Copeptin and Nesfatin-1 Are Interrelated Biomarkers with Roles in the Pathogenesis of Insulin Resistance in Chinese Children with Obesity

2020 ◽  
Vol 76 (4) ◽  
pp. 223-232
Author(s):  
Chunyan Yin ◽  
Weihua Liu ◽  
Erdi Xu ◽  
Meizhen Zhang ◽  
Weicheng Lv ◽  
...  

<b><i>Background:</i></b> Copeptin and nesfatin-1 have recently been identified as novel peptides that play a role in the pathogenesis of obesity-related insulin resistance in adults. However, the relationship between them has not yet been elucidated, and their circulating levels in children with obesity have not been adequately studied. Therefore, the current study aimed to investigate whether their levels are altered in Chinese children with obesity, as well as to determine the correlation of these 2 peptides with each other, with insulin resistance, and with other biochemical parameters. <b><i>Methods:</i></b> A total of 156 children were enrolled in this study, including 101 children with obesity and 55 lean controls. Anthropometric parameters and clinical data of all subjects were collected, and circulating tumor necrosis factor-α, adiponectin, leptin, copeptin, and nesfatin-1 levels were measured using ELISA. <b><i>Results:</i></b> Serum copeptin and nesfatin-1 levels were significantly elevated in children with obesity and children with insulin resistance compared to control subjects. In addition, nesfatin-1 and copeptin levels were found to be significantly positively correlated with one another by Pearson’s correlation and partial correlation. In multiple regression analysis using nesfatin-1 or copeptin as the dependent parameter, a significant correlation was observed between nesfatin-1 and copeptin, and associations between each of them with homeostasis model assessment of insulin resistance (HOMA-IR) were detected. <b><i>Conclusion:</i></b> These novel findings shed light on the possible interplay role of these 2 molecules in obesity-related insulin resistance.

2019 ◽  
Vol 75 (4) ◽  
pp. 205-212 ◽  
Author(s):  
Min Wang ◽  
Chunyan Yin ◽  
Ling Wang ◽  
Yusheng Liu ◽  
Honggang Li ◽  
...  

Objective: Asprosin, a novel peptide that has recently discovered as an important regulatory adipokine, is relevant to obesity in animals and adult humans. Little is known about its roles in children. The aim of the current study was to determine the potential role of asprosin and explore its relationship to various obesity-related markers in children with obesity. Methods: A cross-sectional study was conducted among 119 Chinese children, including 79 children with obesity and 40 lean controls. Anthropometric parameters, clinical data, and circulating tumor necrosis factor-α (TNF-α), adiponectin, leptin, and asprosin levels were measured. Results: Serum asprosin concentrations were significantly elevated in children with obesity compared with lean controls. Children with insulin resistance (IR) had higher asprosin levels than non-IR group. Asprosin was positively correlated with waist-to-hip ratio (WHR), diastolic blood pressure, homoeostasis model of IR (HOMA-IR), leptin-to-adiponectin ratio, TNF-α independent of their body mass index, SDs score, and age. In multivariable linear regression analysis, WHR and HOMA-IR were associated with the circulating level of asprosin. Conclusions: Circulating asprosins are increased in children with obesity and associated with IR. It may be proposed as a novel marker to predict advanced disease.


2020 ◽  
Author(s):  
yanfeng y xiao ◽  
Chunyan Yin ◽  
Weihua Liu ◽  
Erdi Xu ◽  
LV Weicheng ◽  
...  

Abstract Background Recently, copeptin and nesfatin-1 have been identified as interesting novel peptides playing a role in the pathogenesis of obesity-related insulin resistance in adults, respectively. However, the relationship between them has not been elucidated; and their circulating levels in obese children have not been adequately studied. Therefore, the current study aimed to investigate whether their levels are altered in Chinese obese children and to study the correlation of these two peptides with each other and with insulin resistance and other biochemical parameters. Methods A total of 120 children were enrolled in this study, including 80 obese children and 40 lean controls. Anthropometric parameters and clinical data of all subjects were collected and circulating TNF-α, adiponectin, leptin, copeptin and nesfatin-1 levels were detected using enzyme-linked immunosorbent assays. Results Serum copeptin and nesfatin-1 levels were significantly elevated in obese children and children with insulin resistance compared to control subjects. In addition, nesfatin-1 and copeptin levels were found to be significantly positively correlated with one another in pearson’s correlation and partial correlation. More importantly, multiple regression analysis used nesfatin-1or copeptin as the dependent parameters and significant correlation between nesfatin-1 and copeptin with each other and the associations between each of them with HOMA-IR were detected. Conclusion These findings are novel and shed light on the possible interplay role of these two molecules in obesity-related insulin resistance.


