Decreased Sestrin levels in patients with type 2 diabetes and dyslipidemia and their association with the severity of at
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ORIGINAL ARTICLE
Decreased Sestrin levels in patients with type 2 diabetes and dyslipidemia and their association with the severity of atherogenic index S. Sundararajan1 · I. Jayachandran1 · S. C. Subramanian2 · R. M. Anjana3 · M. Balasubramanyam4 · V. Mohan3 · B. Venkatesan1,5 · N. Manickam1 Received: 1 February 2020 / Accepted: 16 September 2020 © Italian Society of Endocrinology (SIE) 2020
Abstract Purpose 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. Methods 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). Results 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. Conclusion 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. Keywords Sestrins · Diabetes · Dyslipidemia · Monocyte · Atherogenesis · CVD
Electronic supplementary material The online version of this article (https://doi.org/10.1007/s40618-020-01429-9) contains supplementary material, which is available to authorized users. * B. Venkatesan [email protected] * N. Manickam [email protected] 1
2
Department of Vascular Biology, Madras Diabetes Research Foundation and ICMR Centre for Advanced Research On Diabetes, Chennai, India
3
Madras Diabetes Research Foundation and Dr. Mohan’s Diabetes Specialities Centre, Who Collaborating Centre for Non-Communicable Diseases Prevention and Control, Chennai, India
4
Department of Cell and Molecular Biology, Madras Diabetes Research Foundation, Chennai, India
5
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