Cyclic @entity377 phosphodiesterases (PDEs) comprise a family of enzymes (PDE1-PDE11) which hydrolyse @entity1919 and @entity8262 to their biologically inactive 5' derivatives. @entity1919 is an important physiological amplifier of @entity413 -induced insulin secretion. As PDEs are the only known mechanism for inactivating @entity8613 , it is important to characterise the PDEs present in the pancreatic islet beta cells. Several studies have shown pancreatic islets or beta cells to contain @entity69402 , @entity45044 and PDE4, with some evidence for @entity69403 . Most evidence suggests that @entity45044 is the most important in relation to the regulation of insulin release, although @entity69402 could have a role. PDE3-selective inhibitors augment @entity413 -induced insulin secretion. In contrast, activation of beta-cell @entity45044 could mediate the inhibitory effect of @entity7424 and leptin on insulin secretion. In vivo, although PDE3 inhibitors augment @entity413 -induced insulin secretion, concomitant inhibition of @entity45044 in liver and adipose tissue induce insulin resistance and PDE3 inhibitors do not induce hypoglycaemia. The development of PDE3 inhibitors as anti- @entity6 agents would require differentiation between @entity45044 in the beta cell and that in hepatocytes and adipocytes. Through their effects in regulating beta-cell cyclic @entity377 concentrations, PDEs could modulate beta-cell growth, differentiation and survival; some work has shown that selective inhibition of PDE4 prevents @entity6 in NOD @entity19 and that selective PDE3 inhibition blocks cytokine-induced @entity842 production in islet cells. Further work is required to understand the mechanism of regulation and role of the various PDEs in islet-cell function and to validate them as targets for drugs to treat and prevent @entity6 .

Cyclic XXXX phosphodiesterases in pancreatic islets.

@entity6 :: ('MESH:D003920', 'Disease') :: ['diabetic', 'diabetes'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity377 :: ('CHEBI:36976', 'Chemical') :: ['nucleotide'] @entity69402 :: ('18575(Tax:10090)', 'Gene') :: ['PDE1C'] @entity8613 :: ('MESH:D009712', 'Chemical') :: ['cyclic nucleotides'] @entity8262 :: ('MESH:D006152', 'Chemical') :: ['cyclic GMP'] @entity1919 :: ('MESH:D000242', 'Chemical') :: ['Cyclic AMP', 'cyclic AMP'] @entity45044 :: ('18576(Tax:10090)', 'Gene') :: ['PDE3B'] @entity69403 :: ('23984(Tax:10090)', 'Gene') :: ['PDE10A'] @entity842 :: ('MESH:D009569', 'Chemical') :: ['nitric oxide'] @entity7424 :: ('16000(Tax:10090)', 'Gene') :: ['IGF-1'] @entity413 :: ('MESH:D005947', 'Chemical') :: ['glucose']
@entity377 :: (CHEBI:36976,Chemical) :: ['nucleotide']
