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 transported and utilized by pancreatic B-cells were examined using the novel glucose-responsive pancreatic B-cell line, BRIN-BD11. Amino acids tested included alpha-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 mumol/l) significantly decreased the secretory response to all amino acids except L-glutamine. Likewise, verapamil (20 mumol/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.
McClenaghan
N H
NH
School of Biomedical Sciences, University of Ulster, Coleraine, UK.
Barnett
C R
CR
O'Harte
F P
FP
Flatt
P R
PR
D000409:Alanine / Q000494:pharmacology; D000596:Amino Acids / Q000494:pharmacology*; D000621:Aminoisobutyric Acids / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002460:Cell Line; D003981:Diazoxide / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005947:Glucose / Q000494:pharmacology; D005973:Glutamine / Q000494:pharmacology; D005985:Glyceraldehyde / Q000494:pharmacology; D005998:Glycine / Q000494:pharmacology; D007328:Insulin / Q000032:analysis / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000187:drug effects / Q000378:metabolism*; D007930:Leucine / Q000494:pharmacology; D008239:Lysine / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011392:Proline / Q000494:pharmacology; D011863:Radioimmunoassay; D051381:Rats; D012694:Serine / Q000494:pharmacology; D013268:Stimulation, Chemical; D014700:Verapamil / Q000494:pharmacology
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D002121:Calcium Channel Blockers; D007328:Insulin; D015221:Potassium Channels; D005973:Glutamine; C100049:2-aminoisobutyric acid; D005985:Glyceraldehyde; D012694:Serine; D001120:Arginine; D011392:Proline; D014700:Verapamil; D007930:Leucine; D005947:Glucose; D008239:Lysine; D003981:Diazoxide; D000409:Alanine; D005998:Glycine