Glucose sensing in L cells: a primary cell study.

Glucose sensing in L cells: a primary cell study.
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DOI:
10.1016/j.cmet.2008.11.002
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发表时间:
2008-12
期刊:
影响因子:
29
通讯作者:
Gribble FM
Gribble FM
中科院分区:
生物学1区
文献类型:
--
作者:
Reimann F;Habib AM;Tolhurst G;Parker HE;Rogers GJ;Gribble FM

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胰高血糖素样肽-1 (GLP-1)是一种肠道激素,可刺激胰岛素分泌,改善2型糖尿病患者的血糖。尽管基于GLP-1的治疗在临床上是可行的,但由于我们对L细胞类型的生理理解有限,增加L细胞内源性GLP-1释放的替代策略受到阻碍。通过培养L细胞特异性表达一种荧光蛋白的转基因小鼠,我们通过电生理、荧光钙成像和表达分析研究了原代L细胞的特征,发现单个L细胞具有电兴奋性和葡萄糖反应性。在单个L细胞和原代培养的激素分泌中评估了对甲磺丁酰胺和低毫摩尔浓度葡萄糖和α-甲基吡喃葡萄糖苷的敏感性,表明GLP-1的释放受葡萄糖钠共转运蛋白1和atp敏感的K+通道的活性调节,这与定量RT-PCR纯化的L细胞中它们的高表达水平一致。使用这种方法确定的这些途径和其他途径将为未来的生理和治疗探索提供令人兴奋的机会。
Glucagon-like peptide-1 (GLP-1) is an enteric hormone that stimulates insulin secretion and improves glycaemia in type 2 diabetes. Although GLP-1-based treatments are clinically available, alternative strategies to increase endogenous GLP-1 release from L cells are hampered by our limited physiological understanding of this cell type. By generating transgenic mice with L cell-specific expression of a fluorescent protein, we studied the characteristics of primary L cells by electrophysiology, fluorescence calcium imaging, and expression analysis and show that single L cells are electrically excitable and glucose responsive. Sensitivity to tolbutamide and low-millimolar concentrations of glucose and α-methylglucopyranoside, assessed in single L cells and by hormone secretion from primary cultures, suggested that GLP-1 release is regulated by the activity of sodium glucose cotransporter 1 and ATP-sensitive K+ channels, consistent with their high expression levels in purified L cells by quantitative RT-PCR. These and other pathways identified using this approach will provide exciting opportunities for future physiological and therapeutic exploration.
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