Fentanyl inhibits glucose-stimulated insulin release from beta-cells in rat pancreatic islets.

Aim: To explore the effects of fentanyl on insulin release from freshly isolated rat pancreatic islets in static culture.

Methods: Islets were isolated from the pancreas of mature Sprague Dawley rats by common bile duct intraductal collagenase V digestion and were purified by discontinuous Ficoll density gradient centrifugation. The islets were divided into four groups according to the fentanyl concentration: control group (0 ng/mL), group I (0.3 ng/mL), group II (3.0 ng/mL), and group III (30 ng/mL). In each group, the islets were co-cultured for 48 h with drugs under static conditions with fentanyl alone, fentanyl + 0.1 microg/mL naloxone or fentanyl + 1.0 microg/mL naloxone. Cell viability was assessed by the MTT assay. Insulin release in response to low and high concentrations (2.8 mmol/L and 16.7 mmol/L, respectively) of glucose was investigated and electron microscopy morphological assessment was performed.

Results: Low- and high-glucose-stimulated insulin release in the control group was significantly higher than in groups II and III (62.33 +/- 9.67 microIU vs 47.75 +/- 8.47 microIU, 39.67 +/- 6.18 microIU and 125.5 +/- 22.04 microIU vs 96.17 +/- 14.17 microIU, 75.17 +/- 13.57 microIU, respectively, P < 0.01) and was lowest in group III (P < 0.01). After adding 1 microg/mL naloxone, insulin release in groups II and III was not different from the control group. Electron microscopy studies showed that the islets were damaged by 30 ng/mL fentanyl.

Conclusion: Fentanyl inhibited glucose-stimulated insulin release from rat islets, which could be prevented by naloxone. Higher concentrations of fentanyl significantly damaged beta-cells of rat islets.