Kimura Yasuhiro, Turner Jerrold R, Braasch Dwaine A, Buddington Randal K
Dept. of Biological Sciences, Mississippi State University, MS 39762, USA.
Am J Physiol Gastrointest Liver Physiol. 2005 Dec;289(6):G1007-14. doi: 10.1152/ajpgi.00085.2005. Epub 2005 Jul 14.
Adenosine modulates the intestinal functions of secretion, motility, and immunity, yet little is known about the regulation of nutrient absorption. Therefore, we measured the carrier-mediated uptake of tracer D-[(14)C]glucose (2 microM) by everted sleeves of the mouse intestine after a lumenal exposure to adenosine and a disodium salt of AMP. Rates of glucose uptake by intact tissues increased almost twofold after a 7-min exposure to 5 mM adenosine (a physiological dose). The response was slightly more pronounced for AMP and could be induced by forskolin. The response to adenosine was blocked by theophylline and the A(2) receptor antagonist 3,7-dimethyl-1-proparglyxanthine but not by the A(1) receptor antagonist 8-phenyltheophylline. Glucose uptake by control and AMP-stimulated tissues was inhibited by phloridzin, implying that sodium-dependent glucose transporter 1 (SGLT1) is the responsive transporter, but the involvement of glucose transporter 2 (GLUT2) cannot be excluded. Of clinical relevance, AMP accelerated the systemic availability of 3-O-methylglucose after an oral administration to mice. Our results indicate that adenosine causes a rapid increase in carrier-mediated glucose uptake that is of clinical relevance and acts via receptors linked to a signaling pathway that involves intracellular cAMP production.
腺苷可调节肠道的分泌、运动和免疫功能，但对于营养物质吸收的调节却知之甚少。因此，我们在肠腔暴露于腺苷和AMP二钠盐后，通过外翻的小鼠肠段测量了载体介导的示踪剂D-[(14)C]葡萄糖（2 microM）的摄取。在暴露于5 mM腺苷（生理剂量）7分钟后，完整组织的葡萄糖摄取率几乎增加了两倍。AMP的反应稍明显一些，且可被福斯高林诱导。腺苷的反应被茶碱和A(2)受体拮抗剂3,7-二甲基-1-丙炔基黄嘌呤阻断，但不被A(1)受体拮抗剂8-苯基茶碱阻断。对照组织和AMP刺激组织的葡萄糖摄取被根皮苷抑制，这意味着钠依赖性葡萄糖转运蛋白1（SGLT1）是反应性转运体，但不能排除葡萄糖转运蛋白2（GLUT2）的参与。具有临床相关性的是，给小鼠口服后，AMP加速了3-O-甲基葡萄糖的全身可用性。我们的结果表明，腺苷会使载体介导的葡萄糖摄取迅速增加，这具有临床相关性，并且通过与涉及细胞内cAMP产生的信号通路相关的受体起作用。
