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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-2-28
pubmed:abstractText
PGC-1alpha mRNA and protein are elevated in islets from multiple animal models of diabetes. Overexpression of PGC-1alpha impairs glucose-stimulated insulin secretion (GSIS). However, it is not well known which metabolic events lead to upregulation of PGC-1alpha in the beta-cells under pathophysiological condition. In present study, we have investigated effects of chronic hyperlipidemia and hyperglycemia on PGC-1alpha mRNA expression in isolated rat islets. Isolated rat islets are chronically incubated with 0, 0.2 and 0.4 mM oleic acid/palmitic acid (free fatty acids, FFA) or 5.5 and 25 mM glucose for 72 h. FFA dose-dependently increases PGC-1alpha mRNA expression level in isolated islets. FFA also increases PGC-1alpha expression in mouse beta-cell-derived beta TC3 cell line. In contrast, 25 mM glucose decreases expression level of PGC-1alpha. Inhibition of PGC-1alpha by siRNA improves FFA-induced impairment of GSIS in islets. These data suggest that hyperlipidemia and hyperglycemia regulate PGC-1alpha expression in islets differently, and elevated PGC-1alpha by FFA plays an important role in chronic hyperlipidemia-induced beta-cell dysfunction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-5793
pubmed:author
pubmed:issnType
Print
pubmed:day
28
pubmed:volume
579
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1446-52
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15733855-Animals, pubmed-meshheading:15733855-Cells, Cultured, pubmed-meshheading:15733855-Fatty Acids, Nonesterified, pubmed-meshheading:15733855-Forskolin, pubmed-meshheading:15733855-Gene Expression Regulation, pubmed-meshheading:15733855-Glucagon, pubmed-meshheading:15733855-Glucagon-Like Peptide 1, pubmed-meshheading:15733855-Glucose, pubmed-meshheading:15733855-Islets of Langerhans, pubmed-meshheading:15733855-Liver, pubmed-meshheading:15733855-Male, pubmed-meshheading:15733855-Mice, pubmed-meshheading:15733855-Peptide Fragments, pubmed-meshheading:15733855-Protein Precursors, pubmed-meshheading:15733855-RNA, Messenger, pubmed-meshheading:15733855-RNA, Small Interfering, pubmed-meshheading:15733855-Rats, pubmed-meshheading:15733855-Rats, Wistar, pubmed-meshheading:15733855-Transcription Factors
pubmed:year
2005
pubmed:articleTitle
Free fatty acids increase PGC-1alpha expression in isolated rat islets.
pubmed:affiliation
Institute of Mecular Medicine and State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, 22 Hankou Road, Nanjing, Jiangsu 210093, PR China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't