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PMID: 3522628 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

Studies on the mechanism of insulin resistance in the liver from humans with noninsulin-dependent diabetes. Insulin action and binding in isolated hepatocytes, insulin receptor structure, and kinase activity.

The Journal of clinical investigation ·Vol. 78 ·No. 1 ·1986-07-00 ·Pages 249-58

Caro JF, Ittoop O, Pories WJ, Meelheim D, Flickinger EG, Thomas F, Jenquin M, Silverman JF, Khazanie PG, Sinha MK

Abstract

We have developed a method to isolate insulin-responsive human hepatocytes from an intraoperative liver biopsy to study insulin action and resistance in man. Hepatocytes from obese patients with noninsulin-dependent diabetes were resistant to maximal insulin concentration, and those from obese controls to submaximal insulin concentration in comparison to nonobese controls. Insulin binding per cell number was similar in all groups. However, insulin binding per surface area was decreased in the two obese groups because their hepatocytes were larger. In addition, the pool of detergent-extractable receptor was further decreased in diabetics. Insulin receptors in all groups were unaltered as determined by affinity-labeling methods. However, insulin-stimulated insulin receptor kinase activity was decreased in diabetics. Thus, in obesity, decreased surface binding could explain resistance to submaximal insulin concentrations. In diabetes, diminished insulin-stimulated protein kinase activity and decreased intracellular pool of receptors could provide an explanation for postinsulin-binding defect(s) of insulin action in human liver.

MeSH Terms
Biopsy Cell Separation Diabetes Mellitus/physiopathology Electrophoresis, Polyacrylamide Gel Humans Insulin/metabolism Insulin Resistance Kinetics Liver/metabolism Obesity/physiopathology Protein Kinases/metabolism Receptor, Insulin/analysis,metabolism Structure-Activity Relationship
Chemicals
Insulin Protein Kinases Receptor, Insulin
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Caro J F
Ittoop O
Pories W J
Meelheim D
Flickinger E G
Thomas F
Jenquin M
Silverman J F
Khazanie P G
Sinha M K
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Article Info
Journal
The Journal of clinical investigation
Abbr.
J Clin Invest
ISSN
0021-9738
DOI
10.1172/JCI112558
Published
1986-07-00
Pages
249-58
Language
English
Region
United States
NLM ID
7802877
PMCID
PMC329556
Subset
IM
Grants
NIADDK NIH HHS · R01-AM3285-04 · United States
External Links
PubMed source DOI: 10.1172/JCI112558 PMC Full Text View journal details
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