Serum Apelin Levels Research Articles

UTILITY OF IRISIN AND APELIN IN PREDICTION OF HEART FAILURE PHENOTYPES IN TYPE 2 DIABETES MELLITUS PATIENTS

Objective: The aim of the study was to investigate whether serum levels of both irisin and apelin predict HF with preserved ejection fraction (HFpEF) in patients with type 2 diabetes mellitus (T2DM). Design and method: One hundred and eight HF patients with T2DM having HFpEF (n = 58), HF with mildly reduced ejection fraction (HFmrEF, n = 22), HF with reduced ejection fraction (HFrEF, n = 28) aged from 41 to 62 years and 20 non-HF patients with T2DM. Healthy control group was consisted of 25 individuals matched with age and sex. All patients gave voluntary written informed consent to participate in the study. We polled at baseline demographic and anthropometric information, data for hemodynamic performances by B-mode echocardiography, Doppler and TDI, and the levels of biomarkers including irisin, apelin, N-terminal pro-brain natriuretic peptide (NT-proBNP) by ELISA. Results: Using ROC curve we revealed that cut-off points for irisin and apelin that distinguished HFpEF from HFrEF/HFmrEF were (6.50 ng/mL; AUC = 0.78; 95% confidence interval [CI] = 6.85 - 10.66 ng/mL and 4.12 ng/mL, AUC = 0.72; 95% CI = 3.90–5.75 ng/mL, respectively). Then we divided all patients with HF having elevation of NT-proBNP > 750 pmol/mL into three subgroups depending on the biomarkers’ levels. Patients from subgroup A had both irisin and apelin levels higher cut-off points, individuals from group B had higher concentration of one of two biomarkers, and patients from subgroup C demonstrated levels of both peptides lower cut-off points. Multivariate logistic regression analysis revealed that discriminative value of irisin and apelin to predict HFpEF in subgroup B (Odds Ratio [OR] = 2.18; 95% CI = 1.26–3.14; P = 0.001) were substantially higher compared with subgroups A and C (OR = 1.03; 95% CI = 1.00–1.05; P = 0.64 and OR = 0.92; 95% CI = 0.89–1.01; P = 0.62, respectively). Adding irisin and apelin to NT-proBNP as independent variables to the predictive model sufficiently improved discriminative ability of whole model for HFpEF. Conclusions: Multidirectional changes in the levels of irisin and apelin in T2DM patients had better predictive value for HFpEF that simultaneous increase and decrease in the circulating levels of these peptides.

Serum Chemerin and Apelin Levels in Obese Children: Relation to Endothelial Function and Inflammation from a Cross-sectional Case–Control Study

BACKGROUND: Childhood obesity is a global threat with subsequent health problems among which and most important is cardiovascular problems. It is now claimed that adipokines secreted by adipose tissue are responsible for such consequences. Newly discovered adipokines chemerin and apelin are under investigation for their link with obesity related co-morbidites. AIM: The aim of the present study was to assess the serum levels of chemerin and apelin in obese children and to explore the correlation between these two biomarkers and the inflammatory as well as the endothelial cell activation markers PATIENTS AND METHODS: This study was a cross-sectional case control study that comprised 45 pre-pubertal obese children aged (6– < 12) years old of both sexes (22 males and 23 females), in addition to 45 matched age and sex lean children serving as controls (21 males and 24 females). Serum levels of chemerin, apelin, ICAM-1, E-selectin and hs-CRP were measured for obese and controls. RESULTS: Obese children showed higher levels of chemerin, apelin, ICAM-1 and E-selectin than controls. Chemerin and apelin showed significant correlations with all parameters except for age. Anthropometric parameters with hs-CRP revealed significant correlation even after adjustment for age and sex while apelin only showed a significant correlation with age. Multiple regression analyses with hs -CR , E-selectin and ICAM-1 as dependent variables and BMI Z score ,age, sex, chemerin and apelin as independent variables showed the effect of chemerin and apelin on the increased levels of hs -CR , E-selectin and ICAM-1 . CONCLUSION: Elevated levels of chemerin and apelin may serve as indices of ongoing obesity-related disorders in obese children.

