Abstract
Gluconeogenesis from amino acids was investigated with isolated rat livers perfused with Krebs bicarbonate buffer containing bovine red cells and serum albumin. In livers from fasted rats perfused with a mixture of amino acids at various multiples of their normal plasma concentrations, glucose production was half-maximal at normal amino acid concentrations and approached saturation at three times normal concentrations. Urea production also rose with increasing concentrations of amino acids, but was not saturated at four times normal levels. It is concluded that the rate of release of amino acids from peripheral tissues can be important in controlling hepatic gluconeogenesis. In livers perfused with physiological levels of amino acids, glucagon increased alanine conversion to glucose 3.5-fold and produced changes in the steady state concentrations of intermediates of the gluconeogenic pathway which indicated stimulation of the conversion of pyruvate to phosphopyruvate. With high concentrations of alanine, transamination became a significant rate-limiting step for gluconeogenesis. Under these conditions glucagon or cyclic 3',5'-AMP increased alanine conversion to glucose 2- to 3-fold, and the changes in intermediates indicated that they also stimulated the transport of alanine into the cell. Maximum gluconeogenesis from alanine was reached only when the perfusate concentration of alanine was 20 times the normal, physiological level. Glucagon stimulated both glucose and urea production from the amino acid mixture at all amino acid concentrations studied. Urea production was also stimulated by epinephrine and cyclic 3',5'-AMP in livers perfused with or without amino acids. It is proposed that glucagon and possibly catecholamines play a role in the physiological regulation of gluconeogenesis from amino acids by increasing the formation of cyclic 3',5'AMP, which acts to stimulate both the transport of amino acids into the hepatic cell and the conversion of pyruvate to P-pyruvate.
Highlights
MethodsAnimaZs-Liver donors were male Sprague-Dawley rats Uniformly labeledn-alanine-14Cand L-lactate-14Cwereobtained weighing 90 to 150 g and were fed Purina Laboratory Chow ad from Amersham/Searle
In livers from fasted rats perfused with a mixture of amino acids at various multiples of their normal plasma concentrations, glucose production was half-maximal at normal amino acid concentrations and approached saturation at three times normal concentrations
In livers perfused with physiological levels of amino acids, glucagon increased alanine conversion to glucose 3.5-fold and produced changes in the steady state concentrations of intermediates of the gluconeogenic pathway which indicated stimulation of the conversion of pyruvate to phosphopyruvate
Summary
AnimaZs-Liver donors were male Sprague-Dawley rats Uniformly labeledn-alanine-14Cand L-lactate-14Cwereobtained weighing 90 to 150 g and were fed Purina Laboratory Chow ad from Amersham/Searle. Technique of Liver Perfusion--The perfusion procedureand Hormones-L-Epinephrine hydrochloride was from Parkeapparatus have been described[2]. Crystalline glucagon,Lot 258-234B-167-1w, asa generperfusionmediumwasnot recirculated,andthe supplyof medium ousgift of Dr 0. Glucagonand in the reservoir was maintainedby the addition of oxygenated epinephrine solutions were prepared as describedearlier [3]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
