PDE3B: A key regulator of cAMP/cGMP signaling in metabolic and cardiovascular health

•  Gene Information: PDE3B encodes phosphodiesterase 3B, an enzyme that hydrolyzes cyclic AMP (cAMP) and cyclic GMP (cGMP), with a higher affinity for cAMP. It plays a critical role in maintaining intracellular cyclic nucleotide levels and regulating key physiological processes, including insulin signaling, lipolysis, and cardiac function. 
• Protein Expression: PDE3B is mainly expressed in adipose tissue. 
• Signaling Pathway: PDE3B activation enhances cAMP hydrolysis to suppress catecholamine-induced lipolysis via the PKA–HSL/perilipin pathway, while insulin activates PDE3B through the IRS–PI3K–PKB/AKT signaling cascade to regulate cAMP levels, glucose uptake, and lipogenesis. 
• Therapeutic Method:  By inhibiting PDE3, these drugs effectively increase the intracellular concentrations of cAMP, leading to enhanced signaling and subsequent physiological effects.

PDE3B

•  A CDS that encodes human PDE3B followed by 3’UTR STOP is inserted right after mouse Pde3b ATG to replace the first coding exon of the mouse Pde3b gene. 
• The human PDE3B protein expression will be driven by the mouse endogenous promoter. 
•  The mouse Pde3b gene transcription and translation will be disrupted. 

Strain specific analysis of PDE3B mRNA expression in wild-type C57BL/6JNifdc mice and homozygous B-hPDE3B mice by RT-PCR. Subcutaneous fat and brown fat RNA were isolated from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hPDE3B mice (H/H), then cDNA libraries were synthesized by reverse transcription, followed by PCR with mouse or human PDE3B primers. Human PDE3B mRNA was detectable only in homozygous B-hPDE3B mice but not in wild-type mice. Mouse Pde3b mRNA was only detectable in wild-type mice.

Western blot analysis of PDE3B protein expression in homozygous B-hPDE3B mice. Various tissue lysates were collected from wild-type C57BL/6JNifdc mice (+/+) and homozygous B-hPDE3B mice (H/H), and then analyzed by western blot with anti-PDE3B antibody (Abcam, ab317026). 40 μg total proteins were loaded for western blotting analysis. Human PDE3B protein was only detectable in homozygous B-hPDE3B mice.