Low serum apelin levels are associated with mild cognitive impairment in Type 2 diabetic patients

BackgroundApelin is a new adipokine that is secreted by adipocytes, and is associated with insulin resistance (IR), inflammation, and obesity. This study was designed to investigate the role of apelin in type 2 diabetes mellitus (T2DM) patients with mild cognitive impairment (MCI).MethodsA total of 235 patients with T2DM were included. The cognitive function of patients was evaluated using Montreal Cognitive Assessment (MoCA) tool, then patients were divided into MCI group and non-MCI group according to the MoCA score. Blood sample was analyzed for the level of apelin by enzyme-linked immunosorbent assay (ELISA).ResultsThe MCI group (n = 73) presented lower serum apelin levels compared with the patients with normal cognitive function (P < 0.001). Apelin levels showed significantly negative correlation with diabetes duration, triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C, creatinine and high sensitivity C-reactive protein (hs-CRP), and positive correlation with high-density lipoprotein cholesterol (HDL-C) and brain-derived neurotrophic factor (BDNF). Multivariable logistic regression analysis indicated that serum apelin (OR = 0.304, 95%CI: 0.104–0.886, P = 0.029), as well as education levels, diabetes duration, cardiovascular disease, serum HbA1c, HDL-C, creatinine, and BDNF, were independent risk factors of MCI in patients with T2DM.ConclusionsSerum apelin level is reduced in T2DM patients with MCI. Apelin might has protective effect against cognitive impairment and serve as a serum biomarker of T2DM.

Predictive value of both irisin and apelin for heart failure with preserved ejection fraction in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Irisin is skeletal muscle-derived peptide, the expression of which is under close control of peroxisome proliferator-activated receptor-γ co-activator 1α. Apelin is a peptide having positive inotrope ability and acting as an autocrine regulator of cardiac and vascular reparation. Type 2 diabetes mellitus (T2DM). The aim of the study was to investigate whether serum levels of both irisin and apelin predict HF with preserved ejection fraction (HFpEF) in patients with T2DM. Methods One hundred and eight HF patients with T2DM having HFpEF (EF&amp;gt;50%; n=58), HF with mildly reduced ejection fraction (HFmrEF, EF&amp;lt;40%; n=22), HF with reduced ejection fraction (HFrEF, EF&amp;lt;40%; n=28) aged from 41 to 62 years and 20 non-HF patients with T2DM. Healthy control group was consisted of 25 individuals matched with age and sex. All patients gave voluntary written informed consent to participate in the study. We polled at baseline demographic and anthropometric information, data for hemodynamic performances by B-mode echocardiography, Doppler and TDI, and the levels of biomarkers including irisin, apelin, N-terminal pro-brain natriuretic peptide (NT-proBNP) by ELISA. Results We found that the levels of irisin were significantly higher in HFpEF patients than in HFrEF individuals, whereas healthy volunteers and T2DM non-HF patients demonstrated lower concentrations of these peptides. On contrary, apelin levels were significantly increased in HF patients mainly with HFrEF. There were not significant differences between the levels of these biomarkers in HFrEF and HFmrEF (P=0.42 for all cases). Using ROC curve we revealed that cut-off points for irisin and apelin that distinguished HFpEF from HFrEF/HFmrEF were (6.50 ng/mL; AUC=0.78; 95% confidence interval [CI] = 6.85 - 10.66 ng/mL and 4.12 ng/mL, AUC=0.72; 95% CI=3.90-5.75 ng/mL, respectively). Then we divided all patients with HF having elevation of NT-proBNP &amp;gt; 750 pmol/mL into three subgroups depending on the biomarkers’ levels. Patients from subgroup A had both irisin and apelin levels higher cut-off points, individuals from group B had higher concentration of one of two biomarkers, and patients from subgroup C demonstrated levels of both peptides lower cut-off points. Multivariate logistic regression analysis revealed that discriminative value of irisin and apelin to predict HFpEF in subgroup B (Hazard Ratio [HR]= 2.18; 95% CI=1.26-3.14; P=0.001) were substantially higher compared with subgroups A and C (HR = 1.03; 95% CI=1.00-1.05; P=0.64 and HR = 0.92; 95% CI=0.89-1.01; P=0.62, respectively). Adding irisin and apelin to NT-proBNP as independent variables to the predictive model sufficiently improved discriminative ability of whole model for HFpEF. In conclusion: We found that multidirectional changes in the levels of irisin and apelin in T2DM patients had better predictive value for HFpEF that simultaneous increase and decrease in the circulating levels of these peptides.

Elevated levels of apelin predict favorable clinical course of heart failure in type 2 diabetes mellitus patients

