scholarly journals Adipose Depots, Not Disease-related Factors, Account for Skeletal Muscle Insulin Sensitivity in Established and Treated Rheumatoid Arthritis

2014 ◽  
Vol 41 (10) ◽  
pp. 1974-1979 ◽  
Author(s):  
Hiba AbouAssi ◽  
K. Noelle Tune ◽  
Brian Gilmore ◽  
Lori A. Bateman ◽  
Gary McDaniel ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Physical Activity ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Insulin Sensitivity ◽  
Systemic Inflammation ◽  
Geometric Mean ◽  
Related Factors ◽  
Intravenous Glucose ◽  
Skeletal Muscle Insulin Sensitivity

Objective.In prior reports, individuals with rheumatoid arthritis (RA) exhibited increased insulin resistance. However, those studies were limited by either suboptimal assessment methods for insulin sensitivity or a failure to account for important determinants such as adiposity and lack of physical activity. Our objectives were to carefully assess, compare, and determine predictors of skeletal muscle insulin sensitivity in RA, accounting for adiposity and physical activity.Methods.Thirty-nine individuals with established (seropositive or erosions) and treated RA and 39 controls matched for age, sex, race, body mass index, and physical activity underwent a frequently sampled intravenous glucose tolerance test to determine insulin sensitivity. Inflammation, body composition, and physical activity were assessed with systemic cytokine measurements, computed tomography scans, and accelerometry, respectively. Exclusions were diabetes, cardiovascular disease, medication changes within 3 months, and prednisone use over 5 mg/day. This investigation was powered to detect a clinically significant, moderate effect size for insulin sensitivity difference.Results.Despite elevated systemic inflammation [interleukin (IL)-6, IL-18, tumor necrosis factor-α; p < 0.05 for all], persons with RA were not less insulin sensitive [SIgeometric mean (SD): RA 4.0 (2.4) vs control 4.9 (2.1)*10−5min−1/(pmol/l); p = 0.39]. Except for visceral adiposity being slightly greater in controls (p = 0.03), there were no differences in body composition or physical activity. Lower insulin sensitivity was independently associated with increased abdominal and thigh adiposity, but not with cytokines, disease activity, duration, disability, or disease-modifying medication use.Conclusion.In established and treated RA, traditional risk factors, specifically excess adiposity, play more of a role in predicting skeletal muscle insulin sensitivity than do systemic inflammation or other disease-related factors.

scholarly journals Influence of Exercise Training on Skeletal Muscle Insulin Resistance in Aging: Spotlight on Muscle Ceramides

2020 ◽  
Vol 21 (4) ◽  
pp. 1514 ◽  
Author(s):  
Paul T. Reidy ◽  
Ziad S. Mahmassani ◽  
Alec I. McKenzie ◽  
Jonathan J. Petrocelli ◽  
Scott A. Summers ◽  
...  
Keyword(s):  
Physical Activity ◽  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Contraction ◽  
Contractile Activity ◽  
Skeletal Muscle Insulin Resistance ◽  
Ceramide Content ◽  
Subcellular Compartmentalization ◽  
Skeletal Muscle Insulin Sensitivity

Intramuscular lipid accumulation has been associated with insulin resistance (IR), aging, diabetes, dyslipidemia, and obesity. A substantial body of evidence has implicated ceramides, a sphingolipid intermediate, as potent antagonists of insulin action that drive insulin resistance. Indeed, genetic mouse studies that lower ceramides are potently insulin sensitizing. Surprisingly less is known about how physical activity (skeletal muscle contraction) regulates ceramides, especially in light that muscle contraction regulates insulin sensitivity. The purpose of this review is to critically evaluate studies (rodent and human) concerning the relationship between skeletal muscle ceramides and IR in response to increased physical activity. Our review of the literature indicates that chronic exercise reduces ceramide levels in individuals with obesity, diabetes, or hyperlipidemia. However, metabolically healthy individuals engaged in increased physical activity can improve insulin sensitivity independent of changes in skeletal muscle ceramide content. Herein we discuss these studies and provide context regarding the technical limitations (e.g., difficulty assessing the myriad ceramide species, the challenge of obtaining information on subcellular compartmentalization, and the paucity of flux measurements) and a lack of mechanistic studies that prevent a more sophisticated assessment of the ceramide pathway during increased contractile activity that lead to divergences in skeletal muscle insulin sensitivity.

