ether-a-go-go相关基因通道在胰岛β-细胞中的作用
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摘要
目的探究ether-a-go-go相关基因(ether-a-go-go related gene,ERG)通道在胰岛β-细胞中的作用。方法提取野生型(wild type,WT)与ERG基因敲除型(knockout,KO)小鼠胰岛β-细胞,利用全细胞膜片钳技术记录钾离子电流与动作电位,分析敲除ERG基因后钾电流与动作电位的变化。对两组小鼠进行腹腔注射葡萄糖耐量实验,分析基因敲除后小鼠糖耐量的变化,探究ERG基因是否对体内血糖浓度有影响。结果在两组小鼠胰岛β-细胞中记录到的钾离子电流均呈现内向整流趋势,KO组钾离子电流明显减小,动作电位时程明显延长。动物实验中,KO组小鼠糖刺激2 h后血糖浓度较WT组显著降低。结论 ERG通道电流是胰岛β-细胞中钾离子电流的重要组成部分,可显著影响动作电位时程,进而影响体内血糖浓度。
Objective To investigate the function of ether-a-go-go related gene( ERG) channel in pancreatic β-cells. Methods Whole-cell patch clamp technique was conducted to record the potassium currents and action potential in wild type( WT) and ERG knockout( KO) primary cultured pancreatic β-cells. Intra-peritoneal glucose tolerant test( IPGTT) was performed to measure the blood glucose levels in both WT and KO mice. Results KO pancreatic β-cells had decreased potassium currents and prolonged action potential duration 90% compared with WT ones. KO mice had better blood glucose levels during IPGTT. Conclusion ERG plays a role in the potassium currents and action potential in pancreatic β-cells,which may affect the blood glucose levels in vivo.
Objective To investigate the function of ether-a-go-go related gene( ERG) channel in pancreatic β-cells. Methods Whole-cell patch clamp technique was conducted to record the potassium currents and action potential in wild type( WT) and ERG knockout( KO) primary cultured pancreatic β-cells. Intra-peritoneal glucose tolerant test( IPGTT) was performed to measure the blood glucose levels in both WT and KO mice. Results KO pancreatic β-cells had decreased potassium currents and prolonged action potential duration 90% compared with WT ones. KO mice had better blood glucose levels during IPGTT. Conclusion ERG plays a role in the potassium currents and action potential in pancreatic β-cells,which may affect the blood glucose levels in vivo.
引文
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[14] Wang L,Gao P,Zhang M,et al,Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013[J].JAMA,2017,317(24):2515-2523.
[2] Fridlyand L E,Jacobson D A,Philipson L H. Ion channels and regulation of insulin secretion in humanβ-cells:a computational systems analysis[J]. Islets,2013,5(1):1-15.
[3] Braun M,Ramracheya R,Bengtsson M,et al. Voltage-gated ion channels in human pancreaticβ-Cells:electrophysiological characterization and role in insulin secretion[J].Diabetes,2008,57(6):1618-1628.
[4] Jacobson D A,Philipson L H. Action potentials and insulin secretion:new insights into the role of Kv channels[J]. Diabetes Obes Metab,2007,9(Suppl 22):89-98.
[5] Bryan J,Crane A,Vila-Carriles W H,et al. Insulin secretagogues,sulfonylurea receptors and K(ATP)channels[J]. Curr Pharm Des,2005,11(21):2699-2716.
[6] Proks P,Reimann F,Green N,et al. Sulfonylurea stimulation of insulin secretion[J]. Diabetes,2002,51(Supple3):368-376.
[7] Yang J K,Lu J,Yuan S S,et al,From hyper-to hypoinsulinemia and diabetes:effect of KCNH6 on insulin secretion[J] Cell Rep,2018,25(13):3800-3810.
[8] Cho J H,Chen L,Kim M H,et al. Characteristics and functions ofα-amino-3-hydroxy-5-methyl-4-isoxazolepropionate receptors expressed in mouse pancreaticα-cells[J].Endocrinology,2010,151(4):1541-1550.
[9] Guo J H,Chen H,Ruan Y C,et al. Glucose-induced electrical activities and insulin secretion in pancreatic isletβ-cells are modulated by CFTR[J]. Nat Commun,2014,5:4420.
[10] Shao C,Lu Y,Liu M,et al. Electrophysiological study of V535M h ERG mutation of LQT2[J]. J Huazhong Univ Sci Technolog Med Sci,2011,31(6):741-748.
[11] Wimmers S,Bauer C K,Schwarz J R. Biophysical properties of heteromultimeric erg K+channels[J]. Pflugers Arch,2002,445(3):423-430.
[12] Hyltén-Cavallius L,Lepsen E W,Wewer Albrechtsen N J,et al. Patients with long-QT syndrome caused by impaired h ERG-Encoded Kv11. 1 potassium channel have exaggerated endocrine pancreatic and incretin function associated with reactive hypoglycemia[J]. Circulation,2017,135(18):1705-1719.
[13] Fionl-Urdaneta R K,Remedi M S,rasch W,et al. Block of Kv1. 7 potassium currents increases glucose-stimulated insulin secretion[J]. EMBO Mol Med,2012,4(5):424-434.
[14] Wang L,Gao P,Zhang M,et al,Prevalence and Ethnic Pattern of Diabetes and Prediabetes in China in 2013[J].JAMA,2017,317(24):2515-2523.