Taneera Jalal, Yaseen Deema, Youssef Mona, Khalique Anila, Al Shehadat Ola Saed, Mohammed Abdul Khader, Bustanji Yasser, Madkour Mohamed I, El-Huneidi Waseem
Research Institute of Medical and Health Sciences, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates; College of Medicine, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates; Center of Excellence of Precision Medicine, Research Institute of Medical and Health Sciences, University of Sharjah, United Arab Emirates.
Research Institute of Medical and Health Sciences, University of Sharjah, P.O. Box 27272, Sharjah, United Arab Emirates.
Mol Cell Endocrinol. 2025 Apr 1;599:112472. doi: 10.1016/j.mce.2025.112472. Epub 2025 Jan 27.
Vitamin D (VD) has been implicated in regulating insulin secretion and pancreatic β-cell function. Yet, the underlying molecular mechanism of VD in glucose homeostasis is not fully understood. This study investigates the effect of VD in regulating insulin secretion and pancreatic β-cell function. INS-1 β-cells were treated with VD to assess cell viability, reactive oxygen species production (ROS), insulin secretion, glucose uptake, proliferation, gene expression alterations, mitochondria metabolism, calcium influx, as well as the effects of antidiabetic drugs on VDR expression. Additionally, RNA sequencing from human pancreatic islets were utilized to examine VDR expression in relation to clinical parameters such as HbA1c, BMI, age, and gender. VD treatment enhanced glucose-stimulated insulin secretion and elevated intracellular calcium levels without affecting insulin content, glucose uptake, ROS production, proliferation, or mitochondrial metabolism. Expression levels of key β-cell function genes, including Ins, Pdx1, and Glut2, remained unchanged with VD treatment. However, genes associated with calcium channels were upregulated. Cell exposure to rosiglitazone and dexamethasone elevated VDR expression in INS-1 cells, while metformin and insulin had no effect. RNA-seq analysis in human islets showed that VDR expression levels in human islets were significantly higher than in other metabolic tissues and were notably reduced in hyperglycemic donors compared to normoglycemic individuals. Furthermore, VDR expression positively correlated with several genes regulating voltage-gated calcium channels. In conclusion, the study indicates that VD plays a significant role in enhancing insulin secretion through modulation of intracellular calcium dynamics, highlighting its potential therapeutic implications for managing type 2 diabetes.
维生素D（VD）与调节胰岛素分泌和胰腺β细胞功能有关。然而，VD在葡萄糖稳态中的潜在分子机制尚未完全阐明。本研究调查了VD对调节胰岛素分泌和胰腺β细胞功能的影响。用VD处理INS-1β细胞，以评估细胞活力、活性氧生成（ROS）、胰岛素分泌、葡萄糖摄取、增殖、基因表达变化、线粒体代谢、钙内流，以及抗糖尿病药物对VDR表达的影响。此外，利用来自人胰岛的RNA测序来检查VDR表达与诸如糖化血红蛋白、体重指数、年龄和性别等临床参数的关系。VD处理增强了葡萄糖刺激的胰岛素分泌并提高了细胞内钙水平，而不影响胰岛素含量、葡萄糖摄取、ROS生成、增殖或线粒体代谢。包括Ins、Pdx1和Glut2在内的关键β细胞功能基因的表达水平在VD处理后保持不变。然而，与钙通道相关的基因上调。细胞暴露于罗格列酮和地塞米松可提高INS-1细胞中的VDR表达，而二甲双胍和胰岛素则无影响。人胰岛中的RNA测序分析表明，人胰岛中的VDR表达水平显著高于其他代谢组织，并且与血糖正常的个体相比，高血糖供体中的VDR表达水平明显降低。此外，VDR表达与几个调节电压门控钙通道的基因呈正相关。总之，该研究表明VD通过调节细胞内钙动力学在增强胰岛素分泌中起重要作用，突出了其在治疗2型糖尿病方面的潜在意义。
