Glycogenesis in the cultured fetal and adult rat hepatocyte is differently regulated by medium glucose.
We examined the glycogenic response to glucose in cultured fetal and adult rat hepatocytes. After a 48-h culture in Dulbecco's modified Eagle's medium, 1 mM glucose, insulin, and cortisol, cells were cultured for 4 h in serum-free medium containing glucose (1-30 mM) and U-14C-glucose. Incorporation of 14C-glucose into glycogen was greater in fetal hepatocytes compared with adult hepatocytes at all glucose concentrations (p < 0.001). Net glycogenic rate in fetal cells was greatest between 1 and 8.3 mM (7.7- +/- 1.1-fold increase) compared with a 3.8- +/- 0.6-fold increase in adult cells. In contrast, there was a 19.4- +/- 2.7-fold increase in glycogen accumulated between 8.3 and 30 mM glucose in the adult and a 1.6 +/- 0.1-fold increase in the fetus. Total glycogen synthetase activity was higher in fetal than adult hepatocytes (p < 0.001), but the active a form was similar in fetal and adult hepatocytes. Glycogen synthase a/+b was stimulated at 8.3 mM or greater glucose in fetal hepatocytes, and 5.7 mM or greater in adult hepatocytes (p < 0.05). Total phosphorylase did not change with medium glucose, but glycogen phosphorylase a/a4+b decreased in adult hepatocytes incubated in 5.7 mM glucose or greater (p < 0.05). Fetal phosphorylase a/a+b was increased at 8.3 mM or greater glucose (p < 0.05). In contrast, both adult and fetal phosphorylase were activated by glycogen. A glucose-induced increase in active phosphorylase may induce the decrease in net glycogenic rate at high glucose in fetal hepatocytes.(ABSTRACT TRUNCATED AT 250 WORDS)
Zheng
Q
Q
Pediatric Endocrine Unit, Massachusetts General Hospital, Harvard Medical School, Boston 02114.
Levitsky
L L
LL
Fan
J
J
Ciletti
N
N
Mink
K
K
D000818:Animals; D002478:Cells, Cultured; D003470:Culture Media; D005333:Fetus / Q000378:metabolism; D005947:Glucose / Q000378:metabolism / Q000494:pharmacology*; D006006:Glycogen Synthase / Q000378:metabolism; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D008112:Liver Glycogen / Q000096:biosynthesis* / Q000378:metabolism; D008297:Male; D006005:Phosphorylases / Q000378:metabolism; D051381:Rats
D003470:Culture Media; D008112:Liver Glycogen; D006005:Phosphorylases; D006006:Glycogen Synthase; D005947:Glucose