Metformin Protects Rat Skeletal Muscle from Physical Exercise-Induced Injury

Metformin (Met) is a drug commonly prescribed in type 2 diabetes mellitus. Its efficacy isdue to the suppression of hepatic gluconeogenesis, enhancement of peripheral glucose uptake andlower glucose absorption by the intestine. Recent studies have reported Met efficacy in other clinicalapplications, such as age-related diseases. Despite the wide clinical use of Met, its mechanism ofaction on muscle and its effect on muscle performance are unclear. We investigated the effects of Metcombined with training on physical performance (PP) in healthy rats receiving Met for 8 weeks whileundergoing daily moderate exercise. We evaluated the following: PP through graded enduranceexercise test performed before the beginning of the training protocol and 48 h before the end ofthe training period; blood ALT, AST, LDH and CK–MB levels in order to address muscle damage;and several blood and muscle myokines and the expression of factors believed to be involved inmuscle adaptation to exercise. Our data demonstrate that Met does not improve the positive effectsof exercise on performance, although it protects myocytes from exercise-induced damage. Moreover,given that Met positively affects exercise-induced muscle adaptation, our data support the idea of thetherapeutic application of Met when muscle function and structure are compromised