INSULIN ACTION ON GLUCOSE-TRANSPORT IN ISOLATED SKELETAL-MUSCLE FROM PATIENTS WITH LIVER-CIRRHOSIS

Insulin resistance, associated with liver cirrhosis, has been suggeste d to be localized in skeletal muscle. We used an in vitro incubation t echnique to determine insulin action on glucose transport in skeletal muscle obtained from seven patients with clinically stable alcoholic c irrhosis and seven healthy age- and sex-matched individuals. In additi on, a euglycemic-hyperinsulinemic clamp procedure was performed to ass ess whole-body insulin-mediated glucose uptake. Insulin-mediated perip heral glucose utilization was 40% lower (p < 0.05) in the cirrhotic pa tients than in the healthy individuals. Intact skeletal muscle from th e vastus lateralis portion of the quadriceps femoris muscle was obtain ed from each study participant. Thereafter, smaller skeletal muscle st rips (similar to 18 mg) were dissected free and incubated in vitro to assess the rate of non-insulin- and insulin-stimulated 3-O-methylgluco se transport. Insulin increased the rate of 3-O-methylglucose transpor t in a dose-dependent manner, with a maximal response observed in the presence of 200 mu U/ml in skeletal muscle obtained from the cirrhotic patients and healthy individuals. The dose-response curve for insulin -stimulated 3-O-methylglucose transport did not differ between the gro ups. Furthermore, muscle glycogen content of needle biopsy specimens w as comparable in the two groups. In conclusion, the present group of p atients, with liver cirrhosis on an alcoholic basis, had a normal insu lin-stimulated capacity for glucose transport al the cellular level ir respective of the degree of whole-body insulin resistance. The mechani sm for the divergence between the in vivo and in vitro responses to in sulin remains to be elucidated.