Study of Insulin Metabolism in Liver Injury I. Insulin Secretion and Degradation in Patients with Various Liver Diseases

Glucose intolerance and insulin hyperreaction after oral glucose loading have been reported in various liver diseases. Pancreatic hypersecretion and decreased hepatic degradation of insulin have been pointed out as explanation of the high peripheral insulin levels. To clarify the effects of and correlation between these two factors in various stages of liver diseases, serum immunoreactive insulin (IRI), connecting peptide immunoreactivity (CPR) and blood glucose (BG) were determined after 50-g oral glucose tolerance tests. In the acute stage of acute hepatitis, ΣCPR, ΣCPR/ΣBG and ΣIRI/ΣCPR were high, suggesting that both increased secretion and decreased degradation of insulin were responsible for the high peripheral insulin levels. In the convalescent stage, ΣCPR, ΣCPR/ΣBG and ΣIRI/ΣCPR were normal. In chronic hepatitis, increased ΣCPR and normal ΣCPR/ΣBG were observed. ΣIRI/ΣCPR was low in chronic persistent hepatitis, but high in chronic aggressive hepatitis. Thus, in chronic persistent hepatitis, hypersecretion of insulin to compensate for the elevated blood glucose was induced and insulin degradation did not decrease, so that normal peripheral insulin levels were maintained. In chronic aggressive hepatitis, increased secretion and decreased degradation of insulin were responsible for the higher peripheral insulin levels. In compensated liver cirrhosis, ΣCPR and ΣCPR/ΣBG were high, but ΣIRI/ΣCPR was normal. In the decompensated state, ΣCPR was high, ΣCPR/ΣBG normal and ΣIRI/ΣCPR high, suggesting that increased insulin secretion was the major cause of the high peripheral insulin levels in compensated liver cirrhosis. In the decompensated state, both increased secretion and decreased degradation of insulin were responsible for the high peripheral insulin levels. These data indicate that insulin secretion from the pancreas and insulin degradation in the liver are influenced by the stage of the liver disease.