β-Cell secretory products activate α-cell ATP-dependent potassium channels to inhibit glucagon release
β-Cell secretory products activate α-cell ATP-dependent potassium channels to inhibit glucagon release
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DOI：
10.2337/diabetes.54.6.1808
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发表时间：
2005-06-01
期刊：
影响因子：
7.7
通讯作者：
Wollheim, CB
中科院分区：
文献类型：
--
作者：
Franklin, I;Gromada, J;Wollheim, CB
胰岛α细胞分泌的胰高血糖素动员肝脏葡萄糖。在高血糖期间，胰高血糖素分泌被来自其他胰岛细胞的旁分泌因子抑制，但在1型和2型糖尿病患者中，这种抑制丧失。我们研究了β细胞分泌产物锌和胰岛素对大鼠a细胞、完整胰岛和灌注胰腺的影响。胰岛胰高血糖素分泌对锌的敏感性（IC_（50）= 2.7 μ mol/l）明显高于胰岛素释放（IC_（50）= 10.7 μ mol/l）。葡萄糖、线粒体底物丙酮酸盐和ATP敏感性K+通道（K-ATP通道）抑制剂甲苯磺丁脲刺激分离的α细胞电活动和胰高血糖素分泌。锌打开K-ATP通道，抑制电活动和丙酮酸（但不是精氨酸）刺激胰高血糖素分泌α细胞。胰岛素瞬时增加K-ATP通道活性，抑制α细胞的电活动和胰高血糖素分泌，并抑制胰高血糖素输出。胰岛素受体和K-ATP通道亚单位转录本在α细胞中比β细胞中更丰富。在α细胞中未检测到胰高血糖素样肽1（GLP-1）受体的转录物，GLP-1也未刺激α细胞胰高血糖素释放。因此，β-细胞分泌产物锌和胰岛素最可能通过直接激活K-ATP通道来抑制胰高血糖素分泌，从而掩蔽与β-细胞类似的α-细胞代谢分泌偶联途径。
Glucagon, secreted from islet alpha-cells, mobilizes liver glucose. During hyperglycemia, glucagon secretion is inhibited by paracrine factors from other islet cells, but in type 1 and type 2 diabetic patients, this suppression is lost. We investigated the effects of beta-cell secretory products zinc and insulin on isolated rat a-cells, intact islets, and perfused pancreata. Islet glucagon secretion was markedly zinc sensitive (IC50 = 2.7 mu mol/l) more than insulin release (IC50 = 10.7 mu mol/l). Glucose, the mitochondrial substrate pyruvate, and the ATP-sensitive K+ channel (K-ATP channel) inhibitor tolbutamide stimulated isolated alpha-cell electrical activity and glucagon secretion. Zinc opened K-ATP channels and inhibited both electrical activity and pyruvate (but not arginine) stimulated glucagon secretion in alpha-cells. Insulin transiently increased K-ATP channel activity, inhibited electrical activity and glucagon secretion in alpha-cells, and inhibited pancreatic glucagon output. Insulin receptor and K-ATP channel subunit transcripts were more abundant in alpha- than beta-cells. Transcript for the glucagon-like peptide 1 (GLP-1) receptor was not detected in alpha-cells nor did GLP-1 stimulate a-cell glucagon release. beta-Cell secretory products zinc and insulin therefore inhibit glucagon secretion most probably by direct activation of K-ATP channels, thereby masking an alpha-cell metabolism secretion coupling pathway similar to beta-cells.