High Circulating Alarin Levels Are Associated with Presence of Metabolic Syndrome

Background/Aims: Alarin has been reported to be related with increased food intake and body weight. The relationship of circulating Alarin with insulin resistance or metabolic syndrome (MetS), however, is unknown. This study aimed to investigate the physiological role of Alarin and its association with MetS in humans. Methods: Newly diagnosed MetS patients (n=237) and age-matched healthy subjects (n=192) were recruited for this study. Oral glucose tolerance test, treadmill exercise, lipid infusions and euglycemic-hyperinsulinemic clamp (EHCs) were performed. Circulating Alarin and TNFα levels were measured by ELISA. Results: Circulating Alarin levels were significantly higher in MetS patients compared with healthy subjects (0.46 ± 0.22 vs. 0.41 ± 0.14 µg/L, P < 0.01). In all studied subjects, circulating Alarin levels were positively correlated with WC, blood pressure, FBG, triglyceride, HbA1c, HOMA-IR, AUCglucose, and TNFα (P < 0.05 or P < 0.01). Multivariate logistic regression analyses revealed that circulating Alarin levels were correlated with MetS and insulin resistance. There was no significant change of circulating Alarin levels in the subjects with treadmill exercise for 45 min. In healthy individuals, however, glucose challenge, acute hyperglycemia and lipid infusions resulted in increased circulating Alarin levels, while acute hyperinsulinaemia transiently decreased circulating Alarin levels. Conclusion: The present study provides the evidence that circulating Alarin levels are associated with MetS and insulin resistance.

Download Full-text

The Role of Insulin-Like Growth Factor (IGF) Binding Protein-2 in the Insulin-Mediated Decrease in IGF-I Bioactivity

Endocrinology ◽

10.1210/endo.150.11.9996 ◽

2009 ◽

Vol 150 (11) ◽

pp. 5192-5192

Author(s):

Ayman M. Arafat ◽

Martin O. Weickert ◽

Jan Frystyk ◽

Joachim Spranger ◽

Christof Schöfl ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Glucose Tolerance ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Igf System ◽

Igf I ◽

Igf Binding

ABSTRACT Context: Insulin interacts with the GH-IGF system by a reciprocal regulation of IGF-binding proteins (IGFBP) and GH, which in turn regulate insulin sensitivity via bioactive IGF-I. This network is linked to metabolic syndrome and cardiovascular diseases. Objective: We evaluated the effect of glucose and insulin on IGFBP-1-4, particularly IGFBP-2, in the regulation of bioactive IGF-I and its relation to insulin resistance. Setting: The study was conducted at an endocrinology center. Research Design and Methods: Twenty-four healthy subjects (12 men; aged 21–72 yr; body mass index 25.9 ± 0.9 kg/m2) and 19 subjects with impaired glucose tolerance (IGT; eight men; aged 26–71 yr; body mass index 28.9 ± 1.2 kg/m2 ) were prospectively studied using oral glucose tolerance test and hyperinsulinemic euglycemic clamp. Results: During the clamp, insulin decreased IGF-I bioactivity in both IGT subjects and controls (−16.2 ± 2.8 and −13.9 ± 3.3%, respectively; P < 0.01). In addition, insulin increased IGFBP-2 and GH and decreased IGFBP-1 and -4 but did not alter total IGF-I, IGF-II, or IGFBP-3 levels. During the oral glucose tolerance test, GH and IGFBP-1 were markedly suppressed. Subjects with IGT showed more pronounced insulin resistance and lower GH, IGFBP-1, and IGFBP-2 levels (P < 0.05). In multiple regression analysis, IGFBP-2 was an independent predictor of insulin sensitivity (β = 0.36, P < 0.05) and IGF-I bioactivity (β = −0.5, P < 0.05). Conclusions: Our data indicate that insulin acutely decreases IGF-I bioactivity through differential modulation of IGFBPs. Furthermore, IGFBP-2 plays a central role in the insulin-IGF system cross talk and is closely linked to insulin resistance, thereby providing a further explanation for its association with the metabolic syndrome.

