Effect of Insulin and Glucagon on Amino Acid Transport in Isolated Hepatocytes after Partial Hepatectomy in the Rat*

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Abstract
The effects of insulin and glucagon on amino acid transport in the regenerating liver were investigated by measuring the uptake of α-aminoisobutyric acid in isolated hepatocytes from partially (70%) hepatectomized rats and from pancreatectomized-partially hepatectomized animals. Partial hepatectomy induced the emergence of a high affinity (Km ≅ 1 mM) transport component in hepatocytes from the liver remnant; in hepatocytes isolated 3, 6, and 16 h after partial hepatectomy, the Vmax (nanomoles per 1066 cells / min) of this component was 2.7 ± 0.3, 4.9 ± 1.0, 5.1 ± 0.9 (mean ± SE), respectively. Combination of pancreatectomy and partial hepatectomy, which resulted in a marked decrease in plasma insulin but not glucagon immunoreactivity, delayed the emergence of the high affinity component and reduced its capacity (Vmax = 1.5 ± 0.5 nmol / 106 cells/min 6 h after operation). Infusion of exogenous insulin in pancreatictomized-partially hepatectomized rats restored the emergence of the high affinity transport component. Insulin and glucagon at maximally stimulating concentrations in vitro failed to further enhance the capacity of the high affinity transport induced by partial hepatectomy when added to hepatocytes 6 or 16 h after operation. This lack of responsiveness could not be related to a receptor defect. Responsiveness to insulin or glucagon in vitro was restored to values similar to control (sham-operated) rat hepatocytes when pancreatectomy was combined with partial hepatectomy. It is concluded that 1) the capacity of the high affinity component of hepatocyte amino acid transport induced by partial hepatectomy increases during the first hours after operation and is maintained throughout the major part of the prereplicative period; 2) pancreatectomy delays the emergence of this component and markedly reduces its capacity; 3) insulin and glucagon added in vitro fail to further enhance the capacity of this component when it is fully expressed (6 h after partial hepatectomy). The data suggest that pancreatic hormones are involved in vivo in the emergence of the high affinity amino acid transport component that appears in the liver remnant after partial hepatectomy.