Muscle GLUT4 in cirrhosis

Background/Aims

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 (R²=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 (R²=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.

Abbreviations: OGTT, oral glucose tolerance test, NGT, normal glucose tolerance, IGT, impaired glucose tolerance, DM, diabetes mellitus, RT-PCR, reverse transcriptase polymerase chain reaction, HOMA, homeostasis model assessment, GEC, galactose elimination capacity, ANOVA, analysis of variance, ci, confidence interval

Keywords: GLUT4, Liver cirrhosis, Skeletal muscle, Glucose intolerance, Insulin resistance, Clinical research