Regulation of glycogen utilization in ischemic hearts after 24 hours of fasting.
BACKGROUND
Fasting protects the ischemic heart from injury and infarction. Previous studies have shown that hearts from fasted animals have greater glycogen utilization and a lower cytosolic redox state (NADH/NAD+) during global ischemia. While the mechanisms of increased glycogen utilization in fasted animals have not been elucidated, animals that hibernate or are tolerant of anoxia are known to increase the tissue content of the active form of glycogen phosphorylase, phosphorylase a. Therefore, this study was designed to (a) determine whether hearts from fasted animals have increased activity of glycogen phosphorylase during ischemia and (b) define those mechanisms responsible for this increase.


METHODS
Hearts isolated from either fed or fasted (24 h) rats were perfused and freeze-clamped at baseline, and after 1 and 10 min of ischemia, for measurement of phosphorylase activity, phosphorylase kinase activity, and glucose-6-phosphate concentrations.


RESULTS
Fasting increased the phosphorylase a/b ratio under both baseline and ischemic conditions. This increase was not accompanied by an increase in the activity of phosphorylase kinase, either with maximal [Ca2+] or under physiologic [Ca2+]. Glucose 6-phosphate concentrations were lower in hearts from fasted animals under baseline, but not ischemic, conditions.


CONCLUSIONS
Fasting enhances glycogen utilization during ischemia by increasing the active form of glycogen phosphorylase. This increase is not due to a change in phosphorylation by phosphorylase kinase nor end-product inhibition by G-6P. While the precise mechanism of increased glycogen phosphorylase activity in fasted animals is not clear, one likely explanation may be the lower cytosolic redox state demonstrated in the myocardium of fasted animals.
Wang
L F
LF
Division of Cardiovascular Medicine, University of California, Davis 95616, USA.
Ramasamy
R
R
Schaefer
S
S
D000704:Analysis of Variance; D000818:Animals; D005215:Fasting / Q000378:metabolism*; D019298:Glucose-6-Phosphate / Q000378:metabolism; D006003:Glycogen / Q000032:analysis / Q000378:metabolism*; D008297:Male; D017202:Myocardial Ischemia / Q000201:enzymology / Q000378:metabolism*; D009206:Myocardium / Q000201:enzymology / Q000378:metabolism*; D010477:Perfusion; D010764:Phosphorylase Kinase / Q000378:metabolism; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley
D019298:Glucose-6-Phosphate; D006003:Glycogen; D006005:Phosphorylases; D010764:Phosphorylase Kinase