Department of Medical Cell Biology, Uppsala University, Uppsala, Sweden.
J Proteomics. 2010 Apr 18;73(6):1148-55. doi: 10.1016/j.jprot.2010.01.012. Epub 2010 Feb 1.
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.
在 2 型糖尿病患者中，观察到升高的血糖和血脂水平导致胰腺β细胞胰岛素分泌受损。慢性暴露于循环脂肪酸油酸或棕榈酸中的任何一种都对β细胞产生不同的影响。虽然棕榈酸会导致β细胞功能障碍和细胞凋亡，但油酸对β细胞功能和质量只有较小的负面影响。本研究的目的是阐明脂肪酸影响β细胞的不同机制。特别是，目的是确定仅受棕榈酸调节的β细胞蛋白。INS-1E 细胞在补充有棕榈酸或油酸的培养基中培养 24 小时。培养后，细胞裂解并用二维凝胶电泳处理。从凝胶中取出仅受棕榈酸调节的蛋白质，并使用 MALDI-TOF MS 通过肽质量指纹图谱进行鉴定。仅受棕榈酸调节的蛋白质被分类为碳水化合物或蛋白质代谢以及 Ca（2+）或 mRNA 结合蛋白的蛋白质。糖酵解酶、蛋白质周转率和抗凋亡蛋白的特定棕榈酸诱导下调可能有助于解释棕榈酸和油酸对β细胞功能和质量的不同影响。
