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Resveratrol protects against ethanol-induced impairment of insulin secretion in INS-1 cells through SIRT1-UCP2 axis.

白藜芦醇通过 SIRT1-UCP2 轴保护乙醇诱导的 INS-1 细胞胰岛素分泌受损。

  • 影响因子:3.29
  • DOI:10.1016/j.tiv.2020.104808
  • 作者列表:"Luo G","Xiao L","Wang D","Wang N","Luo C","Yang X","Hao L
  • 发表时间:2020-02-19
Abstract

:SIRT1 has been proposed to enhance insulin secretion in β-cell through repressing the expression of uncoupling protein2 (UCP2), but whether ethanol-induced β-cell dysfunction is mediated by the disrupted SIRT1-UCP2 axis remains unknown. This study was conducted to explore the underlying mechanisms by which ethanol resulted in β-cell dysfunction and the potential protective effects of resveratrol in this process. INS-1 cells (rat pancreatic β-cell line) were cultured with ethanol in the presence or absence of resveratrol (2.5, 12.5 μmol/L). The results showed that ethanol exposure reduced glucose-stimulated insulin secretion, ATP production and SIRT1 expression but increased UCP2 expression, while supplementation with resveratrol restored the function of INS-1 cell by upregulating SIRT1 and inhibiting UCP2. Moreover, the critical role of SIRT1-UCP2 axis was further supported by the results that SIRT1 activator SRT1720 reversed ethanol-induced impairment of glucose-stimulated insulin secretion by decreasing UCP2, while SIRT1 inhibitor Ex527 abolished the beneficial effects of resveratrol. Meanwhile, NAD+ booster nicotinamide mononucleotide also counteracted the deleterious effects of ethanol by increasing SIRT1, suggesting the regulation of SIRT1-UCP2 axis may be associated with cellular NAD+/NADH ratio. In conclusion, our observations imply that ethanol induces impaired insulin secretion from INS-1 cell through disrupting SIRT1-UCP2 axis, while resveratrol may reverse this process by augmenting SIRT1 and inhibiting UCP2.

摘要

: SIRT1 被认为通过抑制解偶联蛋白 2 (UCP2) 的表达来增强 β 细胞中的胰岛素分泌, 但乙醇诱导的 β 细胞功能障碍是否由破坏的 SIRT1-UCP2 轴介导仍然未知。本研究旨在探讨乙醇导致 β 细胞功能障碍的潜在机制以及白藜芦醇在此过程中的潜在保护作用。INS-1 细胞 (大鼠胰腺 β 细胞系) 用乙醇在有或无白藜芦醇 (2.5,12.5 μ mol/L) 的条件下培养。结果表明,乙醇暴露降低了葡萄糖刺激的胰岛素分泌、 ATP 产生和 SIRT1 表达,但增加了 UCP2 表达, 而补充白藜芦醇通过上调 SIRT1 和抑制 ucp2 来恢复 INS-1 细胞的功能。此外,SIRT1 激活剂 SRT1720 通过降低 UCP2 逆转乙醇诱导的葡萄糖刺激的胰岛素分泌损伤的结果进一步支持了 SIRT1-UCP2 轴的关键作用, 而 SIRT1 抑制剂 Ex527 消除了白藜芦醇的有益作用。同时,NAD + 升压烟酰胺单核苷酸也通过增加 SIRT1 来抵消乙醇的有害作用,提示 SIRT1-UCP2 轴的调节可能与细胞 NAD +/NADH 比值有关。总之,我们的观察结果意味着乙醇通过破坏 INS-1 细胞轴诱导 SIRT1-UCP2 分泌受损,而白藜芦醇可能通过增强 SIRT1 和抑制 ucp2 来逆转这一过程。

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影响因子:2.76
发表时间:2020-01-30
DOI:10.1152/japplphysiol.00631.2019
作者列表:["Bonomi AG","Ten Hoor GA","De Morree HM","Plasqui G","Sartor F"]

METHODS:BACKGROUND:Low cardiorespiratory fitness (CRF) increases risk of all-cause mortality and cardiovascular events. Periodic CRF assessment can have an important preventive function. OBJECTIVE:To develop a protocol-free method to estimate CRF in daily life based on heart rate (HR) and body acceleration measurements. METHODS:Acceleration and HR data were collected from 37 subjects (M=49%) while performing a standardized laboratory activity protocol (sitting, walking, running, cycling) and during a 5-days free-living monitoring period. CRF was determined by oxygen uptake (VO2max) during maximal exercise testing. A doubly-labeled water validated equation was used to predict total energy expenditure (TEE) from acceleration data. A fitness index was defined as the ratio between TEE and HR (TEE-pulse). Activity recognition techniques were used to process acceleration features and classify sedentary, ambulatory and other activity types. Regression equations based on TEE-pulse data from each activity type were developed to predict VO2max. RESULTS:TEE-pulse measured within each activity type of the laboratory protocol was highly correlated to VO2max (r from 0.74 to 0.91). Averaging the outcome of each activity-type specific equation based on TEE-pulse from the laboratory data led to accurate estimates of VO2max (RMSE: 300.0 mlO2/min or 10%). The difference between laboratory and free-living determined TEE-pulse was 3.7 ± 11% (r =0.85). The prediction method preserved the prediction accuracy when applied to free-living data (RMSE: 367 mlO2/min or 12%). CONCLUSIONS:Measurements of body acceleration and HR can be used to predict VO2max in daily life. Activity-specific prediction equations are needed to achieve highly accurate estimates of CRF.

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影响因子:3.76
发表时间:2020-01-31
DOI:10.1152/ajpgi.00386.2018
作者列表:["Farr S","Stankovic B","Hoffman S","Masoudpoor H","Baker C","Taher J","Dean A","Anakk S","Adeli K"]

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