The role of glucose 6‐phosphate in the control of glycogen synthase

Elevated blood glucose concentrations result in increased intracellular levels of glucose 6‐phosphate in liver, skeletal muscle, and adipose tissue. In liver, blood glucose concentrations are the main factor in control of the synthesis of glycogen; insulin has only a potentiating effect. In skeletal muscle and adipocytes, glucose alone has little effect on the activity of glycogen synthase, the limiting enzyme in glycogen synthesis. However, insulin released as a result of elevated blood glucose stimulates the translocation of specific glucose transporters to the cell membrane, increases the uptake of glucose, and causes the covalent, dephosphorylation‐mediated activation of glycogen synthase. We present evidence that elevated intracellular contents of glucose 6‐phosphate provoke the activation of glycogen synthase in liver, muscle, and adipose tissue. In addition, glucose 6‐phosphate may inhibit the phosphorylation of glycogen synthase by cyclic AMP‐stimulated protein kinase. We show that the stimulated glucose uptake and phosphorylation appear to play a major role in the control by insulin of the enzymes involved in glycogen synthesis.—Villar‐Palasí, C, Guinovart, J. J. The role of glucose 6‐phosphate in the control of glycogen synthase. FASEB J. 11, 544–558 (1997)

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