Abstract Funding Acknowledgements Type of funding sources: None. Background Apelin is a regulatory peptide having positive inotrope and reparative abilities. Type 2 diabetes mellitus (T2DM) is common comorbidity that is associated to occurrence of HF mainly HF with preserved ejection fraction (HFpEF). The discriminative potency of conventional cardiac biomarkers such as natriuretic peptides in HFpEF was found to be sufficiently lower compared to HF with reduced / mildly reduced ejection fraction (HFrEF / HFmrEF). The aim of the study was to investigate whether serum levels of apelin predict HF in patients with T2DM. Methods A total of 108 HF patients (left ventricular ejection fraction [LVEF] &amp;lt;60%) with T2DM were prospectively involved in the study. Entire HF population consisted of 58 HFpEF patients and 50 HFmrEF / HFrEF aged from 41 to 62 years. Cardiac hemodynamic performances were obtained by B-mode echocardiography, Doppler and TDI. The levels of apelin, N-terminal pro-brain natriuretic peptide (NT-proBNP), high sensitive troponin T (hs-TnT) were measured by ELISA. Combined end-point for the study were defined as all-cause death and any non-fatal cardiovascular event or HF hospitalization during 52 weeks. Results The combined end-point occurred in 37 patients (34.3%) from entire population. The levels of apelin in patients who had the combined end-point were significantly lower (3.55 ng/mL, 95% confidence interval [CI]=3.12-3.95 ng/mL) compared with those who did not meet it (5.60 ng/mL; 95% CI = 4.10-7.10 ng/mL; P=0.001). ROC curve revealed that the best-balanced cut-off point for apelin levels, which predicted combined end-point occurrence, was 3.88 ng/mL (AUC=0.82; P=0.001). Cox regression showed that apelin levels &amp;gt; 3.55 ng/mL (Odds Ratio [OR]= 2.02; 95% CI=1.14-3.25; P=0.001), LVEF&amp;lt; 49% (OR=1.48; 95% CI=1.22-1.68, P = 0.001), NT-proBNP &amp;gt; 785 ng/mL (OR =2.08; 95% CI = 1.03–4.12; P = 0.001), global longitudinal strain &amp;lt; -8.6% (OR =2.02; 95% CI = 1.09–3.10; P = 0.001), hs-TnT &amp;gt; 0.4 ng/mL (OR=1.98; 95% CI=1.10-2.93; P=0.001), estimated glomerular filtration rate &amp;lt;60 mL/min/1.73 m2 (OR=1.46; 95% CI=1.09-2.55; P=0.001) and history of atrial fibrillation (OR=1.14; 95% CI=1.02-1.80; P=0.001) predicted the combined end-point. After adjustment for HFpEF, apelin levels &amp;gt; 3.55 ng/mL (OR=2.03; 95% CI=1.10-3.20; P=0.001) and NT-proBNP &amp;gt; 785 ng/mL (OR =2.10; 95% CI = 1.05–3.80; P = 0.001) remain independent predictors for the combined end-point. The addition of apelin to the ABC model (NT-proBNP &amp;gt; 785 ng/mL) improved the relative integrated discrimination indices by 10.5% and net-reclassification improvement for 11.5% for combined end-point. Kaplan – Meier curve showed that patients having the levels of apelin &amp;gt;3.55 ng/mL demonstrated better clinical course of HF compared with those who had lower apelin levels (log rank test p=0.001). In conclusion: We found that apelin levels &amp;gt;3.55 ng/mL regardless of NT-proBNP had positive discriminative ability for clinical course of HF in T2DM patients.

Kynurenine-PARP-1 Link Mediated by MicroRNA 210 May Be Dysregulated in Pulmonary Hypertension.

BackgroundDysregulation of microRNAs is associated with pulmonary hypertension. The present study aimed to determine the alterations in microRNA and microRNA expressions and their role in signaling pathways and investigate the relationship with serum levels of apelin, kynurenine, and endocan in pulmonary hypertension.MethodsThe study design was prospective and single-centered. The study included 32 consecutive treatment-naive patients with precapillary pulmonary hypertension and 55 age and sex-matched healthy controls. All subjects underwent right heart catheterization. mRNA expressions of hypoxia-inducible factor-1 alpha, hypoxia-inducible factor-2 alpha, signal transducer and activator of transcription-3, fibroblast growth factor-2, fibroblast growth factor receptor-1, and poly-ADP-ribose polymerase-1 and microRNA expressions of miRNA-210, miRNA-130a, miRNA-424, miRNA-204, and miRNA-223 were determined by RT-PCR. Concentrations of kynurenine, apelin, and endocan were analyzed by ELISA.ResultsmRNA expressions of hypoxia-inducible factor-2 alpha, signal transducer and activator of transcription-33, and FGF-2 were increased; miRNA-210 and miRNA-130a were increased; miRNA-223 and miRNA-204 were decreased in pulmonary hypertension. Apelin and kynurenine concentrations were decreased in pulmonary hypertension. There were positive correlations: hypoxia-inducible factor-2 alpha-miRNA-424, Apelin-miRNA-424, kynurenine-miRNA-210, signal transducer and activator of transcription-3-PVR, miRNA-210-right atrial pressure, and kynurenine-right atrial pressure. There were negative correlations: poly-ADP-ribose polymerase-1-miRNA-210 and poly-ADP-ribose polymerase-1-right atrial pressure. On multiple logistic regression analyses, miRNA-130a and Apelin were independent risk factors for PH.ConclusionsWe report a novel relationship between the kynurenine and poly-ADP-ribose polymerase-1 signaling pathways that could be mediated by miRNA-210. We also report a connection between the Apelin and hypoxia-inducible factor-2 alpha signaling pathways that could be mediated by miRNA-424. Reduced levels of Apelin and elevated levels of miRNA-130a are associated with pulmonary hypertension. We also find that elevated levels of signal transducer and activator of transcription-3, miRNA-210, and kynurenine and reduced levels of poly-ADP-ribose polymerase-1 correlate with more severe hemodynamics.

