Mechanisms of force loss in diabetic mouse skeletal muscle

Pathologic changes to alpha-motoneurons may contribute to decreases in skeletal muscle strength in diabetes. The present study examines this possibility. Female ICR mice (approximately 25 g) were given a single injection of streptozotocin (200 mg/kg). After 2, 4, and 8 weeks of diabetes, we measured maximum isometric tetanic torque of the fast-twitch anterior crural muscles at the ankle when stimulated through the common peroneal nerve, and maximal isometric tetanic force in the directly stimulated extensor digitorum longus (EDL) muscle. After 4 weeks, the relative loss of torque via nerve stimulation (-43%) was greater (P = 0.02) than the force loss in the directly stimulated muscle (-24%), indicating a functional neural deficit. However, the percent changes in strength in these two methods of stimulation were not different (P = 0.41) in the 8-week diabetic animals, indicating that functional impairment resided in the muscle. This suggests an early distal motoneuron or neuromuscular junction deficit that improved as the intrinsic muscle deficit worsened. Preliminary evidence also suggests excitation-contraction uncoupling may contribute to the loss of strength in fast-twitch muscles.