scholarly journals Metformin Improves Skeletal Muscle Microvascular Insulin Resistance in Metabolic Syndrome

2021 ◽  
Author(s):  
Linda A Jahn ◽  
Lee M Hartline ◽  
Zhenqi Liu ◽  
Eugene J Barrett
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Pulse Wave ◽  
Metabolic Effects ◽  
Large Artery ◽  
Metformin Treatment ◽  
Radial Pulse ◽  
Before And After

Aims: Microvascular insulin resistance is present in metabolic syndrome and may contribute to increased cardiovascular disease risk and the impaired metabolic response to insulin observed. Metformin improves metabolic insulin resistance in humans. Its effects on macro and microvascular insulin resistance has not been defined. Methods: Eleven non-diabetic, metabolic syndrome subjects were studied four times (before and after 12 weeks treatment with placebo or metformin) using a crossover design, with an eight week washout interval between treatments. On each occasion, we measured three indices of large artery function (pulse wave velocity-PWV, radial pulse wave separation analysis (PWSA), brachial artery endothelial function (flow-mediated dilation-FMD) as well as muscle microvascular perfusion (contrast-enhanced ultrasound-CEU) before and 120 min into a 150 min, 1 mU/min/kg euglycemic insulin clamp. RESULTS: Metformin decreased body mass index (BMI), fat weight, and % body fat (P<0.05, each), placebo had no effect. Metformin (not placebo) improved metabolic insulin sensitivity, (clamp glucose infusion rate, P<0.01). PWV, and FMD after insulin were unaffected by metformin treatment. PWSA improved with insulin only after metformin P<0.01). Insulin decreased muscle microvascular blood volume measured by contrast ultrasound both before and after placebo and before metformin (P<0.02 for each) but not after metformin. CONCLUSIONS: Short-term metformin treatment improves both metabolic and muscle microvascular response to insulin. Metformin's effect on microvascular insulin responsiveness may contribute to its beneficial metabolic effects. Metformin did not improve aortic stiffness or brachial artery endothelial function, but enhaced radial pulse wave properties consistent with relaxation of smaller arterioles.

scholarly journals Beneficial Effects of Akkermansia muciniphila Are Not Associated with Major Changes in the Circulating Endocannabinoidome but Linked to Higher Mono-Palmitoyl-Glycerol Levels as New PPARα Agonists

Cells ◽  
2021 ◽  
Vol 10 (1) ◽  
pp. 185
Author(s):  
Clara Depommier ◽  
Rosa Maria Vitale ◽  
Fabio Arturo Iannotti ◽  
Cristoforo Silvestri ◽  
Nicolas Flamand ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Univariate Analysis ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Akkermansia Muciniphila ◽  
Beneficial Effects ◽  
Daily Ingestion ◽  
Before And After ◽  
Palmitoyl Glycerol

Akkermansia muciniphila is considered as one of the next-generation beneficial bacteria in the context of obesity and associated metabolic disorders. Although a first proof-of-concept of its beneficial effects has been established in the context of metabolic syndrome in humans, mechanisms are not yet fully understood. This study aimed at deciphering whether the bacterium exerts its beneficial properties through the modulation of the endocannabinoidome (eCBome). Circulating levels of 25 endogenous endocannabinoid-related lipids were quantified by liquid chromatography with tandem mass spectrometry (LC-MS/MS) in the plasma of overweight or obese individuals before and after a 3 months intervention consisting of the daily ingestion of either alive or pasteurized A. muciniphila. Results from multivariate analyses suggested that the beneficial effects of A. muciniphila were not linked to an overall modification of the eCBome. However, subsequent univariate analysis showed that the decrease in 1-Palmitoyl-glycerol (1-PG) and 2-Palmitoyl-glycerol (2-PG), two eCBome lipids, observed in the placebo group was significantly counteracted by the alive bacterium, and to a lower extent by the pasteurized form. We also discovered that 1- and 2-PG are endogenous activators of peroxisome proliferator-activated receptor alpha (PPARα). We hypothesize that PPARα activation by mono-palmitoyl-glycerols may underlie part of the beneficial metabolic effects induced by A. muciniphila in human metabolic syndrome.

scholarly journals Insulin resistance in PLHIV on HAART and HAART naïve PLHIV: A Cross-sectional Study

