A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line
A novel glucose-sensing mechanism contributing to glucagon-like peptide-1 secretion from the GLUTag cell line
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DOI：
10.2337/diabetes.52.5.1147
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发表时间：
2003-05-01
期刊：
影响因子：
7.7
通讯作者：
Reimann, F
中科院分区：
文献类型：
--
作者：
Gribble, FM;Williams, L;Reimann, F
肠L细胞分泌胰高血糖素样肽-1是由肠道营养物质触发的。我们以前报道过，葡萄糖触发的GLP-1从L细胞模型GLUTag释放涉及关闭ATP敏感的K+(K-ATP)通道。我们发现GLUTag细胞的GLP-1分泌和电活动不仅由可代谢糖(葡萄糖或果糖)触发，而且还由非代谢单糖甲基-α-吡喃葡萄糖苷触发。对葡萄糖和甲基-α-吡喃葡萄糖苷的反应被钠-葡萄糖共转运体(SGLT)抑制剂根茎苷削弱。RT-PCR检测到GLUTag细胞中存在SLGT1和SLG3。而果糖关闭K-ATP通道，甲基-α-吡喃葡萄糖苷增加膜电导并产生内向电流。低浓度的葡萄糖和甲基-α-吡喃葡萄糖苷也触发了小的内向电流，并提高了动作电位频率。我们的结论是，低浓度的可代谢糖通过关闭K-ATP通道来触发GLP-1的分泌，而SGLT底物由于转运体的电生成作用而产生小的内向电流。当底物浓度较高时，或者当K-ATP通道的代谢关闭导致外向电流减少时，这种转运体相关的电流可以触发电活动和分泌。通过SGLTS的电生糖进入为神经内分泌细胞感知葡萄糖提供了一种新的机制。
Glucagon-like peptide 1 (GLP-1) secretion from intestinal L-cells is triggered by luminal nutrients. We reported previously that glucose-triggered GLP-1 release from the L-cell model GLUTag involves closure of ATP-sensitive K+ (K-ATP) channels. We show here that GLP-1 secretion and electrical activity of GLUTag cells is triggered not only by metabolizable sugars (glucose or fructose) but also by the nonmetabolizable monosaccharide methyl-alpha-glucopyranoside. Responses to glucose and methyl-alpha-glucopyranoside were impaired by the sodium-glucose cotransporter (SGLT) inhibitor phloridzin. SLGT1 and 3 were detected in GLUTag cells by RT-PCR. Whereas fructose closed K-ATP channels, methyl-alpha-glucopyranoside increased the membrane conductance and generated an inward current. Low concentrations of glucose and methyl-alpha-glucopyranoside also triggered small inward currents and enhanced the action potential frequency. We conclude that whereas low concentrations of metabolizable sugars trigger GLP-1 secretion via K-ATP channel closure, SGLT substrates generate small inward currents as a result of the electrogenic action of the transporter. This transporter-associated current can trigger electrical activity and secretion when the concentration of substrate is high or when outward currents are reduced by metabolic closure of the K-ATP channels. Electrogenic sugar entry via SGLTs provides a novel mechanism for glucose sensing by neuroendocrine cells.