PDF(Pubmed)
Abstract：
This study unveils verapamil\'s compelling cytoprotective and proliferative effects on pancreatic β-cells amidst diabetic stressors, spotlighting its unforeseen role in augmenting cholecystokinin (CCK) expression. Through rigorous investigations employing MIN6 β-cells and zebrafish models under type 1 and type 2 diabetic conditions, we demonstrate verapamil\'s capacity to significantly boost β-cell proliferation, enhance glucose-stimulated insulin secretion, and fortify cellular resilience. A pivotal revelation of our research is verapamil\'s induction of CCK, a peptide hormone known for its role in nutrient digestion and insulin secretion, which signifies a novel pathway through which verapamil exerts its therapeutic effects. Furthermore, our mechanistic insights reveal that verapamil orchestrates a broad spectrum of gene and protein expressions pivotal for β-cell survival and adaptation to immune-metabolic challenges. In vivo validation in a zebrafish larvae model confirms verapamil\'s efficacy in fostering β-cell recovery post-metronidazole infliction. Collectively, our findings advocate for verapamil\'s reevaluation as a multifaceted agent in diabetes therapy, highlighting its novel function in CCK upregulation alongside enhancing β-cell proliferation, glucose sensing, and oxidative respiration. This research enriches the therapeutic landscape, proposing verapamil not only as a cytoprotector but also as a promoter of β-cell regeneration, thereby offering fresh avenues for diabetes management strategies aimed at preserving and augmenting β-cell functionality.
摘要：
这项研究揭示了维拉帕米在糖尿病应激源中对胰腺β细胞的引人注目的细胞保护和增殖作用，突出其在增加胆囊收缩素（CCK）表达中的不可预见的作用。通过在1型和2型糖尿病条件下使用MIN6β细胞和斑马鱼模型的严格研究，我们证明了维拉帕米显著促进β细胞增殖的能力，增强葡萄糖刺激的胰岛素分泌，增强细胞弹性。我们研究的一个重要启示是维拉帕米诱导CCK，一种肽激素，以其在营养消化和胰岛素分泌中的作用而闻名，这标志着维拉帕米发挥其治疗作用的新途径。此外，我们的机制见解表明,维拉帕米协调广谱的基因和蛋白质表达对于β细胞存活和适应免疫代谢挑战至关重要.斑马鱼幼虫模型的体内验证证实了维拉帕米在甲硝唑后促进β细胞恢复的功效。总的来说，我们的发现提倡维拉帕米作为糖尿病治疗的多方面药物的重新评估，强调其在CCK上调中的新功能，同时增强β细胞增殖，葡萄糖传感，和氧化呼吸。这项研究丰富了治疗领域，提出维拉帕米不仅作为细胞保护剂，而且作为β细胞再生的启动子，从而为旨在保持和增强β细胞功能的糖尿病管理策略提供了新的途径。
