Ascorbic acid synthesis was stimulated by glucagon, dibutyryl cyclic A
MP, as well as phenylephrine, vasopressin or okadaic acid, in hepatocy
tes prepared from fed mice. However, no such effect was observed in gl
ycogen-depleted cells from starved animals, either in the presence or
absence of glucose. The rate of ascorbate synthesis showed close corre
lation with the glucose release by hepatocytes. In mice the injection
of glucagon increased plasma ascorbate concentration fifteenfold, and
caused a sixfold elevation of the ascorbate content of the liver. Thes
e results show that hepatic ascorbate synthesis is dependent on glycog
enolysis, and indicate a regulatory role of ascorbate released by the
liver.