title: Expression and regulation of cyclic nucleotide phosphodiesterases in human and rat pancreatic islets.
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.
authors.affiliation: Department of Experimental Medical Science, Division for Diabetes, Metabolism and Endocrinology, Lund University, Lund, Sweden. emilia.heimann@med.lu.se
authors.forename: Emilia
authors.initials: E
authors.lastname: Heimann
authors.forename: Helena A
authors.initials: HA
authors.lastname: Jones
authors.forename: Svante
authors.initials: S
authors.lastname: Resjö
authors.forename: Vincent C
authors.initials: VC
authors.lastname: Manganiello
authors.forename: Lena
authors.initials: L
authors.lastname: Stenson
authors.forename: Eva
authors.initials: E
authors.lastname: Degerman
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000096:biosynthesis* / Q000235:genetics; D003981:Diazoxide / Q000494:pharmacology; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology; D007340:Insulinoma / Q000378:metabolism; D007515:Islets of Langerhans / Q000201:enzymology*; D008297:Male; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013045:Species Specificity
chemical_list: D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; D005947:Glucose; D003981:Diazoxide