Elevated blood levels of glucose and lipids in individuals with type 2 diabetes mellitus have been observed to cause impairment of insulin secretion from pancreatic beta-cells. Chronic exposure to either of the circulating fatty acid oleate or palmitate has different effects on the beta-cell. Whereas palmitate causes functional impairment of the beta-cell and apoptosis, oleate has only minor negative effects on beta-cell function and mass. The aim of the present study was to delineate mechanisms by which the fatty acids affect the beta-cell differently. In particular, the aim was to identify beta-cell proteins exclusively regulated by palmitate. INS-1E cells were cultured for 24h in medium supplemented with palmitate or oleate. After culture, cells were lysed and subjected to two-dimensional gel electrophoresis. Proteins specifically regulated by palmitate were excised from the gel and identified by peptide mass fingerprinting using MALDI-TOF MS. Proteins exclusively regulated by palmitate were classified into proteins of carbohydrate or protein metabolism and Ca(2+) or mRNA binding proteins. The specific palmitate-induced down-regulation of enzymes of glycolysis, proteins of protein turnover and anti-apoptotic protein may contribute to explain the different effects exerted by palmitate and oleate on beta-cell function and mass.
Copyright 2010 Elsevier B.V. All rights reserved.