System A amino acid transport in incubated muscle: effects of insulin and acute uremia.
The insulin-stimulated increase in amino acid uptake in most cells and tissues involves stimulation of system A transport. In muscle the probes used to study this process have not been specific, making it difficult to determine whether system A is abnormal in insulin-resistant states, such as acute renal failure (ARF). To circumvent this problem, we studied 2-(methylamino) isobutyrate (MeAIB) transport. Its specificity for system A in incubated rat epitrochlearis muscles was documented by showing its uptake by only one carrier that is sodium dependent and insulin responsive and that exhibits adaptive regulation in response to starvation. Using this specific probe we determined whether insulin-stimulated amino acid transport by system A is impaired by ARF. MeAIB uptake was linear for 3 h in muscles of ARF and sham-operated (SO) rats. In the absence (basal) or presence of insulin, MeAIB uptake was significantly lower in ARF, yet the stimulation by insulin was similar in both groups. Likewise, the insulin dose-response relationship confirmed that physiological levels of insulin (less than or equal to 10(2) microU/ml) increased transport by a similar degree. At greater than or equal to 10(2) microU/ml insulin there was a plateau in MeAIB transport in ARF but not in SO muscles. Thus basal system A transport is depressed in ARF, but the stimulation of system A by physiological levels of insulin is preserved. At pharmacological levels of insulin system A transport is impaired by ARF.
D000208:Acute Disease; D058186:Acute Kidney Injury / Q000378:metabolism; D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D005110:Extracellular Space / Q000032:analysis / Q000187:drug effects; D007328:Insulin / Q000494:pharmacology*; D008297:Male; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D013997:Time Factors; D014511:Uremia / Q000378:metabolism*
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D007328:Insulin; C100049:2-aminoisobutyric acid; C017911:2-(methylamino)isobutyric acid