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钾离子通道在糖尿病及其并发症中的关键作用:综述

The crucial role of potassium ion channels in diabetes mellitus and its complications: A review.

作者信息

Yang Xiangdong, Yang Yan

机构信息

Experimental Medicine Center, The Affiliated Hospital of Southwest Medical University, Luzhou, China.

Key Lab of Medical Electrophysiology of Ministry of Education and Medical Electrophysiological Key Lab of Sichuan Province, Collaborative Innovation Center for Prevention and Treatment of Cardiovascular Disease, Institute of Cardiovascular Research, Southwest Medical University, Luzhou, China.

出版信息

Channels (Austin). 2025 Dec;19(1):2531949. doi: 10.1080/19336950.2025.2531949. Epub 2025 Jul 12.

DOI:10.1080/19336950.2025.2531949
PMID:40650956
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12258185/
Abstract

Potassium ion channel (K channel) is a crucial transmembrane protein found on cell membranes that plays a pivotal role in regulating various physiological processes such as cell membrane potential, action potential formation, and cellular excitability. Diabetes, a chronic metabolic disorder characterized by elevated blood glucose levels, can cause abnormal changes in the sensitivity and functioning of K channels over time. This can lead to an increase in intracellular K and Ca, disrupting normal cellular function and metabolism and resulting in a range of physiological and metabolic issues. Recent studies have uncovered the collaborative relationship between K channels auxiliary SUR1 and Kir6.2 gating, as well as the impact of K+ channel mutations such as KCNK11 Leu114Pro, KCNQ1Arg397Trp, KCNJ11Arg136Cys, KCNK16 Leu114Pro, and KCNMA1 Gly356Arg on diabetes mellitus and associated complications. Specifically, issues such as impaired cardiac repolarization, K, Kir, TALK, and K channel remodeling and a higher risk of arrhythmia have been emphasized. Furthermore, structural and dysfunctional K channels (K, K and Kir) can also affect the function of vascular endothelial and smooth muscle cells, leading to impaired vasomotor function, abnormal cell growth, and increased inflammation. These abnormalities can result in cardiovascular damage and lesions, and increase the risk of cardiovascular disease in diabetic individuals. These findings serve as a crucial foundation for a better understanding and addressing cardiovascular issues in patients with diabetes. Moreover, different drugs and treatments targeting the K channel may yield varying effects, offering promising prospects for preventing and managing diabetes and its related complications.

摘要

钾离子通道(K通道)是一种在细胞膜上发现的关键跨膜蛋白,在调节各种生理过程中发挥着核心作用,如细胞膜电位、动作电位形成和细胞兴奋性。糖尿病是一种以血糖水平升高为特征的慢性代谢紊乱疾病,随着时间的推移,可导致K通道的敏感性和功能发生异常变化。这会导致细胞内钾和钙增加,破坏正常的细胞功能和代谢,从而引发一系列生理和代谢问题。最近的研究揭示了K通道辅助蛋白SUR1和Kir6.2门控之间的协同关系,以及K+通道突变(如KCNK11 Leu114Pro、KCNQ1Arg397Trp、KCNJ11Arg136Cys、KCNK16 Leu114Pro和KCNMA1 Gly356Arg)对糖尿病及其相关并发症的影响。具体而言,强调了诸如心脏复极化受损、K、Kir、TALK和K通道重塑以及心律失常风险增加等问题。此外,结构和功能异常的K通道(K、K和Kir)也会影响血管内皮和平滑肌细胞的功能,导致血管舒缩功能受损、细胞生长异常和炎症增加。这些异常可导致心血管损伤和病变,并增加糖尿病患者患心血管疾病的风险。这些发现为更好地理解和解决糖尿病患者的心血管问题提供了关键基础。此外,针对K通道的不同药物和治疗可能会产生不同的效果,为预防和管理糖尿病及其相关并发症提供了有前景的途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/12258185/1ec3efe1b19a/KCHL_A_2531949_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/12258185/f6910af816c9/KCHL_A_2531949_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/12258185/f39d5d29af9d/KCHL_A_2531949_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/12258185/1ec3efe1b19a/KCHL_A_2531949_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/12258185/f6910af816c9/KCHL_A_2531949_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/12258185/f39d5d29af9d/KCHL_A_2531949_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/0026/12258185/1ec3efe1b19a/KCHL_A_2531949_F0003_OC.jpg

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本文引用的文献

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Diabetes Mellitus and Associated Vascular Disease: Pathogenesis, Complications, and Evolving Treatments.糖尿病及相关血管疾病:发病机制、并发症与不断发展的治疗方法
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Diagnosis and Treatment of Neonatal Diabetes Caused by ATP-Channel Mutations: Genetic Insights, Sulfonylurea Therapy, and Future Directions.ATP通道突变所致新生儿糖尿病的诊断与治疗:遗传学见解、磺脲类药物治疗及未来方向
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The roles of melatonin and potassium channels in relaxation response to ang 1-7 in diabetic rat isolated aorta.
褪黑素和钾通道在糖尿病大鼠离体主动脉对血管紧张素1-7舒张反应中的作用
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Dissection of type 2 diabetes: a genetic perspective.2型糖尿病剖析:遗传学视角
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Diabetic Cardiomyopathy: What Clinicians Should Know.糖尿病性心肌病:临床医生应了解的内容。
Am J Med. 2025 Mar;138(3):387-395. doi: 10.1016/j.amjmed.2024.10.026. Epub 2024 Nov 4.
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Loss of electrical β-cell to δ-cell coupling underlies impaired hypoglycaemia-induced glucagon secretion in type-1 diabetes.β 细胞至 δ 细胞电耦联丧失导致 1 型糖尿病患者低血糖诱导的胰高血糖素分泌受损。
Nat Metab. 2024 Nov;6(11):2070-2081. doi: 10.1038/s42255-024-01139-z. Epub 2024 Sep 23.
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Involvement of different K channel subtypes in hydrogen sulfide-induced vasorelaxation of human internal mammary artery.不同 K 通道亚型在内质网氢硫化物诱导的人内乳动脉血管舒张中的作用。
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Targeting endothelial K channels in vivo restores arterial and endothelial function in type 2 diabetic rats.在体靶向内皮 K 通道可恢复 2 型糖尿病大鼠的动脉和内皮功能。
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