Abstract
Background and Objectives: Increasing concentration of cAMP in beta cells stimulates the insulin secretion and almost the cyclic nucleotide phosphodiesterases (PDEs) are the only cAMP degrading enzymes. Between different PDE Families, PDE3 is the most important isoenzyme in pancreas and liver. In this study, PDE inhibitors combined with the stimulating effect of glucose, as the most important physiologic stimulant of insulin secretion, were examined in anesthetized rat (in-vivo) and isolated langerhans islets of rat (in-vitro).
Materials and Methods: The effects of PDE inhibitors such as IBMX (non-selective), Milrinone, Amrinone and Trequinsin (PDE3 selective) and Dipyridamole (PDE5 selective) in the rat’s isolated islets and anesthetized hyperglycemic rats (within 90min) were studied. As, insulin secretion by isolated islets and plasma concentration of glucose and insulin with hepatic glycogen storage after 90 min. hypertonic glucose infusion, were measured.
Results: Milrinone, Amrinone and Trequinsin despite Dipyridamole stimulated islets insulin secretion. All PDE inhibitors with some differences, decreased blood glucose in rats. Dipyridamole and IBMX had no effect on insulin, although Milrinone and Trequinsin increased and Amrinone decreased it. Rats’ liver glycogen storage decreased by Amrinone, Trequinsin and IBMX, while increased by Dipyridamole.
Conclusion: PDE3 inhibitors in rats' isolated islets; despite the PDE5, stimulated insulin secretion. In hyperglycemic rats, PDE inhibitors had different effects. We conclude that PDE inhibitors with different effects act by mechanisms other than PDE inhibition, too.