scholarly journals Salivary Redox Biomarkers in Insulin Resistance: Preclinical Studies in an Animal Model

2021 ◽  
Vol 2021 ◽  
pp. 1-18
Author(s):  
Mateusz Maciejczyk ◽  
Cezary Pawlukianiec ◽  
Małgorzata Żendzian-Piotrowska ◽  
Jerzy Robert Ładny ◽  
Anna Zalewska
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Animal Model ◽  
Tissue Response ◽  
Protein Carbonyls ◽  
Blood Levels ◽  
Standard Diet ◽  
Diagnostic Utility ◽  
Preclinical Studies ◽  
Model Assessment

Insulin resistance (IR) is a condition of impaired tissue response to insulin. Although there are many methods to diagnose IR, new biomarkers are still being sought for early and noninvasive diagnosis of the disease. Of particular interest in laboratory diagnostics is saliva collected in a stress-free, noninvasive, and straightforward manner. The purpose of the study was to evaluate the diagnostic utility of salivary redox biomarkers in preclinical studies in an animal model. The study was conducted on 20 male Wistar rats divided into two equal groups: a standard diet and a high-fat diet (HFD). In all rats fed the HFD, IR was confirmed by an elevated homeostasis model assessment (HOMA-IR) index. We have shown that IR is responsible for the depletion of the enzymatic (↓superoxide dismutase) and nonenzymatic (↓ascorbic acid, ↓reduced glutathione (GSH)) antioxidant barrier at both the central (serum/plasma) and salivary gland (saliva) levels. In IR rats, we also demonstrated significantly higher concentrations of protein/lipid oxidation (↑protein carbonyls, ↑4-hydroxynoneal (4-HNE)), glycation (↑advanced glycation end products), and nitration (↑3-nitrotyrosine) products in both saliva and blood plasma. Salivary nonenzymatic antioxidants and oxidative stress products generally correlate with their blood levels, while GSH and 4-HNE have the highest correlation coefficient. Salivary GSH and 4-HNE correlate with body weight and BMI and indices of carbohydrate metabolism (glucose, insulin, HOMA-IR) and proinflammatory adipokines (leptin, resistin, TNF-α). These biomarkers differentiate IR from healthy controls with very high sensitivity (100%) and specificity (100%). The high diagnostic utility of salivary GSH and 4-HNE is also confirmed by multivariate regression analysis. Summarizing, saliva can be used to assess the systemic antioxidant status and the intensity of systemic oxidative stress. Salivary GSH and 4-HNE may be potential biomarkers of IR progression. There is a need for human clinical trials to evaluate the diagnostic utility of salivary redox biomarkers in IR conditions.

scholarly journals Neurodegeneration in an animal model of Parkinson's disease is exacerbated by a high-fat diet

2010 ◽  
Vol 299 (4) ◽  
pp. R1082-R1090 ◽  
Author(s):  
Jill K. Morris ◽  
Gregory L. Bomhoff ◽  
John A. Stanford ◽  
Paige C. Geiger
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Animal Model ◽  
Locomotor Activity ◽  
Substantia Nigra ◽  
High Fat Diet ◽  
Model Assessment ◽  
High Fat

Despite numerous clinical studies supporting a link between type 2 diabetes (T2D) and Parkinson's disease (PD), the clinical literature remains equivocal. We, therefore, sought to address the relationship between insulin resistance and nigrostriatal dopamine (DA) in a preclinical animal model. High-fat feeding in rodents is an established model of insulin resistance, characterized by increased adiposity, systemic oxidative stress, and hyperglycemia. We subjected rats to a normal chow or high-fat diet for 5 wk before infusing 6-hydroxydopamine (6-OHDA) into the medial forebrain bundle. Our goal was to determine whether a high-fat diet and the resulting peripheral insulin resistance would exacerbate 6-OHDA-induced nigrostriatal DA depletion. Prior to 6-OHDA infusion, animals on the high-fat diet exhibited greater body weight, increased adiposity, and impaired glucose tolerance. Two weeks after 6-OHDA, locomotor activity was tested, and brain and muscle tissue was harvested. Locomotor activity did not differ between the groups nor did cholesterol levels or measures of muscle atrophy. High-fat-fed animals exhibited higher homeostatic model assessment of insulin resistance (HOMA-IR) values and attenuated insulin-stimulated glucose uptake in fast-twitch muscle, indicating decreased insulin sensitivity. Animals in the high-fat group also exhibited greater DA depletion in the substantia nigra and the striatum, which correlated with HOMA-IR and adiposity. Decreased phosphorylation of HSP27 and degradation of IκBα in the substantia nigra indicate increased tissue oxidative stress. These findings support the hypothesis that a diet high in fat and the resulting insulin resistance may lower the threshold for developing PD, at least following DA-specific toxin exposure.

