Insulin resistance and insulin receptors in hepatic cirrhosis.
To explore the influence of extrahepatic factors in the pathogenesis of insulin resistance in hepatic cirrhosis, we studied 125I-insulin binding to erythrocytes and monocytes of 14 clinically stable cirrhotic individuals and compared the results with a normal control group. All patients had fasting normoglycemia at the time of the study but abnormal glucose tolerance was detected in 7 of 9 cirrhotic patients after an oral glucose load. Seven patients (group N) had normal fasting serum insulin levels, and 7 patients (group H) manifested fasting hyperinsulinemia. However, all patients had elevated insulin levels after oral glucose. Insulin binding to erythrocytes was significantly decreased in both cirrhotic subgroups; monocyte studies in 5 hyperinsulinemic patients revealed a similar decrease in binding. Scatchard analysis in monocytes suggests that this decreased binding is secondary to a decrease in the receptor number per cell. No correlation between insulin binding and fasting plasma insulin, glucagon, or growth hormone levels was seen. Sera from 4 patients were examined for the presence of a non-specific inhibitor of insulin binding, but no evidence for such a factor was found. We conclude that the decrease in insulin binding is mediated in the monocyte by a reduction of receptor concentration; in the erythrocyte the mechanism for decreased binding could not be clearly delineated. The insulin resistance seen in cirrhosis may result in part from decreased binding of insulin to target tissues; an additional postreceptor defect cannot be excluded in hyperinsulinemic individuals.
D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000032:analysis; D004912:Erythrocytes / Q000378:metabolism; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood; D007329:Insulin Antagonists / Q000378:metabolism; D007333:Insulin Resistance; D008103:Liver Cirrhosis / Q000097:blood*; D008297:Male; D008875:Middle Aged; D009000:Monocytes / Q000378:metabolism; D011972:Receptor, Insulin / Q000032:analysis*
D001786:Blood Glucose; D007328:Insulin; D007329:Insulin Antagonists; D011972:Receptor, Insulin