2020 ◽  
pp. 1-3
Author(s):  
Prabir Kumar Ganguly ◽  
Niladri Das
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Antiretroviral Therapy ◽  
Cross Sectional Study ◽  
Metabolic Effects ◽  
People Living With Hiv ◽  
Model Assessment ◽  
Sectional Study ◽  
Cross Sectional ◽  
Group I

ABSTRACT HAART (Highly active antiretroviral therapy) has transformed a fatal disease to a chronic, manageable disease. But long term toxicities are emerging after prolonged exposure to antiretroviral therapy(ART). Adverse metabolic effects like dyslipidemia, increased blood pressure, and insulin resistance(IR) have been attributed to HAART. Therefore, the use of HAART raises concerns regarding metabolic disorders and cardiovascular risk in HIV(Human immunodeficiency virus) infected patients. Objective: To determine the prevalence of insulin resistance in a cohort of HIV infected patients on HAART as compared to HAART naïve PLHIV(People living with HIV) Methods: A cross sectional study includes 53 subjects, out of which 26 were PLHIV on ART –Group I, 27 were ART naïve PLHIV-Group II was conducted. Insulin resistance was determined by homeostasis model assessment (HOMA-IR) mathematical model. Statistical analysis was performed to assess the association between demographic, clinical characteristics, laboratory results and insulin resistance. Results: 69.5 % PLHIV on HAART showed IR, as compared to 37 % of ART naïve PLHIV (p= 0.01). MetS(Metabolic Syndrome) was found in 53.8% among PLHIV on ART , compared to 11.1% among ART naïve PLHIV(p= 0.001) .In the multivariate analysis, presence of metabolic syndrome was found to be directly associated with insulin resistance.

scholarly journals Exercise Induced Adipokine Changes and the Metabolic Syndrome

2014 ◽  
Vol 2014 ◽  
pp. 1-16 ◽  
Author(s):  
Saeid Golbidi ◽  
Ismail Laher
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
The Body ◽  
Beneficial Effects ◽  
The Metabolic Syndrome ◽  
Before And After ◽  
Inflammatory State ◽  
Exercise Induced

The lack of adequate physical activity and obesity created a worldwide pandemic. Obesity is characterized by the deposition of adipose tissue in various parts of the body; it is now evident that adipose tissue also acts as an endocrine organ capable of secreting many cytokines that are though to be involved in the pathophysiology of obesity, insulin resistance, and metabolic syndrome. Adipokines, or adipose tissue-derived proteins, play a pivotal role in this scenario. Increased secretion of proinflammatory adipokines leads to a chronic inflammatory state that is accompanied by insulin resistance and glucose intolerance. Lifestyle change in terms of increased physical activity and exercise is the best nonpharmacological treatment for obesity since these can reduce insulin resistance, counteract the inflammatory state, and improve the lipid profile. There is growing evidence that exercise exerts its beneficial effects partly through alterations in the adipokine profile; that is, exercise increases secretion of anti-inflammatory adipokines and reduces proinflammatory cytokines. In this paper we briefly describe the pathophysiologic role of four important adipokines (adiponectin, leptin, TNF-α, and IL-6) in the metabolic syndrome and review some of the clinical trials that monitored these adipokines as a clinical outcome before and after exercise.

Combined aerobic and resistance training and vascular function: effect of aerobic exercise before and after resistance training

2007 ◽  
Vol 103 (5) ◽  
pp. 1655-1661 ◽  
Author(s):  
Takanobu Okamoto ◽  
Mitsuhiko Masuhara ◽  
Komei Ikuta
Keyword(s):  
Resistance Training ◽  
Aerobic Exercise ◽  
Brachial Artery ◽  
Vascular Function ◽  
Pulse Wave ◽  
Aerobic Exercise Training ◽  
Flow Mediated Dilation ◽  
Brachial Artery Diameter ◽  
Combined Training ◽  
Before And After