Homocysteine is the confounding factor of metabolic syndrome-confirmed by siMS score

2018 ◽  
Vol 33 (2) ◽  
pp. 99-103 ◽  
Author(s):  
Branko Srećković ◽  
Ivan Soldatovic ◽  
Emina Colak ◽  
Igor Mrdovic ◽  
Mirjana Sumarac-Dumanovic ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Risk Score ◽  
Continuous Measure ◽  
Model Assessment ◽  
Anthropometric Parameters ◽  
Apo B ◽  
Significant Difference ◽  
Homeostatic Model Assessment

Abstract Background: Abdominal adiposity has a central role in developing insulin resistance (IR) by releasing pro-inflammatory cytokines. Patients with metabolic syndrome (MS) have higher values of homocysteine. Hyperhomocysteinemia correlates with IR, increasing the oxidative stress. Oxidative stress causes endothelial dysfunction, hypertension and atherosclerosis. The objective of the study was to examine the correlation of homocysteine with siMS score and siMS risk score and with other MS co-founding factors. Methods: The study included 69 obese individuals (age over 30, body mass index [BMI] >25 kg/m2), classified into two groups: I-with MS (33 patients); II-without MS (36 patients). Measurements included: anthropometric parameters, lipids, glucose regulation parameters and inflammation parameters. IR was determined by homeostatic model assessment for insulin resistance (HOMA-IR). ATP III classification was applied for diagnosing MS. SiMS score was used as continuous measure of metabolic syndrome. Results: A significant difference between groups was found for C-reactive protein (CRP) (p<0.01) apolipoprotein (Apo) B, HOMA-IR and acidum uricum (p<0.05). siMS risk score showed a positive correlation with homocysteine (p=0.023), while siMS score correlated positively with fibrinogen (p=0.013), CRP and acidum uricum (p=0.000) and homocysteine (p=0.08). Homocysteine correlated positively with ApoB (p=0.036), HbA1c (p=0.047), HOMA-IR (p=0.008) and negatively with ApoE (p=0.042). Conclusions: Correlation of siMS score with homocysteine, fibrinogen, CRP and acidum uricum indicates that they are co-founding factors of MS. siMS risk score correlation with homocysteine indicates that hyperhomocysteinemia increases with age. Hyperhomocysteinemia is linked with genetic factors and family nutritional scheme, increasing the risk for atherosclerosis.

Daily Treatment with Sildenafil Reverses Endothelial Dysfunction and Oxidative Stress in an Animal Model of Insulin Resistance

2008 ◽  
Vol 53 (6) ◽  
pp. 1272-1281 ◽  
Author(s):  
Delphine Behr-Roussel ◽  
Alexandra Oudot ◽  
Stéphanie Caisey ◽  
Olivier L.E. Coz ◽  
Diane Gorny ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Animal Model ◽  
Endothelial Dysfunction ◽  
Daily Treatment ◽  
And Oxidative Stress

Impact of chronic gliclazide therapy in the nuclear oxidative stress and insulin-resistance levels in an animal model of diabetes

2006 ◽  
Vol 40 (6) ◽  
pp. 932-933
Author(s):  
Pedro Monteiro ◽  
Elsa Nunes ◽  
Raquel Seiça ◽  
Lino Gonçalves ◽  
Luís A. Providência
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Animal Model

scholarly journals Association between proinsulin, insulin, proinsulin/insulin ratio, and insulin resistance status with the metabolic syndrome

