Comens P G, Wolf B A, Unanue E R, Lacy P E, McDaniel M L
Diabetes. 1987 Aug;36(8):963-70. doi: 10.2337/diab.36.8.963.
The effects of interleukin 1 (IL-1) on glucose-induced insulin secretion from isolated rat islets of Langerhans have been examined. IL-1 both inhibits and stimulates glucose-induced insulin secretion depending on the experimental design. Inhibition of glucose-induced insulin secretion was observed after a 15-h treatment of islets with either purified IL-1, murine recombinant IL-1 (rIL-1), or human rIL-1, rIL-1 inhibition of glucose-induced insulin secretion was dose dependent with half-maximal inhibition observed at 25 pM human rIL-1. Basal insulin secretion was not affected by rIL-1 treatment. Mannose- and leucine-induced insulin secretion was also inhibited by a 15-h treatment with human rIL-1. Islets treated 15 h with inhibitory concentrations of murine IL-1 were morphologically intact, well granulated, and retained normal concentrations of insulin compared with control islets. Furthermore, human rIL-1 treatment did not affect the islet plasma membrane permeability as assessed by the measurement of the islet intracellular volume. Finally, the viability of islets treated 15 h with murine rIL-1 was demonstrated by the observation that the inhibitory effects of murine rIL-1 on glucose-induced insulin secretion were reversible. In addition to the inhibitory effects of IL-1 on glucose-induced insulin secretion, purified IL-1 and human rIL-1 had stimulatory effects on glucose-induced insulin secretion under the following conditions: a 90-min incubation with purified IL-1 (10% vol/vol) or in the presence of human rIL-1 (1400 pM) or a 15-h incubation with relatively low concentrations of human rIL-1 (0.5 or 5 pM).(ABSTRACT TRUNCATED AT 250 WORDS)
研究了白细胞介素1(IL-1)对分离的大鼠胰岛葡萄糖诱导的胰岛素分泌的影响。根据实验设计,IL-1既抑制又刺激葡萄糖诱导的胰岛素分泌。用纯化的IL-1、鼠重组IL-1(rIL-1)或人rIL-1对胰岛进行15小时处理后,观察到葡萄糖诱导的胰岛素分泌受到抑制。rIL-1对葡萄糖诱导的胰岛素分泌的抑制作用呈剂量依赖性,在25 pM人rIL-1时观察到半数最大抑制。基础胰岛素分泌不受rIL-1处理的影响。用15小时的人rIL-1处理也抑制了甘露糖和亮氨酸诱导的胰岛素分泌。与对照胰岛相比,用抑制浓度的鼠IL-1处理15小时的胰岛形态完整、颗粒良好,且胰岛素浓度正常。此外,通过测量胰岛细胞内体积评估,人rIL-1处理不影响胰岛质膜通透性。最后,通过观察鼠rIL-1对葡萄糖诱导的胰岛素分泌的抑制作用是可逆的,证明了用鼠rIL-1处理15小时的胰岛的活力。除了IL-1对葡萄糖诱导的胰岛素分泌的抑制作用外,纯化的IL-1和人rIL-1在以下条件下对葡萄糖诱导的胰岛素分泌有刺激作用:与纯化的IL-1(10%体积/体积)孵育90分钟或在人rIL-1(1400 pM)存在下,或与相对低浓度的人rIL-1(0.5或5 pM)孵育15小时。(摘要截短至250字)