Download Full-text

Accurate method to estimate insulin resistance from multiple regression models using data of metabolic syndrome and oral glucose tolerance test

Journal of Diabetes Investigation ◽

10.1111/jdi.12155 ◽

2013 ◽

Vol 5 (3) ◽

pp. 290-296 ◽

Cited By ~ 6

Author(s):

Chung-Ze Wu ◽

Jiunn-Diann Lin ◽

Te-Lin Hsia ◽

Chun-Hsien Hsu ◽

Chang-Hsun Hsieh ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Regression Models ◽

Glucose Tolerance Test ◽

Accurate Method ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Multiple Regression Models ◽

Using Data

Download Full-text

Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors

Journal of Pediatric Endocrinology and Metabolism ◽

10.1515/jpem-2014-0533 ◽

2015 ◽

Vol 28 (7-8) ◽

Cited By ~ 3

Author(s):

Rade Vukovic ◽

Dragan Zdravkovic ◽

Katarina Mitrovic ◽

Tatjana Milenkovic ◽

Sladjana Todorovic ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Children And Adolescents ◽

Strong Predictor ◽

Pubertal Development ◽

International Diabetes Federation ◽

Tolerance Test ◽

Oral Glucose ◽

Obese Children ◽

Diet Induced Obesity

AbstractTo assess the prevalence of metabolic syndrome (MS) in obese children and adolescents in Serbia.The study group consisted of 254 subjects (148 female and 106 male), aged 4.6–18.9 years with diet-induced obesity (body mass index ≥95th percentile). Presence of MS using the International Diabetes Federation definition was assessed in all subjects, as well as oral glucose tolerance test and insulin resistance indices.Overall prevalence of MS in all subjects aged ≥10 years was 31.2%, namely, 28.7% in children aged 10 to <16 years and 40.5% in adolescents ≥16 years. When adjusted for age, gender and pubertal development, higher degree of obesity was a strong predictor of MS. Multivariate analysis showed that taller subjects and those with higher degree of insulin resistance were at significantly higher risk of MS, independent of the degree of obesity.High prevalence of MS emphasizes the need for prevention and treatment of childhood obesity.

Download Full-text

Insulin resistance and obesity in childhood

Acta Endocrinologica ◽

10.1530/eje-08-0245 ◽

2008 ◽

Vol 159 (suppl_1) ◽

pp. S67-S74 ◽

Cited By ~ 120

Author(s):

Francesco Chiarelli ◽

Maria Loredana Marcovecchio

Keyword(s):

Insulin Resistance ◽

Cardiovascular Disease ◽

Metabolic Syndrome ◽

Childhood Obesity ◽

Glucose Tolerance ◽

Children And Adolescents ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

The Metabolic Syndrome

Childhood obesity is a significant health problem that has reached epidemic proportions around the world and is associated with several metabolic and cardiovascular complications. Insulin resistance is a common feature of childhood obesity and is considered to be an important link between adiposity and the associated risk of type 2 diabetes and cardiovascular disease. Insulin resistance is also a key component of the metabolic syndrome, and its prevalence in the paediatric population is increasing, particularly among obese children and adolescents. Several factors are implicated in the pathogenesis of obesity-related insulin resistance, such as increased free fatty acids and many hormones and cytokines released by adipose tissue.Valid and reliable methods are essential to assess the presence and the extent of insulin resistance, the associated risk factors and the effect of pharmacological and lifestyle interventions. The two most common tests to assess insulin resistance are the hyperinsulinemic euglycemic clamp and the frequently sampled i.v. glucose tolerance test utilizing the minimal model. However, both these tests are not easily accomplished, are time consuming, expensive and invasive. Simpler methods to assess insulin resistance based on surrogate markers derived from an oral glucose tolerance test or from fasting insulin and glucose levels have been validated in children and adolescents and widely used.Given the strong association between obesity, insulin resistance and the development of metabolic syndrome and cardiovascular disease, prevention and treatment of childhood obesity appear to be essential to prevent the development of insulin resistance and the associated complications.

