RGD Reference Report - Cyclic nucleotide phosphodiesterase 3 expression in vivo: evidence for tissue-specific expression of phosphodiesterase 3A or 3B mRNA and activity in the aorta and adipose tissue of atherosclerosis-prone insulin-resistant rats. - Rat Genome Database

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Cyclic nucleotide phosphodiesterase 3 expression in vivo: evidence for tissue-specific expression of phosphodiesterase 3A or 3B mRNA and activity in the aorta and adipose tissue of atherosclerosis-prone insulin-resistant rats.

Authors: Nagaoka, T  Shirakawa, T  Balon, TW  Russell, JC  Fujita-Yamaguchi, Y 
Citation: Nagaoka T, etal., Diabetes. 1998 Jul;47(7):1135-44.
RGD ID: 2300415
Pubmed: PMID:9648839   (View Abstract at PubMed)

With a view of understanding the potential roles of phosphodiesterase (PDE)3 in the acceleration of atherosclerosis in diabetes, we have analyzed the in vivo levels of low Km cAMP PDE3 and PDE4 activities as well as PDE3A and PDE3B mRNA in a relevant animal model. The JCR:LA-cp rat is a unique strain that develops obesity, insulin resistance, and vasculopathy when homozygous for the autosomal recessive cp gene (cp/cp). Lean rats, bred (designated +/?) as a 2:1 mixture of animals that are heterozygous (cp/+) or homozygous normal (+/+), are metabolically normal. We find that PDE3 activity is the major low Km cAMP activity in the aorta of cp/cp rats and is approximately twofold higher than that in lean +/? rats. PDE3A mRNA levels in middle-aged cp/cp rats are also elevated, approximately threefold, compared with those of +/? rats or young 12-week-old cp/cp rats. Thus, in the aorta of atherosclerosis-prone insulin-resistant cp/cp rats, PDE3A gene expression is upregulated, resulting in significantly higher PDE3 activity. This upregulation of PDE3A mRNA levels was a rather unique phenomenon to the aorta of JCR:LA-cp rats compared with that in the aorta of other rat strains. This result is consistent with our hypothesis that an increased PDE3 activity in aortic smooth muscle cells may contribute to accelerated atherosclerosis in diabetes. Furthermore, determination of PDE3 activity and PDE3A and PDE3B mRNA levels in heart and white and brown fat tissues of JCR:LA-cp rats revealed that PDE3B mRNA and activity in white adipose tissue is downregulated in this diabetic animal model, and that PDE3A and PDE3B genes are tissue-specifically expressed and differentially regulated in aorta and adipose tissue, respectively, under hyperinsulinemic conditions.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDE3AHumanobesity  ISOPde3a (Rattus norvegicus)mRNA:decreased expression:heartRGD 
Pde3aRatobesity  IEP mRNA:decreased expression:heartRGD 
Pde3aMouseobesity  ISOPde3a (Rattus norvegicus)mRNA:decreased expression:heartRGD 

Objects Annotated

Genes (Rattus norvegicus)
Pde3a  (phosphodiesterase 3A)

Genes (Mus musculus)
Pde3a  (phosphodiesterase 3A, cGMP inhibited)

Genes (Homo sapiens)
PDE3A  (phosphodiesterase 3A)

Objects referenced in this article
Gene Pde3b phosphodiesterase 3B Rattus norvegicus

Additional Information