ABSTRACT
The activation and phosphorylation of phosphodiesterase 3B (PDE3B) by 3',5'-cyclic adenosine monophosphate (cAMP)-increasing hormones is thought to be important in feedback regulation of cAMP- and cAMP-mediated responses. The regulatory N-terminal portions of PDE3A and PDE3B are quite divergent and contain large hydrophobic regions with predicted transmembrane helical segments. In summary, the phenotypic characteristics of PDE3B knockout (KO) mice indicate that PDE3B plays a unique role not only in adipocytes but also in pancreatic beta cells and hepatocytes and is not apparently functionally compensated for, by other PDE gene families or by the other PDE3 family member, PDE3A. Although not frankly diabetic, PDE3B KO mice demonstrate alterations in the regulation of energy homeostasis, including signs of insulin resistance and a number of other alterations in the regulation of energy homeostasis. Phosphorylation and activation of PDE3 induced by cAMP-increasing hormones and insulin and insulin-like growth factor-I has been demonstrated in intact adipocytes, hepatocytes, and platelets.
