The endergonic functions of the animal organism are fueled ultimately by A TP which is generated primarily through oxidative metabolism in the mitochon drion and through anaerobic glycolysis. A conventional view is that consump tion of energy causes the formation of ADP which returns to the mitochon drion, stimulating it (acceptor effect-respiratory control) to consume oxygen and rephosphorylate the ADP to ATP, which diffuses back to the sites of utilization. That this view is insufficient is shown by several observations. Studies on muscle contraction have shown little relation between myofibril lar activity energized by myosin ATPase and the availability of ATP. There appears to be insufficient ADP formation during muscle activity to cause significant release from respiratory control even though muscle activity does produce a marked parallel rise in oxygen uptake. On the other hand, there is a close parallel between skeletal and heart muscle activity, the concentration of creatine phosphate, and the activity of creatine phosphokinase. The creatine phosphate shuttle was proposed to explain why when a diabetic individual exercised, the blood glucose level and general metabolism were altered exactly as if a dose of insulin had been given. In all regimes for diabetics the amount and timing of exercise is taken into account in determining dosage of insulin. It was proposed in 1960 (1) that insulin acted to stimulate all endergonic reactions by attaching hexokinase to mitochondria. This could provide for more efficient respiratory control and availability of A TP. Figure 1 shows the proposal as depicted in 1966 (2). Exercise causes a liberation of creatine from contracting muscle fibers. This creatine moves to the mitochondria where nascent ATP would produce creatine phosphate and immediately return ADP, stimulating oxygen uptake, at the same time increasing the flux of creatine phosphate to the muscle fiber.(Figure 2). In the original proposal there were three parts to the creatine phosphate system of respiratory control and energy delivery.