Abstract
The endocannabinoid system has emerged as a potential regulator of insulin secretion, implicating its significance in metabolic diseases such as diabetes. In this study, we sought to elucidate the influence of delta-9 tetrohydrocannabinoid (THC) and other cannabinoids on insulin secretion in a mouse pancreatic cell line (MIN6), which retain their ability to secrete insulin.
First, the components of the endocannabinoid system were quantified using quantitative PCR in MIN6 cells subjected to high (25 mM) and low (2.75 mM) glucose treatments for a 2-hour and 20-hour exposure period. This investigation provided insights into the potential disruption of endocannabinoid signalling under hyperglycaemic conditions. The formation enzyme of one of the main endocannabinoids, 2-arachidnoic-glycerol, was shown to have a significantly lower ΔCq following long-term high-glucose conditions compared to long-term low-glucose conditions (ΔCq 7.2 vs. 9.2, P<0.05, two-way ANOVA, Tukey’s post hoc, n=3), indicating higher levels the enzyme in the cells. No changes were observed in the breakdown enzymes. This is consistent with previous studies suggesting Type 2 diabetics, with consistent elevated blood glucose levels, have elevated endocannabinoid levels.
Subsequently, insulin levels were detected using an alphaLISA detection kit. Various cannabinoid agonists, including THC, were tested on cells in no and high glucose buffer. A significant two-fold increase (P<0.05, two-way ANOVA, Tukey’s post hoc, n=3) in insulin secretion was observed in cells treated with cannabinoid agonists regardless of glucose concentration. In cells treated with a cannabinoid antagonist with and without the agonists, a reduction in insulin secretion was observed.
These results suggest that regular cannabis use could be elevating insulin levels, contributing to a reduction in insulin sensitivity. Furthermore, the elevation in endocannabinoids observed in diabetics could be contributing to β-cell death, contributing to the development of diabetes. Therefore, cannabis use could be detrimental to those at risk of diabetes or could contribute to the development of diabetes. Further research is needed to determine a precise mechanism by which this occurs and to allow for targeting for the treatment of diabetes.