Palmitate-induced changes in protein expression of insulin secreting INS-1E cells.
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.
Hovsepyan
Meri
M
Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden. Meri.Hovsepyan@mcb.uu.se
Sargsyan
Ernest
E
Bergsten
Peter
P
D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism; D015180:Electrophoresis, Gel, Two-Dimensional / Q000379:methods; D005786:Gene Expression Regulation; D006019:Glycolysis; D006801:Humans; D007091:Image Processing, Computer-Assisted; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D008954:Models, Biological; D019301:Oleic Acid / Q000737:chemistry; D010168:Palmitates / Q000494:pharmacology*; D019308:Palmitic Acid / Q000737:chemistry; D040901:Proteomics / Q000379:methods*; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
D010168:Palmitates; D019301:Oleic Acid; D019308:Palmitic Acid