Aerobic exercise training combined with resistance training (RT) might prevent the deterioration of vascular function. However, how aerobic exercise performed before or after a bout of RT affects vascular function is unknown. The present study investigates the effect of aerobic exercise before and after RT on vascular function. Thirty-three young, healthy subjects were randomly assigned to groups that ran before RT (BRT: 4 male, 7 female), ran after RT (ART: 4 male, 7 female), or remained sedentary (SED: 3 male, 8 female). The BRT and ART groups performed RT at 80% of one repetition maximum and ran at 60% of the targeted heart rate twice each week for 8 wk. Both brachial-ankle pulse wave velocity (baPWV) and flow-mediated dilation (FMD) after combined training in the BRT group did not change from baseline. In contrast, baPWV after combined training in the ART group reduced from baseline (from 1,025 ± 43 to 910 ± 33 cm/s, P < 0.01). Moreover, brachial artery FMD after combined training in the ART group increased from baseline (from 7.3 ± 0.8 to 9.6 ± 0.8%, P < 0.01). Brachial artery diameter, mean blood velocity, and blood flow in the BRT and ART groups after combined training increased from baseline ( P < 0.05, P < 0.01, and P < 0.001, respectively). These values returned to the baseline during the detraining period. These values did not change in the SED group. These results suggest that although vascular function is not improved by aerobic exercise before RT, performing aerobic exercise thereafter can prevent the deteriorating of vascular function.

scholarly journals Galantamine alleviates oxidative stress alongside anti-inflammatory and cardio-metabolic effects in subjects with the metabolic syndrome in a randomized trial

2020 ◽  
Author(s):  
Carine Teles Sangaleti ◽  
Keyla Yukari Katayama ◽  
Kátia De Angelis ◽  
Tércio Lemos de Moraes ◽  
Amanda Aparecida Araújo ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Autonomic Regulation ◽  
Metabolic Effects ◽  
Antioxidant Enzyme Activities ◽  
Low Grade ◽  
The Metabolic Syndrome ◽  
Inflammatory State ◽  
Anti Inflammatory

AbstractBackgroundThe metabolic syndrome (MetS) is an obesity-driven disorder with pandemic proportions and limited treatment options. Oxidative stress, low-grade inflammation and altered autonomic regulation, are important components of MetS pathophysiology. We recently reported that galantamine, an acetylcholinesterase inhibitor and an FDA-approved drug (for Alzheimer’s disease) alleviates the inflammatory state in MetS subjects. Here we examined the effects of galantamine on oxidative stress in parallel with inflammatory and cardio-metabolic parameters in subjects with MetS.MethodsThe effects of galantamine treatment, 8 mg daily for 4 weeks, followed by 16 mg daily for 8 weeks or placebo were studied in randomly assigned subjects with MetS (n=22 per group) of both genders. Oxidative stress, including superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase activities, lipid and protein peroxidation, and nitrite levels were analyzed before and at the end of the treatment. In addition, plasma cytokine and adipokine levels, insulin resistance (HOMA-IR) and other relevant cardio-metabolic indices were analyzed. Autonomic regulation was also examined by heart rate variability (HRV) before treatment, and at every 4 weeks of treatment.ResultsGalantamine treatment significantly increased antioxidant enzyme activities, including SOD (+1.65 USOD/mg protein, [95% CI 0.39 to 2.92], P=0.004) and CAT (+0.93 nmol/mg, [95% CI 0.34 to 1.51], P=0.011), decreased lipid peroxidation (thiobarbituric acid reactive substances, -5.45 pmol/mg, [95% CI -10.97 to 0.067], P=0.053) and systemic nitrite levels (-0.05 nit/mg protein, [95% CI -0.21 to 0.10], P=0.038) compared with placebo. In addition, galantamine significantly alleviated the inflammatory state and insulin resistance, and decreased the low frequency/high frequency ratio of HRV, following 8 and 12 weeks of drug treatment.ConclusionLow-dose galantamine alleviates oxidative stress, alongside beneficial anti-inflammatory, and metabolic effects, and modulates autonomic regulation in subjects with MetS. These findings are of considerable interest for further studies with galantamine to ameliorate MetS pathophysiology.

scholarly journals Reduced Levels of Circulating 7α-Hydroxy-Dehydroepiandrosterone in Treated Adolescent Obese Patients

2014 ◽  
pp. 95-101
Author(s):  
L. MÁČOVÁ ◽  
M. BIČÍKOVÁ ◽  
H. ZAMRAZILOVÁ ◽  
M. HILL ◽  
H. KAZIHNITKOVÁ ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Hydroxysteroid Dehydrogenase ◽  
Obese Patients ◽  
Significant Difference ◽  
Before And After ◽  
Reductive Treatment ◽  
Circulating Levels

