Fahim M A, Hasan M Y, Alshuaib W B
Department of Physiology, Faculty of Medicine, United Arab Emirates University, Al Ain, United Arab Emirates.
J Appl Physiol (1985). 2000 Dec;89(6):2235-40. doi: 10.1152/jappl.2000.89.6.2235.
Although skeletal muscle weakness is documented in diabetes, the time course for its development is not established. The present study examined the dorsiflexor muscle from animals that had been diabetic for 2 wk. Adult male c57BL mice were injected once with streptozotocin (STZ) to induce diabetes (60 mg/kg ip). Two weeks later, resting membrane potential and miniature end-plate potentials were recorded, and electron microscopy was utilized for ultrastructural evaluations. After STZ-induced diabetes, both resting membrane potential and miniature end-plate potentials were reduced. Nerve terminals showed less synaptic vesicles and had degenerated mitochondria. Furthermore, in the intramuscular nerves, disorganization of microtubules and neurofilaments was evidenced. Myelin-like figures were present in intramuscular nerves, neuromuscular junctions, and muscle fibers. At the muscle level, mitochondria were swollen, with disorganization of their cristae, disruption of T tubules, and myofibers with more deposition of glycogen granules. The present results revealed early STZ-induced nerve and muscle alterations. Observed ultrastructural modifications resemble those of motoneuron disorders and aging processes. These changes are possibly related to alterations in Ca(2+) mobilization across muscle membrane. Other mechanisms such as free radical-mediated actions may also be implicated in STZ-induced effects on skeletal muscle.
尽管糖尿病患者存在骨骼肌无力的情况，但其发展的时间进程尚未明确。本研究检测了糖尿病病程达2周的动物的背屈肌。成年雄性C57BL小鼠一次性注射链脲佐菌素（STZ）以诱导糖尿病（腹腔注射60 mg/kg）。两周后，记录静息膜电位和微小终板电位，并利用电子显微镜进行超微结构评估。STZ诱导糖尿病后，静息膜电位和微小终板电位均降低。神经末梢显示突触小泡减少，线粒体退化。此外，在肌内神经中，微管和神经丝紊乱。肌内神经、神经肌肉接头和肌纤维中出现髓鞘样结构。在肌肉水平，线粒体肿胀，嵴紊乱，T小管破坏，肌纤维中糖原颗粒沉积增多。本研究结果揭示了STZ早期诱导的神经和肌肉改变。观察到的超微结构改变类似于运动神经元疾病和衰老过程中的改变。这些变化可能与跨肌膜的Ca(2+)动员改变有关。其他机制，如自由基介导的作用，也可能与STZ对骨骼肌的影响有关。