scholarly journals Body composition is distinctly altered in Turner syndrome: relations to glucose metabolism, circulating adipokines, and endothelial adhesion molecules

2006 ◽  
Vol 155 (4) ◽  
pp. 583-592 ◽  
Author(s):  
Claus Højbjerg Gravholt ◽  
Britta Eilersen Hjerrild ◽  
Leif Mosekilde ◽  
Troels Krarup Hansen ◽  
Lars Melholt Rasmussen ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Insulin Sensitivity ◽  
Muscle Mass ◽  
Regression Models ◽  
Skeletal Muscle Mass ◽  
Cell Adhesion Molecule ◽  
Linear Regression Models ◽  
Multiple Linear Regression Models

Background: Body composition in Turner syndrome (TS) is altered with final height of TS decreased; anthropometry and bone mass distinctly changed. Aim: To describe total and regional distribution of fat and muscle mass in TS and the relation to measures of glucose metabolism, sex hormones, IGFs, and markers of inflammation and vascular function. Material and methods: Fifty-four women with TS (mean age, 42.5 ± 9.7 years) and an age-matched group of controls (n = 55) were examined by dual-energy X-ray absorptiometry scans with determination of regional body composition and estimation of visceral fat and skeletal muscle mass. We determined maximal oxygen uptake and assessed physical activity using a questionnaire. We measured serum adiponectin, ghrelin, IGF-I, IGF-binding protein-3 (IGFBP-3), estradiol, testosterone, sex hormone-binding globulin (SHBG), insulin, glucose, cytokines, vascular cell adhesion molecule-I, and intercellular cell adhesion molecule-I. Insulin sensitivity was estimated. Multiple linear regression models were used to examine the relationships between variables. Results: TS had lower total lean body mass (LBM), while body mass index (BMI) and total fat mass (FM) were increased. We found increased visceral FM, and decreased trunk LBM, appendicular LBM, and skeletal muscle mass. VO2max and physical activity were significantly lower in TS, as were most hormone levels, except increased leptin. In multiple linear regression models, status (i.e. TS or control) was a consistent contributing variable. Conclusion: Profound changes are present in body composition in TS, with increased FM, and decreased skeletal muscle mass. Circulating hormones, VO2max, and insulin sensitivity influence body composition. The accumulation of visceral fat would predict a higher risk of development of the insulin resistance syndrome.

scholarly journals SAT0110 SARCOPENIA IN PATIENTS WITH RHEUMATOID ARTHRITIS ON THE TREATMENT WITH BIOLOGIC DISEASE MODIFYING ANTI-RHEUMATIC DRUGS

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 989.1-989
Author(s):  
E. Hasegawa ◽  
S. Ito ◽  
Y. Kurosawa ◽  
S. Taniguchi ◽  
D. Kobayashi ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
Physical Activity ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Nutritional Status ◽  
Disease Activity ◽  
Muscle Mass ◽  
Nutrition Status ◽  
Physical Ability ◽  
Disease Modifying

