Effect of Glucagon, Cyclic 3',5'-Andenosine Monophosphate and Its Dibutyryl Derivative on Amino Acid Uptake by the Isolated Perfused Rat Liver

Abstract

The effects of glucagon and cyclic 3',5'-adenosine monophosphate (and its dibutyryl derivative) on the uptake of amino acid by the isolated perfused rat liver were compared using a nonmetabolizable amino acid analog, α-aminoisobutyric acid (AIB). Glucagon and the cyclic nucleotides produced similar increases in amino acid uptake, glucose release and urea production by the isolated liver. The increased amino acid uptake resulting from administration of either glucagon or dibutyryl cyclic AMP could be blocked by dihydroergotamine at levels of the blocking agent that did not interfere with enhanced glucose release by the isolated liver. Glucagon is known to increase the concentration of cyclic AMP in the liver. This fact, coupled with the similar effects produced by glucagon and cyclic AMP on hepatic uptake of AIB, supports the postulate that cyclic AMP mediates the increase in the transport of the amino acid into the liver which occurs following glucagon administration.Further corroboration for tliis postulate may be found in the inhibition by dihydroergotamine of the effects of both glucagon and cyclic AMP on hepatic transport of AIB. (Endocrinology87: 366, 1970)