Phosphodiesterase 3B gene expression is enhanced in the liver but reduced in the adipose tissue of obese insulin resistant db/db mouse.
Phosphodiesterase (PDE) 3B, when activated by insulin, causes a decrease in intracellular cAMP concentration. The activation of this enzyme results in the reduced output of free fatty acids (FFA) from adipocytes, and an increased lipogenesis in liver. We have recently shown that PDE3B gene expression is reduced in adipose tissues of KKAy mice. We intend to further elucidate the regulation of PDE3B in liver as well as adipose tissues in relation to the insulin resistant state. We examined PDE3B gene expression in liver and adipose tissues of obese, insulin-resistant diabetic db/db mice and also checked the effect of an insulin-sensitizing drug, troglitazone, on this gene expression. In the liver of db/db mice, PDE3B mRNA, its corresponding protein, and the associated catalytic activity were all increased by 2.1, 1.9 and 1.6-fold, respectively, over those in db/+ control mice. Histological examination revealed substantial triglyceride storage in the liver of db/db mice. Conversely, in the adipose tissue of db/db mice, PDE3B mRNA, protein, and its associated activity were all decreased by 0.38, 0.33 and 0.36-fold, respectively. Troglitazone, which has no effect on PDE3B in liver, increased the expression of this gene in adipocytes. This increase is associated with a reduction in the elevated levels of serum insulin, glucose, FFA and triglycerides. The reduced PDE3B gene expression in adipose tissues, which results in the elevation of serum FFA, could be the primary event in the development of insulin resistance in db/db mice. The enhanced PDE3B gene expression may correlate with changes in triglyceride storage in the liver of these mice.
Tang
Y
Y
Department of Laboratory Medicine, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan.
Osawa
H
H
Onuma
H
H
Nishimiya
T
T
Ochi
M
M
Sugita
A
A
Makino
H
H
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000096:biosynthesis* / Q000235:genetics; D000273:Adipose Tissue / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D015153:Blotting, Western; D002839:Chromans / Q000494:pharmacology; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D007004:Hypoglycemic Agents / Q000494:pharmacology; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance / Q000502:physiology; D008099:Liver / Q000187:drug effects / Q000201:enzymology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013844:Thiazoles / Q000494:pharmacology; D045162:Thiazolidinediones; D014280:Triglycerides / Q000097:blood; D000077288:Troglitazone
D001786:Blood Glucose; D002839:Chromans; D005230:Fatty Acids, Nonesterified; D007004:Hypoglycemic Agents; D007328:Insulin; D012333:RNA, Messenger; D013844:Thiazoles; D045162:Thiazolidinediones; D014280:Triglycerides; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517293:Pde3b protein, mouse; D000077288:Troglitazone