Document Detail


Rapamycin partially prevents insulin resistance induced by chronic insulin treatment.
MedLine Citation:
PMID:  12051762     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Chronic insulin exposure induces serine/threonine phosphorylation and degradation of IRS-1 through a rapamycin-sensitive pathway, which results in a down-regulation of insulin action. In this study, to investigate whether rapamycin (an mTOR inhibitor) could prevent insulin resistance induced by hyperinsulinemia, 3T3-L1 adipocytes were incubated chronically in the presence of insulin with or without the addition of rapamycin. Subsequently, the cells were washed and re-stimulated acutely with insulin. Chronic insulin stimulation caused a reduction of GLUT-4 and IRS-1 proteins with a correlated decrease in acute insulin-induced PKB and MAPK phosphorylations as well as a reduction in insulin-stimulated glucose transport. Rapamycin prevented the reduction of IRS-1 protein levels and insulin-induced PKB Ser-473 phosphorylation with a partial normalization of insulin-induced glucose transport. In contrast, rapamycin had no effect on the decrease in insulin-induced MAPK phosphorylation or GLUT-4 protein levels. These results suggest that chronic insulin exposure leads to a down-regulation of PKB and MAPK pathways through different mechanisms in adipocytes.
Authors:
Cathleen E Berg; Brian E Lavan; Cristina M Rondinone
Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Biochemical and biophysical research communications     Volume:  293     ISSN:  0006-291X     ISO Abbreviation:  Biochem. Biophys. Res. Commun.     Publication Date:  2002 May 
Date Detail:
Created Date:  2002-06-07     Completed Date:  2002-06-27     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0372516     Medline TA:  Biochem Biophys Res Commun     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1021-7     Citation Subset:  IM    
Copyright Information:
(c) 2002 Elsevier Science (USA).
Affiliation:
Metabolic Diseases Research, Global Pharmaceutical Research and Development, Abbott Laboratories, Abbott Park, IL 60064, USA.
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MeSH Terms
Descriptor/Qualifier:
Adipocytes / drug effects,  metabolism*
Animals
Biological Transport
Cell Line
Glucose / metabolism
Insulin / administration & dosage,  pharmacology*
Insulin Antagonists / pharmacology*
Insulin Resistance
Mitogen-Activated Protein Kinases / metabolism
Phosphorylation
Phosphoserine / metabolism
Phosphothreonine / metabolism
Protein-Serine-Threonine Kinases*
Proto-Oncogene Proteins / chemistry,  metabolism
Proto-Oncogene Proteins c-akt
Sirolimus / pharmacology*
Time Factors
Chemical
Reg. No./Substance:
0/Insulin Antagonists; 0/Proto-Oncogene Proteins; 11061-68-0/Insulin; 1114-81-4/Phosphothreonine; 17885-08-4/Phosphoserine; 50-99-7/Glucose; 53123-88-9/Sirolimus; EC 2.7.11.1/Protein-Serine-Threonine Kinases; EC 2.7.11.1/Proto-Oncogene Proteins c-akt; EC 2.7.11.24/Mitogen-Activated Protein Kinases

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


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