Early morphological remodeling of neuromuscular junction in a murine modelof diabetes

Although skeletal muscle weakness is documented in diabetes, the time cours e for its development is not established. The present study examined the do rsiflexor muscle from animals that had been diabetic for 2 wk. Adult male c 57BL 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 u ltrastructural evaluations. After STZ-induced diabetes, both resting membra ne potential and miniature end-plate potentials were reduced. Nerve termina ls showed less synaptic vesicles and had degenerated mitochondria. Furtherm ore, in the intramuscular nerves, disorganization of microtubules and neuro filaments was evidenced. Myelin-like figures were present in intramuscular nerves, neuromuscular junctions, and muscle fibers. At the muscle level, mi tochondria 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. Ob served ultrastructural modifications resemble those of motoneuron disorders and aging processes. These changes are possibly related to alterations in Ca2+ mobilization across muscle membrane. Other mechanisms such as free rad ical-mediated actions may also be implicated in STZ-induced effects on skel etal muscle.