Neutral amino acid transport in hepatocytes isolated from streptozotocin-induced diabetic rats.
In the present study, transport by Systems A, ASC, and N was shown to be elevated in hepatocytes isolated from diabetic rats. After the cells were placed in primary culture, the System ASC activity declined rapidly, while the decay of Systems A and N was slower and dependent on protein synthesis. The elevated 2-aminoisobutyric acid uptake was the result of an increase in the Vmax of a single, high affinity system, presumably System A. The stimulation of System A could not be accounted for by an increase in the affinity for Na+; in fact, the apparent Km for the ion was actually greater in the experimental cells. Release from trans-inhibition was also eliminated as a possible explanation. The data suggest that during the development of the diabetic state the liver is triggered to induce the activity of System A by synthesizing the necessary protein components. Treatment of the cultured hepatocytes with insulin could partially reverse the stimulation due to diabetes, indicating that the induction of System A may be the result of the hyperglucagonemia associated with the disease. In support of this hypothesis, the cells from the diabetic rats were resistant to further stimulation of System A by glucagon, yet they did respond to high levels of insulin or to amino acid starvation. Glucagon does not appear to be involved in the induction of System N in the diabetic animal because this system is not responsive to either glucagon or insulin when tested in vitro.
D000315:Adrenalectomy; D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport; D002478:Cells, Cultured; D003513:Cycloheximide / Q000494:pharmacology; D003921:Diabetes Mellitus, Experimental / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D012964:Sodium / Q000378:metabolism
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D003513:Cycloheximide; D012964:Sodium; D000409:Alanine