Department of Vascular Biology, Madras Diabetes Research Foundation and ICMR Centre for Advanced Research On Diabetes, Chennai, India.
Clinical Epidemiology, Madras Diabetes Research Foundation, Chennai, India.
J Endocrinol Invest. 2021 Jul;44(7):1395-1405. doi: 10.1007/s40618-020-01429-9. Epub 2020 Oct 13.
We earlier reported that Sestrin2 regulates monocyte activation and atherogenic events through AMPK-mTOR nexus under high-glucose and dyslipidemic conditions. However, the statuses of Sestrins in diabetes and dyslipidemia are not known. We report here on the status of Sestrins and their association with diabetic dyslipidemia and atherosclerosis.
Individuals with normal glucose tolerance (NGT) (n = 46), dyslipidemia (n = 42), and patients with Type 2 diabetes with (n = 41) and without dyslipidemia (n = 40) were recruited from a tertiary diabetes centre, Chennai, India to study the mRNA expression levels of Sestrins (1, 2, and 3) in monocytes by RT-qPCR. Serum levels of Sestrins were measured using ELISA. Atherogenic index of plasma was calculated as log (triglyceride/HDL).
mRNA expressions of Sestrin1 and Sestrin3 were significantly reduced in monocytes under dyslipidemic conditions but not in diabetes condition. Interestingly, Sestrin2 mRNA expression was significantly reduced in all disease conditions including dyslipidemia, and diabetes with and without dyslipidemia. Sestrin2 mRNA levels were negatively correlated with glycemic and lipid parameters and plasma atherogenic index. Furthermore, circulatory Sestrin2 was also found to be significantly decreased in dyslipidemia (415.2 ± 44.7 pg/ml), diabetes (375 ± 45 pg/ml), and diabetes with dyslipidemia (319.2 ± 26.3 pg/ml) compared to NGT (706.3 ± 77 pg/ml) and negatively correlated with glycemic, lipid parameters, and plasma atherogenic index.
We report for the first time that Sestrins levels are significantly decreased in diabetes and dyslipidemic conditions. More strikingly, Sestrin2 had a strong association with atherogenic risk factors and severity of atherogenic index and we suggest that Sestrin2 may be used as a biomarker for assessing atherogenesis.
我们之前报道过，Sestrin2 通过 AMPK-mTOR 连接在高葡萄糖和血脂异常条件下调节单核细胞激活和动脉粥样硬化形成事件。然而，糖尿病和血脂异常患者中 Sestrins 的状况尚不清楚。我们在此报告 Sestrins 的状况及其与糖尿病血脂异常和动脉粥样硬化的关系。
从印度钦奈的一家三级糖尿病中心招募了糖耐量正常（NGT）（n=46）、血脂异常（n=42）以及伴有（n=41）和不伴有血脂异常（n=40）的 2 型糖尿病患者，以通过 RT-qPCR 研究单核细胞中 Sestrins（1、2 和 3）的 mRNA 表达水平。使用 ELISA 测量血清 Sestrins 水平。计算血浆致动脉粥样硬化指数为 log（甘油三酯/HDL）。
在血脂异常条件下，单核细胞中 Sestrin1 和 Sestrin3 的 mRNA 表达显著降低，但在糖尿病条件下并非如此。有趣的是，在所有疾病条件下，包括血脂异常、伴有和不伴有血脂异常的糖尿病，Sestrin2 mRNA 表达均显著降低。Sestrin2 mRNA 水平与血糖和血脂参数以及血浆致动脉粥样硬化指数呈负相关。此外，还发现循环 Sestrin2 在血脂异常（415.2±44.7 pg/ml）、糖尿病（375±45 pg/ml）和糖尿病伴血脂异常（319.2±26.3 pg/ml）中也显著降低，与 NGT（706.3±77 pg/ml）呈负相关，并与血糖、血脂参数和血浆致动脉粥样硬化指数呈负相关。
我们首次报道，糖尿病和血脂异常条件下 Sestrins 水平显著降低。更引人注目的是，Sestrin2 与致动脉粥样硬化风险因素和致动脉粥样硬化指数的严重程度密切相关，我们认为 Sestrin2 可用作评估动脉粥样发生的生物标志物。
