Department of Animal Physiology and Biochemistry, Poznan University of Life Sciences, Poznan, Poland.
Physiol Res. 2011;60(6):905-11. doi: 10.33549/physiolres.932165. Epub 2011 Oct 12.
Adenosine is known to influence different kinds of cells, including beta-cells of the pancreas. However, the role of this nucleoside in the regulation of insulin secretion is not fully elucidated. In the present study, the effects of adenosine A(1) receptor antagonism on insulin secretion from isolated rat pancreatic islets were tested using DPCPX, a selective adenosine A(1) receptor antagonist. It was demonstrated that pancreatic islets stimulated with 6.7 and 16.7 mM glucose and exposed to DPCPX released significantly more insulin compared with islets incubated with glucose alone. The insulin-secretory response to glucose and low forskolin appeared to be substantially potentiated by DPCPX, but DPCPX was ineffective in the presence of glucose and high forskolin. Moreover, DPCPX failed to change insulin secretion stimulated by the combination of glucose and dibutyryl-cAMP, a non-hydrolysable cAMP analogue. Studies on pancreatic islets also revealed that the potentiating effect of DPCPX on glucose-induced insulin secretion was attenuated by H-89, a selective inhibitor of protein kinase A. It was also demonstrated that formazan formation, reflecting metabolic activity of cells, was enhanced in islets exposed to DPCPX. Moreover, DPCPX was found to increase islet cAMP content, whereas ATP was not significantly changed. These results indicate that adenosine A(1) receptor blockade in rat pancreatic islets potentiates insulin secretion induced by both physiological and supraphysiological glucose concentrations. This effect is proposed to be due to increased metabolic activity of cells and increased cAMP content.
腺苷已知会影响不同类型的细胞，包括胰腺的β细胞。然而，这种核苷在调节胰岛素分泌中的作用尚未完全阐明。在本研究中，使用 DPCPX（一种选择性腺苷 A1 受体拮抗剂）测试了腺苷 A1 受体拮抗作用对分离的大鼠胰岛胰岛素分泌的影响。结果表明，与仅用葡萄糖孵育的胰岛相比，用 6.7 和 16.7mM 葡萄糖刺激的胰岛并暴露于 DPCPX 时释放出明显更多的胰岛素。葡萄糖和低 forskolin 的胰岛素分泌反应似乎被 DPCPX 大大增强，但在葡萄糖和高 forskolin存在下，DPCPX 无效。此外，DPCPX 未能改变葡萄糖和二丁酰基-cAMP（一种不可水解的 cAMP 类似物）组合刺激的胰岛素分泌。对胰岛的研究还表明，DPCPX 对葡萄糖诱导的胰岛素分泌的增强作用被蛋白激酶 A 的选择性抑制剂 H-89 减弱。还证明了 DPCPX 暴露会增强胰岛中的 Formazan 形成，反映细胞的代谢活性。此外，发现 DPCPX 增加了胰岛 cAMP 含量，而 ATP 没有明显变化。这些结果表明，大鼠胰岛中的腺苷 A1 受体阻断增强了生理和超生理葡萄糖浓度诱导的胰岛素分泌。这种作用据说是由于细胞代谢活性增加和 cAMP 含量增加所致。
