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

Abstract

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 μg/mL naloxone or fentanyl + 1.0 μg/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 μIU vs 47.75 ± 8.47 μIU, 39.67 ± 6.18 μIU and 125.5 ± 22.04 μIU vs 96.17 ± 14.17 μIU, 75.17 ± 13.57 μIU, respectively, P < 0.01) and was lowest in group Ⅲ (P < 0.01). After adding 1 μg/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 β-cells of rat islets.

Opioid receptor-dependent modulation of insulin-release in pancreatic beta-cells

“…Green et al 24 first showed that morphine and met-enkephalin were able to stimulate glucose-induced insulin release in isolated pancreatic isles, an effect that was observed to develop rapidly, representing the first phase of pancreatic insulin release and which could be blocked by naloxone pre-treatment and therefore, showing an opioid-receptor mediated effect. A number of studies that followed confirmed the results of Green et al either directly [26][27][28] 24, 26, 27; 28, 29, 32, 33 , while others have shown the opposite inhibitory effect [34][35][36][37][38][39] .…”

“…Similarly to Qian et al 38 who used an MTT viability assay to assess whether opioid effect cellular toxicity of the opioid concentrations used, we used the TB viability assay to account for the potentially different effects of the different opioids used.…”

Effects of testosterone replacement on metabolic and inflammatory markers in men with opioid‐induced androgen deficiency

“…The increasing use of opioids for both cancer and noncancer pain has raised concerns regarding the potential long‐term safety of opioid exposure on cardiovascular risk. Both animal and human studies have demonstrated that opioid administration leads to hyperglycaemia by multiple mechanisms . Indeed, opioid receptors have been identified on pancreatic islets and laboratory studies have shown that opiates inhibit glucose‐stimulated insulin release from the beta cells .…”

“…Both animal and human studies have demonstrated that opioid administration leads to hyperglycaemia by multiple mechanisms. 17,[26][27][28] Indeed, opioid receptors have been identified on pancreatic islets and laboratory studies have shown that opiates inhibit glucose-stimulated insulin release from the beta cells. 26 Damage to the beta cells and desensitization of insulin receptor signalling by opiates have been posited as potential mechanisms.…”

“…17,[26][27][28] Indeed, opioid receptors have been identified on pancreatic islets and laboratory studies have shown that opiates inhibit glucose-stimulated insulin release from the beta cells. 26 Damage to the beta cells and desensitization of insulin receptor signalling by opiates have been posited as potential mechanisms. 26,29 In addition to their effects in causing metabolic dysregulation, recent studies in men have also implicated opioid use as a risk factor for coronary artery disease.…”