Early morphological remodeling of neuromuscular junction in a murine model of diabetes.

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.