Kimura I, Kimura M, Kimura M
Department of Chemical Pharmacology, Faculty of Pharmaceutical Sciences, Toyama Medical and Pharamceutical University, Japan.
Diabetologia. 1990 Feb;33(2):72-6. doi: 10.1007/BF00401043.
Changes in intracellular Ca2+ release in the diaphragm muscle of alloxan-diabetic mice were compared with changes in normal muscles and non-diabetic denervated muscles. We measured Ca2+ transient aequorin luminescence by direct electrical stimulation of these muscles. External Ca2(+)-free solution readily decreased the Ca2+ transient in normal muscles but had less of an effect in diabetic muscles. Only when the muscles were pre-injected with EGTA (reducing intracellular levels of free Ca2+) did the Ca2+ transients decrease significantly in diabetic muscles, however, there was no effect in denervated muscles. The caffeine-induced increase in Ca2+ transients, however, was delayed in both diabetic muscles and non-diabetic denervated muscles. The caffeine response was observed in normal muscles under the external Ca2(+)-free conditions even after EGTA-pretreatment, whereas it was suppressed, after a brief increase, in both diabetic and non-diabetic denervated muscles. These results demonstrate (1) the insensitivity of intracellular Ca2+ mobilization to external Ca2+ levels and the ready accumulation of intracellular Ca2+ in the cytosol in the diabetic state, (2) increased permeability to Ca2+ in the denervated state and (3) impairment of the Ca2+ pool which responds to caffeine in both diabetes and the non-diabetic denervated state. Diabetic neuromyopathy thus appears to be a state of abnormal Ca2(+)-mobilization caused secondarily by high levels of blood glucose.
将四氧嘧啶糖尿病小鼠膈肌细胞内钙离子释放的变化与正常肌肉和非糖尿病去神经支配肌肉的变化进行比较。我们通过直接电刺激这些肌肉来测量钙离子瞬变水母发光蛋白的发光情况。无细胞外钙离子溶液能使正常肌肉中的钙离子瞬变显著降低，但对糖尿病肌肉的影响较小。然而，只有当肌肉预先注射EGTA（降低细胞内游离钙离子水平）时，糖尿病肌肉中的钙离子瞬变才会显著降低，而去神经支配肌肉则无此效应。然而，咖啡因诱导的钙离子瞬变增加在糖尿病肌肉和非糖尿病去神经支配肌肉中均延迟。即使在EGTA预处理后，在无细胞外钙离子条件下的正常肌肉中仍可观察到咖啡因反应，而在糖尿病和非糖尿病去神经支配肌肉中，咖啡因反应在短暂增加后均受到抑制。这些结果表明：（1）细胞内钙离子动员对细胞外钙离子水平不敏感，且在糖尿病状态下细胞内钙离子在细胞质中易于积累；（2）去神经支配状态下对钙离子的通透性增加；（3）在糖尿病和非糖尿病去神经支配状态下，对咖啡因有反应的钙离子池受损。因此，糖尿病性神经病变似乎是一种由高血糖继发引起的异常钙离子动员状态。
