Prostaglandins are lipid mediators involved in physiological processes, such as constriction or dilation of blood vessels, but also pathophysiological processes, which include inflammation, pain and fever. They are produced by almost all cell types in the organism by activation of Prostaglandin endoperoxide synthases/Cyclooxygenases. The inducible Prostaglandin Endoperoxide Synthase 2/Cyclooxygenase 2 (PTGS2/COX2) plays an important role in pathologies associated with inflammatory signaling. The main product derived from PTGS2/COX2 expression and activation is Prostaglandin E2 (PGE2), which promotes a wide variety of tissue-specific effects, pending environmental inputs. One of the major sources of PGE2 are infiltrating inflammatory cells - the production of this molecule increases drastically in damaged tissues. Immune infiltration is a hallmark of type 1 diabetes mellitus, a multifactorial disease that leads to autoimmune-mediated pancreatic beta cell destruction. Controversial effects for the PTGS2/COX2-PGE2 signaling cascade in pancreatic islet cells subjected to diabetogenic conditions have been reported, allocating PGE2 as both, cause and consequence of inflammation. Herein, we review the main effects of this molecular pathway in a tissue-specific manner, with a special emphasis on beta cell mass protection/destruction and its potential role in the prevention or development of T1DM. We also discuss strategies to target this pathway for future therapies.

Genome-wide association studies have detected an association between type 2 diabetes risk and a non-coding SNP located in MTNR1B, the gene encoding melatonin receptor 2 (MT2). Melatonin regulates circadian rhythms and sleep and associates with metabolic disorders. However, the mechanisms underlying these actions are still unclear. Functional genomic, animal and clinical studies have not reached the same conclusions: while some studies have reported that decreased melatonin signalling increases type 2 diabetes risk, others have found the opposite. In this commentary, we have tried to provide an explanation for these contradictions and we suggest how the community may progress to reach a unified picture of the effect of melatonin and its signalling on type 2 diabetes.