Ionic dependence of amino-acid transport in the exocrine pancreatic epithelium: calcium dependence of insulin action.
Rapid unidirectional transport (15 sec) of L-serine and 2-methylaminoisobutyric acid (MeAIB) was studied in the isolated perfused rat pancreas using a dual-tracer dilution technique. Time-course experiments in the presence of normal cation gradients revealed a time-dependent transstimulation of L-serine influx and transinhibition of MeAIB influx. Transport of the model nonmetabolized System A analog MeAIB was Na+ dependent and significantly inhibited during perfusion with 1 mM ouabain. Although transport of L-serine was largely Na+ independent, ouabain caused a time-dependent inhibition of transport. Influx of both amino acids appeared to be inhibited by the ionophore monensin but unaffected by a lowered extracellular potassium concentration. Removal of extracellular calcium had no effect on influx of the natural substrate L-serine, whereas stimulation of transport by exogenous insulin (100 microU/ml) was entirely dependent upon extracellular calcium and unaffected by ouabain. Paradoxically, exogenous insulin had no effect on the time-course of MeAIB influx. The characteristics of L-serine influx described in earlier studies together with our present findings suggest that insulin may modulate the activity of System asc in the exocrine pancreatic epithelium by a calcium-dependent mechanism.
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002118:Calcium / Q000502:physiology*; D004848:Epithelium / Q000378:metabolism; D005934:Glucagon / Q000378:metabolism; D007328:Insulin / Q000502:physiology*; D008297:Male; D008985:Monensin / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D010179:Pancreas / Q000378:metabolism*; D010477:Perfusion; D011188:Potassium / Q000502:physiology; D051381:Rats; D011919:Rats, Inbred Strains; D012694:Serine / Q000378:metabolism; D012964:Sodium / Q000502:physiology
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D007328:Insulin; C017911:2-(methylamino)isobutyric acid; D012694:Serine; D010042:Ouabain; D005934:Glucagon; D008985:Monensin; D012964:Sodium; D011188:Potassium; D002118:Calcium