Source:http://linkedlifedata.com/resource/pubmed/id/18498041
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1-2
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| pubmed:dateCreated |
2008-6-25
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| pubmed:abstractText |
Increasing evidence indicates that beta-cell apoptosis and impaired secretory function were partly mediated by interleukin (IL)-1beta and/or high-glucose-induced beta-cell production of IL-1beta. However, the specific signal transduction pathways and molecular events involved in beta-cell dysfunction remain largely unresolved. In this study, we investigated whether Ca(2+) and extracellular signal-regulated kinase (ERK) activation plays a role for IL-1beta action in rat islets. Exposure of rat islets for 4 days to 33.3 mM glucose and 140 ng/ml IL-1beta- induced beta-cell apoptosis and impaired glucose-stimulated insulin secretion. By Western blotting with phosphospecific antibodies, glucose and IL-1beta were shown to activate ERK. Ca(2+) channel blocker nimodipine or ERK inhibitor PD98059 prevented glucose- and IL-1beta-induced ERK activation, beta-cell apoptosis, and impaired function. Furthermore, treatment with Ca(2+) ionophore ionomycin, or exposure to thapsigargin, an inhibitor of sarco(endo)plasmic reticulum Ca(2+) ATPase, all caused an amplification of IL-1beta-induced ERK activation in rat islet. On the other hand, a chelator of intracellular free Ca(2+) [bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid-acetoxymethyl] (BAPTA/AM) and an inhibitor of calmodulin (W7) diminished IL-1beta-induced phosphorylation of ERK. Finally, islet release of IL-1beta in response to high glucose could be abrogated by nimodipine, mibefradil, or PD98059. Together, these data suggest that glucose- and IL-1beta-induced beta-cell secretory dysfunction and apoptosis are Ca(2+) influx and ERK dependent in rat islets.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/1,2-bis(2-aminophenoxy)ethane-N,N,N'...,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channel Blockers,
http://linkedlifedata.com/resource/pubmed/chemical/Calcium Channels, L-Type,
http://linkedlifedata.com/resource/pubmed/chemical/Egtazic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Extracellular Signal-Regulated MAP...,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Interleukin-1beta,
http://linkedlifedata.com/resource/pubmed/chemical/Ionomycin,
http://linkedlifedata.com/resource/pubmed/chemical/Mibefradil,
http://linkedlifedata.com/resource/pubmed/chemical/Nimodipine,
http://linkedlifedata.com/resource/pubmed/chemical/Sulfonamides,
http://linkedlifedata.com/resource/pubmed/chemical/Thapsigargin,
http://linkedlifedata.com/resource/pubmed/chemical/W 7
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| pubmed:status |
MEDLINE
|
| pubmed:month |
Aug
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| pubmed:issn |
0300-8177
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| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
315
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
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| pubmed:pagination |
75-84
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:18498041-Animals,
pubmed-meshheading:18498041-Apoptosis,
pubmed-meshheading:18498041-Calcium Channel Blockers,
pubmed-meshheading:18498041-Calcium Channels, L-Type,
pubmed-meshheading:18498041-Calcium Signaling,
pubmed-meshheading:18498041-Egtazic Acid,
pubmed-meshheading:18498041-Enzyme Activation,
pubmed-meshheading:18498041-Extracellular Signal-Regulated MAP Kinases,
pubmed-meshheading:18498041-Glucose,
pubmed-meshheading:18498041-Humans,
pubmed-meshheading:18498041-Insulin,
pubmed-meshheading:18498041-Insulin-Secreting Cells,
pubmed-meshheading:18498041-Interleukin-1beta,
pubmed-meshheading:18498041-Ion Channel Gating,
pubmed-meshheading:18498041-Ionomycin,
pubmed-meshheading:18498041-Mibefradil,
pubmed-meshheading:18498041-Nimodipine,
pubmed-meshheading:18498041-Rats,
pubmed-meshheading:18498041-Sulfonamides,
pubmed-meshheading:18498041-Thapsigargin
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| pubmed:year |
2008
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| pubmed:articleTitle |
Requirements of calcium fluxes and ERK kinase activation for glucose- and interleukin-1beta-induced beta-cell apoptosis.
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| pubmed:affiliation |
School of Life Science and Biotechnology, Key Laboratory of Microbial Metabolism, Ministry of Education, Shanghai Jiaotong University, 800 Dongchuan Road, Shanghai, People's Republic of China.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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