Background:Sarcopenia is characterized by loss of muscle mass and strength, which lead to lower physical ability, less quality of life (QoL), frailty and mortality. Rheumatoid arthritis (RA) is considered to be one of the causes of sarcopenia.Objectives:To clarify the effectiveness of biologic disease modifying anti-rheumatic drugs (bDMARDs) on sarcopenia, including physical ability, body composition and nutritional status.Methods:This is a prospective cohort study including consecutive 48 patients (male 11, female 37, age 64.2±15.1) with RA who started bDMARDs in Niigata Rheumatic Center. Diagnosis of sarcopenia was according to the diagnostic algorithm of European Working Group on Sarcopenia in Older People (EWGSOP). We monitored disease activity of RA, physical ability, body composition, nutritional status and QoL at baseline, 6 months and at 12 months. Disease activity was measured by disease activity score-28 joint count based on erythrocyte sedimentation rate (DAS28-ESR), clinical disease activity index (CDAI). Physical activity was measured by Health Assessment Questionnaire (HAQ), 10m walking test (10MWT). Nutritional status was measured by controlling nutrition status (CONUT) score, and prognostic nutritional index (PNI). Overall QoL was measured by EuroQol 5 dimentions (EQ5D).Results:Among 48 patients who started bDMARDs, 21 patients were classified as having sarcopenia. The bDMARDs used were adalimumab in 10 cases, certolizumab pegol in 9 cases, abatacept in 9 cases, golimumab in 7 cases, tocilizumab in 5 cases, infliximab in 5 cases and etanercept in 3 cases. DAS28-ESR (4.7±1.4 vs. 2.7±1.0, p < 0.001) and CDAI (18.4±9.4 vs. 7.4±5.5, p<0.001) were significantly decreased by 12 months of bDMARDs therapy. Physical activity was significantly ameliorated after 12 months of bDMARDs; HAQ(1.1±0.9 vs. 0.6±0.8, p<0.001), 10MWT(1.5±0.7 m/s vs. 1.7±0.6, p=0.002). EQ-5D was also ameliorated(0.63±0.15 vs. 0.74±0.19, p=0.0002). As for body composition analysis, there were significant increase in body weight(54.6±12.4 kg vs. 55.8±13.6, p=0.006), but there was no significant increase in skeletal muscle mass index(5.9±1.1 kg/m2 vs. 5.9±1.1, p=0.229). Among 21 patients who were classified as sarcopenia when starting bDMARDs, the number of patients having sarcopenia significantly decreased after 12 months of bDMARDs (100% vs. 52.3%, p=0.0005) and skeletal muscle index of these patients were significantly increased (5.1±0.5 kg/m2 vs. 5.3±0.7, p=0.046).Conclusion:Twelve months of bDMARDs therapy significantly ameliorated disease activity, nutritional status and physical activity. In RA patients with sarcopenia, bDMARDs significantly increased skeletal muscle and may be effective for treatment of sacrcopenia.Disclosure of Interests: :Eriko Hasegawa: None declared, Satoshi Ito Speakers bureau: Abbvie,Eisai, Yoichi Kurosawa: None declared, Shinji Taniguchi: None declared, Daisuke Kobayashi: None declared, Asami Abe: None declared, Hiroshi Otani: None declared, Kiyoshi Nakazono: None declared, Akira Murasawa: None declared, Ichiei Narita: None declared, Hajime Ishikawa: None declared

Effect of training on insulin binding to rat skeletal muscle sarcolemmal vesicles

1986 ◽  
Vol 250 (5) ◽  
pp. E570-E575
Author(s):  
G. K. Grimditch ◽  
R. J. Barnard ◽  
S. A. Kaplan ◽  
E. Sternlicht
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Exercise Training ◽  
Insulin Binding ◽  
Whole Body ◽  
Rat Skeletal Muscle ◽  
Binding Studies ◽  
Muscle Enzyme ◽  
Intravenous Glucose ◽  
High Affinity

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.

scholarly journals THU0358 NEGATIVE CHANGES OF BODY COMPOSITION IN MYOSITIS PATIENTS AND THEIR ASSOCIATION WITH DISEASE SPECIFIC CHARACTERISTICS, PHYSICAL ACTIVITY AND NUTRITIONAL STATUS.

2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 410.3-410
Author(s):  
S. Oreska ◽  
M. Špiritović ◽  
P. Česák ◽  
O. Marecek ◽  
H. Štorkánová ◽  
...  
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Body Composition ◽  
Lipid Metabolism ◽  
Nutritional Status ◽  
Disease Activity ◽  
Inflammatory Cytokines ◽  
Disease Duration ◽  
Serum Levels ◽  
Muscle Involvement