2007 ◽  
Vol 51 (7) ◽  
pp. 1128-1133 ◽  
Author(s):  
Ivana Pivatto ◽  
Patricia Bustos ◽  
Hugo Amigo ◽  
Ana Maria Acosta ◽  
Antonio Arteaga
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Risk Factor ◽  
Resistance Index ◽  
Cross Sectional Study ◽  
Blood Levels ◽  
Model Assessment ◽  
Cross Sectional ◽  
Predictive Values ◽  
The Metabolic Syndrome

The Metabolic Syndrome (MS) constitutes an independent risk factor of cardiovascular disease. There is evidence that proinsulin blood levels and the proinsulin/insulin ratio are associated to the MS. The purpose of this study was to compare proinsulin and insulin, insulin resistance index, and the proinsulin/insulin ratio as predictors of MS. This is a cross-sectional study involving 440 men and 556 women with a mean age of 24 years. Diagnosis of MS was made according to the National Cholesterol Education Program Adult Treatment Panel III. Blood levels of insulin and proinsulin were measured, and the insulin resistance status was estimated using the homeostatic model assessment (HOMA-IR). The prevalence of MS was 10.1%. HOMA-IR was the best MS risk factor for both women and men (OR = 2.04; 95% CI: 1.68-2.48 and 1.09; 95% CI: 1.05-1.13, respectively). HOMA-IR presented the best positive predictive value for MS: 22% and 36% for men and women, respectively, and was the best MS indicator. The proinsulin/insulin ratio did not show significant association with MS. HOMA-IR, proinsulin, and insulin presented good negative predictive values for both genders that could be used to identify an at-risk population.

Sex-dependent nutritional programming: fish oil intake during early pregnancy in rats reduces age-dependent insulin resistance in male, but not female, offspring

2013 ◽  
Vol 304 (4) ◽  
pp. R313-R320 ◽  
Author(s):  
Fatima L. C. Sardinha ◽  
Flavia S. Fernandes ◽  
Maria G. Tavares do Carmo ◽  
Emilio Herrera
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Early Pregnancy ◽  
Adult Life ◽  
Male Offspring ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Standard Diet ◽  
Model Assessment

Prenatal and early postnatal nutritional status may predispose offspring to impaired glucose tolerance and changes in insulin sensitivity in adult life. The long-term consequences of changes in maternal dietary fatty acid composition were determined in rats. From day 1 until day 12 of pregnancy, rats were given isocaloric diets containing 9% nonvitamin fat based on soybean, olive, fish (FO), linseed, or palm oil. Thereafter, they were maintained on the standard diet; offspring were studied at different ages. Body weight at 4, 8, and 12 mo and lumbar adipose tissue and liver weights at 12 mo did not differ between females on the different diets, whereas in males the corresponding values were all lower in the offspring from the FO group compared with the other dietary groups. Plasma glucose concentrations (both basal and after an oral glucose load) did not change with sex or dietary group, but plasma insulin concentrations were lower in females than in males and, in males, were lowest in the FO group. Similar relations were found with both the homeostasis model assessment of insulin resistance and insulin sensitivity index. In conclusion, the intake of more n–3 fatty acids (FO diet) during early pregnancy reduced both fat accretion and age-related decline in insulin sensitivity in male offspring but not in females. It is proposed that the lower adiposity caused by the increased n–3 fatty acids during the intrauterine life was responsible of the lower insulin resistance in male offspring.