Apelin controls emotional behavior in age- and metabolic state-dependent manner

Apelin is a small peptide secreted by the adipose tissue notably in conditions of obesity-induced hyper-insulinemia. Apelin exerts a range of physiological functions at the periphery including the improvement of insulin sensitivity and the increase of muscle strength or cardiac contractibility. Interestingly, the brain is endowed with a high density of APJ, the single target of apelin, and growing evidence suggests various central actions of this adipokine. Recent studies reported that the intracerebroventricular infusion of apelin modulates emotional states in middle age stressed animals. However, results are so far been mixed and have not allowed for definitive conclusions about the impact of apelin on anxio-depressive-like phenotype. This study aims 1) to evaluate whether serum apelin levels are associated with mood in older adults and 2) to determine the impact of the genetic apelin inactivation in 12-month old mice fed a standard diet (STD) or in 6-month old mice fed a high fat diet (HFD). A higher plasma apelin level was associated with higher depressive symptoms in older adults. In line with these clinical findings, 12-month old apelin knock-out (Ap-/-) mice displayed a spontaneous antidepressant-like phenotype. In a marked contrast, 6-month old Ap-/- mice harbored a higher degree of peripheral insulin resistance than wild-types in response to HFD and were more prone to develop anxiety while the depressive-like state was not modified. We also provided evidence that such anxious behavior was associated with an impairment of central serotonergic and dopaminergic neuronal activities. Finally, although the insulin sensitizing drug metformin failed to reverse HFD-induced insulin resistance in 6-month old Ap-/- mice, it reversed their anxious phenotype. These results emphasize a complex contribution of apelin in the regulation of emotional state that might depend on the age and the metabolic status of the animals. Further investigations are warranted to highlight the therapeutic potential of manipulating the apelinergic system in mood-related disorders.

Predictive and Diagnostic Value of Serum Adipokines in Pregnant Women with Intrahepatic Cholestasis.

The objective of this study was to assess the value of serum leptin, adiponectin, apelin, and ghrelin as biomarkers for the prediction and diagnosis of intra-hepatic cholestasis (ICP). This prospective study included pregnant women in the third trimester of pregnancy: 63 with ICP, 48 and 15 of whom had mild and severe disease, respectively, and 32 as controls. ICP women had increased median levels of serum leptin, adiponectin, apelin, and ghrelin compared to the controls (p < 0.05). These biomarkers meaningfully changed regarding the severity of ICP: While leptin was reduced, apelin and ghrelin were increased, and adiponectin was increased somewhat. To predict and diagnose ICP, the predictive values of serum leptin, adiponectin, and apelin need to be accepted as comparable, with moderate to high sensitivity and specificity; however, the predictive value of serum ghrelin was somewhat lower. More research is needed to clarify the potential properties of adipokines to gain acceptance as a predictive or diagnostic biomarker for ICP.

Discriminative Utility of Apelin-to-NT-Pro-Brain Natriuretic Peptide Ratio for Heart Failure with Preserved Ejection Fraction among Type 2 Diabetes Mellitus Patients.

Background: Apelin is a regulatory vasoactive peptide, which plays a pivotal role in adverse cardiac remodeling and heart failure (HF) with reduced ejection fraction. The purpose of the study was to investigate whether serum levels of apelin is associated with HF with preserved election fraction (HFpEF) in patients with T2DM. Methods: The study retrospectively involved 101 T2DM patients aged 41 to 62 years (48 patients with HFpEF and 28 non-HFpEF patients). The healthy control group consisted of 25 individuals with matched age and sex. Data collection included demographic and anthropometric information, hemodynamic performances and biomarkers of the disease. Transthoracic B-mode echocardiography, Doppler and TDI were performed at baseline. Serum levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and apelin were measured by ELISA in all patients at the study entry. Results: Unadjusted multivariate logistic model yielded the only apelin to NT-proBNP ratio (OR = 1.44; p = 0.001), BMI > 34 кг/м2 (OR = 1.07; p = 0.036), NT-proBNP > 458 pmol/mL (OR = 1.17; p = 0.042), LAVI > 34 mL/m2 (OR = 1.06; p = 0.042) and E/e’ > 11 (OR = 1.04; p = 0.044) remained to be strong predictors for HFpEF. After obesity adjustment, multivariate logistic regression showed that the apelin to NT-proBNP ratio < 0.82 × 10−2 units remained sole independent predictor for HFpEF (OR = 1.44; 95% CI: 1.18–2.77; p = 0.001) HFpEF in T2DM patients. In conclusion, we found that apelin to NT-proBNP ratio < 0.82 × 10−2 units better predicted HFpEF in T2DM patients than apelin and NT-proBNP alone. This finding could open new approach for CV risk stratification of T2DM at higher risk of HF.

