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 incre ased lipogenesis in liver. We have recently shown that PDE3B gene expressio n is reduced in adipose tissues of KKAy mice. We intend to further elucidat e the regulation of PDE3B in liver as well as adipose tissues in relation t o the insulin resistant state. We examined PDE3B gene expression in liver a nd adipose tissues of obese. insulin-resistant diabetic db/db mice and also checked the effect of an insulin-sensitizing drug, troglitazone, on this g ene expression. In the liver of db/db mice, PDE3B mRNA, its corresponding p rotein, 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/d b mice. Conversely, in the adipose tissue of db/db mice, PDE3B mRNA, protei n, and its associated activity were all decreased by 0.38, 0.33 and 0.36-fo ld, respectively. Troglitazone. which has no effect on PDE3B in liver, incr eased the expression of this gene in adipocytes. This increase is associate d with a reduction in the elevated levels of serum insulin, glucose, FFA an d triglycerides. The reduced PDE3B gene expression in adipose tissues, whic h 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 ex pression may correlate with changes in triglyceride storage in the liver of these mice. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.