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Title: Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver

Clearance of porcine insulin, glucagon, and human growth hormone was measured in intact perfused cirrhotic and normal rat livers. Binding and degradation of /sup 125/I-insulin by hepatocytes isolated from cirrhotic and normal livers were also studied. The half-lives (t/sub 1/2/) 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. 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.
Authors:
; ;
Publication Date:
OSTI Identifier:
6801525
Resource Type:
Journal Article
Resource Relation:
Journal Name: Am. J. Physiol.; (United States); Journal Volume: 252:6
Research Org:
Univ. of Tennessee, Memphis (USA)
Country of Publication:
United States
Language:
English
Subject:
59 BASIC BIOLOGICAL SCIENCES; LABELLED COMPOUNDS; BIODEGRADATION; CLEARANCE; LIVER; BIOLOGICAL FUNCTIONS; PEPTIDE HORMONES; FIBROSIS; GLUCAGON; GLUCOSE; INJURIES; INSULIN; IODINE 125; LIVER CELLS; LIVER CIRRHOSIS; PERFUSED TISSUES; SWINE; ALDEHYDES; ANIMAL CELLS; ANIMAL TISSUES; ANIMALS; BETA DECAY RADIOISOTOPES; BODY; CARBOHYDRATES; CHEMICAL REACTIONS; DAYS LIVING RADIOISOTOPES; DECOMPOSITION; DIGESTIVE SYSTEM; DIGESTIVE SYSTEM DISEASES; DISEASES; DOMESTIC ANIMALS; ELECTRON CAPTURE RADIOISOTOPES; FUNCTIONS; GLANDS; HEXOSES; HORMONES; INTERMEDIATE MASS NUCLEI; IODINE ISOTOPES; ISOTOPES; MAMMALS; MONOSACCHARIDES; NUCLEI; ODD-EVEN NUCLEI; ORGANIC COMPOUNDS; ORGANS; PATHOLOGICAL CHANGES; PEPTIDES; POLYPEPTIDES; PROTEINS; RADIOISOTOPES; SACCHARIDES; SOMATIC CELLS; TISSUES; VERTEBRATES 551001* -- Physiological Systems-- Tracer Techniques