Pek S B, Walsh M F
Proc Natl Acad Sci U S A. 1984 Apr;81(7):2199-202. doi: 10.1073/pnas.81.7.2199.
We and others had observed that drugs that inhibit the lipoxygenase enzymes inhibit insulin release. The aim of the study was to search for evidence that, among the products of lipoxygenase-activated metabolism of arachidonic acid, leukotrienes (LTs) promote insulin release. Synthetic LTB4, LTC4, LTD4, and LTE4 were administered over 1-min periods to the isolated, perfused rat pancreas in the presence of 5.6 mM glucose. Perfusion effluent levels of insulin and glucagon were measured by radioimmunoassay. LTB4 and LTC4 and, to a lesser extent, LTE4 and LTD4 stimulated insulin release in a dose-related manner, in the concentration range of 10(-11) to 10(-7) M. Only 10(-7) M LTC4 stimulated glucagon release. We conclude that (i) among the arachidonic acid metabolites, LTs are involved in the modulation of secretion of pancreatic islet hormones and (ii) LTs preferentially promote insulin release.
我们和其他人曾观察到，抑制脂氧合酶的药物会抑制胰岛素释放。本研究的目的是寻找证据，证明在花生四烯酸经脂氧合酶激活代谢的产物中，白三烯（LTs）能促进胰岛素释放。在存在5.6 mM葡萄糖的情况下，将合成的LTB4、LTC4、LTD4和LTE4在1分钟内给予离体灌注的大鼠胰腺。通过放射免疫测定法测量胰岛素和胰高血糖素的灌注流出水平。LTB4和LTC4，以及程度较轻的LTE4和LTD4，在10(-11)至10(-7) M的浓度范围内以剂量相关的方式刺激胰岛素释放。只有10(-7) M的LTC4刺激胰高血糖素释放。我们得出结论：（i）在花生四烯酸代谢产物中，LTs参与调节胰岛激素的分泌；（ii）LTs优先促进胰岛素释放。