Correlation of serum apelin level with carotid intima–media thickness and insulin resistance in a sample of Egyptian patients with type 2 diabetes mellitus

Background:Type 2 diabetes mellitus (T2DM) is a growing health problem in Egypt, with a significant impact on morbidity and mortality. Measurement of the carotid Intima-media thickness (CIMT) allows early detection of atherosclerotic blood vessel diseases. Apelin is an adipose tissue-derived hormone that may be associated with insulin resistance (IR). This study aimed to assess the level of serum apelin in patients with T2DM and its relation to IR and CIMT.Materials and Methods:A case-control study was conducted on 60 patients with T2DM and 30 healthy controls. T2DM was diagnosed based on American Diabetes Association criteria. The study was carried out at Al-Zahraa University Hospital, Cairo, Egypt, through the period from June to December 2019. The laboratory investigations included serum apelin and blood glucose hemostasis markers. CIMT was assessed using B-mode ultrasonography.Results:Patients’ group had a statistically significant higher apelin level than healthy controls (407.96 ± 291.07 versus 83.32 ± 10.55 ng/dL, P < 0.001). The correlation analysis showed that the serum apelin level correlated positively with glycemic indices, body weight, and waist circumference (P < 0.05). At cutoff value of >96 ng/dL, the serum apelin exhibited a sensitivity of 98.3% and specificity of 96.7%, positive predictive value of 98.1%, and negative predictive value of 96.5%, with a diagnostic accuracy of 95.1%. Serum apelin correlated positively with CIMT (r = 0.296, P = 0.022). Logistic regression analysis showed that systolic and diastolic blood pressures, Homeostasis Model Assessment of IR, and CIMT were independent predictors of serum apelin.Conclusion:Serum apelin may be correlated with the degree of carotid atherosclerosis and hence can be used as a prognostic biomarker.

Correlation between Apelin and Some Angiogenic Factors in the Pathogenesis of Preeclampsia: Apelin-13 as Novel Drug for Treating Preeclampsia and Its Physiological Effects on Placenta.

Preeclampsia (PE) is one of the commonest causes for maternal and fetal morbidity and mortality. Imbalances of angiogenic factors, oxidative stress, and inflammatory response have a role in the pathogenesis of PE. Data regarding the circulating apelin level and its role in PE remains controversial. This study was formulated to assess the serum apelin level in PE, investigate its correlation with some inflammatory, oxidative stress, and angiogenic proteins in a nitric oxide synthase inhibitor; the N (gamma)-nitro-L-arginine methyl ester (L-NAME)-induced rat model of PE and determine whether apelin administration could protect against development of PE. 40 healthy adult female albino rats and 10 adult male albino rats were used in this study. The pregnant female rats were randomly divided into three groups: group 1 (normal pregnant group), group 2 (PE-induced group), injected subcutaneously with 75 mg L-NAME/kg bodyweight/day starting from day 9 to 20 of gestation, and group 3 (PE-induced group supplemented with apelin (PE + apelin)); PE induced as before and simultaneously subcutaneously injected with apelin-13 (6 × 10−8 mol/kg bodyweight/twice daily) beginning from day 6 to 20 of gestation. In all groups, blood pressure and urine protein were determined at gestation days (GD) 0, 10, and 18. Moreover, serum apelin, placental growth factor (PLGF), vascular endothelial growth factor (VEGF), soluble fms-like tyrosine kinase-1 (sFlt-1), soluble endoglin (sEng), interferon-gamma (IFN-γ), and interleukin-10 (IL-10) levels and serum superoxide dismutase enzyme (SOD) and catalase (CAT) activities of all groups were estimated at the end of experiment. Placental histopathological examination was also performed. PE-induced rats showed significantly decreased serum apelin levels. Moreover, they showed significantly increased blood pressures, urine proteins, sFlt-1, sEng, and IFN-γ (mean arterial blood pressure, urine proteins, sFlt-1, sEng, and IFN-γ showed significant negative correlations with serum apelin level), but it showed significantly decreased VEGF, PLGF, IL-10, SOD, and CAT (VEGF, PLGF, IL-10, and SOD showed significant positive correlations with serum apelin level). In contrast, exogenous apelin administration significantly ameliorated these parameters together with improvement in the placental histoarchitecture in the apelin-supplemented PE group. This study demonstrated the protective effects of apelin administration on the pathogenesis of PE.

Predictive Value of Apelin and Vaspin on Hemorrhagic Transformation in Patients with Acute Ischemic Stroke after Intravenous Thrombolysis and Analysis of Related Factors.

