Muscle GLUT4 in cirrhosis.
OBJECTIVE
The insulin-dependent glucose transporter GLUT4 mediates 50-80% of whole body glucose uptake, but its relation to the frequent glucose intolerance in patients with liver cirrhosis is unknown.


METHODS
Thirty patients and seven healthy controls underwent a 2-h oral glucose tolerance test and later a muscle biopsy. Levels of GLUT4 total protein and mRNA content were determined in muscle biopsies by polyclonal antibody labelling and RT-PCR, respectively.


RESULTS
GLUT4 protein content in the cirrhosis group was not different from that of the controls, but at variance with the control subjects it correlated closely with measures of glucose tolerance (R(2)=0.45; p=0.003). GLUT4 mRNA of the patients with cirrhosis was reduced to 56% of control value (95% ci: 27-86%; p=0.015) and was inversely related to the level of basal hyper-insulinemia (R(2)=0.39; p=0.004).


CONCLUSIONS
In cirrhosis GLUT4 protein content was quantitatively intact, while limiting glucose tolerance. This indicates loss of redundancy of the major glucose transport system, possibly related to the markedly decreased expression of its gene. Hyper-insulinemia may be a primary event. Our findings implicate the muscular GLUT4 system in the glucose intolerance of liver cirrhosis by a mechanism different from that in diabetes.
Holland-Fischer
Peter
P
Department of Medicine V (Hepatology and Gastroenterology), Aarhus University Hospital, 44 Noerrebrogade, DK-8000 Aarhus C, Denmark. phf@svf.au.dk
Andersen
Per Heden
PH
Lund
Sten
S
Pedersen
Steen Bønnelykke
SB
Vinter-Jensen
Lars
L
Nielsen
Michael F
MF
Kaal
Andreas
A
Dall
Rolf
R
Schmitz
Ole
O
Vilstrup
Hendrik
H
D000328:Adult; D005260:Female; D005951:Glucose Tolerance Test; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D006946:Hyperinsulinism / Q000209:etiology; D008103:Liver Cirrhosis / Q000097:blood / Q000378:metabolism* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism
D051275:Glucose Transporter Type 4; D012333:RNA, Messenger