title: Fatty acids and beta-cell toxicity.
abstract: OBJECTIVE
  The rising incidence of type 2 diabetes is due, in part, to the detrimental effects of certain fatty acids on pancreatic beta-cell function and viability. The present review examines recent advances in the understanding of the molecular mechanisms by which fatty acids influence the life and death of beta cells.
  
  
  RESULTS
  There are important differences in the cytotoxic potential of fatty acids, with long-chain saturated molecules being the most potent. By contrast, monounsaturates and polyunsaturates are relatively well tolerated and, in some cases, are actively cytoprotective. The mechanisms underlying the toxicity of the saturates may reflect a decrease in protein processing, which drives the accumulation of unfolded proteins in the endoplasmic reticulum. This triggers an apoptotic response by virtue of enhanced endoplasmic reticulum stress and induction of CHOP-10 synthesis. Alterations in the regulatory control of other proapoptotic genes via changes in microRNA synthesis may also contribute. The cytoprotection deriving from incubation with long-chain mono-unsaturates is probably receptor mediated and involves antagonistic actions on the effector arm of the endoplasmic reticulum stress pathway.
  
  
  CONCLUSIONS
  The findings have implications for the development of new therapeutic agents designed to minimize beta-cell dysfunction and the loss of beta-cell viability in type 2 diabetes.
authors.affiliation: Institute of Biomedical and Clinical Science, Peninsula Medical School, Plymouth, UK. noel.morgan@pms.ac.uk
authors.forename: Noel G
authors.initials: NG
authors.lastname: Morgan
mesh_terms: D002470:Cell Survival / Q000187:drug effects; D019610:Cytoprotection; D004041:Dietary Fats / Q000009:adverse effects*; D005227:Fatty Acids / Q000009:adverse effects* / Q000378:metabolism; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects*; D008562:Membrane Glycoproteins / Q000378:metabolism
chemical_list: D004041:Dietary Fats; D005227:Fatty Acids; D008562:Membrane Glycoproteins