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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
3
|
| pubmed:dateCreated |
1998-4-7
|
| pubmed:abstractText |
Glucose-induced insulin release is decreased in the spontaneously diabetic GK rat, a nonobese rodent model of type 2 diabetes. Forskolin restores the impaired insulin release in both the isolated perfused pancreas and isolated islets from these rats (Abdel-Halim et al., Diabetes 45:934-940, 1996). We demonstrate here that the insulinotropic effect of forskolin in the GK rat is due to increased generation of cAMP and that it is associated with overexpression of adenylyl cyclase (AC)-III mRNA and gene mutations. The AC-III mRNA overexpression was demonstrated by in situ hybridization using oligonucleotide probes binding to different regions of the rat AC-III mRNA. It was associated with the presence of two point mutations identified at positions -28 bp (A --> G) and -358 bp (A --> C) of the promoter region of the AC-III gene and was demonstrable in both GK rat islets and peripheral blood cells. Transfection of COS cells with a luciferase reporter gene system revealed up to 25-fold increased promoter activity of GK AC-III promoter when compared with normal rat promoter (P < 0.0001). In conclusion, forskolin restores the impaired insulin release in islets of the GK rat through enhanced cAMP generation. This is linked to overexpression of AC-III mRNA in GK islets due to two functional point mutations in the promoter region of the AC-III gene.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
AIM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Adenylate Cyclase,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclic AMP,
http://linkedlifedata.com/resource/pubmed/chemical/DNA Primers,
http://linkedlifedata.com/resource/pubmed/chemical/Insulin,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Mar
|
| pubmed:issn |
0012-1797
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:volume |
47
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
498-504
|
| pubmed:dateRevised |
2011-11-17
|
| pubmed:meshHeading |
pubmed-meshheading:9519762-Adenylate Cyclase,
pubmed-meshheading:9519762-Animals,
pubmed-meshheading:9519762-Base Sequence,
pubmed-meshheading:9519762-Cohort Studies,
pubmed-meshheading:9519762-Cyclic AMP,
pubmed-meshheading:9519762-DNA Primers,
pubmed-meshheading:9519762-Diabetes Mellitus, Type 2,
pubmed-meshheading:9519762-Disease Models, Animal,
pubmed-meshheading:9519762-Gene Expression Regulation, Enzymologic,
pubmed-meshheading:9519762-In Situ Hybridization,
pubmed-meshheading:9519762-Insulin,
pubmed-meshheading:9519762-Islets of Langerhans,
pubmed-meshheading:9519762-Male,
pubmed-meshheading:9519762-Mutation,
pubmed-meshheading:9519762-Polymerase Chain Reaction,
pubmed-meshheading:9519762-Promoter Regions, Genetic,
pubmed-meshheading:9519762-RNA, Messenger,
pubmed-meshheading:9519762-Rats,
pubmed-meshheading:9519762-Rats, Inbred Strains,
pubmed-meshheading:9519762-Rats, Wistar
|
| pubmed:year |
1998
|
| pubmed:articleTitle |
Mutations in the promoter of adenylyl cyclase (AC)-III gene, overexpression of AC-III mRNA, and enhanced cAMP generation in islets from the spontaneously diabetic GK rat model of type 2 diabetes.
|
| pubmed:affiliation |
Department of Molecular Medicine, Karolinska Hospital, Stockholm, Sweden. samy.abdel-halim@molmed.ki.se
|
| pubmed:publicationType |
Journal Article,
Comparative Study,
In Vitro,
Research Support, Non-U.S. Gov't
|