Diabetes provides an unfavorable environment for muscle mass and function after muscle injury in mice.

It is of common knowledge that diabetes decreases skeletal muscle contractility and induces atrophy. However, how hyperglycemia and insulin deficiency modify muscle mass and neuromuscular recovery after muscle injury is not well known. We have analyzed two models of diabetes: streptozotocin (STZ)-treated Swiss mice and Akita mice that spontaneously develop diabetes. A fast muscle, the tibialis anterior, was injured following injection of a myotoxic agent (cardiotoxin). Neuromuscular function was evaluated by examining in situ isometric contractile properties of regenerating muscles in response to nerve stimulation 14, 28 and 56 days after myotoxic injury. We found that STZ-induced diabetes reduces muscle weight and absolute maximal tetanic force in both regenerating and uninjured muscles (p = 0.0001). Moreover, it increases specific maximal tetanic force and tetanic fusion in regenerating and uninjured muscles (p = 0.04). In the Akita mice, diabetes decreases muscle weight and absolute maximal tetanic force, and increases tetanic fusion in both regenerating and uninjured muscles (p < or = 0.003). Interestingly, STZ-induced diabetes exerts more marked effects than diabetes of genetic origin, in particular on muscle weight. This reduction in muscle mass was not due to an increased expression of the atrogenes MuRF1 and atrogin-1 during STZ-induced diabetes. The present study in mice demonstrates that both models of diabetes impair regenerating muscles as well as uninjured muscles. Regenerating fast muscles are weaker, lighter and slower in diabetic compared with nondiabetic mice.