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

被引:93
作者
McClenaghan, NH [1 ]
Barnett, CR [1 ]
OHarte, FPM [1 ]
Flatt, PR [1 ]
机构
[1] UNIV ULSTER,SCH BIOMED SCI,COLERAINE BT52 1SA,LONDONDERRY,NORTH IRELAND
关键词
D O I
10.1677/joe.0.1510349
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
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 mu mol/l) significantly decreased the secretory response to all amino acids except L-glutamine. Likewise, verapamil (20 mu mol/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 mechanism of nutrient regulation of insulin secretion.
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页码:349 / 357
页数:9
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