Review and an experimental study on the physiological and quantitative aspects of gluconeogenesis in lactating...

A short review describes quantitative aspects of glucose metabolism in lactating ruminants, including the contribution of different substrates to glucose synthesis as affected by nutritional and hormonal regulation. Gluconeogenesis from propionate (the major gluconeogenic substrate in the fed state) is mainly regulated by feed intake and increased propionate availability and is less affected by insulin and glucagon. Quantitative estimates of amino acid contribution to glucose synthesis are highly variable (from 2 to 40% of glucose flux), but no conclusive data exist by which this large variation can be explained. An experimental model is described by which nutrient exchanges across the liver as well as the contribution of different substrates to glucose synthesis can be quantitated. The novel approach is continuous infusion of differently labelled (3H and 14C) gluconeogenic substrates into multi-catheterized goats. Results are reported from a preliminary experiment using this model. A goat in mid-lactation was fed hay ad libitum, and the experimental treatments were continuous infusion into a mesenteric vein of either sodium propionate or a complete mixture of amino acids. Measurements were nutrient exchanges across portal-drained viscera and liver, whole body glucose flux rate, and hepatic gluconeogenesis from propionate, lactate and glycerol. Glucose synthesis from amino acids was estimated by difference. Net portal appearance and hepatic uptake of propionate and of amino acids were increased by propionate and amino acid infusions, respectively. Glucose flux rate and hepatic glucose output were not affected by treatments. With propionate infusion, the proportions of liver glucose derived from propionate and amino acids were 62 and 19%, respectively. With amino acid infusion, the corresponding figures were 24 and 36%. Glucagon concentration in portal blood plasma was 2.7 times higher on the amino acid than on the propionate treatment. It is concluded that the hepatic metabolism of propionate and glucogenic amino acids into glucose synthesis is regulated to a great extent by the availability of these substrates, and that glucagon may be involved in this regulation. It is further concluded that the described experimental approach is suitable for investigations of nutrient absorption and hepatic gluconeogenesis.