1999 ◽  
Vol 84 (1) ◽  
pp. 272-278 ◽  
Author(s):  
Bernard Zinman ◽  
Anthony J. G. Hanley ◽  
Stewart B. Harris ◽  
Jeremy Kwan ◽  
I. George Fantus

Recent research suggests that tumor necrosis factor-α (TNFα) may play an important role in obesity-associated insulin resistance and diabetes. We studied the relationship between TNFα and the anthropometric and physiological variables associated with insulin resistance and diabetes in an isolated Native Canadian population with very high rates of type 2 diabetes mellitus (DM). A stratified random sample (n = 80) of participants was selected from a population-based survey designed to determine the prevalence of type 2 DM and its associated risk factors. Fasting blood samples for glucose, insulin, triglyceride, leptin, and TNFα were collected; a 75-g oral glucose tolerance test was administered, and a second blood sample was drawn after 120 min. Insulin resistance was estimated using the homeostasis assessment (HOMA) model. Systolic and diastolic blood pressure (BP), height, weight, and waist and hip circumferences were determined, and percent body fat was estimated using biological impedance analysis. The relationship between circulating concentrations of TNFα and the other variables was assessed using Spearman correlation coefficients, analysis of covariance, and multiple linear regression. The mean TNFα concentration was 5.6 pg/mL (sd = 2.18) and ranged from 2.0–12.9 pg/mL, with no difference between men and women (P = 0.67). There were moderate, but statistically significant, correlations between TNFα and fasting insulin, HOMA insulin resistance (HOMA IR) waist circumference, fasting triglyceride, and systolic BP (r = 0.23–0.34; all P &lt; 0.05); in all cases, coefficients for females were stronger than those for males. Individuals with normal glucose tolerance had lower log TNFα concentrations than those with impaired glucose tolerance or type 2 DM (both P = 0.03, adjusted for age and sex), although differences were not significant after adjustment for HOMA IR (both P &gt; 0.25). Regression analysis indicated that log HOMA IR and log systolic BP were significant independent contributors to variations in log TNFα concentration (model r2 = 0.32). We conclude that in this homogeneous Native Canadian population, circulating TNFα concentrations are positively correlated with insulin resistance across a spectrum of glucose tolerance. The data suggest a possible role for TNFα in the pathophysiology of insulin resistance.


2021 ◽  
pp. 3229-3234
Author(s):  
Arifa Mustika ◽  
Nurmawati Fatimah ◽  
Gadis Meinar Sari

Background and Aim: Metaflammation plays a significant role in the pathogenesis, development, and complication of diabetes mellitus (DM). This inflammation is associated with insulin resistance. Therefore, the inflammatory pathways have been targeted for pharmacological treatment. Petiveria alliacea can decrease blood glucose levels and has anti-inflammatory and antioxidant activities; however, there are still insufficient data regarding its efficacy for the treatment of DM. This study aimed to investigate the effect of the self-nanoemulsifying drug delivery system (SNEDDS) of P. alliacea leaf extract on the homeostatic model assessment (HOMA)-insulin resistance (IR) value and interleukin (IL)-6 and tumor necrosis factor-α (TNF-α) levels in a streptozotocin (STZ)-induced diabetic rat model. Materials and Methods: Thirty-five diabetic rat models were randomly divided into five groups. The first group received the SNEDDS of P. alliacea leaf extract at a dose of 50 mg/kg body weight (BW), the second group received it at a dose of 100 mg/kg BW, the third group received it at a dose of 200 mg/kg BW, the fourth group received 18 mg of metformin, and the fifth group only received the SNEDDS formula. The treatment was administered once a day, orally, for 14 days. On the 15th day after treatment, the rats were sacrificed to obtain blood samples for cardiac examination. The IL-6, TNF-α, and insulin levels in the serum were measured using the enzyme-linked immunosorbent assay method. The HOMA-IR value was calculated using a formula. Results: The mean IL-6 and TNF-α levels were low in the group that received the SNEDDS of P. alliacea leaf extract. There was no significant difference in the insulin level in all treatment and control groups. However, a significant difference in the HOMA-IR value was noted between the group that received the SNEDDS of P. alliacea leaf extract and metformin and the group that did not receive treatment (p<0.05). Conclusion: The SNEDDS of P. alliacea leaf extract reduced the HOMA-IR value and suppressed the TNF-α and IL-6 levels in the STZ-induced diabetic rat model.


