Reduced gluconeogenesis and lactate clearance in Huntington's disease

被引：33
作者：
Josefsen, Knud [1 ]
Nielsen, Signe M. B. [2 ]
Campos, Andre
Seifert, Thomas [4 ]
Hasholt, Lis [2 ]
Nielsen, Jorgen E. [2 ,3 ]
Norremolle, Anne [2 ]
Skotte, Niels H. [2 ]
Secher, Niels H. [4 ]
Quistorff, Bjorn [5 ]
机构：
[1] Rigshosp, Bartholin Inst, Copenhagen Bioctr, DK-2200 Copenhagen N, Denmark
[2] Univ Copenhagen, Dept Cellular & Mol Med, Neurogenet Sect, Copenhagen, Denmark
[3] Rigshosp, Memory Disorders Res Grp, Neurogenet Clin, DK-2200 Copenhagen N, Denmark
[4] Rigshosp, Dept Anaesthesia, Copenhagen Muscle Res Ctr, DK-2200 Copenhagen N, Denmark
[5] Univ Copenhagen, Dept Biomed Sci, Nucl Magnet Resonance Ctr, Copenhagen, Denmark
来源：
NEUROBIOLOGY OF DISEASE | 2010年 / 40卷 / 03期
关键词：
Glucose; Exercise; Liver perfusion; Gluconeogenesis; Brain metabolism; TRANSGENIC MOUSE MODEL; PITUITARY-ADRENAL AXIS; EXPANDED CAG REPEAT; HEPATIC GLUCONEOGENESIS; ENERGY-METABOLISM; MAXIMAL EXERCISE; GENE; MUSCLE; BRAIN; DYSREGULATION;
D O I：
10.1016/j.nbd.2010.08.009
中图分类号：
Q189 [神经科学];
学科分类号：
071006 ;
摘要：
We studied systemic and brain glucose and lactate metabolism in Huntington's disease (HD) patients in response to ergometer cycling. Following termination of exercise, blood glucose increased abruptly in control subjects, but no peak was seen in any of the HD patients (2.0 +/- 0.5 vs. 0.0 +/- 0.2 mM, P<2 x 10(-6)). No difference was seen in brain metabolism parameters. Reduced hepatic glucose output in the HD mouse model R6/2 following a lactate challenge, combined with reduced phosphoenolpyruvate carboxykinase and increased pyruvate kinase activity in the mouse liver suggest a reduced capacity for gluconeogenesis in HD, possibly contributing to the clinical symptoms of HD. We propose that blood glucose concentration in the recovery from exercise can be applied as a liver function test in HD patients. (C) 2010 Elsevier Inc. All rights reserved.
引用
收藏
页码：656 / 662
页数：7
相关论文
共 61 条
  • [51] CENTRAL AND REGIONAL CIRCULATORY EFFECTS OF ADDING ARM EXERCISE TO LEG EXERCISE
    SECHER, NH
    CLAUSEN, JP
    KLAUSEN, K
    NOER, I
    TRAPJENSEN, J
    [J]. ACTA PHYSIOLOGICA SCANDINAVICA, 1977, 100 (03): : 288 - 297
  • [52] Supply and demand in cerebral energy metabolism: the role of nutrient transporters
    Simpson, Ian A.
    Carruthers, Anthony
    Vannucci, Susan J.
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2007, 27 (11) : 1766 - 1791
  • [53] Impact of flow rate on lactate uptake and gluconeogenesis in glucagon-stimulated perfused livers
    Sumida, KD
    Urdiales, JH
    Donovan, CM
    [J]. AMERICAN JOURNAL OF PHYSIOLOGY-ENDOCRINOLOGY AND METABOLISM, 2006, 290 (01): : E185 - E191
  • [54] Striatal specificity of gene expression dysregulation in Huntington's disease
    Thomas, Elizabeth A.
    [J]. JOURNAL OF NEUROSCIENCE RESEARCH, 2006, 84 (06) : 1151 - 1164
  • [55] Metabolic characterization of the R6/2 transgenic mouse model of Huntington's disease by high-resolution MAS 1H NMR spectroscopy
    Tsang, TA
    Woodman, B
    McLoughlin, GA
    Griffin, JL
    Tabrizi, SJ
    Bates, GP
    Holmes, E
    [J]. JOURNAL OF PROTEOME RESEARCH, 2006, 5 (03) : 483 - 492
  • [56] Blood lactate is an important energy source for the human brain
    van Hall, Gerrit
    Stromstad, Morten
    Rasmussen, Peter
    Jans, Ole
    Zaar, Morten
    Gam, Christian
    Quistorff, Bjorn
    Secher, Niels H.
    Nielsen, Henning B.
    [J]. JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM, 2009, 29 (06) : 1121 - 1129
  • [57] Testicular degeneration in Huntington disease
    Van Raamsdonk, Jeremy M.
    Murphy, Zoe
    Selva, David M.
    Hamidizadeh, Reza
    Pearson, Jacqueline
    Petersen, Asa
    Bjorkqvist, Maria
    Muir, Cameron
    Mackenzie, Ian R.
    Hammond, Geoffrey L.
    Vogl, A. Wayne
    Hayden, Michael R.
    Leavitt, Blair R.
    [J]. NEUROBIOLOGY OF DISEASE, 2007, 26 (03) : 512 - 520
  • [58] Thermoregulatory and metabolic defects in Huntington's disease transgenic mice implicate PGC-1α in Huntington's disease neurodegeneration
    Weydt, Patrick
    Pineda, Victor V.
    Torrence, Anne E.
    Libby, Randell T.
    Satterfield, Terrence F.
    Lazarowski, Eduardo R.
    Gilbert, Merle L.
    Morton, Gregory J.
    Bammler, Theodor K.
    Strand, Andrew D.
    Cui, Libin
    Beyer, Richard P.
    Easley, Courtney N.
    Smith, Annette C.
    Krainc, Dimitri
    Luquet, Serge
    Sweet, Ian R.
    Schwartz, Michael W.
    La Spada, Albert R.
    [J]. CELL METABOLISM, 2006, 4 (05) : 349 - 362
  • [59] Aspects of the Control of Phosphoenolpyruvate Carboxykinase Gene Transcription
    Yang, Jianqi
    Reshef, Lea
    Cassuto, Hanoch
    Aleman, Gabriela
    Hanson, Richard W.
    [J]. JOURNAL OF BIOLOGICAL CHEMISTRY, 2009, 284 (40) : 27031 - 27035
  • [60] Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1
    Yoon, JC
    Puigserver, P
    Chen, GX
    Donovan, J
    Wu, ZD
    Rhee, J
    Adelmant, G
    Stafford, J
    Kahn, CR
    Granner, DK
    Newgard, CB
    Spiegelman, BM
    [J]. NATURE, 2001, 413 (6852) : 131 - 138
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