Decreased Sestrin levels in patients with type 2 diabetes and dyslipidemia and their association with the severity of atherogenic index

Sundararajan, Saravanakumar; Jayachandran, Isaivani; Subramanian, Savitha; Anjana, R M; Balasubramanyam, Muthuswamy; Mohan, Viswanathan; Venkatesan, Balachandar; Manickam, Nagaraj

doi:10.1007/s40618-020-01429-9

Cited by 25 publications

(17 citation statements)

References 31 publications

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“…The results of the current work agree with the results of Mohany and Al Rugaie [2020] who found significant lower levels of serum sestrin2 in patients with T2DM than the healthy control group [50]. Also, they agree with Sundararajan et al [2020] who reported low serum sestrins levels in patients with dyslipidemia and T2DM and these levels correlated negatively with atherogenic factors and the severity of atherogenic index [51]. Moreover, Nourbakhsh et al [2017] found significant lower levels of sestrin2 in obese than the non-obese participants [19].…”

Section: Discussionsupporting

confidence: 92%

Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study

et al. 2021

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Aim The present work investigated serum levels of miR-29a, miR-122 and sestrin2 in obese children with/without type-2-diabetes mellitus (T2DM), and their correlations with inflammatory, metabolic and anthropometric parameters. Methods The study included 298 children, divided into: G1 (control, n = 136), G2 (obese without diabetes, n = 90) and G3 (obese with T2DM, n = 72). Metabolic and anthropometric parameters, miR-29a, miR-122 relative expressions, and sestrin2, high sensitivity C-reactive protein (hsCRP), interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) levels were measured by their specific methods. The data was processed and analyzed by SPSS V.26 using the corresponding tests. After testing the variables’ normality, Kruskal–Wallis one-way-ANOVA, Spearman correlations coefficient were used. Results Significant higher serum miR-29a, miR-122, IL-6, hsCRP and TNF-α and lower sestrin2 levels were found in G2 and G3 than G1 and in G3 than G2 (p= > 0.001 for all). Especially in G3, miR-29a and miR-122 levels correlated positively while sestrin2 levels correlated negatively with waist circumference and BMI percentiles, serum levels of LDL-cholesterol, triacylglycerol, total cholesterol, HbA1c%, glucose, insulin, c-peptide, homeostatic model assessment-insulin resistance (HOMA-IR), IL-6, hsCRP and TNF-α. Conclusion The change in the serum miR-29a, miR-122 and sestrin2 levels in obese children with/without T2DM may suggest a possible role of these biomarkers in the pathogenesis of childhood obesity and their accompanied complications e.g. inflammations and T2DM. Also, further studies are required to test drugs that antagonize the action miR-29a and miR-122 or upregulate sestrin2 in the management of these cases.

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Section: Discussionsupporting

confidence: 92%

Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study

et al. 2021

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“…Initially, the upregulation of Sestrins is observed as a defense mechanism in the tissues under metabolic stress and inflammation or during predisposition stage of metabolic syndrome (Lee et al, 2012;Ro et al, 2016), as chronic stress conditions sustain, the level of Sestrins is dramatically suppressed in the etiology of disease conditions such as type 2 diabetes, dyslipidemia, colon cancer development and muscle aging progression (Wei J.L. et al, 2015;Ro et al, 2016;Segales et al, 2020;Sundararajan et al, 2020). In recent human studies, secreted Sestrin2 level in the serum of obese children, diabetic nephropathy patients, and elderly sarcopenia adults is significantly lower and associated with metabolic dysfunction (Nourbakhsh et al, 2017;Mohany and Al Rugaie, 2020;Rajan et al, 2020), suggesting that the expression or the secretion of Sestrin2 is somehow blocked in the disease state.…”

Section: Perspective On Sestrins As Stress Sensing-proteins In Metabomentioning

confidence: 99%

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Fay

Cyuzuzo

et al. 2020

Front. Cell Dev. Biol.

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Proper timely management of various external and internal stresses is critical for metabolic and redox homeostasis in mammals. In particular, dysregulation of mechanistic target of rapamycin complex (mTORC) triggered from metabolic stress and accumulation of reactive oxygen species (ROS) generated from environmental and genotoxic stress are well-known culprits leading to chronic metabolic disease conditions in humans. Sestrins are one of the metabolic and environmental stress-responsive groups of proteins, which solely have the ability to regulate both mTORC activity and ROS levels in cells, tissues and organs. While Sestrins are originally reported as one of several p53 target genes, recent studies have further delineated the roles of this group of stress-sensing proteins in the regulation of insulin sensitivity, glucose and fat metabolism, and redox-function in metabolic disease and aging. In this review, we discuss recent studies that investigated and manipulated Sestrins-mediated stress signaling pathways in metabolic and environmental health. Sestrins as an emerging dynamic group of stress-sensor proteins are drawing a spotlight as a preventive or therapeutic mechanism in both metabolic stress-associated pathologies and aging processes at the same time.

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“…In a recent study, serum levels of sestrins are significantly decreased in patients with diabetes and dyslipidemia. It appears that sestrin2 levels are robustly associated with diabetes, dyslipidemia, atherosclerosis, and the atherogenic index [74]. Declined serum sestrin2 levels were also observed in diabetic patients with nephropathy, particularly in those with macroalbuminuria [75].…”

Section: Sestrin2 In Age-related Clinical Conditionsmentioning

confidence: 96%

Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

et al. 2021

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Alzheimer's disease (AD) is the most common age-related neurodegenerative disease. It presents with progressive memory loss, worsens cognitive functions to the point of disability, and causes heavy socioeconomic burdens to patients, their families, and society as a whole. The underlying pathogenic mechanisms of AD are complex and may involve excitotoxicity, excessive generation of reactive oxygen species (ROS), aberrant cell cycle reentry, impaired mitochondrial function, and DNA damage. Up to now, there is no effective treatment available for AD, and it is therefore urgent to develop an effective therapeutic regimen for this devastating disease. Sestrin2, belonging to the sestrin family, can counteract oxidative stress, reduce activity of the mammalian/mechanistic target of rapamycin (mTOR), and improve cell survival. It may therefore play a crucial role in neurodegenerative diseases like AD. However, only limited studies of sestrin2 and AD have been conducted up to now. In this article, we discuss current experimental evidence to demonstrate the potential roles of sestrin2 in treating neurodegenerative diseases, focusing specifically on AD. Strategies for augmenting sestrin2 expression may strengthen neurons, adapting them to stressful conditions through counteracting oxidative stress, and may also adjust the autophagy process, these two effects together conferring neuronal resistance in cases of AD.

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Decreased Sestrin levels in patients with type 2 diabetes and dyslipidemia and their association with the severity of atherogenic index

Cited by 25 publications

References 31 publications

Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study

Investigation of the levels of circulating miR-29a, miR-122, sestrin 2 and inflammatory markers in obese children with/without type 2 diabetes: a case control study

SESTRINs: Emerging Dynamic Stress-Sensors in Metabolic and Environmental Health

Potential Roles of Sestrin2 in Alzheimer’s Disease: Antioxidation, Autophagy Promotion, and Beyond

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