REGULATION OF GLUCONEOGENESIS BY INSULIN AND GLUCAGON IN THE NEONATALBOVINE

Hepatocyte monolayers from neonatal calves were used to determine the effects of glucagon and insulin on incorporation of carbon from [2-C-1 4]propionate, [1-C-14]lactate, [U-C-14]lactate, and [1,3-C-14]glycerol into glucose and glycogen. Glucagon increased gluconeogenesis (nmol s ubstrate incorporated into glucose or glycogen.mu g DNA(-1) h(-1)) fro m propionate and lactate but not from glycerol. Insulin decreased gluc oneogenesis from [2-C-14]propionate but was without effect on gluconeo genesis from [U-C-14]lactate or [1,3-C-14]glycerol. Net de novo glycog enesis (nmol substrate retained in cell glycogen.mu g DNA(-1) h(-1)) f rom propionate, lactate, and glycerol was decreased by glucagon and in creased by insulin. Glucagon effects on gluconeogenesis, but not glyco genesis, were mimicked by dibutyryl adenosine 3',5'-cyclic monophospha te. Lactate flux through pyruvate carboxylase accounts for greater tha n or equal to 91% of lactate carbon flux to glucose, and this proporti on was unchanged by glucagon or insulin. Gluconeogenesis from propiona te and lactate is regulated by substrate concentration and glucagon in bovine hepatocyte monolayers. The data indicate that, in neonatal bov ine liver, glucagon acts on a process common to lactate and propionate to increase gluconeogenesis, and insulin opposes these effects on glu coneogenesis from propionate but not lactate.