Na+ cotransport by metabolizable and nonmetabolizable amino acids stimulates a glucose-regulated insulin-secretory response.
The involvement of Na+ in insulin-secretory responses to metabolizable and nonmetabolizable amino acids known to be cotransported with Na+, were examined using islet-derived BRIN-BD11 cells. At stimulatory (16.7 mM) glucose, 10 mM of l-alanine, alpha-aminoisobutyric acid (AIB) or l-proline stimulated 1.3- to 10. 4-fold (p < 0.01) insulin-secretory responses. In each case, these effects were significantly greater than those observed at nonstimulatory (1.1 mM) glucose (p < 0.01). While, tetrodotoxin blockade of voltage-dependent Na+ channels exerted no significant effect on insulin release, Na/K pump blockade with ouabain significantly promoted the amino acid-induced effects (p < 0.05). Replacement of extracellular Na+ with equimolar N-methyl-d-glucamine+ and omission of extracellular K+ or Ca2+ were all effective in removing the actions of each amino acid, confirming the critical role of ionic fluxes in the secretory responses to these amino acids. Collectively these results demonstrate that metabolizable and nonmetabolizable amino acids can induce glucose-dependent insulin-secretory responses by modulating electrogenic Na+ transport.
School of Biomedical Sciences, University of Ulster, Coleraine, BT52 1SA, Northern Ireland. nhmcclenaghan@ulst.ac.uk
N H
NH
McClenaghan
C R
CR
Barnett
P R
PR
Flatt
D000409:Alanine / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D001692:Biological Transport; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D005947:Glucose / Q000494:pharmacology*; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects* / Q000378:metabolism*; D008536:Meglumine / Q000494:pharmacology; D010042:Ouabain / Q000494:pharmacology; D011392:Proline / Q000494:pharmacology; D012964:Sodium / Q000378:metabolism*; D015222:Sodium Channels / Q000502:physiology; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D007328:Insulin; D015222:Sodium Channels; C100049:2-aminoisobutyric acid; D013779:Tetrodotoxin; D010042:Ouabain; D008536:Meglumine; D011392:Proline; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D005947:Glucose; D000409:Alanine; D002118:Calcium