Reduced gluconeogenesis and lactate clearance in Huntington's disease

Knud Josefsen; Signe M B Nielsen; André Campos; Thomas Seifert; Lis Hasholt; Jørgen E Nielsen; Anne Nørremølle; Niels H Skotte; Niels H Secher; Bjørn Quistorff

doi:10.1016/j.nbd.2010.08.009

Reduced gluconeogenesis and lactate clearance in Huntington's disease

Knud Josefsen, Signe M B Nielsen, André Campos, Thomas Seifert, Lis Hasholt, Jørgen E Nielsen, Anne Nørremølle, Niels H Skotte, Niels H Secher, Bjørn Quistorff

26 Citationer (Scopus)

Abstract

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±0.2mM, P<2×10^-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.

Originalsprog	Engelsk
Tidsskrift	Neurobiology of Disease
Vol/bind	40
Udgave nummer	3
Sider (fra-til)	656-62
Antal sider	7
ISSN	0969-9961
DOI	https://doi.org/10.1016/j.nbd.2010.08.009
Status	Udgivet - 1 dec. 2010

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10.1016/j.nbd.2010.08.009

Citationsformater

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title = "Reduced gluconeogenesis and lactate clearance in Huntington's disease",

abstract = "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±0.2mM, P<2×10-6). 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.",

keywords = "Animals, Blood Glucose, Blotting, Western, Brain, Exercise, Exercise Test, Female, Gluconeogenesis, Humans, Huntington Disease, Lactic Acid, Liver, Liver Function Tests, Male, Mice, Mice, Transgenic, Middle Aged, Reverse Transcriptase Polymerase Chain Reaction",

author = "Knud Josefsen and Nielsen, {Signe M B} and Andr{\'e} Campos and Thomas Seifert and Lis Hasholt and Nielsen, {J{\o}rgen E} and Anne N{\o}rrem{\o}lle and Skotte, {Niels H} and Secher, {Niels H} and Bj{\o}rn Quistorff",

year = "2010",

month = dec,

day = "1",

doi = "10.1016/j.nbd.2010.08.009",

language = "English",

volume = "40",

pages = "656--62",

journal = "Neurobiology of Disease",

issn = "0969-9961",

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TY - JOUR

T1 - Reduced gluconeogenesis and lactate clearance in Huntington's disease

AU - Josefsen, Knud

AU - Nielsen, Signe M B

AU - Campos, André

AU - Seifert, Thomas

AU - Hasholt, Lis

AU - Nielsen, Jørgen E

AU - Nørremølle, Anne

AU - Skotte, Niels H

AU - Secher, Niels H

AU - Quistorff, Bjørn

PY - 2010/12/1

Y1 - 2010/12/1

N2 - 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±0.2mM, P<2×10-6). 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.

AB - 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±0.2mM, P<2×10-6). 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.

KW - Animals

KW - Blood Glucose

KW - Blotting, Western

KW - Brain

KW - Exercise

KW - Exercise Test

KW - Female

KW - Gluconeogenesis

KW - Humans

KW - Huntington Disease

KW - Lactic Acid

KW - Liver

KW - Liver Function Tests

KW - Male

KW - Mice

KW - Mice, Transgenic

KW - Middle Aged

KW - Reverse Transcriptase Polymerase Chain Reaction

U2 - 10.1016/j.nbd.2010.08.009

DO - 10.1016/j.nbd.2010.08.009

M3 - Journal article

C2 - 20727971

SN - 0969-9961

VL - 40

SP - 656

EP - 662

JO - Neurobiology of Disease

JF - Neurobiology of Disease

IS - 3

ER -

Reduced gluconeogenesis and lactate clearance in Huntington's disease

Abstract

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