Reduced gluconeogenesis and lactate clearance in Huntington's disease.
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.
Josefsen
Knud
K
The Bartholin Institute, Rigshospitalet, Copenhagen, Denmark. knud@eln.dk
Nielsen
Signe M B
SM
Campos
André
A
Seifert
Thomas
T
Hasholt
Lis
L
Nielsen
Jørgen E
JE
Nørremølle
Anne
A
Skotte
Niels H
NH
Secher
Niels H
NH
Quistorff
Bjørn
B
D000818:Animals; D001786:Blood Glucose / Q000032:analysis*; D015153:Blotting, Western; D001921:Brain / Q000378:metabolism*; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test / Q000379:methods; D005260:Female; D005943:Gluconeogenesis / Q000502:physiology*; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000503:physiopathology; D019344:Lactic Acid / Q000378:metabolism*; D008099:Liver / Q000378:metabolism / Q000503:physiopathology; D008111:Liver Function Tests / Q000379:methods; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008875:Middle Aged; D020133:Reverse Transcriptase Polymerase Chain Reaction
D001786:Blood Glucose; D019344:Lactic Acid