Skeletal muscle amino acid metabolism in chronic uremia.
The kinetics and factors regulating acid release were studied in epitrochlaris preparations of control and chronically uremic rats. These data were correlated with abnormal glucose and glucose precursor kinetics of azotemic patients and the impact of hemodialysis on these precursor-product interrelationships. In chronically uremic rat skeletal muscle, a subsensitivity to catecholamines was evident. A 1000-fold greater concentration of epinephrine was required in uremic muscle to inhibit alanine release compared to control preparations. The dose-response curve for cAMP formation stimulated by epinephrine was shifted 1 log unit to the right in uremic muscle and adenylyl cyclase stimulation by epinephrine was shifted 1 log unit. Using simultaneous primed-injection-continuous infusions [U-14C]-alanine and [2-3H]glucose, rates of metabolite turnovers were calculated from the plateau portions of the specific activity curves. In 14 azotemic patients, alanine and glucose turnover rates were found to be increased 276 and 154%, respectively, over that of the control group of 17 subjects. Glucose production was found to be 3-fold greater. Hemodialysis decreased alanine turnover by 35% and glucose production by 19%. However, glucose turnover was not affected by dialysis. Although the percentage of glucose produced from alanine approached normal levels, the percent of alanine used for gluconeogenesis increased 60%. These studies demonstrate that abnormal carbohydrate metabolism in uremia is a result of multiple factors. Diminished response of adenylyl cyclase and decreased levels of cAMP contributes to, but does not entirely account for, increased amino acid release. The increased alanine synthesis in skeletal muscle supports glucose overproduction found in chronic azotemia. Hemodialysis ameliorates but does not fully normalize glucose and alanine metabolism and may actually introduce additional abnormalities.
D000328:Adult; D000409:Alanine / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000818:Animals; D003994:Bucladesine / Q000494:pharmacology; D002908:Chronic Disease; D004837:Epinephrine / Q000494:pharmacology; D005459:Fluorides / Q000494:pharmacology; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D008875:Middle Aged; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D014511:Uremia / Q000378:metabolism*
D000596:Amino Acids; D007328:Insulin; D005973:Glutamine; D003994:Bucladesine; D000409:Alanine; D005459:Fluorides; D004837:Epinephrine