The effects of murine muscular dystrophy on the metabolic and homeostatic functions of the skeletal muscles

Abstract

The maintenance of blood glucose is largely dependent on the ability of the skeletal muscles to regulate the supply of amino acids for hepatic glucose production. This study shows that when muscles are damaged in muscular dystrophy the mechanisms by which this control is exerted are impaired. In normally fed congenitally dystrophic mice the blood glucose level was raised and there were significant reductions of the levels of the principal gluconeogenic amino acids in the circulation. This was a result of abnormal exchange of amino acids between the dystrophic muscles and the blood, apparently due to the use of amino acids to a considerable extent in place of glucose for energy metabolism within the diseased muscles. When dystrophic animals were fasted, further reductions in the levels of amino acids in the circulation, to abnormally low values, were caused by an increased use of these amino acids by the liver for gluconeogenesis. Although the reason for the excessive metabolism of amino acids in dystrophic muscle is not clear, such changes will favour muscle protein breakdown, and a stress such as fasting will further aggravate the process of muscle wasting by depleting still further the pool of amino acids in the body.