1. Investigación

Rats chronically treated with two daily doses of tolbutamide, glibenclamide or glipentide were compared with animals treated with placebo. Plasma individual amino acids were determined at 0, 3, 7, 10, 12, 14, 17, 24, 27 and 29 days of treatment 16 hours after the administration of the drug. Rats were fasted for 48 h periods at days 10 to 12 and 27 to 29 of the experiment. Sulfonylurea treated animals show minor changes in the plasma aminogram, although glipentide and glibenclamide produced greater effects than tolbutamide. At the 3rd day after the onset of the treatment, plasma levels of glutamate+ glutamine, arginine and histidine appeared significantly reduced in glipentide and glibenclamide treated animals. When plasma samples were collected 3 h after the drug administration at the 24th day of treatment, the only observed change was a decrease in the levels of arginine in the glipentide treated animals. Fasting produced decreases in plasma levels of alanine, pro line, cysteine, tyrosine, methionine +ornithine and tryptophan, there were no changes in serine, aspartate + asparagine, threonine citruline, arginine and lysine; and glycine, glutamate+ glutamine and leucine + isoleucine show increases. These changes were rapidly compensated with refeeding, appearing a "rebound effect" in certain amino acids. Both fasting and refeeding affect very little the effect of sultonylureas on plasma amino acid levels, although for some individual amino acid they reduce or enhance the effect of the fasting. These small effect of sulfonylureas on plasma amino acid levels could be the result of the juxtaposition of different factors, including the effects of these drugs on circulating insulin levels, on protein biosynthesis and amino acids transamination and hepatic gluconeogenesis.

The effects of food deprivation for up to 24 hours on plasma metabolic parameters in the rat have been studied. Liver dry weight and glycogen content dropped significantly from a hours of food deprivation onwards. Total muscle glycogen supplied about as much glycosyl residues or precursors as did the liver. Plasma glucose, urea, lactate and total and essential amino acids decreased significantly from 3 hours of fasting onwards. Glycerol, free fatty acids, beta-hydroxybutyrate and acetoacetate showed significant increases with fasting. Alanine, serine, arginine, threonine, aspartate plus asparagine and proline showed significant decreases with fasting. Several other amino acids showed almost nc change with fasting. Lysine, leucine plus isoleucine and taurine showed biphasic changes in their concentrations with a minimum at 6 hours and a transient recovery at 12 hours of fasting. Essential amino acids decreased more than the non essential ones. With fasting there is a shift in ammonia disposal with lower urea concentrations as nitrogen is better conserved. The results seem to suggest that there i~ a constant release of substrates, through liver and peripheral tissue proteolysis, that is counteracted by differential utilization of amino acids during fasting.