scholarly journals Novel Interactions of Adiponectin with the Endocrine System and Inflammatory Parameters

2003 ◽  
Vol 88 (6) ◽  
pp. 2714-2718 ◽  
Author(s):  
José Manuel Fernández-Real ◽  
Abel López-Bermejo ◽  
Roser Casamitjana ◽  
Wifredo Ricart

Several markers of chronic immune activation have been found in association with obesity and insulin resistance. We aimed to study the interaction of adiponectin with chronic inflammation and known components of the insulin resistance syndrome. Insulin sensitivity (minimal model analysis) and plasma soluble fractions of TNF-α receptor 1 (sTNFR1) and 2 (sTNFR2), adrenal and thyroid function, and adiponectin were evaluated in 68 apparently healthy subjects. An additional group of type 2 diabetic patients (n = 19) similarly studied, except for insulin sensitivity, were also included in the analysis. As reported by others, serum adiponectin concentrations were higher in women than in men (13.55 ± 9.79 vs. 8.64 ± 7.83 mg/liter; P = 0.018). They were also higher in healthy subjects compared with diabetic patients (10.35 ± 8.48 vs. 7.41 ± 8.31 mg/liter; P = 0.021). As expected also, circulating adiponectin was significantly associated with waist to hip ratio (r = −0.28; P = 0.013), diastolic blood pressure (r = −0.25; P = 0.027), fasting plasma high-density lipoprotein cholesterol (r = 0.35; P = 0.001), triglycerides (r = −0.37; P = 0.001), and insulin sensitivity (r = 0.30; P = 0.011). Additionally, subjects in the higher quartile of circulating adiponectin had lower sTNFR2 concentrations (3.05 vs. 4.37 μg/liter; P = 0.012), a trend to lower sTNFR1 concentrations (1.76 vs. 2.20 μg/liter; P = 0.055), higher concentration of serum morning cortisol (16.86 vs. 13.52 μg/dl; P = 0.027), and higher serum free T4 levels (1.31 vs. 1.20 ng/dl; P = 0.038). Multiple regression analysis models were constructed to predict adiponectin concentrations. Predictive variables in these models included insulin sensitivity, waist to hip ratio and free T4, contributing to 17%, 10%, and 8% of adiponectin variance, respectively, These findings suggest that circulating adiponectin differentially modulates insulin action and that thyroid-axis, inflammatory cytokines, and the adrenal cortex might intervene in this modulation.

2004 ◽  
Vol 287 (5) ◽  
pp. E919-E925 ◽  
Author(s):  
Thomas Nyström ◽  
Arne Nygren ◽  
Åke Sjöholm

Tetrahydrobiopterin (BH4) is an essential cofactor of nitric oxide synthase that improves endothelial function in diabetics, smokers, and patients with hypercholesterolemia. Insulin resistance has been suggested as a contributing factor in the development of endothelial dysfunction via an abnormal pteridine metabolism. We hypothesized that BH4 would restore flow-mediated vasodilation (FMD, endothelial-dependent vasodilation), which may affect insulin resistance in type 2 diabetic patients. Thirty-two subjects (12 type 2 diabetic subjects, 10 matched nondiabetic subjects, and 10 healthy unmatched subjects) underwent infusion of BH4 or saline in a random crossover study. Insulin sensitivity index (SI) was measured by hyperinsulinemic isoglycemic clamp. FMD was measured using ultrasonography. BH4 significantly increased SI in the type 2 diabetics [3.6 ± 0.6 vs. 4.9 ± 0.7 × 10−4 dl·kg−1·min−1/(μU/ml), P < 0.05], while having no effects in nondiabetics [8.9 ± 1.1 vs. 9.0 ± 0.9 × 10−4 dl·kg−1·min−1/(μU/ml), P = 0.92] or in healthy subjects [17.5 ± 1.6 vs. 18 ± 1.8 × 10−4 dl·kg−1·min−1/(μU/ml), P = 0.87]. BH4 did not affect the relative changes in brachial artery diameter from baseline FMD (%) in type 2 diabetic subjects (2.3 ± 0.8 vs. 1.8 ± 1.0%, P = 0.42), nondiabetic subjects (5.3 ± 1.1 vs. 6.6 ± 0.9%, P = 0.32), or healthy subjects (11.9 ± 0.6 vs. 11.0 ± 1.0%, P = 0.48). In conclusion, BH4 significantly increases insulin sensitivity in type 2 diabetic patients without any discernible improvement in endothelial function.