Background Acute ischemic stroke (CIS) is a high-risk condition among the elderly, and intravenous thrombolytic therapy (ITT) is the most effective means for it. However, ITT is prone to induce hemorrhagic transformation (HT) that further threatens the life and health of patients. As paramount substances in cardiovascular and cerebrovascular diseases, adipocyte factor (Apelin) and serine protease inhibitor (Vaspin) are strongly bound up with CIS. Objective To analyze the predictive significance of Apelin and Vaspin on HT in CIS patients after ITT and offer effective reference to HT prevention in the future. Methods A total of 109 CIS patients treated with intravenous thrombolysis (IT) in two hospitals between June 2017 and February 2018 were enrolled. Among them, 48 patients who suffered HT after therapy were assigned to the research group (Res group) and the other 61 patients who did not suffer it after therapy were assigned to the control group (Con group). Serum Apelin, Vaspin, inflammatory factors, and oxidative stress levels were quantified, and receiver operating characteristic (ROC) curves were drawn for analyzing the predictive value of Apelin and Vaspin on HT after ITT and their associations with inflammatory factors and oxidative stress. CIS patients who suffered HT were followed up for 3 years for prognostic significance analysis of Apelin and Vaspin. Results After ITT, the Res group showed lower Apelin and Vaspin levels than the Con group (all P < 0.05), and patients with a higher HT grade had lower Apelin and Vaspin levels (all P < 0.05). The joint detection of Apelin and Vaspin showed a sensitivity of 77.08% and a specificity of 73.77% for forecasting HT in CIS patients after thrombolytic therapy (all P < 0.001). In addition, after thrombolytic therapy, the Res group presented higher levels of interleukin-1β (IL-1β) and IL-6 as well as malondialdehyde (MDA) than the Con group, and the levels had negative associations with Apelin and Vaspin (all P < 0.05). The Res group showed a lower superoxide dismutase (SOD) level than the Con group, and the level presented a positive association with Apelin and Vaspin (all P < 0.05). According to Logistic analysis, IL-1β, IL-6, and MDA were independent risk factors for HT in CIS patients after IT, while Apelin, Vaspin, and SOD were independent protective factors (all P < 0.05). According to the follow-up results, Apelin and Vaspin demonstrated excellent value in forecasting the death of patients with both CIS and HT (P < 0.05), and their lower levels indicate a higher risk of death (all P < 0.05). Conclusion Apelin and Vaspin can help effectively forecast the occurrence of HT in CIS patients after ITT as independent protective factors of HT, so they are of a high clinical application value.

Study of Circulating Apelin in Type 1 Diabetic Patients and its Association with Glycemic Control in a Group of Egyptian Population

Abstract Background Type 1 diabetes mellitus (T1DM) is one of the most common chronic and metabolic diseases worldwide. The incidence of T1DM is reported to be increasing by 3-5% per year, and the number of people with diabetes is estimated to reach 380 million by 2025. Several studies have shown that TIDM is associated with metabolic abnormalities and alteration of adipose tissue hormones (adipokines). Apelin, one of the most abundantly expressed adipocytokine, is a bioactive peptide and produces its effects through a cell surface G protein-coupled receptor called APJ.The apelinergic system, is involved in a wide range of functions including regulation of body fluid homeostasis, cardiovascular system, angiogenesis and energy metabolism . Additionally, apelin participates in pathological processes, including obesity and diabetes. Apelin plays a beneficial role in energy metabolism. Objectives The aim of this study is to evaluate serum Apelin levels in patients with type 1 diabetes and to correlate the serum Apelin level and glycemic control. Patients and Methods This study was a cross sectional study. Participants were classified into two groups. The first group included 60 patient with T1DM recruited from Ain Shams University Endocrinology and Diabetes outpatient clinics in Cairo during the period from June 2019 to January2002 and the second group included 40 healthy controls. Serum apelin (APLN), FBS, 2hrPP, HbA1c, lipid profile and eGDR were measured for each case. Results Comparison between T1DM patients and controls revealed that serum apelin levels, were significantly increased in cases compared to controls. Negative correlations were found between Apelin and HbA1c% in the diabetic group as a marker for glycemic control so apelin may have a promising role as biomarkers in T1DM. Conclusion Our study showed that apelin concentrations were increased in type 1 diabetic patients compared to healthy controls. The potential association of apelin with insulin secretion and action may reveal new pathways in the pathogenesis of type 1 diabetes. Apelin in T1DM patients may be considered as promising adipokines for predicting glycemic control.

Low ratio of serum levels of apelin and NT-pro-BRAIN natriuretic peptide predicted the development of heart failure with preserved ejection fraction among type 2 diabetes mellitus patients

Background and Aims: Apelin is a potent inotrope and cardioprotective regulatory peptide, which plays a pivotal role in adverse cardiac remodeling and the occurrence of heart failure (HF) with reduced ejection fraction in type 2 diabetes mellitus (T2DM). The purpose of the study was to investigate whether serum levels of apelin predict HF with preserved ejection fraction (HFpEF) in patients with T2DM.

