Document Detail


Correlation between insulin receptor occupancy and tyrosine kinase activity at low insulin concentrations and effect of major histocompatibility complex class I-derived peptide.
MedLine Citation:
PMID:  8246175     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
In rat adipocytes, insulin dose-response curves were determined for the following effects in the same cells under the same conditions: glucose uptake, binding to insulin receptors (IR), IR autophosphorylation in vivo and in vitro, IR tyrosine kinase activity and insulin-stimulated phosphatidylinositol (PI) kinase. All the EC50 values were essentially the same (mean +/- S.E.M. was 7 +/- 1 nM), except for glucose uptake, which was 170 pM. Using an improved method, we were able to measure PI kinase activity at picomolar concentrations of insulin (> 30 pM) corresponding to the EC50 for glucose uptake. These experiments showed that insulin-stimulated increase in glucose uptake was associated with an increase in antiphosphotyrosine antibody precipitable PI kinase activity, consistent with the view that IR tyrosine kinase activity may be involved in insulin-mediated signaling of glucose uptake. Small peptides (17-25 residues long) derived from major histocompatibility complex class I have previously been shown to inhibit IR internalization without any effect on the affinity of insulin to the receptor. It is now shown that the peptide-mediated inhibition of internalization, which doubles the number of insulin-occupied receptors at an insulin concentration of 70 pM, also results in a corresponding enhancement of PI kinase activity and glucose uptake. Thus, the receptors arrested on the cell surface by the peptide are biologically active.
Authors:
J Stagsted; T Hansen; R A Roth; A Goldstein; L Olsson
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  The Journal of pharmacology and experimental therapeutics     Volume:  267     ISSN:  0022-3565     ISO Abbreviation:  J. Pharmacol. Exp. Ther.     Publication Date:  1993 Nov 
Date Detail:
Created Date:  1994-01-06     Completed Date:  1994-01-06     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0376362     Medline TA:  J Pharmacol Exp Ther     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  997-1001     Citation Subset:  IM    
Affiliation:
Reception, Inc., Concord, California.
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MeSH Terms
Descriptor/Qualifier:
1-Phosphatidylinositol 4-Kinase
Adipocytes / drug effects,  metabolism
Amino Acid Sequence
Animals
Glucose / pharmacokinetics
Histocompatibility Antigens Class I / pharmacology*
Insulin / metabolism*,  pharmacology*
Kinetics
Macromolecular Substances
Major Histocompatibility Complex / genetics,  immunology
Molecular Sequence Data
Peptide Fragments / pharmacology*
Phosphorylation
Phosphotransferases (Alcohol Group Acceptor) / metabolism
Protein-Tyrosine Kinases / antagonists & inhibitors,  metabolism*
Rats
Rats, Wistar
Receptor, Insulin / metabolism*
Stimulation, Chemical
Chemical
Reg. No./Substance:
0/Histocompatibility Antigens Class I; 0/Macromolecular Substances; 0/Peptide Fragments; 11061-68-0/Insulin; 50-99-7/Glucose; EC 2.7.1.-/Phosphotransferases (Alcohol Group Acceptor); EC 2.7.1.67/1-Phosphatidylinositol 4-Kinase; EC 2.7.10.1/Protein-Tyrosine Kinases; EC 2.7.10.1/Receptor, Insulin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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