In the paraventricular hypothalamic nucleus (PVN), the acyl ethanolamides and the cannabinoid signalling system could downregulate the hypothalamic-pituitary-adrenal (HPA) axis, as oral treatment of lean and obese Zucker rats with the cannabinoid-1 receptor (CB1) antagonist rimonabant, an anorectic drug, leads to increase in basal corticosterone levels19, similar to the higher fasting plasma cortisol levels that we observed in the T2D and T2D-DN groups. This evidence concerns the gene CNR1 and type 2 diabetes mellitus.