Regulation of gluconeogenesis by insulin and glucagon in the neonatal bovine

Abstract

Hepatocyte monolayers from neonatal calves were used to determine the effects of glucagon and insulin on incorporation of carbon from [2-14C]propionate, [1-14C]lactate, [U-14C]lactate, and [1,3-14C]glycerol into glucose and glycogen. Glucagon increased gluconeogenesis (nmol substrate incorporated into glucose or glycogen.micrograms DNA-1.h-1) from propionate and lactate but not from glycerol. Insulin decreased gluconeogenesis from [2-14C]propionate but was without effect on gluconeogenesis from [U-14C]lactate or [1,3-14C]glycerol. Net de novo glycogenesis (nmol substrate retained in cell glycogen.micrograms DNA-1.h-1) from propionate, lactate, and glycerol was decreased by glucagon and increased by insulin. Glucagon effects on gluconeogenesis, but not glycogenesis, were mimicked by dibutyryl adenosine 3',5'-cyclic monophosphate. Lactate flux through pyruvate carboxylase accounts for > or = 91% of lactate carbon flux to glucose, and this proportion was unchanged by glucagon or insulin. Gluconeogenesis from propionate and lactate is regulated by substrate concentration and glucagon in bovine hepatocyte monolayers. The data indicate that, in neonatal bovine liver, glucagon acts on a process common to lactate and propionate to increase gluconeogenesis, and insulin opposes these effects on gluconeogenesis from propionate but not lactate.