title: Inhibition of phosphodiesterase 3B in insulin-secreting cells of normal and streptozocin-nicotinamide-induced diabetic rats: implications for insulin secretion.
abstract: Cyclic adenosine monophosphate (cAMP) plays important role in the potentiation of insulin secretion in pancreatic B-cells. However, the relevance of cAMP-degrading enzymes in the regulation of insulin secretion is not fully elucidated. The present work was undertaken to determine effects of inhibition of phosphodiesterase 3B (PDE3B) by amrinone on insulin secretion from pancreatic islets and perfused pancreas of normal and mildly diabetic rats. Inhibition of this enzyme was demonstrated to substantially increase insulin-secretory response to 6.7 mM glucose in the isolated islets and perfused pancreas of non-diabetic rats. Increment in glucose-induced insulin secretion resulting from inhibition of PDE3B was accompanied by an increase in islet cAMP levels and was suppressed by inhibition of protein kinase A. It was also demonstrated that insulin secretion stimulated by glucose and 1 μM forskolin was only slightly elevated in the presence of amrinone. Moreover, insulin release induced by succinate instead of glucose was also augmented by inhibition of PDE3B in rat islets. However, exposure of the pancreatic islets of streptozotocin-nicotinamide-induced diabetic rats to amrinone appeared to be without any effect on glucose-induced insulin secretion. Similar lack of response was shown in the perfused pancreas of diabetic rats. These results indicate that inhibition of PDE3B by amrinone significantly augments insulinotropic action of physiological glucose in B-cells of normal rats. This effect is mediated via protein kinase A and may be also induced in the presence of metabolizable stimuli other than glucose. Effects generated by amrinone were demonstrated to be, however, insufficient to enhance glucose-induced insulin secretion in B-cells of streptozotocin-nicotinamide-induced diabetic rats.
authors.affiliation: Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland. tszkudel@jay.up.poznan.pl.
authors.forename: A
authors.initials: A
authors.lastname: Zywert
authors.forename: K
authors.initials: K
authors.lastname: Szkudelska
authors.forename: T
authors.initials: T
authors.lastname: Szkudelski
mesh_terms: D000676:Amrinone / Q000737:chemistry / Q000494:pharmacology*; D000818:Animals; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3 / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000187:drug effects* / Q000201:enzymology* / Q000378:metabolism; D007515:Islets of Langerhans / Q000378:metabolism; D008297:Male; D009536:Niacinamide; D010726:Phosphodiesterase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013311:Streptozocin; D013329:Structure-Activity Relationship
chemical_list: D007328:Insulin; D010726:Phosphodiesterase Inhibitors; D009536:Niacinamide; D013311:Streptozocin; D054684:Cyclic Nucleotide Phosphodiesterases, Type 3; C517294:Pde3b protein, rat; D000676:Amrinone