Hallberg A, Berne C, Andersson A
Biochem Pharmacol. 1984 May 1;33(9):1465-70. doi: 10.1016/0006-2952(84)90414-3.
Pancreatic islets accumulate the amphiphilic drug, chloroquine, which leads to a marked impairment of the insulin production of the B-cells in vitro. In this study the effects of the drug on islet lipid metabolism in vitro were investigated. It was found that exposure of islets to chloroquine (10(-5) M) for one week induced an increase of D-[U-14C]glucose incorporation into phospholipids and triacylglycerols of about two-fold and into diacylglycerols of about six-fold. Furthermore, two-dimensional thin-layer chromatography showed an increased rate of D-[U-14C]glucose incorporation into all major phospholipid classes. A 17% increase of the total islet phospholipid content indicated that an accumulation of islet cell phospholipids occurred. Pulse-chase experiments with D-[U-14C]glucose showed that the rate of degradation of islet phospholipids was decreased after prolonged exposure to chloroquine. No short-term effects of chloroquine upon either the de novo biosynthesis of islet lipids or upon phospholipid degradation could be demonstrated. The present data therefore suggest that chloroquine impairs the rate of islet lipid degradation in long-term experiments, which may be a primary lesion in the sequence of events leading to functional impairment of the B-cell.
胰岛会蓄积两亲性药物氯喹，这会导致体外培养的B细胞胰岛素分泌显著受损。本研究对该药物在体外对胰岛脂质代谢的影响进行了调查。结果发现，胰岛在10⁻⁵ M氯喹中暴露一周后，D-[U-¹⁴C]葡萄糖掺入磷脂和三酰甘油的量增加了约两倍，掺入二酰甘油的量增加了约六倍。此外，二维薄层色谱显示D-[U-¹⁴C]葡萄糖掺入所有主要磷脂类别的速率均有所增加。胰岛总磷脂含量增加了17%，表明胰岛细胞磷脂发生了蓄积。用D-[U-¹⁴C]葡萄糖进行的脉冲追踪实验表明，长时间暴露于氯喹后，胰岛磷脂的降解速率降低。未发现氯喹对胰岛脂质的从头生物合成或磷脂降解有短期影响。因此，目前的数据表明，在长期实验中氯喹会损害胰岛脂质的降解速率，这可能是导致B细胞功能受损的一系列事件中的原发性病变。
