Mechanisms of amino acid-induced insulin secretion from the glucose-responsive BRIN-BD11 pancreatic B-cell line

Abstract

Abstract The effects of different classes of amino acids known to be transported and utilized by pancreatic B-cells were examined using the novel glucose-responsive pancreatic B-cell line, BRIN-BD11. Amino acids tested included α-aminoisobutyric acid, l-alanine, l-arginine, l-glutamine, glycine, l-leucine, l-lysine, l-proline and l-serine. At non-stimulatory (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. Raising glucose to 16·7 mmol/l enhanced the effects of all amino acids except l-glutamine, and increased insulin output at 10 mmol/l compared with 1 mmol/l amino acid. Glyceraldehyde (10 mmol/l) also served to promote 10 mmol/l amino acid-induced insulin secretion with the exceptions of l-arginine, glycine, l-lysine and l-proline. At 16·7 mmol/l glucose, diazoxide (300 μmol/l) significantly decreased the secretory response to all amino acids except l-glutamine. Likewise, verapamil (20 μmol/l) or depletion of extracellular Ca2+ reduced insulin output indicating the importance of Ca2+ influx in the actions of amino acids. These data indicate that BRIN-BD11 cells transport and utilize amino acids, acting in association with glycolysis, K+-ATP channels and/or voltage-dependent Ca2+ channels to promote Ca2+ influx and insulin secretion. The response of BRIN-BD11 cells to glucose and amino acids indicates that this is a useful cell line for future research on the mechanisms of nutrient regulation of insulin secretion. Journal of Endocrinology (1996) 151, 349–357