Diabetes Research Unit, Institute for Drug Research, School of Pharmacy, Faculty of Medicine
Beta cells operate an hormetic mechanism to alleviate cytotoxic effects of free fatty acids. We have previously discovered that both high glucose and increasing palmitic acid levels induce substantial remodelling of membrane phospholipids and alter the relative abundance of saturated-, mono-unsaturated- and poly-unsaturated fatty acids. We aim at investigating the impact of the transformation of arachidonic acid into endocannabinoids under hyperglycemia and hyperlipidemic conditions. We have already reported that both conditions increase PLA2 activity and the hydrolysis of arachidonic acid from membrane phospholipids. Peroxidation of arachidonic acid leads to the generation of 4 hydroxynonenal that activates PPARδ and upregulates insulin secretion. Other studies assigned a regulatory role for endocannabinoids in beta cell function. We will investigate the mechanisms by which endocannabinoid biosynthesis is regulated in beta cells under nutrient overload stress.