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螺旋贝母兰叶提取物可刺激 GLUTag L 细胞分泌 GLP-1,并对 BRIN-BD11β 细胞具有细胞保护作用。

Costus pictus D. Don leaf extract stimulates GLP-1 secretion from GLUTag L-cells and has cytoprotective effects in BRIN-BD11 β-cells.

机构信息

Department of Biological and Biomedical Sciences, School of Health and Life Sciences, Glasgow Caledonian University, Cowcaddens Road, Glasgow, G4 0BA, UK.

出版信息

J Ethnopharmacol. 2020 Oct 5;260:112970. doi: 10.1016/j.jep.2020.112970. Epub 2020 May 16.

Abstract

ETHNOPHARMACOLOGICAL RELEVANCE

Costus pictus D. Don, commonly known as insulin plant, is a traditional Indian antidiabetic herbal medicine with glucose-lowering and insulin secretory effects having been reported in animal models and humans with Type 2 diabetes. However, its effects on GLP-1 secretion from intestinal endocrine L-cells and potential metabolic and protective effects in insulin secreting pancreatic β-cells are not yet fully understood.

AIM OF THE STUDY

This study is aimed to elucidate the effects of Costus pictus D. Don leaf extract (CPE) on L-cell function and GLP-1 secretion using the established murine GLUTag L-cell model and to investigate its potential cytoprotective effects against detrimental effects of palmitate and cytokines in pancreatic β-cells using BRIN-BD11 cells.

METHODS

Costus pictus D. Don dried leaf powder was extracted by soxhlet method. Cell viability was determined by MTT assay. Changes in gene and protein expression were quantified by qPCR and western blotting, respectively. GLP-1 and insulin secretion were measured by ELISA.

RESULTS

CPE significantly enhanced the percentage of viable BRIN-BD11 and GLUTag cells and protected BRIN-BD11 cells against palmitate- and proinflammatory cytokine-induced toxicity. CPE enhanced acute GLP-1 secretion 6.4-16.3-fold from GLUTag cells at both low (1.1 mM) and high (16.7 mM) glucose (P < 0.01) concentrations. Antioxidant (Nrf2, Cat & Gpx1) and pro-proliferative (Erk1 and Jnk1) gene expression were upregulated by 24 h culture with CPE, while proinflammatory transcription factor NF-κB was downregulated.

CONCLUSION

Diminished postprandial GLP-1 secretion and loss of insulin secreting β-cells are known contributors of T2DM. Our data suggests that CPE acutely stimulates GLP-1 secretion from L-cells. Long term exposure of the BRIN-BD11 cells to CPE enhances cell number and may protect against palmitate and proinflammatory cytokines by activating multiple pathways. Thus, the current study suggests that the possible antidiabetic properties of CPE may be linked to enhanced GLP-1 secretion and β-cell protection which could be beneficial in the management of T2DM.

摘要

民族药理学相关性

Costus pictus D. Don,俗称胰岛素植物,是一种传统的印度抗糖尿病草药,已在动物模型和 2 型糖尿病患者中报道具有降低血糖和促进胰岛素分泌的作用。然而,其对肠道内分泌 L 细胞中 GLP-1 的分泌以及对胰岛素分泌的胰腺β细胞的潜在代谢和保护作用尚不完全清楚。

研究目的

本研究旨在使用已建立的鼠 GLUTag L 细胞模型阐明 Costus pictus D. Don 叶提取物(CPE)对 L 细胞功能和 GLP-1 分泌的影响,并使用 BRIN-BD11 细胞研究其对棕榈酸和细胞因子对胰腺β细胞的有害作用的潜在细胞保护作用。

方法

用索氏提取法提取 Costus pictus D. Don 干叶粉。通过 MTT 测定法测定细胞活力。通过 qPCR 和 Western blotting 分别定量基因和蛋白表达的变化。通过 ELISA 测量 GLP-1 和胰岛素的分泌。

结果

CPE 显著增加了 BRIN-BD11 和 GLUTag 细胞的存活率,并保护 BRIN-BD11 细胞免受棕榈酸和促炎细胞因子引起的毒性。CPE 在低(1.1 mM)和高(16.7 mM)葡萄糖浓度下分别使 GLUTag 细胞中的急性 GLP-1 分泌增加 6.4-16.3 倍(P <0.01)。用 CPE 培养 24 小时后,抗氧化(Nrf2、Cat 和 Gpx1)和促增殖(Erk1 和 Jnk1)基因表达上调,而促炎转录因子 NF-κB 下调。

结论

餐后 GLP-1 分泌减少和胰岛素分泌β细胞丧失是 2 型糖尿病的已知致病因素。我们的数据表明,CPE 可急性刺激 L 细胞中 GLP-1 的分泌。BRIN-BD11 细胞长期暴露于 CPE 中可通过激活多种途径增加细胞数量并可能预防棕榈酸和促炎细胞因子的作用。因此,本研究表明,CPE 的可能抗糖尿病特性可能与增强 GLP-1 分泌和β细胞保护有关,这可能有益于 2 型糖尿病的治疗。

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