Hormonal regulation of hepatic amino acid transport

Abstract

The transport of 2-aminoisobutyric acid (AIB) into liver tissue was increased by both insulin and glucagon. We have now shown that these hormones do not stimulate the same transport system. Glucagon, possibly via cAMP, increased the hepatic uptake of AIB by a mechanism which resembled system A. This glucagon-sensitive system could be monitored by the use of the model amino acid MeAIB. In contrast, the insulin-stimulated system exhibited little or no affinity for MeAIB and will be referred to as system B. On the basis of other reports that the hepatic transport of AIB is almost entirely Na+ dependent and the present finding that the uptake of 2-aminobicyclo [2,2]heptane-2-carboxylic acid (BCH) was not stimulated by either hormone, we conclude that system B is Na+ dependent. Furthermore, insulin added to the perfusate of livers from glucagon-pretreated donors suppressed the increase in AIB or MeAIB uptake. Depending upon the specificities of systems A and B, both of which are unknown for liver tissue, the insulin/glucagon ratio may alter the composition of the intracellular pool of amino acids.

Neutral amino acid transport systems in animal cells: Potential targets of oncogene action and regulators of cellular growth

“…These results suggest that the protein responsible for system A transport may exhibit structural differences in various cell types. It should be noted that MeAIB, but not AIB, is a specific substrate of system A in many cell types including liver cells (Kilberg & Neuhaus, 1977;Boerner & Saier, 1982a). Consequently, although hepatoma cells appear to lack system ASC, the interpretation of the study of Dudeck et al (1987), which resulted from studies only with AIB, must be considered somewhat equivocal.…”

“…Studies involving membrane vesicles derived from 3T3 mouse fibroblasts implicated cAMP and the cAMP-dependent protein kinase as a negative regulator of system A transport (NilsonHamilton & Hamilton, 1979). However, convincing evidence for a correlation between cAMP levels and system A transport in any cell line is at present lacking, and a stimulatory effect of glucagon, which also stimulates cyclic AMP production, increased system A activity in liver cells (Kilberg & Neuhaus, 1977). Recent work involving the use of MDCK cells grown in a defined medium showed a requirement for low concentrations of prostaglandin E1 for maximal system A activity, but high concentrations of this hormone lowered the activity in the presence of repressive amino acids (Boerner & Saier, 1985a,b).…”

Ionic dependence of amino-acid transport in the exocrine pancreatic epithelium: Calcium dependence of insulin action

“…5A) and insensitive to ouabain (Table). As in the pancreas, MeAIB transport in the perfused rat liver is insulin-insensitive but stimulated by glucagon [19]. Although insulin hyperpolarizes pancreatic acinar cells [18,39], it seems unlikely that stimulation of L-serine transport by insulin was dependent upon activation of the sodium pump.…”

Role of glucagon suppression on gluconeogenesis during insulin treatment of the conscious diabetic dog

“…This theory would also explain why the fractional extraction of alanine by the liver decreased when the glucagon concentration decreased and returned to starting levels when glucagon was replaced. However, glucagon has also been shown to affect amino acid transport across the liver cell membrane both in vivo [11,21,29,30] and in vitro [31][32][33][34], thus at least part of the change in the hepatic fractional extraction of alanine may have been related to changes in alanine transport. Since the plasma alanine concentration rose by about 50%, despite little change in alanine uptake by the liver, alanine release from peripheral tissues must have increased.…”