2007 ◽  
Vol 64 (6) ◽  
pp. 391-397 ◽  
Author(s):  
Radivoj Kocic ◽  
Dusica Pavlovic ◽  
Gordana Kocic ◽  
Milica Pesic

Background/Aim. Oxidative stress plays a critical role in the pathogenesis of various diseases. Recent reports indicate that obesity may induce systemic oxidative stress. The aim of the study was to potentiate oxidative stress as a factor which may aggravate peripheral insulin sensitivity and insulinsecretory response in obesity in this way to potentiate development of diabetes. The aim of the study was also to establish whether insulin-secretory response after glucagonstimulated insulin secretion is susceptible to prooxidant/ antioxidant homeostasis status, as well as to determine the extent of these changes. Methods. A mathematical model of glucose/insulin interactions and C-peptide was used to indicate the degree of insulin resistance and to assess their possible relationship with altered antioxidant/prooxidant homeostasis. The study included 24 obese healthy and 16 obese newly diagnozed non-insulin dependent diabetic patients (NIDDM) as well as 20 control healthy subjects, matched in age. Results. Total plasma antioxidative capacity, erythrocyte and plasma reduced glutathione level were significantly decreased in obese diabetic patients, but also in obese healthy subjects, compared to the values in controls. The plasma lipid peroxidation products and protein carbonyl groups were significantly higher in obese diabetics, more than in obese healthy subjects, compared to the control healthy subjects. The increase of erythrocyte lipid peroxidation at basal state was shown to be more pronounced in obese daibetics, but the apparent difference was obtained in both the obese healthy subjects and obese diabetics, compared to the control values, after exposing of erythrocytes to oxidative stress induced by H2O2. Positive correlation was found between the malondialdehyde (MDA) level and index of insulin sensitivity (FIRI). Conclusion. Increased oxidative stress together with the decreased antioxidative defence seems to contribute to decreased insulin sensitivity and impaired insulin secretory response in obese diabetics, and may be hypothesized to favour the development of diabetes during obesity.


2011 ◽  
Vol 106 (3) ◽  
pp. 383-389 ◽  
Author(s):  
Pál Brasnyó ◽  
Gergő A. Molnár ◽  
Márton Mohás ◽  
Lajos Markó ◽  
Boglárka Laczy ◽  
...  

Although resveratrol has widely been studied for its potential health benefits, little is known about its metabolic effects in humans. Our aims were to determine whether the polyphenol resveratrol improves insulin sensitivity in type 2 diabetic patients and to gain some insight into the mechanism of its action. After an initial general examination (including blood chemistry), nineteen patients enrolled in the 4-week-long double-blind study were randomly assigned into two groups: a resveratrol group receiving oral 2 × 5 mg resveratrol and a control group receiving placebo. Before and after the second and fourth weeks of the trial, insulin resistance/sensitivity, creatinine-normalised ortho-tyrosine level in urine samples (as a measure of oxidative stress), incretin levels and phosphorylated protein kinase B (pAkt):protein kinase B (Akt) ratio in platelets were assessed and statistically analysed. After the fourth week, resveratrol significantly decreased insulin resistance (homeostasis model of assessment for insulin resistance) and urinary ortho-tyrosine excretion, while it increased the pAkt:Akt ratio in platelets. On the other hand, it had no effect on parameters that relate to β-cell function (i.e. homeostasis model of assessment of β-cell function). The present study shows for the first time that resveratrol improves insulin sensitivity in humans, which might be due to a resveratrol-induced decrease in oxidative stress that leads to a more efficient insulin signalling via the Akt pathway.


2016 ◽  
Vol 2016 ◽  
pp. 1-12 ◽  
Author(s):  
Ditte Søgaard ◽  
Torben Østergård ◽  
Agnieszka U. Blachnio-Zabielska ◽  
Marcin Baranowski ◽  
Andreas Hansen Vigelsø ◽  
...  

Ceramide and diacylglycerol (DAG) may be involved in the early phase of insulin resistance but data are inconsistent in man. We evaluated if an increase in insulin sensitivity after endurance training was accompanied by changes in these lipids in skeletal muscle. Nineteen first-degree type 2 diabetes Offsprings (Offsprings) (age:33.1±1.4 yrs; BMI:26.4±0.4 kg/m2) and sixteen matched Controls (age:31.3±1.5 yrs; BMI:25.3±0.7 kg/m2) performed 10 weeks of endurance training three times a week at 70% of VO2max on a bicycle ergometer. Before and after the intervention a hyperinsulinemic-euglycemic clamp and VO2max test were performed and muscle biopsies obtained. Insulin sensitivity was significantly lower in Offsprings compared to control subjects (p<0.01) but improved in both groups after 10 weeks of endurance training (Off:17±6%; Con:12±9%,p<0.01). The content of muscle ceramide, DAG, and their subspecies were similar between groups and did not change in response to the endurance training except for an overall reduction in C22:0-Cer (p<0.05). Finally, the intervention induced an increase in AKT protein expression (Off:27±11%; Con:20±24%,p<0.05). This study showed no relation between insulin sensitivity and ceramide or DAG content suggesting that ceramide and DAG are not major players in the early phase of insulin resistance in human muscle.


2010 ◽  
Vol 13 (3) ◽  
pp. 378 ◽  
Author(s):  
Giuseppe Derosa ◽  
Pamela Maffioli ◽  
Ilaria Ferrari ◽  
Ilaria Palumbo ◽  
Sabrina Randazzo ◽  
...  

