ATP敏感性钾通道病：聚焦于胰岛素分泌
ATP-sensitive potassium channelopathies: focus on insulin secretion.
作者信息
Ashcroft Frances M
机构信息
University Laboratory of Physiology, Oxford University, Oxford, United Kingdom.
出版信息
J Clin Invest. 2005 Aug;115(8):2047-58. doi: 10.1172/JCI25495.
Abstract
ATP-sensitive potassium (K(ATP)) channels, so named because they are inhibited by intracellular (ATP), play key physiological roles in many tissues. In pancreatic beta cells, these channels regulate glucose-dependent insulin secretion and serve as the target for sulfonylurea drugs used to treat type 2 diabetes. This review focuses on insulin secretory disorders, such as congenital hyperinsulinemia and neonatal diabetes, that result from mutations in K(ATP) channel genes. It also considers the extent to which defective regulation of K(ATP) channel activity contributes to the etiology of type 2 diabetes.
摘要
ATP敏感性钾（K(ATP)）通道，因其受细胞内ATP抑制而得名，在许多组织中发挥关键的生理作用。在胰腺β细胞中，这些通道调节葡萄糖依赖性胰岛素分泌，并作为用于治疗2型糖尿病的磺脲类药物的靶点。本综述聚焦于由K(ATP)通道基因突变导致的胰岛素分泌紊乱，如先天性高胰岛素血症和新生儿糖尿病。它还探讨了K(ATP)通道活性调节缺陷在2型糖尿病病因学中的作用程度。
相似文献
1
ATP-sensitive potassium channelopathies: focus on insulin secretion.ATP敏感性钾通道病：聚焦于胰岛素分泌
J Clin Invest. 2005 Aug;115(8):2047-58. doi: 10.1172/JCI25495.
2
K(ATP) channelopathies in the pancreas.胰腺中的 K(ATP)通道病。
Pflugers Arch. 2010 Jul;460(2):307-20. doi: 10.1007/s00424-009-0756-x. Epub 2009 Nov 18.
3
The K(ATP) channel and neonatal diabetes.钾离子通道与新生儿糖尿病
Endocr J. 2009;56(2):165-75. doi: 10.1507/endocrj.k08e-160. Epub 2008 Jun 20.
4
K(ATP) channels and islet hormone secretion: new insights and controversies.K(ATP) 通道与胰岛激素分泌：新的认识与争议。
Nat Rev Endocrinol. 2013 Nov;9(11):660-9. doi: 10.1038/nrendo.2013.166. Epub 2013 Sep 17.
5
Hyperinsulinism of infancy: the regulated release of insulin by KATP channel-independent pathways.婴儿期高胰岛素血症：通过不依赖KATP通道的途径调节胰岛素释放。
Diabetes. 2001 Feb;50(2):329-39. doi: 10.2337/diabetes.50.2.329.
6
Treating diabetes today: a matter of selectivity of sulphonylureas.今日糖尿病治疗：磺酰脲类药物的选择性问题。
Diabetes Obes Metab. 2012 Jan;14 Suppl 1:9-13. doi: 10.1111/j.1463-1326.2011.01507.x.
7
Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.因三磷酸腺苷敏感性钾通道基因隐性突变所致先天性高胰岛素血症患儿的基因型-表型相关性
J Clin Endocrinol Metab. 2005 Feb;90(2):789-94. doi: 10.1210/jc.2004-1604. Epub 2004 Nov 23.
8
The molecular genetics of sulfonylurea receptors in the pathogenesis and treatment of insulin secretory disorders and type 2 diabetes.磺酰脲受体的分子遗传学在胰岛素分泌紊乱和 2 型糖尿病发病机制和治疗中的作用。
Curr Diab Rep. 2011 Dec;11(6):543-51. doi: 10.1007/s11892-011-0233-8.
9
Selective enhancement of nutrient-induced insulin secretion by ATP-sensitive K+ channel-blocking imidazolines.通过ATP敏感性钾通道阻断咪唑啉对营养物质诱导的胰岛素分泌进行选择性增强。
J Pharmacol Exp Ther. 2009 Dec;331(3):1033-41. doi: 10.1124/jpet.109.152751. Epub 2009 Sep 10.
10
Shortcomings of current models of glucose-induced insulin secretion.当前葡萄糖诱导胰岛素分泌模型的缺陷。
Diabetes Obes Metab. 2009 Nov;11 Suppl 4:168-79. doi: 10.1111/j.1463-1326.2009.01109.x.
引用本文的文献
1
Real-world experience with the use of diazoxide among people living with congenital hyperinsulinism and their caregivers.先天性高胰岛素血症患者及其护理人员使用二氮嗪的真实世界经验。
Front Endocrinol (Lausanne). 2025 Aug 21;16:1628125. doi: 10.3389/fendo.2025.1628125. eCollection 2025.
2
Genetic and clinical insights into acute kidney injury in maturity-onset diabetes of the young caused by the c.2500C>T mutation: Potential risk factors associated with SGLT2 inhibitors.由c.2500C>T突变引起的青年成年型糖尿病急性肾损伤的遗传和临床见解：与钠-葡萄糖协同转运蛋白2抑制剂相关的潜在危险因素。
Exp Ther Med. 2025 Jun 26;30(2):164. doi: 10.3892/etm.2025.12914. eCollection 2025 Aug.
3
Revealing the role of increased SK3 expression in sulfonylurea resistance triggered by prolonged exposure.揭示长时间暴露引发的磺脲类药物抵抗中SK3表达增加的作用。
Nutr Diabetes. 2025 Jun 20;15(1):29. doi: 10.1038/s41387-025-00384-9.
