Action of epinephrine on muscle glucose uptake depending on Ca++ and phosphate

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Abstract
Studies were made of the involvement of inorganic phosphate (Pi) and Ca++ in the mechanism by which epinephrine-induced inhibition of muscle glucose utilization was abolished during either alkalosis in vivo or incubation of the isolated rat diaphragm in vitro at a higher pH level. An increase in the concentration of Pi in muscle tissues was closely associated with prevention of the inhibitory action of epinephrine on glucose uptake. The interrelationship of Ca++ and Pi in aqueous solutions, and the additional observations that glucose uptake by rat diaphragm was accelerated in anaerobiosis only in the absence of Ca++, indicate a significance of Ca++ in muscle glucose metabolism. Assay of hexokinase activity in cell-free muscle preparations revealed that the inhibition of the enzyme activity by glucose 6-phosphate was profoundly influenced by the presence of Ca++ and Pi and was dependent on the concentration of adenosine triphosphate (ATP). It is suggested that Ca++ may provide the primary point of influence of epinephrine on glucose metabolism of the muscle.