Metabolism of Hexose Phosphate Esters

Shortly after the discovery of insulin, it was shown by a number of investigators (Wigglesworth, Woodrow, Smith & Winter, 1923; Harrop & Benedict, 1924; Bollinger & Hartman, 1925) that there was a decrease in the inorganic phosphorus content of the blood in normal and diabetic animals following the injection ofinsulin. These observations first led to the hypothesis that insulin was concerned with the phosphorylation of carbohydrates, and a number of investigators tried to correlate the decrease in the inorganic phosphorus of the blood with an increase in the hexose monophosphate of muscle. Cori & Cori (1932) and Soskin, Levine & Hechter (1941), however, considered that the increase in hexose monophosphate of muscle is probably a secondary effect of insulin due to an output of adrenaline. Nelson, Rapoport, Guest & Mirsky (1942) suggested that the decrease in inorganic phosphorus of the blood following insulin injections could be accounted for at least in part by the increase in the acid-soluble phosphorus fraction of the liver. Kaplan & Greenberg (1943, 1944), working with radioactive phosphate, concluded from their results that insulin accelerates the transfer of phosphorus from the blood stream to the tissues, increases the hexose monophosphate content of muscle, and (in agreement with the results obtained by Nelson et al. 1942) increases the phosphorylation processes in the liver, as shown by the increased incorporation of the injected radioactive phosphorus into the acidsoluble phosphorus fraction and into the labile phosphate groups of adenosine triphosphate. Sacks (1945), also using radioactive phosphorus, studied the effect of insulin on phosphate turnover in cat striated muscle. He reported an increased turnover rate of phosphocreatine, adenosine triphosphate and glucose 6-phosphate. Haugaard, Marsh & Stadie (1951) studied the changes in the phosphorylated intermediates in rat diaphragm muscle after incubation in a glucose-containing medium in the presence and absence of insulin. They