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Effect of Prolonged Starvation on Glycogen Synthase and Glycogen Synthase Phosphatase Activity in Rat Heart

Department of Medicine and The Section of Endocrinology and Metabolism, Minneapolis VA Medical Center and The University of Minnesota, Minneapolis, MN 55417

Rats were fasted 24, 48 or 72 hours to determine the effect of several days without food on glycogen synthase and synthase phosphatase activity in heart. The basal percentage of synthase I decreased gradually from approximately 20% in fed animals to approximately 6% in rats starved for 72 hours. Glycogen increased progressively from 4.6 mg/g wet weight in fed rats to 7.6 mg/g wet weight in 72-hour starved rats. Thus, there was an inverse relationship between the glycogen concentration and the basal percentage of synthase I. The total synthase phosphatase activity measured at a standardized glycogen concentration decreased 50% by 24 hours of starvation and then was unchanged up to 72 hours. The 50% decrease in phosphatase activity correlated directly with insulin concentration in rats fasted 24–72 hours. The rapid stimulatory effect of insulin on synthase activity observed in fed rats was delayed in rats starved 24 and 48 hours. This correlated with a progressively slower synthase phosphatase response to insulin. The stimulatory effect of insulin was lost completely in 72-hour fasted rats. The proposed mechanism for the delayed response in rats starved 24 and 48 hours and lack of response in rats starved 72 hours is insulin resistance. The mechanism remains to be elucidated.

KEY WORDS: • rat heart • starvation • fasting • glycogen • glycogen synthase • synthase phosphatase • insulin activitation • insulin resistance

¹ The data were taken from a dissertation submitted by Mary C. Gannon to the Graduate School of the University of Minnesota in partial fulfillment of the requirements for a Doctor of Philosophy degree in Food Science and Nutrition.

² Recipient of a Medical Investigatorship Award from the Veterans Administration.

Manuscript received 20 April 1984.