Effects of insulin on the pattern of glucose metabolism in the perfused working and Langendorff heart of normal and insulin-deficient rats.
Effects of insulin on the pattern of glucose metabolism in the perfused working and Langendorff heart of normal and insulin-deficient rats.
复制标题
胰岛素对正常和胰岛素缺乏大鼠灌注工作心脏和兰根多夫心脏中葡萄糖代谢模式的影响。
作者：
E. Chain;K. Mansford;L. Opie
1.本文研究了离体大鼠心脏[U-（14）C]葡萄糖的代谢模式，在有和无胰岛素的情况下，用逆行主动脉（Langendorff）和心房（工作）灌流制备物，在正常动物中，使动物胰岛素缺乏（通过注射抗胰岛素血清1小时）。在切除心脏之前）和在使用前7天通过注射链脲佐菌素使动物患糖尿病。2.心脏提取物的放射性自色谱图显示，心肌中的葡萄糖代谢模式比膈肌中的葡萄糖代谢模式更复杂。除了（14）CO（2）、糖原、寡糖、磷酸化糖和乳酸（膈肌中[（14）C]葡萄糖形成的主要代谢物）外，[（14）C]葡萄糖的（14）C标记在心肌中以谷氨酸、谷氨酰胺、天冬氨酸和丙氨酸以及三羧酸循环中间产物的形式出现。3.通过二维色谱图的定量扫描技术，发现机械工作负荷刺激葡萄糖代谢，使（14）C掺入上述所有代谢物（乳酸和磷酸化糖除外）增加2-3倍，其中（14）C掺入实际上减少了;（14）CO（2）的产生同样受到刺激。4.向工作心脏的灌注液中加入胰岛素可使（14）C掺入增加，使（14）CO（2）掺入增加约1.5倍，使糖原、乳酸盐和磷酸化糖掺入增加约3-5倍，使谷氨酸和三羧酸循环中间产物掺入增加约2-3倍，使天冬氨酸掺入增加约0.5倍，而掺入丙氨酸和谷氨酰胺不受影响。因此，工作负荷对葡萄糖代谢模式的影响与胰岛素的影响不同。5.将灌注液中葡萄糖浓度从1增加到20 mm，导致葡萄糖代谢模式的变化，不同于胰岛素所带来的变化。（14）CO（2）的产生稳步增加，而[（14）C]乳酸和糖原的产生在10 mm-葡萄糖时趋于稳定，其值远低于胰岛素存在时所达到的值。6.抗胰岛素血清或链脲佐菌素使Langendorff心脏出现胰岛素缺乏，葡萄糖摄取、（14）CO（2）和[（14）C]乳酸盐的形成以及（14）C掺入糖原和寡糖的情况减少。然而，在胰岛素缺乏的工作心脏中，葡萄糖摄取和（14）CO（2）的产生是正常的，而（14）C掺入糖原和[（14）C]乳酸盐的产生大大减少。7.在抗胰岛素血清导致胰岛素缺乏的动物的Langendorff心脏中，向灌注液中加入胰岛素可恢复（14）C从葡萄糖掺入（14）CO（2）、糖原和乳酸;在链脲佐菌素糖尿病动物的心脏中，加入胰岛素可恢复（14）C掺入糖原和乳酸，但（14）CO（2）的产生仍低于正常水平约50%。8.这些结果对胰岛素的作用方式的问题的轴承进行了讨论。
1. The metabolic pattern of [U-(14)C]glucose in the isolated rat heart has been studied, with both retrograde aortic (Langendorff) and atrially (working) perfused preparations in the presence and absence of insulin, in normal animals, animals rendered insulin-deficient (by injection of anti-insulin serum 1hr. before excision of the heart) and animals rendered diabetic by streptozotocin injection 7 days before use. 2. Radioautochromatograms of heart extracts show that the pattern of glucose metabolism in heart muscle is more complex than in diaphragm muscle. In addition to (14)CO(2), glycogen, oligosaccharides, phosphorylated sugars and lactate (the main metabolites formed from [(14)C]glucose in diaphragm muscle), (14)C label from [(14)C]glucose appears in heart muscle in glutamate, glutamine, aspartate and alanine, and in tricarboxylic acid-cycle intermediates. 3. By a quantitative scanning technique of two-dimensional chromatograms it was found that a mechanical work load stimulates glucose metabolism, increasing by a factor of 2-3 incorporation of (14)C into all the metabolites mentioned above except lactate and phosphorylated sugars, into which (14)C incorporation is in fact diminished; (14)CO(2) production is equally stimulated. 4. Addition of insulin to the perfusion fluid of the working heart causes increases in (14)C incorporation, by a factor of about 1.5 into (14)CO(2), by a factor of about 3-5 into glycogen, lactate and phosphorylated sugars, by a factor of about 2-3 into glutamate and tricarboxylic acid-cycle intermediates and by a factor of about 0.5 into aspartate, whereas incorporation into alanine and glutamine is not affected. The effect of a work load on the pattern of glucose metabolism is thus different from that of insulin. 5. Increasing the concentration of glucose in the perfusion fluid from 1 to 20mm leads to changes of the pattern of glucose metabolism different from that brought about by insulin. (14)CO(2) production steadily increases whereas [(14)C]lactate and glycogen production levels off at 10mm-glucose, at values well below those reached in the presence of insulin. 6. In Langendorff hearts of animals rendered insulin-deficient by anti-insulin serum or streptozotocin, glucose uptake, formation of (14)CO(2) and [(14)C]lactate, and (14)C incorporation into glycogen and oligosaccharides are decreased. In insulin-deficient working hearts, however, glucose uptake and (14)CO(2) production are normal, whereas incorporation of (14)C into glycogen and [(14)C]lactate production are greatly decreased. 7. Insulin added to the perfusion fluid restores (14)C incorporation from glucose into (14)CO(2), glycogen and lactate in the Langendorff heart from animals rendered insulin-deficient by anti-insulin serum; in hearts from streptozotocin-diabetic animals addition of insulin restores (14)C incorporation into glycogen and lactate, but (14)CO(2) production remains about 50% below normal. 8. The bearing of these results on the problem of the mode of action of insulin is discussed.