Strohfeldt P, Strubel-Obermaier U, Kettl H
Arzneimittelforschung. 1977;27(5):1034-6.
In view of the experience that after short- or long-term oral administration of biguanides to rats no glycogenolysis in the muscle tissue occurs or even an increase of the muscle glycogen content and a high rate of incorporation of radioglucose into the muscle glycogen, the glycogen synthetase activity of skeletal muscle in a concentrated muscle homogenate and the effect of isoproterenol on glycogenolysis were investigated in normal rats after short-term oral administration of 1-butylbiguanide (buformin). The basal synthetase activity and the ATP inhibition of the enzyme were not affected by buformin, but the cyclic AMP mediated inactivation was significantly inhibited after buformin pretreatment. This inhibition was reversed by running the assay in the presence of Mg2+. Buformin also inhibited the isoproterenol induced glycogenolysis of the skeletal muscle tissue. From our results we suppose that biguanides may influence the regulation of glycogen metabolism by inhibiting the inactivating synthetase kinase and the activating phosphorylase kinase. It is possible that divalent cations like Mg2+ as an activator of kinase reactions are concerned.
鉴于对大鼠短期或长期口服双胍类药物后，肌肉组织中未发生糖原分解，甚至肌肉糖原含量增加且放射性葡萄糖掺入肌肉糖原的速率很高这一经验，在正常大鼠短期口服1-丁基双胍（二甲双胍）后，研究了浓缩肌肉匀浆中骨骼肌的糖原合成酶活性以及异丙肾上腺素对糖原分解的影响。二甲双胍不影响基础合成酶活性和该酶的ATP抑制作用，但二甲双胍预处理后，环磷酸腺苷介导的失活作用受到显著抑制。在镁离子存在的情况下进行测定，这种抑制作用可被逆转。二甲双胍还抑制异丙肾上腺素诱导的骨骼肌组织糖原分解。从我们的结果推测，双胍类药物可能通过抑制失活的合成酶激酶和激活的磷酸化酶激酶来影响糖原代谢的调节。像镁离子这样的二价阳离子作为激酶反应的激活剂可能与之有关。
