TY - JOUR
T1 - Na+ cotransport by metabolizable and nonmetabolizable amino acids stimulates a glucose-regulated insulin-secretory response
AU - McClenaghan, Neville
AU - Barnett, CR
AU - Flatt, Peter
PY - 1998/8
Y1 - 1998/8
N2 - 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. (C) 1998 Academic Press.
AB - 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. (C) 1998 Academic Press.
M3 - Article
VL - 249
SP - 299
EP - 303
JO - Biochemical and Biophysical Research Communications
JF - Biochemical and Biophysical Research Communications
SN - 0006-291X
IS - 2
ER -