Accelerated glycogenolysis in uremia and under sucrose feeding:
role of phosphorylase-a regulators.
Bakkour, Zena, Denise Laouari, Sophie Dautrey, Jean-Pierre Yvert,
Claire Kleinknecht .
INSERM U. 426, Facult[acute]e Xavier Bichat, Paris, Service de
pharmacie, H[circumflex]opital Bichat, Paris, Service de biochimie,
H[circumflex]opital B[acute]egin, St-Mand[acute]e, France
APStracts 4:0063E, 1997.
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, 18 hrs after food removal, in uremic
and pair-fed control rats fed either sucrose or cornstarch diet for
21 days. Other uremic and control rats fasted for 18 hours were refed
a sucrose meal to measure glycogen increment. Glycogen storage in
uremia was normal suggesting effective glycogen synthesis. During
short fast, sucrose-feeding and uremia enhanced net glycogenolysis
through different but additive mechanisms. Under sucrose-feeding,
there were high phosphorylase-a levels associated with hepatic
insulin resistance. In uremia, phosphorylase-a levels were low but
the enzyme was probably activated in vivo by a fall of inhibitors
(ATP, [alpha]-GP, F-1,6-P2, 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.
Received 19 June 1996; accepted in final form 17 February 1997.
APS Manuscript Number E296-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1997 The American Physiological Society.
Published in APStracts on 12 March 1997