Differential regulation of gene expression and insulin-induced activation of phosphodiesterase 3B in adipocytes of lean insulin-resistant IRS-1 (-/-) mice.
Phosphodiesterase (PDE) 3B, a major isoform of PDE in adipocytes, mediates the antilipolytic action of insulin. PDE3B gene expression is generally reduced in adipocytes of either monogenic or polygenic rodent models of obese, insulin-resistance. An increased fat cell size, a common feature of obesity, could account for this reduction. Insulin receptor substrate-1 (IRS-1) (-/-) mice are lean with a reduced fat cell size and have insulin resistance due to a primary defect of insulin signaling. To determine whether the regulation of PDE3B gene expression is correlated with fat cell size, we examined this gene expression in adipose tissues of IRS-1 (-/-) mice. In IRS-1 (-/-) mice, PDE3B mRNA and protein levels were increased 1.24- and 1.35-fold those in C57BL/6J control mice, respectively. Independently, the fold induction of PDE activity by insulin (insulin-induced/basal) was 1.7-fold in control mice, but was reduced to 1.35-fold in IRS-1 (-/-) mice. Thus, PDE3B gene expression may be inversely correlated with a fat cell size, whereas insulin-induced PDE3B activation is mediated through IRS-1.
Hasegawa
Masaaki
M
Department of Laboratory Medicine, Ehime University School of Medicine, Shigenobu, Ehime 791-0295, Japan.
Tang
Yan
Y
Osawa
Haruhiko
H
Onuma
Hiroshi
H
Nishimiya
Tatsuya
T
Ochi
Masaaki
M
Terauchi
Yasuo
Y
Kadowaki
Takashi
T
Makino
Hideichi
H
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000187:drug effects / Q000235:genetics* / Q000378:metabolism; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005230:Fatty Acids, Nonesterified / Q000097:blood; D015971:Gene Expression Regulation, Enzymologic; D007328:Insulin / Q000097:blood / Q000494:pharmacology*; D055504:Insulin Receptor Substrate Proteins; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D010750:Phosphoproteins / Q000172:deficiency / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics; D012016:Reference Values; D014158:Transcription, Genetic
D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D012333:RNA, Messenger; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517293:Pde3b protein, mouse