Mesh : Animals Isothiocyanates / pharmacology Rats Insulin / metabolism Membrane Potential, Mitochondrial / drug effects Cell Survival / drug effects Cell Line Cell Proliferation / drug effects Insulin-Secreting Cells / drug effects metabolism Apoptosis / drug effects Reactive Oxygen Species / metabolism Homeodomain Proteins / genetics metabolism Mitochondria / drug effects metabolism TRPA1 Cation Channel Trans-Activators

来  源:   DOI:10.26402/jpp.2024.3.04

Abstract:
Allyl isothiocyanate (AITC) is the pungent ingredient of brassica species, used as a food additive and flavoring agent, including condiments such as wasabi, horseradish, and mustard. Currently, there is much evidence that AITC modulates glucose and lipids metabolism. Interestingly, AITC has been shown to improve glycaemia, and insulin action along with the induction of a deepened decline in blood insulin levels in T2DM rats. Therefore, in the present study, we characterized the role of AITC at a wide concentration range (5, 10, 25, 50, 100 μM) in controlling viability, proliferation, apoptosis, mitochondrial condition, mRNA expression of encoding pancreatic and duodenal homeobox 1 (Pdx1), and Ins1, Ins2 genes, and insulin content in INS-1E cells. The INS-1E cell line is a suitable, and well-characterized model to study beta cell functions. We demonstrate that AITC reduced the viability (p≤0.001) (also in the presence of transient receptor potential cation subfamily A member 1 (TRPA1) selective antagonist; HC-030031; p≤0.05), and proliferation of INS-1E cells (p≤0.001). AITC evoked a significant reduction of mitochondrial membrane potential (p≤0.01) and decreased the intracellular level of adenosine triphosphate (ATP) (p≤0.001) without influence on reactive oxygen species (ROS) level. Additionally, AITC inhibited the insulin mRNA expression (p≤0.001) in INS-1E cells along with insulin content (p≤0.05). Mitochondrial dysfunction is proposed to be a significant disruption mechanism of AITC in INS-1E cells, and it was independent of ROS, and the influx of external calcium.
摘要:
异硫氰酸烯丙酯(AITC)是芸苔属植物的刺激性成分,用作食品添加剂和调味剂,包括芥末等调味品,辣根,还有芥末.目前,有许多证据表明AITC调节葡萄糖和脂质代谢。有趣的是,AITC已被证明可以改善血糖,和胰岛素作用以及诱导T2DM大鼠血胰岛素水平下降的加深。因此,在本研究中,我们表征了AITC在宽浓度范围(5,10,25,50,100μM)在控制生存力中的作用,扩散,凋亡,线粒体状况,编码胰腺和十二指肠同源异型盒1(Pdx1)的mRNA表达,和Ins1,Ins2基因,和INS-1E细胞中的胰岛素含量。INS-1E细胞系是合适的,和特征明确的模型来研究β细胞功能。我们证明AITC降低了活力(p≤0.001)(同时存在瞬时受体电位阳离子亚家族A成员1(TRPA1)选择性拮抗剂;HC-030031;p≤0.05),和INS-1E细胞的增殖(p≤0.001)。AITC引起线粒体膜电位显着降低(p≤0.01),并降低细胞内三磷酸腺苷(ATP)水平(p≤0.001),而不影响活性氧(ROS)水平。此外,AITC抑制INS-1E细胞中胰岛素mRNA的表达(p≤0.001)以及胰岛素含量(p≤0.05)。线粒体功能障碍被认为是AITC在INS-1E细胞中的重要破坏机制,它独立于ROS,和外部钙的流入。
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