Sörhede Winzell Maria, Magnusson Caroline, Ahrén Bo
Department of Clinical Sciences, Division of Medicine, Lund University, B11 BMC, SE-221 84 Lund, Sweden.
Regul Pept. 2005 Nov;131(1-3):12-7. doi: 10.1016/j.regpep.2005.05.004.
Apelin is the endogenous ligand of the G-protein coupled apj receptor. Apelin is expressed in the brain, the hypothalamus and the stomach and was recently shown also to be an adipokine secreted from the adipocytes. Although apelin has been suggested to be involved in the regulation of food intake, it is not known whether the peptide affects islet function and glucose homeostasis. We show here that the apj receptor is expressed in pancreatic islets and that intravenous administration of full-length apelin-36 (2 nmol/kg) inhibits the rapid insulin response to intravenous glucose (1 g/kg) by 35% in C57BL/6J mice. Thus, the acute (1-5 min) insulin response to intravenous glucose was 682+/-23 pmol/l after glucose alone (n=17) and 445+/-58 pmol/l after glucose plus apelin-36 (n=18; P=0.017). This was associated with impaired glucose elimination (the 5-20 min glucose elimination was 2.9+/-0.1%/min after glucose alone versus 2.3+/-0.2%/min after glucose plus apelin-36, P=0.008). Apelin (2 nmol/kg) also inhibited the insulin response to intravenous glucose in obese insulin resistant high-fat fed C57BL/6J mice (P=0.041). After 60 min incubation of isolated islets from normal mice, insulin secretion in the presence of 16.7 mmol/l glucose was inhibited by apelin-36 at 1 mumol/l, whereas apelin-36 did not significantly affect insulin secretion at 2.8 or 8.3 mmol/l glucose or after stimulation of insulin secretion by KCl. Islet glucose oxidation at 16.7 mmol/l was not affected by apelin-36. We conclude that the apj receptor is expressed in pancreatic islets and that apelin-36 inhibits glucose-stimulated insulin secretion both in vivo and in vitro. This may suggest that the islet beta-cells are targets for apelin-36.
阿片肽是G蛋白偶联阿片肽受体（apj受体）的内源性配体。阿片肽在大脑、下丘脑和胃中表达，最近还被证明是脂肪细胞分泌的一种脂肪因子。尽管有人提出阿片肽参与食物摄入的调节，但尚不清楚该肽是否影响胰岛功能和葡萄糖稳态。我们在此表明，apj受体在胰岛中表达，并且在C57BL/6J小鼠中，静脉注射全长阿片肽-36（2 nmol/kg）可使对静脉注射葡萄糖（1 g/kg）的快速胰岛素反应抑制35%。因此，单独注射葡萄糖后（n = 17），对静脉注射葡萄糖的急性（1 - 5分钟）胰岛素反应为682±23 pmol/l，而在葡萄糖加阿片肽-36后（n = 18；P = 0.017）为445±58 pmol/l。这与葡萄糖清除受损有关（单独注射葡萄糖后5 - 20分钟的葡萄糖清除率为2.9±0.1%/分钟，而葡萄糖加阿片肽-36后为2.3±0.2%/分钟，P = 0.008）。阿片肽（2 nmol/kg）也抑制肥胖胰岛素抵抗的高脂喂养C57BL/6J小鼠对静脉注射葡萄糖的胰岛素反应（P = 0.041）。在来自正常小鼠的分离胰岛孵育60分钟后，1 μmol/l的阿片肽-36抑制了在16.7 mmol/l葡萄糖存在下的胰岛素分泌，而阿片肽-36在2.8或8.3 mmol/l葡萄糖时或在氯化钾刺激胰岛素分泌后并未显著影响胰岛素分泌。阿片肽-36不影响16.7 mmol/l时的胰岛葡萄糖氧化。我们得出结论，apj受体在胰岛中表达，并且阿片肽-36在体内和体外均抑制葡萄糖刺激的胰岛素分泌。这可能表明胰岛β细胞是阿片肽-36的作用靶点。
