Unsaturated fatty acids as cytoprotective agents in the pancreatic β-cell

It is widely accepted that, in type 2 diabetes, elevated levels of free fatty acids and glucose contribute to a state of glucolipotoxicity in which β-cell function declines and, ultimately, cell viability is compromised. This suggests that β-cells do not readily tolerate chronic elevations in fatty acid levels. In vitro studies suggest, however, that β-cells respond differentially to long chain fatty acids, such that saturated species are lipotoxic whereas long chain mono-unsaturated fatty acids can provide cytoprotection. This difference does not appear to be mediated by a mutual metabolic antagonism between saturated and unsaturated species (although differential alterations in neutral lipid disposition may occur in response to these fatty acids) and the mechanisms remain unclear. This review summaries the current understanding of the actions of mono-unsaturated fatty acids in β-cells and highlights areas of controversy as well as key unresolved issues which require to be addressed.