AJP - Endocrinology and Metabolism, Vol 273, Issue 1 E17-E27, Copyright © 1997 by American Physiological Society
Accelerated glycogenolysis in uremia and under sucrose feeding: role of phosphorylase alpha regulators
Z. Bakkour, D. Laouari, S. Dautrey, J. P. Yvert and C. Kleinknecht
Institut National de la Sante et de la Recherche Medicale Unite 426, Faculte Xavier Bichat, Paris, France.
To understand the mechanism of hepatic glycogen depletion found in uremia
and under sucrose feeding, we examined net hepatic
glycogenolysis-associated active enzymes and metabolites during fasting.
Liver was taken 2, 7, and 18 h after food removal in uremic and pair-fed
control rats fed either a sucrose or cornstarch diet for 21 days. Other
uremic and control rats fasted for 18 h were refed a sucrose meal to
measure glycogen increment. Glycogen storage in uremia was normal,
suggesting effective glycogen synthesis. During a short fast, sucrose
feeding and uremia enhanced net glycogenolysis through different but
additive mechanisms. Under sucrose feeding, there were high phosphorylase
alpha levels associated with hepatic insulin resistance. In uremia,
phosphorylase alpha levels were low, but the enzyme was probably activated
in vivo by a fall of inhibitors (ATP, alpha-glycerophosphate,
fructose-1,6-diphosphate, and glucose) and a rise of Pi, as verified in
vitro. Enhanced gluconeogenesis was also suggested, but excessive hepatic
glucose production was unlikely in uremia. During fasting, hypoglycemia
occurred in uremia due to reduced glycogenolysis, inefficient hepatic
gluconeogenesis, and impaired renal gluconeogenesis. This may be relevant
to poor fasting tolerance in uremia, which could be aggravated under
excessive sucrose intake.
