Association of serum sestrin 2 and betatrophin with serum neutrophil gelatinase associated lipocalin levels in type 2 diabetic patients with diabetic nephropathy

Abstract

Purpose Understanding the pathogenesis and the molecular mechanisms of diabetic nephropathy (DN) helps its timely detection and prevention. The current work aims tomeasure serum sestrin 2 and betatrophin levels in healthy and type diabetic (T2DM)subjects with/or without diabetic nephropathy (DN) and also to test their correlation with serum neutrophil gelatinase associated lipocalin (sNGAL); indicator of DN. Methods This study included 96 subjects; 20 healthy (G1) and 76 T2DM [22 normoalbuminuric (G2), 35 microalbuminuric (G3) and 19 macroalbuminuric (G4)]. Serum sestrin 2, betatrophin and NGAL were measured by their corresponding kits. Results Significant low levels of serum sestrin 2 andhigh levels of serum betatrophin were found in T2DM group when compared to G1 (p = 0.002,p > 0.001, respectively) and this difference is manifested in G4 followed, in order, by G3, G2 then G1 (p= > 0.001 for both). Also, serum sestrin2 levels showed significant negative correlations with sNGAL in G1 (r = −0.497, p = 0.026), G2 (r = −0.784, p > 0.001), G3 (r = −0.894, p > 0.001) and G4 (r = −0.896, pp. > 0.001) while serum betatrophin levels showed significant positive correlations with sNGAL in G2 (r = 0.681, p > 0.001), G3 (r = 0.518, p > 0.001) and G4 (r = 0.727, p > 0.001). Conclusion Serum sestrin 2 levels decrease significantly while betatrophin levels increase significantly in T2DM patients with DN especially those with macroalbuminuria. These levels have significant effect strengths on the indicator of diabetic nephropathy; sNGAL which might indicate theirvaluablerole in the timely detection and prevention of the development of DN. Keywords Serum sestrin2. Serum betatrophin. sNGAL. Diabetic nephropathy Abbreviations T2DM type 2 diabetes mellitus DN diabetic nephropathy sNGAL serum neutrophil gelatinase associated lipocalin KDa kilodalton ACR urinary albumn to creatinine ratio EDTA ethylendiaminetetraacetic acid ELISA enzyme-linked immunosorbant assay SPSS statistical package for social sciences ANOVA analysis of variance AMP adenosine monophosphate AMPK AMP-dependent protein kinase mTOR-C1 mammalian target of rapamycin complex 1 Dur duration of diabetes in years BMI body mass index s-FG serum fasting glucose s-Cr serum creatinine s-alb serum albumin GA% serum glycated albumin% HbA1c% glycosylated hemoglobin%.

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

“…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].…”

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

“…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. Measuring tissue-or individual patient-specific Sestrins level could be used as a direct health or stress sensors, and proper timely administration of active Sestrins would be emerging preventive or therapeutic methods for those who are suffering from metabolic diseases and aging-associated pathologies.…”

Association between circulating microRNAs 486, 146b and 15b and serum betatrophin levels in obese; type 2 diabetic and non-diabetic children

“…MicroRNAs are small non-coding RNAs that regulates the gene expression post-transcriptionally either by preventing the translation of their targeted mRNAs or by degrading them [ 9 ]. They have a recognizable role in pathogenesis, prevention and diagnosis of many diseases including obesity and diabetes mellitus [ 5 , 10 – 12 ]. In the current study, the circulating microRNA-486, −146b and -15b levels are found to be higher in obese children with/without T2DM than the healthy control.…”

“…They negatively regulate mRNAs translation or enhance their degradation [ 9 ]. Abnormal expression of microRNAs participates in the pathogenesis of many adverse events such as obesity, dyslipidemias, impaired glucose tolerance and diabetes mellitus [ 5 , 10 – 12 ]. The exact role of microRNAs in obese and/or diabetic children is still under investigations.…”