4
LRRC8 channel complexes counterbalance KATP channels to mediate swell-secretion coupling in mouse pancreatic β cells.LRRC8通道复合物与KATP通道相互制衡，以介导小鼠胰腺β细胞中的肿胀-分泌偶联。
JCI Insight. 2025 Apr 29;10(11). doi: 10.1172/jci.insight.188020. eCollection 2025 Jun 9.
5
Recent advances in immunopathogenesis and clinical practice: mastering the challenge-managing of non-tuberculous mycobacteria.免疫发病机制与临床实践的最新进展：应对非结核分枝杆菌感染的挑战与管理
Front Immunol. 2025 Mar 19;16:1554544. doi: 10.3389/fimmu.2025.1554544. eCollection 2025.
6
AI-based discovery and cryoEM structural elucidation of a K channel pharmacochaperone.基于人工智能发现并通过冷冻电镜阐明一种钾通道药物伴侣的结构
Elife. 2025 Mar 26;13:RP103159. doi: 10.7554/eLife.103159.
7
Inflammasomes and idiopathic inflammatory myopathies.炎性小体与特发性炎症性肌病
Front Immunol. 2024 Dec 11;15:1449969. doi: 10.3389/fimmu.2024.1449969. eCollection 2024.
8
The role of the adenylate kinase 5 gene in various diseases and cancer.腺苷酸激酶5基因在各种疾病和癌症中的作用。
J Clin Transl Sci. 2024 Aug 19;8(1):e96. doi: 10.1017/cts.2024.536. eCollection 2024.
9
The Interlinking Metabolic Association between Type 2 Diabetes Mellitus and Cancer: Molecular Mechanisms and Therapeutic Insights.2型糖尿病与癌症之间的相互关联代谢联系：分子机制与治疗见解
Diagnostics (Basel). 2024 Sep 25;14(19):2132. doi: 10.3390/diagnostics14192132.
10
Co-inheritance of Rare Variants of Maturity-Onset Diabetes of the Young (MODY): A Case Report and Review of the Literature.青年发病的成年型糖尿病（MODY）罕见变异的共遗传：一例病例报告及文献综述
Cureus. 2024 Sep 9;16(9):e69039. doi: 10.7759/cureus.69039. eCollection 2024 Sep.
本文引用的文献
1
A gating mutation at the internal mouth of the Kir6.2 pore is associated with DEND syndrome.Kir6.2 孔道内口处的门控突变与 DEND 综合征相关。
EMBO Rep. 2005 May;6(5):470-5. doi: 10.1038/sj.embor.7400393.
2
The C42R mutation in the Kir6.2 (KCNJ11) gene as a cause of transient neonatal diabetes, childhood diabetes, or later-onset, apparently type 2 diabetes mellitus.Kir6.2（KCNJ11）基因中的C42R突变是导致短暂性新生儿糖尿病、儿童糖尿病或迟发性2型糖尿病的原因。
J Clin Endocrinol Metab. 2005 Jun;90(6):3174-8. doi: 10.1210/jc.2005-0096. Epub 2005 Mar 22.
3
Relapsing diabetes can result from moderately activating mutations in KCNJ11.复发性糖尿病可能由KCNJ11基因中的中度激活突变引起。
Hum Mol Genet. 2005 Apr 1;14(7):925-34. doi: 10.1093/hmg/ddi086. Epub 2005 Feb 17.
4
Functional analysis of a structural model of the ATP-binding site of the KATP channel Kir6.2 subunit.KATP通道Kir6.2亚基ATP结合位点结构模型的功能分析
EMBO J. 2005 Jan 26;24(2):229-39. doi: 10.1038/sj.emboj.7600487. Epub 2005 Jan 13.
5
Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features.与新生儿糖尿病或伴有神经学特征的新生儿糖尿病相关的Kir6.2突变的分子基础。
Proc Natl Acad Sci U S A. 2004 Dec 14;101(50):17539-44. doi: 10.1073/pnas.0404756101. Epub 2004 Dec 6.
6
KCNJ11 activating mutations in Italian patients with permanent neonatal diabetes.意大利永久性新生儿糖尿病患者中的KCNJ11激活突变
Hum Mutat. 2005 Jan;25(1):22-7. doi: 10.1002/humu.20124.
7
Genotype-phenotype correlations in children with congenital hyperinsulinism due to recessive mutations of the adenosine triphosphate-sensitive potassium channel genes.因三磷酸腺苷敏感性钾通道基因隐性突变所致先天性高胰岛素血症患儿的基因型-表型相关性
J Clin Endocrinol Metab. 2005 Feb;90(2):789-94. doi: 10.1210/jc.2004-1604. Epub 2004 Nov 23.
8
Identification of a functionally important negatively charged residue within the second catalytic site of the SUR1 nucleotide-binding domains.在SUR1核苷酸结合结构域的第二个催化位点内鉴定出一个功能重要的带负电荷残基。
Diabetes. 2004 Dec;53 Suppl 3:S123-7. doi: 10.2337/diabetes.53.suppl_3.s123.
9
Glibenclamide treatment in permanent neonatal diabetes mellitus due to an activating mutation in Kir6.2.由于Kir6.2激活突变导致的永久性新生儿糖尿病中的格列本脲治疗。
J Clin Endocrinol Metab. 2004 Nov;89(11):5504-7. doi: 10.1210/jc.2004-1241.
10
Common variants of the hepatocyte nuclear factor-4alpha P2 promoter are associated with type 2 diabetes in the U.K. population.肝细胞核因子-4α P2启动子的常见变异与英国人群中的2型糖尿病相关。
Diabetes. 2004 Nov;53(11):3002-6. doi: 10.2337/diabetes.53.11.3002.
Zotero 插件