Effects of Neuromuscular Electrical Stimulation in Combination with Glutamine Administration on Skeletal Muscle Atrophy in Colon-26 Tumor-Bearing Mice

Abstract

The depressed protein synthetic response, a phenomenon termed anabolic resistance, has been shown to be involved in muscle wasting induced by cancer cachexia. Moreover, a positive relationship between the protein synthetic rate and intracellular glutamine (GLN) concentration has been found in skeletal muscles. This study investigated the effects of neuromuscular electrical stimulation (ES) and GLN administration on muscle wasting and GLN metabolism in colon-26 (C-26) tumor-bearing mice. CD2F1 mice were divided into 8 groups: control (CNT), CNT+ES, CNT+GLN, CNT+ES+GLN, C-26, C-26+ES, C-26+GLN, C-26+ES+GLN. Cancer cachexia was induced by subcutaneous injection of C-26 cells and developed for four weeks. ES was performed on the left plantar flexor muscles every other day, and GLN (1 g/kg) was administered daily intraperitoneally starting one day after the C-26 injection. Tumor-free body mass and fast-twitch gastrocnemius (Gas) muscle weight were lower in the C-26 group than in the CNT group (-19% and -17%, respectively). Neither ES training nor GLN administration, alone or in combination, ameliorated the loss of Gas muscle weight in the C-26 mice. However, ES training in combination with GLN administration inhibited the increased expression of GLN synthetase (GS) in the C-26 muscles. Thus, it is likely that GLN plays a critical role in muscle protein metabolism and, therefore, can be targeted as a tentative treatment of cancer cachexia.