Effect of leptin on the gallbladder in patients with metabolic syndrome

2016 ◽  
Vol 94 (4) ◽  
pp. 285-289 ◽  
Author(s):  
Natalia G. Virstyuk ◽  
N. R. Senyutovich
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
International Diabetes Federation ◽  
Resistance Index ◽  
High Density Lipoproteins ◽  
Control Group ◽  
Blood Levels ◽  
Model Assessment ◽  
Functional Changes ◽  
Group I

The study involved 58 patients with chronic noncalculous cholecystitis (CNC) divided into two groups. Group I included 30 CNC patients with metabolic syndrome (MS), group II 28 CNC patients without MS. The control group consisted of 20 healthy people. MS was diagnosed according to International Diabetes Federation guidelines (2005). The following anthropometric parameters were determined: body mass index (BMI), waist to hip ratio, blood lipid profile (total cholesterol, triglycerides, high density lipoproteins (HDL), and low density lipoproteins (LDL)). Leptin and insulin levels were measured using commercial ELISA kits «Leptin ELISA» and «Insulin ELISA» (DRG International, Inc., USA) respectively. Insulin resistance index HOMA-IR (Homeostasis Model Assessment of Insulin Resistance) was calculated. It was shown that leptin level in CNC patients with MS was 2.61 times that in healthy subjects (p <0.001) and 2.47 times higher than in CNC patients without MS (p <0.001). Significant direct correlations between leptin blood levels andBMI, HOMA-IR index, triglycerides, and cholesterol were documented. The relationships between blood levels of leptin and the thickness of the gallbladder (GB) wall, the amount of cholesterol crystals in bile, and decreased bile release rate from GB which suggests effect of leptin on the structural and functional changes in GB.

scholarly journals Circulating obestatin levels and the ghrelin/obestatin ratio in obese women

2007 ◽  
Vol 157 (3) ◽  
pp. 295-301 ◽  
Author(s):  
Valentina Vicennati ◽  
Silvia Genghini ◽  
Rosaria De Iasio ◽  
Francesca Pasqui ◽  
Uberto Pagotto ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Tolerance Test ◽  
Normal Weight ◽  
Metabolic Parameters ◽  
Blood Levels ◽  
Oral Glucose ◽  
Sensitivity Index ◽  
Model Assessment ◽  
Obese Women ◽  
Glucose Levels

Objective: We measured blood levels of obestatin, total ghrelin, and the ghrelin/obestatin ratio and their relationship with anthropometric and metabolic parameters, adiponectin and insulin resistance, in overweight/obese and normal-weight women. Design: Outpatients Unit of Endocrinology of the S Orsola-Malpighi Hospital of Bologna, Italy. Methods: Fasting obestatin, ghrelin, adiponectin and lipid levels, fasting and glucose-stimulated oral glucose tolerance test insulin, and glucose levels were measured in 20 overweight/obese and 12 controls. The fasting ghrelin/obestatin ratio was calculated; the homeostasis model assessment-IR (HOMA-IR) and insulin sensitivity index (ISIcomposite) were calculated as indices of insulin resistance. Results: Obese women had higher obestatin and lower ghrelin blood levels, and a lower ghrelin/obestatin ratio compared with controls. In all subjects, obestatin was significantly and positively correlated with total cholesterol and triglycerides, but not with ghrelin, anthropometric, and metabolic parameters. In the obese women, however, obestatin and ghrelin concentrations were positively correlated. By contrast, the ghrelin/obestatin ratio was significantly and negatively correlated with body mass index, waist, waist-to-hip ratio, fasting insulin, and HOMA-IR, and positively with ISIcomposite but not with adiponectin. None of these parameters were correlated with the ghrelin/obestatin ratio in the obese. Conclusions: Increased obestatin, decreased ghrelin levels, and a decreased ghrelin/obestatin ratio characterize obesity in women. This supports the hypothesis that the imbalance of ghrelin and obestatin may have a role in the pathophysiology of obesity. On the other hand, some relevant differences between our data on circulating levels of obestatin and the ghrelin/obestatin ratio in obese subjects and those reported in the few studies published so far imply that further research is needed.

Impact of chronic metformin therapy in the nuclear oxidative stress and insulin-resistance levels in an animal model of diabetes

2006 ◽  
Vol 40 (6) ◽  
pp. 929
Author(s):  
Pedro Monteiro ◽  
Elsa Nunes ◽  
Raquel Seiça ◽  
Lino Gonçalves ◽  
LuísA. Providência
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Animal Model ◽  
Metformin Therapy
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