Source:http://linkedlifedata.com/resource/pubmed/id/12169692
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
40
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| pubmed:dateCreated |
2002-9-30
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| pubmed:abstractText |
Cyclic AMP potentiates glucose-stimulated insulin release and mediates the stimulatory effects of hormones such as glucagon-like peptide 1 (GLP-1) on pancreatic beta-cells. By inhibition of cAMP-degrading phosphodiesterase (PDE) and, in particular, selective inhibition of PDE3 activity, stimulatory effects on insulin secretion have been observed. Molecular and functional information on beta-cell PDE3 is, however, scarce. To provide such information, we have studied the specific effects of the PDE3B isoform by adenovirus-mediated overexpression. In rat islets and rat insulinoma cells, approximate 10-fold overexpression of PDE3B was accompanied by a 6-8-fold increase in membrane-associated PDE3B activity. The cAMP concentration was significantly lowered in transduced cells (INS-1(832/13)), and insulin secretion in response to stimulation with high glucose (11.1 mm) was reduced by 40% (islets) and 50% (INS-1). Further, the ability of GLP-1 (100 nm) to augment glucose-stimulated insulin secretion was inhibited by approximately 30% (islets) and 70% (INS-1). Accordingly, when stimulating with cAMP, a substantial decrease (65%) in exocytotic capacity was demonstrated in patch-clamped single beta-cells. In untransduced insulinoma cells, application of the PDE3-selective inhibitor OPC3911 (10 microm) was shown to increase glucose-stimulated insulin release as well as cAMP-enhanced exocytosis. The findings suggest a significant role of PDE3B as an important regulator of insulin secretory processes.
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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/3',5'-Cyclic-AMP Phosphodiesterases,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic Nucleotide...,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Glucose,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/Pde3b protein, rat
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| pubmed:status |
MEDLINE
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| pubmed:month |
Oct
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
4
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| pubmed:volume |
277
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
37446-55
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| pubmed:dateRevised |
2011-11-17
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| pubmed:meshHeading |
pubmed-meshheading:12169692-3',5'-Cyclic-AMP Phosphodiesterases,
pubmed-meshheading:12169692-Animals,
pubmed-meshheading:12169692-Base Sequence,
pubmed-meshheading:12169692-Cells, Cultured,
pubmed-meshheading:12169692-Cyclic AMP,
pubmed-meshheading:12169692-Cyclic Nucleotide Phosphodiesterases, Type 3,
pubmed-meshheading:12169692-DNA Primers,
pubmed-meshheading:12169692-Exocytosis,
pubmed-meshheading:12169692-Glucose,
pubmed-meshheading:12169692-Insulin,
pubmed-meshheading:12169692-Insulinoma,
pubmed-meshheading:12169692-Islets of Langerhans,
pubmed-meshheading:12169692-Kinetics,
pubmed-meshheading:12169692-Male,
pubmed-meshheading:12169692-Pancreatic Neoplasms,
pubmed-meshheading:12169692-Rats,
pubmed-meshheading:12169692-Rats, Sprague-Dawley,
pubmed-meshheading:12169692-Reverse Transcriptase Polymerase Chain Reaction,
pubmed-meshheading:12169692-Tumor Cells, Cultured
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| pubmed:year |
2002
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| pubmed:articleTitle |
Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta-cell exocytosis and release of insulin.
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| pubmed:affiliation |
Department of Cell and Molecular Biology, Biomedical Centre, C11, Lund University, SE-221 84 Lund, Sweden. Linda.Harndahl@medkem.lu.se
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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