Document Detail


Defect in cooperativity in insulin receptors from a patient with a congenital form of extreme insulin resistance.
MedLine Citation:
PMID:  6345588     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Previously, we have described a novel qualitative defect in insulin receptors from a patient with a genetic form of extreme insulin resistance (leprechaunism). Receptors from this insulin-resistant child are characterized by two abnormalities: (a) an abnormally high binding affinity for insulin, and (b) a markedly reduced sensitivity of 125I-insulin binding to alterations in pH and temperature. In this paper, we have investigated the kinetic mechanism of this abnormality in steady-state binding. The increased binding affinity for 125I-insulin results from a decrease in the dissociation rate of the hormone-receptor complex. In addition, the cooperative interactions among insulin binding sites are defective with insulin receptors from this child with leprechaunism. With insulin receptors on cultured lymphocytes from normal subjects, both negative and positive cooperativity may be observed. Porcine insulin accelerates the dissociation of the hormone-receptor complex (negative cooperativity). In contrast, certain insulin analogs such as desoctapeptide-insulin and desalanine-desasparagine-insulin retard the dissociation of the hormone-receptor complex (positive cooperativity). With insulin receptors from the leprechaun child, positive cooperativity could not be demonstrated, although negative cooperativity appeared to be normal. It seems likely that the same genetic defect may be responsible for the abnormalities in both insulin sensitivity and positive cooperativity.
Authors:
S I Taylor; S Leventhal
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Publication Detail:
Type:  Case Reports; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  The Journal of clinical investigation     Volume:  71     ISSN:  0021-9738     ISO Abbreviation:  J. Clin. Invest.     Publication Date:  1983 Jun 
Date Detail:
Created Date:  1983-08-11     Completed Date:  1983-08-11     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  7802877     Medline TA:  J Clin Invest     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1676-85     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Cells, Cultured
Child
Diabetes Mellitus / congenital*,  metabolism
Female
Humans
Hydrogen-Ion Concentration
Insulin / analogs & derivatives,  metabolism,  pharmacology
Insulin Resistance*
Kinetics
Lymphocytes / metabolism
Receptor, Insulin / drug effects,  metabolism*
Temperature
Chemical
Reg. No./Substance:
11061-68-0/Insulin; 12584-26-8/insulin, des-Asn(A21)-des-Ala(B30)-; 39416-70-1/insulin, desoctapeptide-; EC 2.7.10.1/Receptor, Insulin
Comments/Corrections

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


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