Glycogen Synthesis in Rat Diaphragm in Vivo: a Biphasic Effect of Insulin on Glycogen Synthetase Enzyme

During enhanced glycogen synthesis an increase in the activity of the enzyme rate‐limiting for glycogen synthesis is expected. This enzyme, glycogen synthetase (UDP‐glucose: α‐1,4‐glucan, α‐4‐glucosyltransferase; EC 2.4.1.11), can be activated by transformation of its D‐form to I‐form. Insulin is known to stimulate glycogen synthesis in skeletal muscle. However, Søvik did not find any change in I‐form in the rat diaphragm 30–240 min after an intraperitoneal (i.p.) injection of insulin, although glycogen synthesis was highly stimulated (O. Søvik, Acta physiol. scand. 1966.68.246–254). In the present study glycogen content and synthetase enzyme activity were measured in rat diaphragms 10–120 min after i.p. injection of insulin. Phosphorylase enzyme activity was also measured. Insulin administration produced a biphasic change in the synthetase enzyme; compared to controls there was an increase of the % I‐form after 10 and 20 min and a decrease after 50, 80 and 120 min. Phosphorylase enzyme activity was unaffected. Glycogen increased continuously up to 120 min. Thus, the increase in I‐form was shown to be a transient effect of insulin. In Søvik's experiment this increase had probably subsided at the time of the first measurement. To account for the increase in glycogen when the % I‐form was decreased, an activation of the synthetase enzyme through an increase of its activator, glucose‐6‐phosphate, may be considered.