Background:Skeletal muscle, pulmonary and articular involvement in idiopathic inflammatory myopathies (IIM) limit the mobility/self-sufficiency of patients, and can have a negative impact on body composition.Objectives:The aim was to assess body composition and physical activity of IIM patients and healthy controls (HC) and the association with selected inflammatory cytokines/chemokines and laboratory markers of nutrition and lipid metabolism.Methods:54 patients with IIM (45 females; mean age 57.7; disease duration 5.8 years; polymyositis (PM, 22) / dermatomyositis (DM, 25) / necrotizing myopathy (IMNM, 7)) and 54 age-/sex-matched HC (45 females, mean age 57.7) without rheumatic/tumor diseases were included. PM/DM patients fulfilled Bohan/Peter criteria for PM/DM. We assessed body composition (densitometry: iDXA Lunar, bioelectric impedance: BIA2000-M), physical activity (Human Activity Profile, HAP questionnaire), serum levels of 27 cytokines/chemokines (commercial multiplex ELISA kit, Bio-Rad Laboratories) and serum levels of selected parameters of nutrition and lipidogram. Disease activity (MITAX and MYOACT activity score) and muscle involvement (manual muscle testing, MMT-8, and functional index 2, FI2) were evaluated. Data are presented as mean±SD.Results:Compared to HC, patients with IIM had a trend towards significantly increased body fat % (BF%; iDXA: 39.9±7.1 vs. 42.4±7.1 %, p=0.077), but significantly decreased lean body mass (LBM; iDXA: 45.6±8.1 vs. 40.6±7.2 kg, p=0.001; BIA: 52.6±8.8 vs. 48.7±9.0 kg, p=0.023), increased extracellular mass/body cell mass (ECM/BCM) ratio (1.06±0.15 vs. 1.44±0.42, p<0.001), reflecting deteriorated nutritional status and predisposition for physical activity, and significantly lower bone mineral density (BMD: 1.2±0.1 vs. 1.1±0.1 g/cm2, p<0.001). Disease duration negatively correlated with BMD and LBM-BIA. Disease activity (MITAX, MYOACT) positively correlated with LBM (by BIA and DXA), similarly as with basal metabolic rate (BMR), and fat free mass (FFM). CRP was positively associated with BF% (BIA and DXA). Higher BF%-DEXA was associated with worse physical endurance (FI2) and worse ability to perform physical activity (HAP). MMT-8 score negatively correlated with ECM/BCM ratio. Serum levels of several inflammatory cytokines/chemokines (specifically IL-1ra, MCP, IL-10) and markers of nutrition (specifically albumin, C3-, C4-complement, cholinesterase, amylase, insulin and C-peptide, vitamin-D, orosomucoid), and lipid metabolism (specifically triglycerides, high-density lipoprotein, apolipoprotein A and B, atherogenic index of plasma) were significantly associated with alterations of body composition in IIM patients. (p<0.05 for all correlations)Conclusion:Compared to healthy age-/sex-matched individuals we found significant negative changes in body composition of our IIM patients associated with their disease activity and duration, inflammatory status, skeletal muscle involvement, and physical activity. These data could reflect their impaired nutritional status and predispositions for physical exercise, aerobic fitness and performance.Serum levels of certain inflammatory cytokines/chemokines and markers of nutrition and lipid metabolism were associated with alterations of body composition in IIM patients. This might further support the role of systemic inflammation and nutritional status on the negative changes in body composition of IIM patients.Acknowledgments:Supported by AZV NV18-01-00161A, MHCR 023728, SVV 260373 and GAUK 312218Disclosure of Interests:Sabina Oreska: None declared, Maja Špiritović: None declared, Petr Česák: None declared, Ondrej Marecek: None declared, Hana Štorkánová: None declared, Barbora Heřmánková: None declared, Kateřina Kubinova: None declared, Martin Klein: None declared, Lucia Vernerová: None declared, Olga Růžičková: None declared, Karel Pavelka Consultant of: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Speakers bureau: Abbvie, MSD, BMS, Egis, Roche, UCB, Medac, Pfizer, Biogen, Ladislav Šenolt: None declared, Heřman Mann: None declared, Jiří Vencovský: None declared, Michal Tomčík: None declared

Interactions between insulin and exercise

2021 ◽  
Vol 478 (21) ◽  
pp. 3827-3846
Author(s):  
Erik A. Richter ◽  
Lykke Sylow ◽  
Mark Hargreaves
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Regular Exercise ◽  
Fuel Storage ◽  
Storage Effects ◽  
Glucose Storage ◽  
Glycogen Stores

The interaction between insulin and exercise is an example of balancing and modifying the effects of two opposing metabolic regulatory forces under varying conditions. While insulin is secreted after food intake and is the primary hormone increasing glucose storage as glycogen and fatty acid storage as triglycerides, exercise is a condition where fuel stores need to be mobilized and oxidized. Thus, during physical activity the fuel storage effects of insulin need to be suppressed. This is done primarily by inhibiting insulin secretion during exercise as well as activating local and systemic fuel mobilizing processes. In contrast, following exercise there is a need for refilling the fuel depots mobilized during exercise, particularly the glycogen stores in muscle. This process is facilitated by an increase in insulin sensitivity of the muscles previously engaged in physical activity which directs glucose to glycogen resynthesis. In physically trained individuals, insulin sensitivity is also higher than in untrained individuals due to adaptations in the vasculature, skeletal muscle and adipose tissue. In this paper, we review the interactions between insulin and exercise during and after exercise, as well as the effects of regular exercise training on insulin action.

