TY - JOUR
T1 - Phosphodiesterase 3B gene expression is enhanced in the liver but reduced in the adipose tissue of obese insulin resistant db/db mouse
AU - Tang, Yan
AU - Osawa, Haruhiko
AU - Onuma, Hiroshi
AU - Nishimiya, Tatsuya
AU - Ochi, Masaaki
AU - Sugita, Atsuro
AU - Makino, Hideichi
N1 - Funding Information:
This work was supported by Grant-in-Aid for Scientific Research on Priority Areas (C) from the Ministry of Education, Science, Sports and Culture (No. 12204007), Grant-in-Aid for Scientific Research (C) from Japan Society for the Promotion of Science (No. 11671122 and 11671124), Sankyo Company LTD, Miura Educational Foundation, Sasakawa Health Science Foundation, Charitable Trust Clinical Pathology Research Foundation in Japan, and Ehime Health Foundation. We thank Dr I. Ikeuti, Dr Okukawa, Dr S. Masuda, Dr T. Yagi, and Dr M. Murase for technical assistance and suggestions.
PY - 2001
Y1 - 2001
N2 - 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.
AB - 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.
KW - Adipocyte
KW - Gene expression
KW - Liver
KW - Phosphodiesterase 3B
KW - Type 2 diabetes
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U2 - 10.1016/S0168-8227(01)00271-6
DO - 10.1016/S0168-8227(01)00271-6
M3 - Article
C2 - 11689269
AN - SCOPUS:0034748311
SN - 0168-8227
VL - 54
SP - 145
EP - 155
JO - Diabetes Research and Clinical Practice
JF - Diabetes Research and Clinical Practice
IS - 3
ER -