Accelerated glycogenolysis in uremia and under sucrose feeding: role of phosphorylase alpha regulators.
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.
Bakkour
Z
Z
Institut National de la Santé et de la Recherche Médicale Unité 426, Faculté Xavier Bichat, Paris, France.
Laouari
D
D
Dautrey
S
S
Yvert
J P
JP
Kleinknecht
C
C
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003404:Creatinine / Q000097:blood; D004040:Dietary Carbohydrates; D019422:Dietary Sucrose / Q000494:pharmacology*; D006006:Glycogen Synthase / Q000378:metabolism; D007668:Kidney / Q000502:physiology / Q000503:physiopathology; D008099:Liver / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000378:metabolism*; D008297:Male; D009929:Organ Size; D010762:Phosphorylase a / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012016:Reference Values; D013213:Starch; D013997:Time Factors; D014508:Urea / Q000097:blood; D014511:Uremia / Q000378:metabolism*; D015430:Weight Gain
D001786:Blood Glucose; D004040:Dietary Carbohydrates; D019422:Dietary Sucrose; D008112:Liver Glycogen; D014508:Urea; D013213:Starch; D003404:Creatinine; D010762:Phosphorylase a; D006006:Glycogen Synthase