Download Full-text

Pharmacological and Toxicological Threshold of Bisammonium Tetrakis 4-(N,N-Dimethylamino)pyridinium Decavanadate in a Rat Model of Metabolic Syndrome and Insulin Resistance

Bioinorganic Chemistry and Applications ◽

10.1155/2018/2151079 ◽

2018 ◽

Vol 2018 ◽

pp. 1-13 ◽

Cited By ~ 5

Author(s):

Samuel Treviño ◽

Alfonso Díaz ◽

Eduardo Sánchez-Lara ◽

Víctor Enrique Sarmiento-Ortega ◽

José Ángel Flores-Hernández ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Rat Model ◽

Title Compound ◽

Tolerance Test ◽

Oral Glucose ◽

Severe Insulin Resistance ◽

Abdominal Perimeter ◽

Toxicological Profile ◽

Do So

Vanadium(IV/V) compounds have been studied as possible metallopharmaceutical drugs against diabetes mellitus. However, mechanisms of action and toxicological threshold have been tackled poorly so far. In this paper, our purposes were to evaluate the metabolic activity on dyslipidemia and dysglycemia, insulin signaling in liver and adipose tissue, and toxicology of the title compound. To do so, the previously reported bisammonium tetrakis 4-(N,N-dimethylamino)pyridinium decavanadate, the formula of which is [DMAPH]4(NH4)2[V10O28]·8H2O (where DMAPH is 4-dimethylaminopyridinium ion), was synthesized, and its dose-response curve on hyperglycemic rats was evaluated. A Long–Evans rat model showing dyslipidemia and dysglycemia with parameters that reproduce metabolic syndrome and severe insulin resistance was generated. Two different dosages, 5 µmol and 10 µmol twice a week of the title compound (equivalent to 2.43 mg·V/kg/day and 4.86 mg·V/kg/day, resp.), were administered intraperitoneal (i.p.) for two months. Then, an improvement on each of the following parameters was observed at a 5 µmol dose: weight reduction, abdominal perimeter, fatty index, body mass index, oral glucose tolerance test, lipid profile, and adipokine and insulin resistance indexes. Nevertheless, when the toxicological profile was evaluated at a 10 µmol dose, it did not show complete improvement, tested by the liver and adipose histology, as well as by insulin receptor phosphorylation and GLUT-4 expression. In conclusion, the title compound administration produces regulation on lipids and carbohydrates, regardless of dose, but the pharmacological and toxicological threshold for cell regulation are suggested to be up to 5 µmol (2.43 mg·V/kg/day) dose twice per week.

Download Full-text

Metabolic Syndrome and Hypertension Resulting from Fructose Enriched Diet in Wistar Rats

BioMed Research International ◽

10.1155/2017/2494067 ◽

2017 ◽

Vol 2017 ◽

pp. 1-10 ◽

Cited By ~ 19

Author(s):

Julie Dupas ◽

Annie Feray ◽

Christelle Goanvec ◽

Anthony Guernec ◽

Nolwenn Samson ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Glucose Tolerance ◽

Wistar Rats ◽

Liver Weight ◽

Tolerance Test ◽

Male Rats ◽

Oral Glucose ◽

Sensitivity Index ◽

Long Term Effects

Increased sugar consumption, especially fructose, is strongly related to the development of type 2 diabetes (T2D) and metabolic syndrome. The aim of this study was to evaluate long term effects of fructose supplementation on Wistar rats. Three-week-old male rats were randomly divided into 2 groups: control (C;n=14) and fructose fed (FF;n=18), with a fructose enriched drink (20–25% w/v fructose in water) for 21 weeks. Systolic blood pressure, fasting glycemia, and bodyweight were regularly measured. Glucose tolerance was evaluated three times using an oral glucose tolerance test. Insulin levels were measured concomitantly and insulin resistance markers were evaluated (HOMA 2-IR, Insulin Sensitivity Index for glycemia (ISI-gly)). Lipids profile was evaluated on plasma. This fructose supplementation resulted in the early induction of hypertension without renal failure (stable theoretical creatinine clearance) and in the progressive development of fasting hyperglycemia and insulin resistance (higher HOMA 2-IR, lower ISI-gly) without modification of glucose tolerance. FF rats presented dyslipidemia (higher plasma triglycerides) and early sign of liver malfunction (higher liver weight). Although abdominal fat weight was increased in FF rats, no significant overweight was found. In Wistar rats, 21 weeks of fructose supplementation induced a metabolic syndrome (hypertension, insulin resistance, and dyslipidemia) but not T2D.