2010 ◽  
Vol 162 (1) ◽  
pp. 121-126 ◽  
Author(s):  
Panayota Mitrou ◽  
Eleni Boutati ◽  
Vaia Lambadiari ◽  
Aikaterini Tsegka ◽  
Athanasios E Raptis ◽  
...  

ObjectiveAlthough insulin resistance is a common finding in hyperthyroidism, the implicated mechanisms are obscure. The aim of this study was to investigate whether interleukin 6 (IL6) and tumour necrosis factor α (TNFα) are related to the development of insulin resistance in hyperthyroidism of nonautoimmune origin.Design and methodsA meal was given to ten hyperthyroid (HR) and ten euthyroid (EU) women. Plasma samples were taken for 360 min from the radial artery for measurements of glucose, insulin, and nonesterified fatty acids (NEFA). IL6 and TNFα were measured preprandially from the superficial epigastric vein and from the radial artery.Resultsi) In HR versus EU: (a) arterial glucose was similar (AUC0–3602087±57 vs 2010±43 mM×min), but insulin was increased (AUC0–36017 267±2447 vs 10 331±666 μU/ml×min,P=0.01), (b) homeostasis model assessment (HOMA) was increased (2.3±0.4 vs 1±0.1 kg/m2,P=0.007), (c) arterial NEFA were increased (AUC0–360136±18 vs 89±7 mmol/l×min,P=0.03), (d) arterial IL6 (2±0.3 vs 0.9±0.1 pg/ml,P=0.0009) and TNFα (4.2±0.8 vs 1.5±0.2 pg/ml,P=0.003) were increased, and (e) IL6 production from the subcutaneous adipose tissue (AT) was increased (18±6 vs 5±1 pg/min per 100 ml tissue,P=0.04). ii) (a) Subcutaneous venous IL6 was positively associated with HOMA (β-coefficient=1.7±0.7,P=0.049) and (b) although TNFα was not produced by the subcutaneous AT, arterial TNFα was positively associated with NEFA (AUC0–360;β-coefficient=0.045±0.01,P=0.005).ConclusionsIn hyperthyroidism: i) glucose and lipid metabolism are resistant to insulin, ii) subcutaneous AT releases IL6, which could then act as an endocrine mediator of insulin resistance, iii) although there is no net secretion of TNFα by the subcutaneous AT, increased systemic TNFα levels may be related to the development of insulin resistance in lipolysis.


2006 ◽  
Vol 110 (3) ◽  
pp. 361-368 ◽  
Author(s):  
Richard G. Ijzerman ◽  
Jasper J. Voordouw ◽  
Mirjam M. Van Weissenbruch ◽  
John S. Yudkin ◽  
Erik H. Serné ◽  
...  

The mechanism by which TNF-α (tumour necrosis factor-α) may cause insulin resistance is not clear. On the basis of experiments in rats, TNF-α has been suggested to cause defects in capillary function, with a decreased access of insulin and glucose to tissues. To test this hypothesis in humans, we assessed serum TNF-α concentrations, skin capillary recruitment and insulin sensitivity in a group of 37 healthy adults. In addition, we measured these variables in 21 of their prepubertal children. Serum TNF-α levels were measured by sandwich enzyme immunoassay, and insulin sensitivity was assessed with the hyperinsulinaemic euglycaemic clamp technique. Capillary recruitment during post-occlusive reactive hyperaemia was evaluated by videomicroscopy. In the adults, serum TNF-α levels were associated with both capillary recruitment (r=−0.40, P=0.02) and insulin sensitivity (r=−0.33, P=0.05). In addition, capillary recruitment was associated with insulin sensitivity (r=0.34, P=0.04). Regression analysis showed that the association between TNF-α and insulin sensitivity [−0.527 mg·kg−1 of body weight·min−1 per pmol/l per pg/ml TNF-α (95% confidence interval, −1.066 to 0.011); P=0.05] decreased by 30% after adjustment for capillary recruitment. In the children, neither capillary recruitment (r=0.33, P=0.2) nor insulin sensitivity (r=−0.24, P=0.4) was significantly associated with TNF-α. In conclusion, in adults, but not in children, serum TNF-α levels are associated with capillary recruitment during post-occlusive hyperaemia, which, in part, can explain the relationship between TNF-α and insulin resistance. Our data suggest that these relationships are initiated during growth from childhood to adulthood.


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