOGENESIS; ANTAGONISTS; MECHANISMS; DISCOVERY; ACTIVATOR; PATHWAYS; FRUCTOSE;
D O I
10.3390/metabo11110712
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Despite being first published over 40 years ago, the combination of C-13 nuclear magnetic resonance spectroscopy (NMR) and the isolated perfused liver preparation remains a unique and relevant approach in investigating the effects of pharmacological interventions on hepatic metabolism. The use of intact, perfused livers maintains many metabolic reactions at their respective rates in vivo, while the use of C-13-labelled substrates in combination with C-13 NMR allows for a detailed study of specific pathways, as well as the design of robust assays which can be used to evaluate novel pharmacological agents. In this review article, we share some of the methods used to probe glucose metabolism, and highlight key findings and successes derived from the application of this specialized technique to the area of drug development for diabetes and related metabolic disorders.
引用
收藏
页数:14
相关论文
共 50 条
  • [11] Hepatic UDP-glucose 13C isotopomers from [U-13C]glucose:: A simple analysis by 13C NMR of urinary menthol glucuronide
    Mendes, Ana C.
    Caldeira, M. Madalena
    Silva, Claudia
    Burgess, Shawn C.
    Merritt, Matthew E.
    Gomes, Filipe
    Barosa, Cristina
    Delgado, Teresa C.
    Franco, Fatima
    Monteiro, Pedro
    Providencia, Luis
    Jones, John G.
    MAGNETIC RESONANCE IN MEDICINE, 2006, 56 (05) : 1121 - 1125
  • [12] An in vivo 13C NMR analysis of the anaerobic yeast metabolism of 1-13C-glucose
    Giles, BJ
    Matsche, Z
    Egeland, RD
    Reed, RA
    Morioka, SS
    Taber, RL
    JOURNAL OF CHEMICAL EDUCATION, 1999, 76 (11) : 1564 - 1566
  • [13] In vivo 1H-[13C]-NMR spectroscopy of cerebral metabolism
    de Graaf, RA
    Mason, GF
    Patel, AB
    Behar, KL
    Rothman, DL
    NMR IN BIOMEDICINE, 2003, 16 (6-7) : 339 - 357
  • [14] Probing Molecular Motion by Double-Quantum (13C,13C) Solid-State NMR Spectroscopy: Application to Ubiquitin
    Schneider, Robert
    Seidel, Karsten
    Etzkorn, Manuel
    Lange, Adam
    Becker, Stefan
    Baldus, Marc
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2010, 132 (01) : 223 - 233
  • [15] Investigating Cardiac Metabolism in the Isolated Perfused Mouse Heart with Hyperpolarized [1-13C]Pyruvate and 13C/31P NMR Spectroscopy
    Shaul, David
    Sapir, Gal
    Lev-Cohain, Naama
    Sosna, Jacob
    Gomori, J. Moshe
    Katz-Brull, Rachel
    JOVE-JOURNAL OF VISUALIZED EXPERIMENTS, 2023, (194):
  • [16] Cerebral metabolic compartmentation as revealed by 13C NMR analysis of [1-13C]glucose metabolism
    Aureli, T
    Di Cocco, ME
    Puccetti, C
    Ricciolini, R
    Capuani, G
    Calvani, M
    Conti, F
    NEUROCHEMISTRY: CELLULAR, MOLECULAR, AND CLINICAL ASPECTS, 1997, : 1065 - 1070
  • [17] 13C NMR study of the effects of leptin treatment on kinetics of hepatic intermediary metabolism
    Cohen, SM
    Werrmann, JG
    Tota, MR
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (13) : 7385 - 7390
  • [18] 13C NMR study of the effects of leptin treatment on kinetics of hepatic intermediary metabolism
    Cohen, SM
    Werrmann, JG
    Tota, MR
    FASEB JOURNAL, 1998, 12 (08): : A1380 - A1380
  • [19] Detection of [1,6-13C2]-glucose metabolism in rat brain by in vivo 1H[13C]-NMR spectroscopy
    de Graaf, RA
    Brown, PB
    Mason, GF
    Rothman, DL
    Behar, KL
    MAGNETIC RESONANCE IN MEDICINE, 2003, 49 (01) : 37 - 46
  • [20] Probing dynamics and conformational change of the GroEL-GroES complex by 13C NMR spectroscopy
    Nishida, Noritaka
    Motojima, Fumihiro
    Idota, Mayu
    Fujikawa, Hiroshi
    Yoshida, Masasuke
    Shimada, Ichio
    Kato, Koichi
    JOURNAL OF BIOCHEMISTRY, 2006, 140 (04): : 591 - 598