Download Full-text

Assessment of HOMA1-IR, Matsuda and ISSI-2 indices in relation to the metabolic syndrome features and oral glucose tolerance test in young people

Diagnostyka Laboratoryjna ◽

10.5604/01.3001.0013.7973 ◽

2017 ◽

Vol 53 (3) ◽

pp. 131-138

Author(s):

Sylwia Płaczkowska ◽

Izabela Kokot ◽

Lilla Pawlik-Sobecka ◽

Agnieszka Piwowar

Keyword(s):

Insulin Resistance ◽

Metabolic Syndrome ◽

Glucose Tolerance ◽

Oral Glucose Tolerance Test ◽

Pancreatic Beta Cells ◽

Glucose Tolerance Test ◽

Tolerance Test ◽

Oral Glucose ◽

Oral Glucose Tolerance ◽

Matsuda Index

Background: Insulin resistance and reduced ability of pancreatic beta cells to secrete insulin preside carbohydrate disorders development and this condition is one of the stages in the type 2 diabetes development. Indirect indices of insulin resistance, sensitivity and pancreatic beta cells function, are used in clinical practice. They are calculated based on glucose and insulin concentration under fasting and postprandial condition. Aim: The aim of this study was to examine relationship between HOMA1-IR, Matsuda Index, and ISSI-2 with metabolic syndrome (MS) features and shape of glycemic curve in young, potentially healthy people. Material and method: The study group consisted of 152 volunteers (108 women, 44 men) aged 19-28. Participants underwent the questionnaire, anthropometric and arterial blood pressure examination. In blood samples under fasting condition lipid profiles, glucose, and insulin were measured. Glucose and insulin were measured also in 60 and 120 minutes of Oral Glucose Tolerance Test (OGTT). Based on the results, MS features were identified and HOMA1-IR, Matsuda Index and ISSI-2 values were calculated. Results: The value of HOMA1-IR was significant higher in patients with metabolic syndrome while lower values of Matsuda and ISSI-2 were observed in participants with the MS as well as with glucose concentration in 120-minute of OGTT higher than under fasting condition. Conclusions: MS is associated with an increase in hepatic insulin resistance. Both MS and retardation of glucose returning to fasting values during OGTT are related to peripheral insulin resistance and reduction of pancreatic beta cell ability to insulin secretion.

Download Full-text

Association of the components of metabolic syndrome with the circulating levels of cytokine clusters in young women

Endocrine Connections ◽

10.1530/ec-20-0569 ◽

2020 ◽

Author(s):

Xingrong Tan ◽

Wenjing Hu ◽

Shan Yang ◽

Han Dai ◽

Shangcheng Xu ◽

...

Keyword(s):

Metabolic Syndrome ◽

Young Women ◽

Healthy Subjects ◽

Enzyme Linked Immunosorbent Assay ◽

Oral Glucose ◽

Euglycemic Hyperinsulinemic Clamp ◽

Cross Sectional ◽

Healthy Women ◽

Circulating Levels

Background: The purpose of this study was to investigate the relationship between circulating zinc α 2-glycoprotein (ZAG), Irisin, betatrophin and adiponectin concentrations and metabolic syndrome (MetS) components and to analyze the effects of blood glucose and insulin on these cytokine concentrations in vivo. Methods: A total of 196 young women, including 78 healthy women and 118 women with MetS components, were recruited for this cross-sectional study. An oral glucose tolerance test and euglycemic-hyperinsulinemic clamp (EHC) were performed in healthy subjects and women with MetS components. An enzyme-linked immunosorbent assay kit was used to measure serum ZAG, irisin, betatrophin, and adiponectin levels, and their relationship with the MetS components was analyzed. Results: In women with MetS components, circulating irisin and betatrophin levels were significantly higher than those in the healthy women, but circulating ZAG and adiponectin levels were significantly lower . FBG, WC, and Triglyceride were significantly correlated with the circulating levels of these four cytokines (p < 0.001 or < 0.05). All four cytokines were associated with MetS and its components. In response to increasing insulin levels, circulating ZAG concentrations were markedly increased in both healthy subjects and women with MetS components during the EHC. However, serum irisin, betatrophin, and adiponectin levels in both healthy subjects and women with MetS components were significantly reduced compared with baseline. Conclusion: Serum ZAG, Irisin, betatrophin and adiponectin were associated with MetS and might be biomarkers for screening MetS components.

Download Full-text