Purpose. Comparison of the effects of one year treatment with sibutramine compared to placebo on body weight, glycemic control, lipid profile, and insulin resistance parameters in type 2 diabetic patients. Methods. Two hundred and forty-six patients with uncontrolled type 2 diabetes mellitus in therapy with different oral hypoglycemic agents or insulin were enrolled in this study and randomised to take sibutramine 10 mg or placebo for one year. We evaluated at baseline, and after 3, 6, 9, and 12 months these parameters: body weight, body mass index (BMI), glycated hemoglobin (HbA1c), fasting plasma glucose (FPG), post-prandial plasma glucose (PPG), fasting plasma insulin (FPI), homeostasis model assessment insulin resistance index (HOMA-IR), total cholesterol (TC), low density lipoprotein-cholesterol (LDL-C), high density lipoprotein-cholesterol (HDL-C), triglycerides (Tg), retinol binding protein-4 (RBP-4), resistin, visfatin, and high sensitivity-C reactive protein (Hs-CRP). Results. We observed a faster improvement of HbA1c, FPG and PPG with sibutramine compared to the control group; furthermore we recorded a decrease of FPI, TC, LDL-C, body weight, and BMI in the sibutramine group, but not in the control group. A faster decrease of HOMA-IR, resistin, and RBP-4 was recorded with sibutramine compared to the control group. We observed a significant decrease of Hs-CRP in both groups. Conclusions. Sibutramine gave a faster improvement of glycemic control, and of insulin resistance parameters compared to placebo; furthermore sibutramine gave also an improvement of lipid profile, and body weight.


2006 ◽  
Vol 154 (2) ◽  
pp. 319-324 ◽  
Author(s):  
Irina Kowalska ◽  
Marek Strączkowski ◽  
Agnieszka Nikolajuk ◽  
Agnieszka Krukowska ◽  
Ida Kinalska ◽  
...  

Objective: There is growing evidence that adiponectin function is related to the pathogenesis of insulin resistance. Insulin resistance might be present even in lean subjects with a strong family history of type 2 diabetes. The aim of the study was to look for adiponectin’s role in the pathogenesis of insulin resistance in offspring of type 2 diabetic patients, and its relation to the activity of the tumor necrosis factor (TNF)-α system. Research design and methods: The study was carried out in 23 lean offspring of type 2 diabetic subjects and in 23 controls matched for age, sex and body mass index. The oral glucose tolerance test for glucose and insulin estimations and hyperinsulinemic, euglycemic clamp studies were performed in all patients. The plasma concentration of adiponectin, TNF-α, soluble TNF receptors 1 and 2 (sTNFR1, sTNFR2), HbA1c, total cholesterol, high-density lipoprotein (HDL)-cholesterol, low-density lipoprotein-cholesterol and triglycerides were estimated. Results: The insulin sensitivity index, normalized for fat-free mass (Mffm) and adiponectin concentrations were markedly decreased in offspring of type 2 diabetic subjects compared with the control group (P = 0.0046 and P = 0.00 058 respectively). TNF-α and sTNFR1 concentrations did not differ between the studied groups; however the concentration of sTNFR2 was markedly increased in the offspring of type 2 diabetic patients (P = 0.0002). Adiponectin concentration was positively correlated to the insulin sensitivity index (r = 0.34; P = 0.020) and to HDL-cholesterol (r = 0.29, P = 0.047) and was inversely related to sTNFR2 (r = −0.33, P = 0.027). Conclusions: The obtained results suggest that adiponectin could play a role in the pathogenesis of insulin resistance in lean offspring of type 2 diabetic subjects.


2018 ◽  
Vol 88 (1) ◽  
Author(s):  
Seyed Hamid Borsi ◽  
Homeira Rashidi ◽  
Maryam Shaabanpour ◽  
Hanieh Raji

Asthma is an inflammatory disease, which causes airflow limitation and increase insulin resistance. The present study was carried out in order to investigate insulin resistance and the effect of inhaled corticosteroid (ICS) on insulin sensitivity in asthmatic patients. A registered (IRCT201605247411N2) interventional, quasi-experimental trial was performed from 2014 to 2015 in Imam Khomeini hospital Ahvaz, Iran. Patients with mild to moderate asthma participated in this study. Spirometry, fasting blood sugar (FBS), blood sugar 2 hour post prandial (BS2HPP), HbA1C, low density lipoprotein (LDL), high density lipoprotein (HDL), Insulin Level, and C reactive protein (CRP) were measured. Then Homeostatic Model Assessment-Insulin Resistance [HOMA-IR] Index calculated. Data were analyzed using paired t-test and McNemar’s test using SPSS 20.0 Software. The study consisted of 35 non-diabetic patients suffering from asthma (20 men and 15 women) with a mean age of 36.6 ±12.3 years. Inhaled corticosteroid had a significant effect on spirometric parameters, but it had no significant effect on other variables. At baseline, mean HbA1C, insulin level and HOMA-IR were 5.5%, 10.9 mIU/L and 2.7 respectively. None of these values changed significantly after treatment with inhaled corticosteroid for two months. The results indicated that there is no relationship between ICS and increased insulin resistance in asthmatic patients.


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