Substrate utilization in perfused skeletal muscle

During a fast, fatty acids and later ketone bodies readily replace glucose as a fuel for muscle. This switch in muscle fuels is one of the first steps man takes to restrict the unnecessary use of carbohydrates and thereby limit the need for gluconeogenesis from protein when he is deprived of food. Although diminished circulating levels of insulin and glucose undoubtedly contribute to these changes, other mechanisms such as diminished insulin sensitivity and inhibition of glucose metabolism by lipid substrates may also play a role. In order to study this problem, the authors have evaluated some of the factors governing the metabolism of glucose in skeletal muscle using the isolated perfused rat hindquarter preparation. This report deals with the effects of starvation, moderately severe diabetes, and acetoacetate on glucose uptake and disposition in resting and exercising muscle.