Document Detail

Evidence against the involvement of oxidative stress in fatty acid inhibition of insulin secretion.
MedLine Citation:
PMID:  15448091     Owner:  NLM     Status:  MEDLINE    
Prolonged exposure to elevated levels of fatty acids adversely affects pancreatic beta-cell function. Here we investigated 1) whether ceramide synthesis, which we reported to mediate fatty acid inhibition of insulin gene expression, also inhibits insulin secretion and 2) whether fatty acid inhibition of insulin secretion involves the generation of reactive oxygen species (ROS), nitric oxide (NO), or prostaglandin E(2) (PGE(2)). A 72-h culture of islets in the presence of palmitate or oleate resulted in a marked decrease in glucose-induced insulin release assessed in 1-h static incubations. This effect was reproduced by exogenous diacylglycerol, but not by a cell-permeable analog of ceramide. Culture in the presence of fatty acids was not associated with an increase in intracellular peroxide or NO levels, neither was insulin secretion restored by antioxidants or an inhibitor of NO production. Exposure to fatty acids led to an increase in PGE(2) release, but an inhibitor of cyclooxygenase 2 was unable to prevent fatty acid inhibition of insulin secretion. These results indicate that fatty acid inhibition of insulin secretion 1) is not mediated by de novo ceramide synthesis, ROS, NO, or PGE(2), and 2) is likely to be caused by the generation of signals or metabolites downstream of diacylglycerol.
Patrick C Moore; Marco A Ugas; Derek K Hagman; Susan D Parazzoli; Vincent Poitout
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Diabetes     Volume:  53     ISSN:  0012-1797     ISO Abbreviation:  Diabetes     Publication Date:  2004 Oct 
Date Detail:
Created Date:  2004-09-27     Completed Date:  2004-11-16     Revised Date:  2014-05-01    
Medline Journal Info:
Nlm Unique ID:  0372763     Medline TA:  Diabetes     Country:  United States    
Other Details:
Languages:  eng     Pagination:  2610-6     Citation Subset:  AIM; IM    
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MeSH Terms
Cells, Cultured
Dinoprostone / physiology*
Insulin / secretion*
Islets of Langerhans / cytology,  drug effects,  secretion*
NG-Nitroarginine Methyl Ester / pharmacology
Nitrites / metabolism
Oxidative Stress / physiology*
Palmitic Acid / pharmacology*
Proinsulin / secretion
Protein Precursors / secretion
Rats, Wistar
Reactive Oxygen Species / metabolism
Grant Support
Reg. No./Substance:
0/Insulin; 0/Nitrites; 0/Protein Precursors; 0/Reactive Oxygen Species; 2V16EO95H1/Palmitic Acid; 61116-24-3/preproinsulin; 9035-68-1/Proinsulin; K7Q1JQR04M/Dinoprostone; V55S2QJN2X/NG-Nitroarginine Methyl Ester

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

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