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

¹ Department of Biological Chemistry, Faculty of Pharmaceutical Sciences, Hokkaido University School of Medicine, Sapporo, Japan

Studies have been made of the involvement of inorganic phosphate (P_i) 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 P_i in muscle tissues was closely associated with prevention of the inhibitory action of epinephrine on glucose uptake. The interrelationship of Ca⁺⁺ and P_i 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 P_i and was dependent on the concentration of ATP. It is suggested that Ca⁺⁺ may provide the primary point of influence of epinephrine on glucose metabolism of the muscle.

Key Words: glucose uptake by rat diaphragm • anaerobiosis and glucose utilization • hexokinase inhibition by Glc-6-P • effect of Ca⁺⁺ and P_i on hexokinase

Submitted on April 20, 1964