Salehi Albert, Parandeh Fariborz, Fredholm Bertil B, Grapengiesser Eva, Hellman Bo
Department of Clinical Science, CRC, University of Lund, Malmö, Sweden.
Life Sci. 2009 Sep 9;85(11-12):470-6. doi: 10.1016/j.lfs.2009.08.001. Epub 2009 Aug 12.
Extracellular ATP modulates pulsatile release of insulin, glucagon and somatostatin by activating P2Y(1) receptors. The present study examines if adenosine via A(1) receptors (A(1)R) interferes with pulsatile islet hormone release.
Pancreas was perfused in mice expressing or lacking the A(1) receptor and the hormones measured with radioimmunoassay. Cytoplasmic Ca(2+) was recorded in isolated beta-cells using the fura-2 indicator.
Addition of 10 microM adenosine removed the Ca(2+) transients supposed to coordinate the insulin release pulses. This effect of adenosine was counteracted by 100 nM of the A(1)R antagonist DPCPX. In situ perfusion of the pancreas indicated two phases of islet hormone release when glucose was raised from 3.3 to 16.7 mM. The first phase was characterized by a brief dip followed by a peak, which was more pronounced for insulin and somatostatin than for glucagon. The second phase was markedly affected by knock out of A(1)R. The wild-type A(1)R (+/+) mice, usually lacked statistically verified insulin pulses but generated antisynchronous glucagon and somatostatin pulses with half-widths of 4 min. In the A(1)R (-/-) mice time-average release of insulin during the second phase was almost three times higher than in the controls and 30% of the hormone was released as distinct pulses with half-widths of 3 min. The absence of the A(1)R receptor resulted in 50% prolongation of the pulse cycles of glucagon and somatostatin and loss of their antisynchronous relationship.
The A(1)R receptor is important both for the amplitude (insulin) and duration (glucagon and somatostatin) of islet hormone pulses.
细胞外ATP通过激活P2Y(1)受体调节胰岛素、胰高血糖素和生长抑素的脉冲式释放。本研究检测腺苷是否通过A(1)受体（A(1)R）干扰胰岛激素的脉冲式释放。
对表达或缺乏A(1)受体的小鼠胰腺进行灌注，并用放射免疫分析法测定激素。使用fura-2指示剂记录分离的β细胞中的细胞质Ca(2+)。
添加10微摩尔腺苷可消除本应协调胰岛素释放脉冲的Ca(2+)瞬变。100纳摩尔的A(1)R拮抗剂DPCPX可抵消腺苷的这种作用。当葡萄糖浓度从3.3毫摩尔升至16.7毫摩尔时，胰腺原位灌注显示胰岛激素释放有两个阶段。第一阶段的特征是短暂下降后出现峰值，胰岛素和生长抑素的峰值比胰高血糖素更明显。第二阶段明显受A(1)R基因敲除的影响。野生型A(1)R（+/+)小鼠通常缺乏经统计学验证的胰岛素脉冲，但会产生半峰宽为4分钟的反同步胰高血糖素和生长抑素脉冲。在A(1)R（-/-）小鼠中，第二阶段胰岛素的时间平均释放量几乎是对照组的三倍，30%的激素以半峰宽为3分钟的明显脉冲形式释放。A(1)R受体的缺失导致胰高血糖素和生长抑素的脉冲周期延长50%，并失去它们的反同步关系。
A(1)R受体对胰岛激素脉冲的幅度（胰岛素）和持续时间（胰高血糖素和生长抑素）都很重要。
