Abstract
As shown by transgenic mouse models and by using phosphodiesterase 3 (PDE3) inhibitors, PDE3B has an important role in the regulation of insulin secretion in pancreatic β-cells. However, very little is known about the regulation of the enzyme. Here, we show that PDE3B is activated in response to high glucose, insulin and cAMP elevation in rat pancreatic islets and INS-1 (832/13) cells. Activation by glucose was not affected by the presence of diazoxide. PDE3B activation was coupled to an increase as well as a decrease in total phosphorylation of the enzyme. In addition to PDE3B, several other PDEs were detected in human pancreatic islets: PDE1, PDE3, PDE4C, PDE7A, PDE8A and PDE10A. We conclude that PDE3B is activated in response to agents relevant for β-cell function and that activation is linked to increased as well as decreased phosphorylation of the enzyme. Moreover, we conclude that several PDEs are present in human pancreatic islets.
Highlights
Cyclic nucleotide phosphodiesterases (PDEs) are enzymes with the function to hydrolyze cyclic AMP and cyclic GMP [1,2]
We show that PDE1, phosphodiesterase 3 (PDE3), PDE4C, PDE7A, PDE8A and PDE10A are expressed in human pancreatic islets
We could detect PDE4C, PDE7A, PDE8A and PDE10A. These results show that PDE1, PDE3, PDE4C, PDE7A, PDE8A and PDE10A are present in human pancreatic islets
Summary
Cyclic nucleotide phosphodiesterases (PDEs) are enzymes with the function to hydrolyze cyclic AMP (cAMP) and cyclic GMP (cGMP) [1,2]. More recently mRNAs for PDE1B-C, PDE2A, PDE3A-B, PDE4A-D, PDE5A, PDE8A-B, PDE9A, PDE10A and PDE11A as well as the proteins PDE3A-B, PDE4B and PDE8A have been detected in rodent pancreatic islets and b-cell lines [8,10,11,13]. Of these PDEs, PDE8B and PDE10A have potential in the context of b-cell function, since diminished activity of PDE8B [13] as well as PDE10A inhibition [14] potentiated insulin secretion in response to glucose in rat pancreatic islets
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
