Role of μ-opioid receptors in insulin release in the presence of inhibitory and excitatory secretagogues

Garcı́a-Barrado, Marı́a José; Iglesias-Osma, María Carmen; Rodrı́guez, Raquel E.; Martı́n, M.a Isabel; Moratinos, Julio

doi:10.1016/s0014-2999(02)01897-6

Cited by 19 publications

(13 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These observations have yielded conflicting results with marked variations between species. Therefore, it could not be hypothesized whether fentanyl inhibits insulin release [13] . Our results clearly demonstrate that fentanyl inhibited glucose-stimulated insulin release from islets in vitro.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

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

Qian¹,

Wang²,

Liu³

et al. 2009

WJG

View full text Add to dashboard Cite

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.

show abstract

Section: Discussionmentioning

confidence: 99%

“…In mouse pancreatic islets incubated under static conditions, glucose-stimulated insulin release is inhibited by β-endorphin and endomorphin-1, endogenous opioid receptor agonists. This inhibition could be prevented by naloxone, an opioid receptor antagonist [13] . Therefore, we hypothesized that fentanyl would affect insulin release.…”

Section: Introductionmentioning

confidence: 99%

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

Qian¹,

Wang²,

Liu³

et al. 2009

WJG

View full text Add to dashboard Cite

show abstract

“…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] .…”

Section: Introductionmentioning

confidence: 74%

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

Paul¹,

Guven²,

Dietis

2014

PBJ

View full text Add to dashboard Cite

In this study we aimed to look at the effects of opioid-receptor selective agonists and antagonists on insulin secretion in the pancreatic β-cell line RIN-5F. Cells were treated for 24 hours with 1μM of selective agonists (DAMGO for MOP, DPDPE for DOP, U50488 for KOP) in the presence or absence of 10μM of selective antagonists (CTOP for MOP, naltrindole for DOP, norBNI for KOP).An enzyme-based immunoassay was used to detect the amount of insulin in the supernatant, using a standard curve generated from known concentrations of rat insulin. A trypan blue viability assay was performed to assess the toxicity of each treatment and the secreted insulin was expressed as per 10 3 viable cells. Treatment with DAMGO or DPDPE caused an increase in secreted insulin by 94.2% and 76.3% respectively, compared to the non-treated controls. Cotreatment of DAMGO and CTOP was able to cancel out the agonists' effect. However, CTOP itself was able to increase insulin secretion by 72% when compared to control. These results suggest that opioid-induced insulin secretion may be based on G-protein independent mechanisms. In addition, none of the KOP-receptor selective ligands tested here were able to significantly affect insulin secretion compared to control, whereas naltrindole was highly toxic to pancreatic β-cells since it induced maximum cell death. Collectively, these findings suggest that MOP and DOP receptor-binding opioids might be more relevant in increasing insulin secretion from pancreatic β-cells than KOP receptor ligands.

show abstract

“…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 .…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

Section: Discussionmentioning

confidence: 99%

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

Huang

Travison

Maggio

et al. 2016

Clinical Endocrinology

View full text Add to dashboard Cite

show abstract

Role of μ-opioid receptors in insulin release in the presence of inhibitory and excitatory secretagogues

Cited by 19 publications

References 48 publications

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

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

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

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

Contact Info

Product

Resources

About