AJP - Endocrinology and Metabolism, Vol 252, Issue 6 E772-E777, Copyright © 1987 by American Physiological Society
Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver
T. P. Shankar, S. Drake and S. S. Solomon
Clearance of porcine insulin, glucagon, and human growth hormone was
measured in intact perfused cirrhotic and normal rat livers. Binding and
degradation of 125I-insulin by hepatocytes isolated from cirrhotic and
normal livers were also studied. The half-lives (t1/2) of immunoreactive
insulin and glucagon were 14.0 +/- 3.1 and 9.6 +/- 2.1 min in normal livers
and 26.0 +/- 6.1 and 25.0 +/- 7.1 min in cirrhotic livers (P less than
0.001). Insulin binding and degradation by hepatocytes from control and
cirrhotic livers showed no significant differences. Intraportal insulin
infusion in perfusion studies suppressed glucagon-stimulated increases in
glucose output from control livers but failed to suppress glucose
production by cirrhotic livers, suggesting the presence of hepatic insulin
resistance in cirrhosis. Impaired clearance of insulin and glucagon by the
intact cirrhotic liver and normal binding and degradation of insulin by
isolated hepatocytes suggest that factors such as intrahepatic fibrosis and
shunting and postbinding defects may be responsible for the impaired
hormone clearance and hepatic insulin resistance.
