Best L, Trebilcock R, Tomlinson S
Department of Medicine, University of Manchester, U.K.
Biochem Pharmacol. 1991 Feb 1;41(3):405-9. doi: 10.1016/0006-2952(91)90537-f.
The transport of L-lactate into rat pancreatic islets and RINm5F insulinoma cells was inhibited by alpha-cyano-4-hydroxycinnamate, alpha-fluorocinnamate, quercetin and by p-chloromercuribenzene-sulphonic acid. The addition of each of these compounds to perifused islets resulted in an immediate, marked stimulation of insulin release. Enhanced insulin secretion was accompanied by a similarly rapid and pronounced increase in the rate of 45Ca2+ efflux from pre-loaded, perifused islets. In general, these stimulatory effects were most pronounced in the presence of a threshold concentration of glucose (5 mM) in the perifusion medium. In islets pre-loaded with 86Rb+, the addition of alpha-fluorocinnamate or quercetin caused a modest diminution in efflux rate whilst enhanced rates of 86Rb+ outflow were apparent in the presence of 5 mM glucose. It is suggested that these inhibitors of lactic acid transport stimulate the beta-cell, at least in part, by increasing the intracellular: extracellular lactate gradient, thereby promoting the electrogenic efflux of endogenous lactate from the cell.
α-氰基-4-羟基肉桂酸、α-氟肉桂酸、槲皮素以及对氯汞苯磺酸均可抑制L-乳酸转运至大鼠胰岛和RINm5F胰岛素瘤细胞。将这些化合物中的每一种添加至灌注的胰岛中，都会立即显著刺激胰岛素释放。胰岛素分泌增强的同时，预加载的灌注胰岛中45Ca2+流出速率也会出现类似的快速且显著的增加。一般来说，在灌注培养基中存在阈值浓度的葡萄糖（5 mM）时，这些刺激作用最为明显。在预加载86Rb+的胰岛中，添加α-氟肉桂酸或槲皮素会使流出速率略有降低，而在存在5 mM葡萄糖的情况下，86Rb+流出速率会明显增加。有人认为，这些乳酸转运抑制剂至少部分是通过增加细胞内：细胞外乳酸梯度来刺激β细胞的，从而促进内源性乳酸从细胞中发生电致流出。
