细胞内脂肪堆积和β细胞增殖的关系

Accumulation of lipid and the proliferation of pancreatic islet beta cells

目的研究脂肪酸(FA)对β细胞增殖抑制与细胞内的脂肪堆积的关系及相关的葡萄糖(Glu)浓度的影响。方法培养胰岛β细胞株Ins1E细胞,用3H胸腺嘧啶和3H棕榈酸掺入的方法分别研究β细胞增殖及β细胞内脂肪堆积。利用RTPCR方法测定肉毒碱棕榈酰转移酶1(CPT1)基因表达。结果与3.3mmol/LGlu比较,24小时后6.6mmol/L和11mmol/LGlu使细胞增殖增加2.27和3.04倍(P<0.05);加入0.4mmol/L棕榈酸后细胞增殖降为1.1和0.86倍(与无棕榈酸相比P<0.05)。高浓度的Glu使细胞内脂肪堆积增加15%～92%。TriacsinC或Wy14643能减少13%～54%的脂肪堆积,同时缓解FA对细胞增殖的抑制作用48%～71%。FA刺激CPT1基因的表达,Glu对其有剂量依赖性的抑制,20mmol/LGlu使CPT1基因的表达减少50%(P<0.05)。结论FA对β细胞增殖的抑制与脂肪在细胞内堆积有关,Glu可能通过抑制FA刺激CPT1基因的表达,增加FA堆积从而介导FA对细胞增殖的抑制作用。

Objective To explore whether an excessive accumulation of lipids is involved in the suppression of β cell proliferation and to determine the role of glucose in this experiment. Methods The proliferation of the Ins-1E cells was studied by s H-thymidine incorporation. The accumulation of fatty acids in beta cells was studied by ^3H-palmitate incorporation. Using Taqman real-time RT- PCR, we measured the expression of carnitine palmitoyltransferase-1 （CPT-1） gene. Results As compared with 3.3 mmol/L glucose, the 6.6 mmol/L and 11 mmol/L glucose increased the cell proliferation by 2.27 and 3.04 folds （P〈0.05）, and the supplemented 0.4 mmol/L palmitate blunted the glucose-induced cell proliferation （1.1 and 0. 86 fold, at 6.6 and 11 mmol/L glucose, respectively）. With increasing glucose levels, the incorporation of palmitate was augmented, which ranged from 15 to 92%. Wy 14 643 and Triacsin C alleviated the palmitate-induced inhibition of cell proliferation and reduced the incorporation of palmitate. Glucose did not change the expression of CPT-1 gene, but inhibited the palmitate-induced expression in a dose dependent manner. Conclusions The FA-stimulated CPT-1 gene expression is inhibited by glucose, which increases the FA accumulation in β cells and inhibits their proliferation. This could be underlying the mechanism of glucose-dependent lipotoxicity.