PDE3B is a dual-specificity cyclic nucleotide phosphodiesterase that hydrolyzes both cAMP and cGMP, serving as a critical regulator of multiple physiological processes 12. Functionally, PDE3B negatively regulates lipolysis by suppressing the cAMP-protein kinase A signaling axis in adipose tissue, with insulin mediating antidiabetic effects through PDE3B-dependent pathways distinct from the FGF1/PDE4D mechanism 3. Additionally, PDE3B regulates angiogenesis by inhibiting RAPGEF3 and downstream phosphatidylinositol 3-kinase gamma signaling 2. At the molecular level, PDE3B functions as a copper-dependent signaling enzyme and metalloallosteric regulator, linking copper metabolism to cell proliferation and lipolysis control 4. Clinically, PDE3B variants associate with fat distribution and local adiposity traits independent of BMI, with rare variant associations particularly impacting visceral and abdominal subcutaneous adipose tissue composition 5. These genetic associations with adiposity distribution have important implications for cardiometabolic health outcomes, including type 2 diabetes and coronary artery disease risk 5. The PDE3B/Akt signaling pathway is also implicated in therapeutic responses to natural compounds with antidiabetic and cardiovascular protective properties 6.