Lozeman F J, Challiss R A, Leighton B, Newsholme E A
Department of Biochemistry, University of Oxford, United Kingdom.
Pflugers Arch. 1987 Sep;410(1-2):192-7. doi: 10.1007/BF00581915.
Adenosine has been shown to modulate the sensitivity of skeletal muscle to insulin (Budohoski et al. 1984). In an attempt to further characterize the modulatory action of adenosine on insulin sensitivity in skeletal muscle we have investigated the effect of the nucleoside transport inhibitor dipyridamole in isolated incubated soleus muscle strips. At a concentration of 50 microM, dipyridamole increased the concentration of adenosine in the soleus muscle by 36% and in the incubation medium by 32%. At this concentration of dipyridamole, the basal rates (in the presence of 1 microunit of insulin/ml) of lactate formation, 2-deoxy [2,6-3H]glucose phosphorylation and glucose oxidation were decreased by 48%, 43% and 47% respectively, whilst the rate of glycogen synthesis was unaffected. Insulin-stimulated rates (in the presence of 10,000 microunits of insulin/ml) of lactate formation, 2-deoxy [2,6-3H] glucose phosphorylation, glycogen synthesis and glucose oxidation were decreased by 70%, 30%, 26% and 20% respectively in the presence of 50 microM dipyridamole. Although 50 microM dipyridamole was required to exert a significant effect on medium and soleus muscle adenosine concentrations, statistically significant effects on glycolytic rate were observed at concentrations as low as 2 microM dipyridamole. It is concluded that the results are not consistent with dipyridamole exerting an effect on skeletal muscle carbohydrate metabolism solely through elevation of the intracellular or interstitial adenosine concentration, but strongly suggest that dipyridamole inhibits glucose transport and/or phosphorylation in skeletal muscle.
已证明腺苷可调节骨骼肌对胰岛素的敏感性（布多霍斯基等人，1984年）。为了进一步阐明腺苷对骨骼肌胰岛素敏感性的调节作用，我们研究了核苷转运抑制剂双嘧达莫对离体孵育的比目鱼肌条的影响。在50微摩尔浓度下，双嘧达莫使比目鱼肌中的腺苷浓度增加了36%，使孵育培养基中的腺苷浓度增加了32%。在此双嘧达莫浓度下，乳酸生成、2-脱氧[2,6-³H]葡萄糖磷酸化和葡萄糖氧化的基础速率（在每毫升含1微单位胰岛素的情况下）分别降低了48%、43%和47%，而糖原合成速率未受影响。在50微摩尔双嘧达莫存在的情况下，胰岛素刺激的速率（在每毫升含10,000微单位胰岛素的情况下），乳酸生成、2-脱氧[2,6-³H]葡萄糖磷酸化、糖原合成和葡萄糖氧化分别降低了70%、30%、26%和20%。尽管需要50微摩尔双嘧达莫才能对培养基和比目鱼肌中的腺苷浓度产生显著影响，但在低至2微摩尔双嘧达莫的浓度下就观察到了对糖酵解速率的统计学显著影响。结论是，这些结果与双嘧达莫仅通过提高细胞内或细胞间腺苷浓度对骨骼肌碳水化合物代谢产生影响不一致，但强烈表明双嘧达莫抑制骨骼肌中的葡萄糖转运和/或磷酸化。
