Glucagon-Like Peptide 1(7-36) Amide Stimulates Exocytosis in Human Pancreatic β-Cells by Both Proximal and Distal Regulatory Steps in Stimulus-Secretion Coupling
Glucagon-Like Peptide 1(7-36) Amide Stimulates Exocytosis in Human Pancreatic β-Cells by Both Proximal and Distal Regulatory Steps in Stimulus-Secretion Coupling
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胰高血糖素样肽 1(7-36) 酰胺通过刺激分泌耦合中的近端和远端调节步骤刺激人胰腺 β 细胞的胞吐作用
DOI：
10.2337/diab.47.1.57
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发表时间：
1998
期刊：
影响因子：
7.7
通讯作者：
P. Rorsman
中科院分区：
文献类型：
--
作者：
J. Gromada;K. Bokvist;W. Ding;J. Holst;J. Nielsen;P. Rorsman
在单个人β细胞中探索胰高血糖素样肽1（7 - 36）酰胺[GLP-1（7-36）酰胺]对膜电位、全细胞ATP敏感性钾通道（KATP）和Ca 2+电流、胞浆Ca 2+浓度和胞吐的影响。GLP-1（7-36）酰胺诱导与全细胞KATP电流抑制相关的膜去极化。此外，GLP-1（7-36）酰胺（和毛喉素）产生大于四倍的Ca 2+依赖性胞吐增强。后者的作用部分（40%）是由于通过电压依赖性（L型）Ca 2+通道加速Ca 2+内流。更重要的是，GLP- 1（7-36）酰胺（通过产生环AMP和激活蛋白激酶A）在细胞质Ca 2+浓度升高远端部位增强胞吐作用。当胞质Ca 2+浓度被钳制在>170 nmol/l时，笼状cAMP的光释放产生2 - 3倍的胞吐增强。GLP-1（7-36）酰胺的作用被胰岛激素生长抑素拮抗。对膜电位、离子电导和胞吐作用的类似作用在葡萄糖依赖性促胰岛素多肽（GIP）（第二种主要肠促胰岛素）中观察到。目前的数据表明，GLP-1（7-36）酰胺和GIP在人体中的强烈促胰岛素作用是由于其与刺激-分泌偶联中的几个近端和远端重要调控步骤相互作用所致。
The effect of glucagon-like peptide 1(7–36) amide [GLP-l(7–36) amide] on membrane potential, wholecell ATP-sensitive potassium channel (KATP) and Ca2+ currents, cytoplasmic Ca2+ concentration, and exocytosis was explored in single human β-cells. GLP-1(7–36) amide induced membrane depolarization that was associated with inhibition of whole-cell KATP current. In addition, GLP-l(7–36) amide (and forskolin) produced greater than fourfold potentiation of Ca2+-dependent exocytosis. The latter effect resulted in part (40%) from acceleration of Ca2+ influx through voltage-dependent (L-type) Ca2+ channels. More importantly, GLP- 1(7–36) amide (via generation of cyclic AMP and activation of protein kinase A) potentiated exocytosis at a site distal to a rise in the cytoplasmic Ca2+ concentration. Photorelease of caged cAMP produced a two- to threefold potentiation of exocytosis when the cytoplasmic Ca2+ concentrations were clamped at >170 nmol/1. The effect of GLP-1(7–36) amide was antagonized by the islet hormone somatostatin. Similar effects on membrane potential, ion conductances, and exocytosis were observed with glucose-dependent insulinotropic polypeptide (GIP), the second major incretin. The present data suggest that the strong insulinotropic action of GLP-1(7–36) amide and GIP in humans results from its interaction with several proximal as well as distal important regulatory steps in the stimulus-secretion coupling.
影响因子：
4.8
作者：
M. Wheeler;M. Lu;J. S. Dillon;X. Leng;Chuan Chen;A. E. Boyd
通讯作者：
M. Wheeler;M. Lu;J. S. Dillon;X. Leng;Chuan Chen;A. E. Boyd