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

Abstract

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:
Research Org.:
Univ. of Tennessee, Memphis (USA)
OSTI Identifier:
6801525
Resource Type:
Journal Article
Resource Relation:
Journal Name: Am. J. Physiol.; (United States); Journal Volume: 252:6
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

Citation Formats

Shankar, T.P., Drake, S., and Solomon, S.S. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver. United States: N. p., 1987. Web.
Shankar, T.P., Drake, S., & Solomon, S.S. Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver. United States.
Shankar, T.P., Drake, S., and Solomon, S.S. 1987. "Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver". United States. doi:.
@article{osti_6801525,
title = {Insulin resistance and delayed clearance of peptide hormones in cirrhotic rat liver},
author = {Shankar, T.P. and Drake, S. and Solomon, S.S.},
abstractNote = {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.},
doi = {},
journal = {Am. J. Physiol.; (United States)},
number = ,
volume = 252:6,
place = {United States},
year = 1987,
month = 6
}
  • The metabolism of radiosilver was studied in the human. It was found that radiosilver incubated with autogenous plasma and introduced into the subject by intravenous injection will be removed from the plasma principally by the liver. The rate of this removal is less in the cirrhotic subject than in the noneirrhotic. Silver accumulated in the liver is excreted from that organ with a normal half-time value of approximately 11 days; this function is also retarded in the cirrhotic liver, where the half-time value is approximately 20 days. (auth)
  • The authors have studied the structure and function of the partially purified insulin receptors from liver and skeletal muscle in a rat model of severe chronic uremia. {sup 125}I-insulin binding was higher in the liver from uremic rats when compared with ad libitum- and pair-fed controls. Furthermore, the ability of insulin to stimulate the autophosphorylation of the {beta}-subunit and insulin receptor kinase activity using Glu{sup 80}, Tyr{sup 20} as exogenous phosphoacceptor was increased in the liver of the uremic animals. The structural characteristics of the receptors, as determined by electrophoretic mobilities of affinity labeled {alpha}-subunit and the phosphorylated {beta}-subunit, weremore » normal in uremia. {sup 125}I-insulin binding and insulin receptor kinase activity were similar in the skeletal muscle from uremic and pair- and ad libitum-fed animals. Thus the data are supportive of the hypothesis that in liver and muscle of chronic uremic rats, insulin resistance is due to a defect(s) distal to the insulin receptor kinase.« less
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