Evaluation of the effects of new synthetic methylquinolinone derivatives on glucose-induced insulin secretion from rat's isolated Langerhans islets

Selective PDE3 inhibitors, via cyclic adenosine monophosphate (cAMP) accumulation increase cardiac contraction and augment glucose-induced insulin secretion. In this study, the effects of some synthetic methylquinolinone derivatives (MC1-MC10) on glucose-induced insulin secretion in rat's isolated Langerhans islets model were investigated. After the digestion of isolated pancreas using collagenase-IV, the isolated islets were collected manually under a stereomicroscope and were incubated in carboxyl buffer having 3mM glucose for 30 minutes. Then, they were incubated at 37°C presented to basal (3mM) and stimulatory (10mM) dose of glucose with or without different methylquinolinone derivatives and 3-isobutyl-1-methylxanthine (IBMX) (as standard) in 100µM concentration. After 60 minutes of incubation, the secreted insulin was measured using a radioimmunoassay method. Glucose significantly increased insulin release with 10mM concentration in comparison with 3mM concentration (P<0.01). IBMX (100µM) significantly augmented glucose-induced insulin secretion (P<0.01). However, among the investigated ten compounds only MC7 and MC9 significantly increased glucose-induced insulin secretion (P<0.01) which was comparable with IBMX. In spite of having similar structure, the effect of the test compounds (MC1-MC10) on insulin secretion varied widely which may be due to their tissue-specific effects. Finally, it is hoped that the ligands will probably be used in the treatment of diabetes in the future.