title: Kinetics of glucose metabolism in relation to insulin concentrations in patients with alcoholic cirrhosis and in healthy persons.
abstract: To characterize the insulin resistance in alcoholic cirrhosis we determined in vivo insulin-glucose disposal dose-response relationships in 6 patients with alcoholic cirrhosis of varying severity and in 6 control subjects, using the glucose-insulin clamp technique. Each subject was infused sequentially with insulin at rates of 0.5, 1.0, 2.0, and 10 mU/min X kg, each rate for 2 h. Euglycemia was maintained by a continuous servo-adjusted glucose infusion. The amount of glucose infused during the last 40 min of each 2-h period, corrected for accumulation in the glucose space, reflects overall net glucose metabolism. The dose-response curves demonstrated saturation kinetics. Lineweaver-Burk plots were consistently convex, rejecting a simple Michaelis-Menten relationship, but were linear when accommodated to allosterism with two active sites. The calculated affinity constant (i.e., the concentration of insulin leading to half-maximum glucose metabolism) of patients with cirrhosis was higher than that of normal controls (104 +/- 30 vs. 32 +/- 3 mU/L, mean +/- SD). In addition the maximum rate of glucose metabolism was significantly lower than that of normals (53 +/- 9 vs. 72 +/- 16 mumol/min X kg). We conclude that, in patients with alcoholic cirrhosis, insulin resistance is caused both by a marked decrease in sensitivity to insulin and a decreased maximum effect of insulin, indicating a combined receptor-postreceptor defect as the underlying cause.
mesh_terms: D000328:Adult; D000368:Aged; D001786:Blood Glucose / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000097:blood*; D007333:Insulin Resistance; D007700:Kinetics; D008104:Liver Cirrhosis, Alcoholic / Q000097:blood*; D008297:Male; D008875:Middle Aged; D008954:Models, Biological
chemical_list: D001786:Blood Glucose; D007328:Insulin