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

Abstract

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.

The immune-opioid axis in prediabetes: predicting prediabetes with insulin resistance by plasma interleukin-10 and endomorphin-2 to kappa-opioid receptors ratio

“…In muscle tissues and cells, an association occurs between MOR and IRS [ 32 ]. It is found that opioid-induced insulin secretion may be based on G-protein independent mechanisms [ 49 ]. Based on a linear regression analysis, βEP is the strongest protein associated with the β-cell function [ 20 ].…”