Ontology of the apelinergic system in mouse pancreas during pregnancy and relationship with \u03b2-cell mass

The apelin receptor (Aplnr) and its ligands, Apelin and Apela, contribute to metabolic control. The insulin resistance associated with pregnancy is accommodated by an expansion of pancreatic β-cell mass (BCM) and increased insulin secretion, involving the proliferation of insulin-expressing, glucose transporter 2-low (Ins+Glut2LO) progenitor cells. We examined changes in the apelinergic system during normal mouse pregnancy and in pregnancies complicated by glucose intolerance with reduced BCM. Expression of Aplnr, Apelin and Apela was quantified in Ins+Glut2LO cells isolated from mouse pancreata and found to be significantly higher than in mature β-cells by DNA microarray and qPCR. Apelin was localized to most β-cells by immunohistochemistry although Aplnr was predominantly associated with Ins+Glut2LO cells. Aplnr-staining cells increased three- to four-fold during pregnancy being maximal at gestational days (GD) 9–12 but were significantly reduced in glucose intolerant mice. Apelin-13 increased β-cell proliferation in isolated mouse islets and INS1E cells, but not glucose-stimulated insulin secretion. Glucose intolerant pregnant mice had significantly elevated serum Apelin levels at GD 9 associated with an increased presence of placental IL-6. Placental expression of the apelinergic axis remained unaltered, however. Results show that the apelinergic system is highly expressed in pancreatic β-cell progenitors and may contribute to β-cell proliferation in pregnancy.

Coregulation Analysis of Mechanistic Biomarkers in Autosomal Dominant Polycystic Kidney Disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the most common hereditary kidney disorder leading to deterioration of kidney function and end stage kidney disease (ESKD). A number of molecular processes are dysregulated in ADPKD but the exact mechanism of disease progression is not fully understood. We measured protein biomarkers being linked to ADPKD-associated molecular processes via ELISA in urine and serum in a cohort of ADPKD patients as well as age, gender and eGFR matched CKD patients and healthy controls. ANOVA and t-tests were used to determine differences between cohorts. Spearman correlation coefficient analysis was performed to assess coregulation patterns of individual biomarkers and renal function. Urinary epidermal growth factor (EGF) and serum apelin (APLN) levels were significantly downregulated in ADPKD patients. Serum vascular endothelial growth factor alpha (VEGFA) and urinary angiotensinogen (AGT) were significantly upregulated in ADPKD patients as compared with healthy controls. Arginine vasopressin (AVP) was significantly upregulated in ADPKD patients as compared with CKD patients. Serum VEGFA and VIM concentrations were positively correlated and urinary EGF levels were negatively correlated with urinary AGT levels. Urinary EGF and AGT levels were furthermore significantly associated with estimated glomerular filtration rate (eGFR) in ADPKD patients. In summary, altered protein concentrations in body fluids of ADPKD patients were found for the mechanistic markers EGF, APLN, VEGFA, AGT, AVP, and VIM. In particular, the connection between EGF and AGT during progression of ADPKD warrants further investigation.

Serum apelin levels in polycystic ovary syndrome and its relationship with adiposity profile in females.

Objectives: The purpose of the current study was to compare the serum Apelin level in patients with and without polycystic ovarian syndrome to assess this as a diagnostic marker for PCOS. In a case-control study 60 polycystic ovarian syndrome patients diagnosed according to Rotterdam criteria and 20 healthy controls of reproductive age group were recruited. Study Design: Case Control study. Setting: Jinnah Postgraduate Medical Center in Collaboration with Aga Khan University, Karachi. Period: August 2017 and February 2019. Material &amp; Methods: Blood samples were collected after 12 hours fasting and was used to test serum Apelin, insulin, cortisol and fasting blood glucose levels. Results: Seventy percent PCO subjects had irregular menstrual cycle and 68% suffered from hirsutism; while all PCO subjects had more than 10 antral follicle seen on ultrasound in either one or both ovaries in comparison of 15% controls (p&lt;0.05). Higher Apelin and Testosterone levels in PCO group was reported when compared with controls (p&lt;0.05) across all BMI categories. Apelin showed a positive correlation with number of ovarian cysts (r=0.429; p=0.000); irregular menstrual cyle (r=0.276;p=0.13); blood glucose level (r=0.270; p=0.015) and BMI (r=0.229; p=0.14). Apelin remained independently associated with the risk of PCOS (p=0.020) and elevated testosterone levels (p=0.030). Conclusion: Serum Apelin showed a strong association with irregular menstruation, hirsutism, ovarian cysts, testosterone and deranged blood glucose levels. Therefore, Apelin appears as a potential source for several risk factor in PCOS women of all BMI types.

