Cyclic Nucleotide Phosphodiesterase Families in Intracellular Signaling and Diabetes

  • Claire Lugnier
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 498)

Abstract

Cyclic nucleotide phosphodiesterases (PDE), by hydrolyzing cyclic AMP (cAMP) and cyclic GMP (cGMP), play a major role in intracellular signal transduction and participate in the regulation of pathophysiological states. This enzymatic system, is made up of at least 10 gene families (PDE1 to PDE10), differently distributed in tissues (Lugnier et al., 1983) and subcellular compartments and characterized by different substrate affinities and sensitivities to endogenous effectors (cGMP and calcium-calmodulin). The most studied families are PDE1 to PDE5. They are selectively inhibited by specific and very potent inhibitors (Beavo et al., 1994; Stoclet et al., 1995). These enzymes, when present in specific tissues implicated in pathophysiological states, are up-or down-regulated by various phosphorylating processes or by protein induction (Dousa, 1999). Therefore the altered PDE family could be a therapeutic target for the studied disease. PDE3 and PDE4 may represent new classes of drug targets for diabetes since it was reported that insulin-induced phosphorylation activates PDE3 (Degerman et al., 1990) and that PDE4 inhibitors may prevent installation of diabetes (Liang et al., 1998). Since these two PDE families play a major role in cardiovascular functions (Stoclet et al., 1995), PDE3 and PDE4 inhibitors may be especially useful in cardiovascular diseases associated to diabetes.

Keywords

Nitric Oxide Proliferative Diabetic Retinopathy Phosphodiesterase Inhibitor Diabetic Heart Nephrogenic Diabetes Insipidus 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer Science+Business Media New York 2001

Authors and Affiliations

  • Claire Lugnier
    • 1
  1. 1.Pharmacologie et Physico-Chimie des Interactions Moléculaires et CellulairesCNRS UMR 7034Université Louis Pasteur de Strasbourg,Faculté de PharmacieIllkirchFrance

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