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


CONCLUSIONS
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.
Qian
Tao-Lai
TL
Department of Pain Management, Shanghai East Hospital, Tongji University, 150 Jimo Road, Shanghai 2000120, China. qiantaolai@sina.com
Wang
Xin-Hua
XH
Liu
Sheng
S
Ma
Liang
L
Lu
Ying
Y
D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D005283:Fentanyl / Q000494:pharmacology*; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley
D000701:Analgesics, Opioid; D007328:Insulin; D009270:Naloxone; D005947:Glucose; D005283:Fentanyl