MECHANISMS OF AMINO ACID-INDUCED INSULIN-SECRETION FROM THE GLUCOSE-RESPONSIVE BRIN-BD11 PANCREATIC B-CELL LINE

The effects of different classes of amino acids known to be transporte d and utilized by pancreatic B-cells were examined using the novel glu cose-responsive pancreatic B-cell line, BRIN-BD11. Amino acids tested included alpha-aminoisobutyric acid, L-alanine, L-arginine, L-glutamin e, glycine, L-leucine, L-lysine, L-proline and L-serine. At non-stimul atory (1.1 mmol/l) glucose, acute incubations with either 1 or 10 mmol /l amino acid evoked 1.3- to 4.7-fold increases of insulin release. Ra ising glucose to 16.7 mmol/l enhanced the effects of all amino acids e xcept L-glutamine, and increased insulin output at 10 mmol/l compared with 1 mmol/l amino acid. Glyceraldehyde (10 mmol/l) also served to pr omote 10 mmol/l amino acid-induced insulin secretion with the exceptio ns of L-arginine, glycine, L-lysine and L-proline. At 16.7 mmol/l gluc ose, diazoxide (300 mu mol/l) significantly decreased the secretory re sponse to all amino acids except L-glutamine. Likewise, verapamil (20 mu mol/l) or depletion of extracellular Ca2+ reduced insulin output in dicating the importance of Ca2+ influx in the actions of amino acids. These data indicate that BRIN-BD11 cells transport and utilize amino a cids, acting in association with glycolysis, K+-ATP channels and/or vo ltage-dependent Ca2+ channels to promote Ca2+ influx and insulin secre tion. The response of BRIN-BD11 cells to glucose and amino acids indic ates that this is a useful cell line for future research on the mechan ism of nutrient regulation of insulin secretion.