Insulin action on glucose transport in isolated skeletal muscle from patients with liver cirrhosis.
Insulin resistance, associated with liver cirrhosis, has been suggested to be localized in skeletal muscle. We used an in vitro incubation technique to determine insulin action on glucose transport in skeletal muscle obtained from seven patients with clinically stable alcoholic cirrhosis and seven healthy age- and sex-matched individuals. In addition, a euglycemic-hyperinsulinemic clamp procedure was performed to assess whole-body insulin-mediated glucose uptake. Insulin-mediated peripheral glucose utilization was 40% lower (p < 0.05) in the cirrhotic patients than in the healthy individuals. Intact skeletal muscle from the vastus lateralis portion of the quadriceps femoris muscle was obtained from each study participant. Thereafter, smaller skeletal muscle strips (approximately 18 mg) were dissected free and incubated in vitro to assess the rate of non-insulin- and insulin-stimulated 3-O-methylglucose transport. Insulin increased the rate of 3-O-methylglucose transport in a dose-dependent manner, with a maximal response observed in the presence of 200 microU/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 groups. Furthermore, muscle glycogen content of needle biopsy specimens was comparable in the two groups. In conclusion, the present group of patients, with liver cirrhosis on an alcoholic basis, had a normal insulin-stimulated capacity for glucose transport at the cellular level irrespective of the degree of whole-body insulin resistance. The mechanism for the divergence between the in vivo and in vitro responses to insulin remains to be elucidated.
Johansson
U
U
Dept. of Medicine, Huddinge Hospital, Sweden.
Eriksson
L S
LS
Galuska
D
D
Zierath
J R
JR
Wallberg-Henriksson
H
H
D019325:3-O-Methylglucose; D000328:Adult; D001692:Biological Transport / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005260:Female; D005947:Glucose / Q000378:metabolism*; D015309:Glucose Clamp Technique; D006801:Humans; D066298:In Vitro Techniques; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D008104:Liver Cirrhosis, Alcoholic / Q000378:metabolism*; D008297:Male; D008757:Methylglucosides / Q000378:metabolism; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*
D007328:Insulin; D008757:Methylglucosides; D019325:3-O-Methylglucose; D005947:Glucose