scholarly journals Dual X-ray absorptiometry whole body composition of adipose tissue in rheumatoid arthritis

2015 ◽  
Vol 53 (3) ◽  
pp. 237-247
Author(s):  
C. Popescu ◽  
Violeta Bojincă ◽  
Daniela Opriş ◽  
Ruxandra Ionescu
Keyword(s):  
Rheumatoid Arthritis ◽  
Physical Activity ◽  
Body Composition ◽  
Adipose Tissue ◽  
Disease Duration ◽  
Whole Body ◽  
Glucocorticoid Treatment ◽  
X Ray ◽  
Body Adiposity ◽  
Postmenopausal Female

Abstract Aim. Rheumatoid arthritis (RA) may influence not only abdominal fat, but also whole body adiposity, since it is associated with chronic inflammation and disability. The study aims to evaluate the whole body adiposity of RA patients and to assess potential influences of disease specific measures. Methods. The study was designed to include Caucasian postmenopausal female RA patients and age-matched postmenopausal female controls. Each subject underwent on the same day clinical examination, laboratory tests, whole body dual X-ray absorptiometry (DXA) composition and physical activity estimation using a self-administered questionnaire. Results. A total of 107 RA women and 104 matched controls were included. Compared to controls, the RA group had less physical activity and a higher prevalence of normal weight obesity. Overfat RA women had a significantly higher toll of inflammation, disease activity, glucocorticoid treatment and sedentary behavior. RA women with inflammation, glucocorticoid treatment and higher disease activity class had higher whole body and trunk adipose tissue indices and higher prevalence of overfat status. Glucocorticoid treatment, inflammation, disease duration and severity correlated with whole body adipose tissue and significantly predicted high adiposity content and overfat phenotypes. Conclusions. RA disease duration and severity are associated with higher whole body and regional adiposity. Low-dose glucocorticoid treatment seems to contribute to adiposity gain and redistribution. Clinicians may need to assess body composition and physical activity in RA patients in order to fully manage cardiovascular outcomes and quality of life.

scholarly journals Hepatokine ERAP1 impairs skeletal muscle insulin sensitivity via ADRB2/PKA pathway

2020 ◽  
Author(s):  
Feifan Guo ◽  
Yuguo Niu ◽  
Haizhou Jiang ◽  
Hanrui Yin ◽  
Fenfen Wang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Neutralizing Antibodies ◽  
Leptin Receptor ◽  
Whole Body ◽  
C2c12 Myotubes ◽  
Insulin Resistant ◽  
Skeletal Muscle Insulin Sensitivity ◽  
Pka Pathway

Abstract The current study aimed to investigate the role of endoplasmic reticulum aminopeptidase 1 (ERAP1), a novel hepatokine, in whole-body glucose metabolism. Here, we found that hepatic ERAP1 levels were increased in insulin-resistant leptin-receptor-mutated (db/db) and high-fat diet (HFD)-fed mice. Consistently, hepatic ERAP1 overexpression attenuated skeletal muscle (SM) insulin sensitivity, whereas knockdown ameliorated SM insulin resistance. Furthermore, serum and hepatic ERAP1 levels were positively correlated, and recombinant mouse ERAP1 or conditioned medium with high ERAP1 content (CM-ERAP1) attenuated insulin signaling in C2C12 myotubes, and CM-ERAP1 or HFD-induced insulin resistance was blocked by ERAP1 neutralizing antibodies. Mechanistically, ERAP1 reduced ADRB2 expression and interrupted ADRB2-dependent signaling in C2C12 myotubes. Finally, ERAP1 inhibition via global knockout or the inhibitor thimerosal improved insulin sensitivity. Together, ERAP1 is a hepatokine that impairs SM and whole-body insulin sensitivity, and its inhibition might provide a therapeutic strategy for diabetes, particularly for those with SM insulin resistance.

Age-Related Decline of Skeletal Muscle Insulin Sensitivity in Rats: Effect of Sex and Muscle Type

2011 ◽  
Vol 14 (2) ◽  
pp. 153-161 ◽  
Author(s):  
Yolanda Gómez-Pérez ◽  
Magdalena Gianotti ◽  
Ana M. Proenza ◽  
Isabel Lladó
Keyword(s):  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Muscle Type ◽  
Age Related ◽  
Skeletal Muscle Insulin Sensitivity
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