Elevated levels of glucocorticoids lead to the development of obesity and metabolic syndrome. Local glucocorticoid levels are regulated through the enzyme 11β-hydroxysteroid dehydrogenase 1 (11β-HSD 1), an enzyme that regenerates active cortisol from inert cortisone. Increased expression of 11β-HSD 1 in adipose tissue promotes higher body mass index (BMI), insulin resistance, hypertension, and dyslipidemia. Human 11β-HSD 1 is also responsible for inter-conversion of 7-hydroxylate metabolites of dehydroepiandrosterone (7-OH-DHEA) to their 7-oxo-form. To better understanding the mechanism of the action, we focused on 7-OH- and 7-oxo-DHEA, and their circulating levels during the reductive treatment in adolescent obese patients. We determined plasma levels of 7α-OH-DHEA, 7β-OH-DHEA, and 7-oxo-DHEA in 55 adolescent patients aged 13.04-15.67 years, BMI greater than 90th percentile. Samples were collected before and after one month of reductive therapy. Circulating levels of 7α-OH-DHEA decreased during the reductive therapy from 1.727 (1.614; 1.854, transformed mean with 95 % confidence interval) to 1.530 nmol/l (1.435; 1.637, p<0.05) in girls and from 1.704 (1.583; 1.842) to 1.540 nmol/l (1.435; 1.659, p<0.05) in boys. With regard to the level of 7-oxo-DHEA, a significant reduction from 1.132 (1.044; 1.231) to 0.918 nmol/l (0.844; 1.000, p<0.05) was found after the treatment, but only in boys. No significant difference in 7β-OH-DHEA levels was observed. In conclusions, diminished levels of 7α-OH-DHEA indicate its possible effect on activity of 11β-HSD 1. Further studies are necessary to clarify whether competitive substrates for 11β-HSD 1 such as 7α-OH-DHEA could inhibit production of glucocorticoids and may be involved in metabolic processes leading to reduction of obesity.

Retrograde shear rate in formerly preeclamptic and healthy women before and after exercise training: relationship with endothelial function

2014 ◽  
Vol 307 (3) ◽  
pp. H418-H425 ◽  
Author(s):  
Ralph R. Scholten ◽  
Marc E. A. Spaanderman ◽  
Daniel J. Green ◽  
Maria T. E. Hopman ◽  
Dick H. J. Thijssen
Keyword(s):  
Shear Rate ◽  
Exercise Training ◽  
Endothelial Function ◽  
Brachial Artery ◽  
Low Frequency ◽  
Power Spectral Analysis ◽  
Aerobic Exercise Training ◽  
Before And After ◽  
The Impact ◽  
Retrograde Shear

Blood flow patterns in conduit arteries characterized by high levels of retrograde shear stress can be detrimental for vascular health. In this study we examined whether retrograde shear rate and endothelial function are related in healthy and formerly preeclamptic (PE) women and whether this relationship is altered by exercise training. Formerly PE women (32 ± 4 yr, n = 20) and controls (32 ± 4 yr, n = 20), all 6–12 mo postpartum, performed 12-wk aerobic exercise training. We measured brachial artery shear rate (SR) and endothelial function by flow-mediated dilation (FMD, echo-Doppler). We additionally performed power spectral analysis of heart rate variability and calculated low-frequency/high-frequency (LF/HF) ratio. Antegrade SR was not different between groups, while retrograde SR was significantly higher and FMD% lower in PE women compared with controls (both P < 0.05). Retrograde shear correlated strongly with FMD% in PE women and controls ( P < 0.05). LF/HF ratio inversely correlated with brachial artery retrograde SR and FMD% (both P < 0.05) in PE women and controls. Exercise training reduced retrograde shear, improved FMD%, and reduced LF/HF ratios similarly in both groups (all P < 0.05). Training-induced changes in retrograde SR correlated with changes in FMD% and LF/HF ratio. A higher brachial artery retrograde SR relates to lower brachial artery endothelial function, in both controls and formerly PE women. Exercise training improves retrograde SR, while the magnitude of this change correlated strongly with improvements in FMD and reductions in LF/HF ratio. Therefore, the impact of PE and exercise training on endothelial health may, at least partly, be related to retrograde shear rate.

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