TY - JOUR
T1 - Differential regulation of gene expression and insulin-induced activation of phosphodiesterase 3B in adipocytes of lean insulin-resistant IRS-1 (-/-) mice
AU - Hasegawa, Masaaki
AU - Tang, Yan
AU - Osawa, Haruhiko
AU - Onuma, Hiroshi
AU - Nishimiya, Tatsuya
AU - Ochi, Masaaki
AU - Terauchi, Yasuo
AU - Kadowaki, Takashi
AU - Makino, Hideichi
N1 - Funding Information:
This work was supported by a Grant-in-Aid for Scientific Research on Priority Areas (C) ‘Medical Genome Science’ from the Ministry of Education, Culture, Sports, Science, and Technology of Japan (No. 12204007), Grant-in-Aid for Scientific Research (C) from the Japan Society for the Promotion of Science (Nos. 11671122 and 11671124) and the Charitable Trust Clinical Pathology Research Foundation in Japan. We thank Dr K. Okukawa, Dr S. Masuda, Dr T. Yagi and Dr M. Murase for technical assistance and suggestions.
PY - 2002/11
Y1 - 2002/11
N2 - 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.
AB - 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.
KW - Adipocyte
KW - Gene expression
KW - IRS-1
KW - Insulin resistance
KW - Phosphodiesterase 3B
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U2 - 10.1016/S0168-8227(02)00132-8
DO - 10.1016/S0168-8227(02)00132-8
M3 - Article
C2 - 12213348
AN - SCOPUS:0036836781
SN - 0168-8227
VL - 58
SP - 79
EP - 85
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
IS - 2
ER -
