High impact information on Pde3b

• A phosphatidylinositol 3-kinase phosphodiesterase 3B-cyclic AMP pathway in hypothalamic action of leptin on feeding [1].
• Here, we show a novel leptin signaling mechanism that requires phosphoinositide 3-kinase (PI 3-kinase)-dependent activation of cyclic nucleotide phosphodiesterase 3B (PDE3B) and subsequent suppression of cAMP levels [2].
• In pancreatic beta cells, leptin causes the activation of PDE3B, which leads to marked inhibition of glucagon-like peptide-1-stimulated insulin secretion [2].
• Important role of phosphodiesterase 3B for the stimulatory action of cAMP on pancreatic beta-cell exocytosis and release of insulin [3].
• Furthermore, both PKB and the kinase that phosphorylates PDE 3B were found to translocate to membranes in response to peroxovanadate stimulation of adipocytes in a wortmannin-sensitive way [4].

Biological context of Pde3b

• However, rapamycin had no effect on the insulin-induced phosphorylation/activation of PDE 3B or the activation of the kinase that phosphorylates PDE 3B [4].
• Phosphodiesterase 3B isoform messenger RNA is uniformly expressed in germinal neuroepithelium and mature neurons, with distribution generally reflecting cell density [5].
• The insulin-induced phosphorylation of the 50 kDa protein was also detected in a cell free system against the N-terminal and the catalytic regions, which are more than 700 amino acids apart recognize the 50 kDa protein, suggesting that it is not a proteolytic product, but an associated protein with PDE3B [6].
• Contrary to cAMP, the activation of glycogen catabolism promoted by 8-Br-cAMP (0.3 microM), a cAMP analogue more resistant to hydrolysis by phosphodiesterase 3B (PD3B), was inhibited (p < 0.05) not only by insulin (20 microU/ml) but also by leptin (10 ng/ml) [7].

Anatomical context of Pde3b

• Pretreatment of adipocytes with the MAP kinase kinase inhibitor PD 98059 was without effect on the insulin-induced activation of PDE 3B [4].

Associations of Pde3b with chemical compounds

• Insulin stimulation of adipocytes results in serine phosphorylation/activation of phosphodiesterase 3B (PDE 3B) and activation of a kinase that phosphorylates PDE 3B in vitro, key events in the antilipolytic action of this hormone [4].
• Furthermore, phorbol myristate acetate stimulation did not result in phosphorylation/activation of PDE 3B or activation of the kinase that phosphorylates PDE 3B [4].

Enzymatic interactions of Pde3b

• The effect of leptin is abolished when insulin secretion is induced with cAMP analogues that cannot be hydrolyzed by PDE3B [2].

Regulatory relationships of Pde3b

• Here we show that glucocorticoids stimulate endocannabinoid biosynthesis and release via a Galpha(s)-cAMP-protein kinase A-dependent mechanism and that leptin blocks glucocorticoid-induced endocannabinoid biosynthesis and suppression of excitation in the PVN via a phosphodiesterase-3B-mediated reduction in intracellular cAMP levels [8].

Other interactions of Pde3b

• Using Mono Q and Superdex chromatography, the kinase that phosphorylates PDE 3B was found to co-elute with PKB, but not with p70 S6 kinase or MAP kinases [4].

References