Gross R, Hillaire-Buys D, Bertrand G, Ribes G, Loubatieres-Mariani M M
Faculty of Medicine, Pharmacology Laboratory, Unité de Recherche Associeé 599 du Centre National de la Recherche Scientifique, Montpellier, France.
Diabetes. 1989 Oct;38(10):1291-5. doi: 10.2337/diab.38.10.1291.
Previous studies have shown that adenosine, by activation of purinergic A2-receptors, stimulates glucagon secretion and increases vascular flow rate in isolated perfused pancreases from nondiabetic rats. Because alpha-cell function and blood flow control are known to be disturbed in diabetes, we investigated whether adenosine was still effective in streptozocin-induced diabetic (STZ-D) rats. Our experiments were performed on isolated perfused rat pancreases. Whereas, in normal rats, adenosine (1.65 microM) induced a 200% increase in glucagon output and a 25% rise in the pancreatic vascular flow rate, in rats diabetic for 5-6 wk, this nucleoside was ineffective on glucagon secretion, and its vasodilatory effect was strongly reduced. Long-term in vivo insulin treatment that reversed high glycemia levels was able to restore in large part both adenosine effects. In contrast, a short-term in vitro pretreatment with insulin was unable to restore the nucleoside effects. We conclude that STZ-D suppresses the stimulatory effect of adenosine on alpha-cells and strongly reduces its vasodilator properties; these abnormalities may be corrected in large part by long-term insulin treatment with normalization of glycemia.
先前的研究表明，腺苷通过激活嘌呤能A2受体，刺激胰高血糖素分泌，并增加非糖尿病大鼠分离灌注胰腺的血管流速。由于已知糖尿病患者的α细胞功能和血流控制受到干扰，我们研究了腺苷在链脲佐菌素诱导的糖尿病（STZ-D）大鼠中是否仍然有效。我们的实验在分离灌注的大鼠胰腺上进行。在正常大鼠中，腺苷（1.65微摩尔）可使胰高血糖素分泌增加200%，胰腺血管流速提高25%，而在糖尿病5-6周的大鼠中，这种核苷对胰高血糖素分泌无效，其血管舒张作用也大大降低。长期体内胰岛素治疗可逆转高血糖水平，在很大程度上恢复腺苷的两种作用。相比之下，短期体外胰岛素预处理无法恢复核苷的作用。我们得出结论，STZ-D抑制了腺苷对α细胞的刺激作用，并大大降低了其血管舒张特性；长期胰岛素治疗使血糖正常化，可能在很大程度上纠正这些异常。