Supplement therapy with apelin for improving the TSH level and lipid disorders in PTU-induced hypothyroid rats.

Hyperlipidemia is a common metabolic disorder in the general population, which may arise in hypothyroidism. Apelin is an endogenous ligand that acts as an adiponectin, and is involved in energy storage and metabolism. This study evaluated the effects of apelin administration per se or in combination with T4 on the serum level of thyroid-stimulating hormone (TSH), body weight, and lipid profile, along with the serum level of apelin, and its mRNA expression in heart, in 6-propyl-2-thiouracil (PTU)-induced hypothyroid rats. Male Wistar rats were assigned to five different groups: control, H (hypothyroid), H+A, H+T, and H+A+T. All groups except the control one received PTU (0.05%) in the drinking water for 6 weeks. In addition to PTU, the H+A, H+T, and H+A+T groups received apelin (200μg/kg/day, i.p.), l-thyroxin (T4) (20μg/kg/day, via gavage tube), and apelin+T4 during the last 14 days of the trial, respectively. A combined application of T4 and apelin in the H+A+T group effectively diminished mean TSH level, low-density-lipoprotein cholesterol/high-density-lipoprotein cholesterol ratio, and atherogenic index in these animals when compared with these values for the H group. Coadministration of apelin with T4 may offer valuable therapeutic benefits, specifically lowering blood plasma TSH, lipid disorder, and atherosclerosis biomarkers in PTU-induced hypothyroid rats.

Clinical significance of apelin in the treatment of type 2 diabetic peripheral neuropathy.

Background:Diabetic peripheral neuropathy (DPN) is one of the most common chronic complications of diabetes. As apelin is an adipocytokine closely associated with diabetes, this study explored the clinical significance of serum apelin levels in patients with type 2 DPN before and after treatment.Methods:In total, 44 patients with T2DM without DPN (non-DPN group), 41 patients with DPN who received antihyperglycemic treatment (DPN-A group), 44 patients with DPN who received antihyperglycemic treatment combined with nutritional neurotherapy (DPN-B group), and 40 healthy control individuals (NC group) were selected continuously enrolled in the present study. Enzyme-linked immunosorbent assays (ELISA) were performed to determine serum levels of apelin and tumor necrosis factor-α (TNF-α). Related apelin, fasting blood glucose (FBG), glycosylated hemoglobin A1c, TNF-α, body mass index, fasting C peptide, and nerve conduction velocity (NCV) were recorded in each group before and after treatment.Results:Serum levels of apelin and TNF-α were higher in patients with diabetes than those in the NC group, as well as in the DPN group as compared to the non-DPN group; furthermore, some NCV values were significantly reduced in the DPN group. After treatment, the serum levels of apelin, TNF-α, and FBG reduced in patients with diabetes; moreover, apelin levels were found significantly lower in the DPN-B group as compared to the DPN-A group, while some NCV values significantly increased in the DPN-B group. Apelin was negatively correlated with part of NCV values and positively correlated with TNF-α and FBG (P < .01).Conclusion:Our results show that the increase in serum apelin levels is an important clinical reference index for DPN, while a decrease indicates that the DPN treatment is effective.

Effects of acupoint thread-embedding therapy on serum apelin and GLP-1 in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen

To observe the effects of acupoint thread-embedding therapy on serum apelin and glucagon-like peptide-1 (GLP-1) in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen. Sixty-six patients were randomly divided into a control group and an observation group according to the random number table method, with 33 cases in each group. Patients in the control group were treated with exenatide and metformin, while patients in the observation group were treated with additional acupoint thread-embedding. After 12-week treatment, the obesity-related indicators, including body mass index (BMI), waist circumference and body fat rate, the glycometabolism indicators, including fasting blood glucose, 2 h postprandial blood glucose and glycosylated hemoglobin, and the lipid metabolism indicators, including total cholesterol (TC), triglyceride (TG) and low-density lipoprotein cholesterol (LDL-C), as well as serum apelin and GLP-1 levels were observed in patients of the two groups. After treatment, the BMI, waist circumference and body fat rate of patients in the two groups were all reduced (all P 0.05); the TC, TG and LDL-C levels were all significantly reduced in the observation group (all P<0.05), lower than those in the control group (all P<0.05); the serum apelin level was decreased (P<0.05) and the serum GLP-1 level was increased (P<0.05) in the observation group, statistically different from those in the control group (both P<0.05). Combined with the conventional medication, acupoint thread-embedding therapy can significantly improve the obesity-related indicators, glycometabolism and lipid metabolism in type 2 diabetes mellitus patients with obesity due to dampness-heat encumbering spleen. This may be achieved by regulating the serum apelin and GLP-1 levels.