Long-term treadmill training ameliorates endothelium-dependent vasorelaxation mediated by insulin and insulin-like growth factor-1 in hypertension

Dysfunction of insulin and insulin-like growth factor-1 (IGF-1) is associated with the pathophysiology of hypertension. The influence of long-term exercise on vascular dysfunction caused by hypertension remains unclear. We investigated whether long-term treadmill training improved insulin- and IGF-1-mediated vasorelaxation in hypertensive rats. Eight-week-old male spontaneously hypertensive rats (SHR) were randomly divided into sedentary and exercise (SHR-EX) groups. The SHR-EX group was trained on a treadmill for 60 min/day, 5 days/wk, for 8 wk. Wistar-Kyoto rats (WKY) were used as the normal control group. After training, aortic insulin- and IGF-1-mediated vasorelaxation was evaluated in organ baths. Additionally, the roles of phosphatidylinositol 3-kinase (PI3K), nitric oxide synthase (NOS), and aortic protein expression were examined in the three groups. Compared with sedentary SHR and WKY groups, insulin- and IGF-1-mediated vasorelaxation was significantly enhanced to a nearly normal level in the SHR-EX group. After endothelial denudation, blunted and comparable vasorelaxation was found among the three groups. Pretreatment with selective PI3K and NOS inhibitors attenuated insulin- and IGF-1-mediated vasorelaxation, and no significant difference was found among the three groups after the pretreatment. The aortic protein levels of the insulin receptor (IR), IGF-1 receptor (IGF-1R), insulin receptor substrate-1 (IRS-1), and endothelial NOS (eNOS) were also significantly increased in the SHR-EX group compared with the other two groups. These results suggested that treadmill training elicited the amelioration of endothelium-dependent insulin/IGF-1-mediated vasorelaxation partly via the increased activation of PI3K and NOS, as well as the enhancement of protein levels of IR, IGF-1R, IRS-1, and eNOS, in hypertension.

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Twelve-Week Protocatechuic Acid Administration Improves Insulin-Induced and Insulin-Like Growth Factor-1-Induced Vasorelaxation and Antioxidant Activities in Aging Spontaneously Hypertensive Rats

Nutrients ◽

10.3390/nu11030699 ◽

2019 ◽

Vol 11 (3) ◽

pp. 699 ◽

Cited By ~ 3

Author(s):

Kunanya Masodsai ◽

Yi-Yuan Lin ◽

Rungchai Chaunchaiyakul ◽

Chia-Ting Su ◽

Shin-Da Lee ◽

...

Keyword(s):

Growth Factor ◽

Spontaneously Hypertensive Rats ◽

Protocatechuic Acid ◽

Antioxidant Activities ◽

Vehicle Control ◽

Insulin Like Growth Factor ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Significant Difference ◽

Nos Inhibitors

Protocatechuic acid (PCA), a strong antioxidant, has been reported for its cardiovascular-protective effects. This study aimed to investigate the effects of PCA administration on vascular endothelial function, mediated by insulin and insulin-like growth factor-1 (IGF-1), and antioxidant activities in aging hypertension. Thirty-six-week-old male aging spontaneously hypertensive rats were randomly divided into vehicle control (SHR) and PCA (SHR+PCA) groups, while age-matched Wistar–Kyoto rats (WKY) served as the normotensive vehicle control group. The oral PCA (200 mg/kg/day) was administered daily for a total of 12 weeks. When the rats reached the age of 48 weeks, the rat aortas were isolated for the evaluation of vascular reactivity and Western blotting. Also, nitric oxide (NO) production and antioxidant activities were examined among the three groups. The results showed that, when compared with the SHR group, the insulin-induced and IGF-1-induced vasorelaxation were significantly improved in the SHR+PCA group. There was no significant difference in the endothelium-denuded vessels among the three groups. After the pre-incubation of phosphatidylinositol 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the vasorelaxation was abolished and comparable among the three groups. The protein levels of insulin receptors, IGF-1 receptors, phospho-protein kinase B (p-Akt)/Akt, and phospho-endothelial NOS (p-eNOS)/eNOS in aortic tissues were significantly enhanced in the SHR+PCA group when compared with the SHR group. Moreover, significant improvements of nitrate/nitrite concentration and antioxidant activities, including superoxide dismutase, catalase, and total antioxidants, were also found in the SHR+PCA group. In conclusion, the 12 weeks of PCA administration remarkably improved the endothelium-dependent vasorelaxation induced by insulin and IGF-1 in aging hypertension through enhancing the PI3K–NOS–NO pathway. Furthermore, the enhanced antioxidant activities partly contributed to the improved vasorelaxation.

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Aging Additively Influences Insulin- and Insulin-Like Growth Factor-1-Mediated Endothelial Dysfunction and Antioxidant Deficiency in Spontaneously Hypertensive Rats

Biomedicines ◽

10.3390/biomedicines9060676 ◽

2021 ◽

Vol 9 (6) ◽

pp. 676

Author(s):

Kunanya Masodsai ◽

Yi-Yuan Lin ◽

Sih-Yin Lin ◽

Chia-Ting Su ◽

Shin-Da Lee ◽

...

Keyword(s):

Growth Factor ◽

Endothelial Dysfunction ◽

Spontaneously Hypertensive Rats ◽

No Production ◽

Organ Bath ◽

Insulin Like Growth Factor ◽

Hypertensive Rats ◽

Spontaneously Hypertensive ◽

Nos Inhibitors ◽

Wistar Kyoto

This study aimed to investigate the aging-related endothelial dysfunction mediated by insulin and insulin-like growth factor-1 (IGF-1) and antioxidant deficiency in hypertension. Male spontaneously hypertensive rats (SHRs) and age-matched normotensive Wistar–Kyoto rats (WKYs) were randomly divided into 24-week-old (younger) and 48-week-old (older) groups, respectively. The endothelial function was evaluated by the insulin- and IGF-1-mediated vasorelaxation of aortic rings via the organ bath system. Serum levels of nitric oxide (NO), malondialdehyde (MDA), catalase, and total antioxidant capacity (TAC) were examined. The insulin- and IGF-1-mediated vasorelaxation was significantly impaired in both 24- and 48-week-old SHRs compared with age-matched WKYs and was significantly worse in the 48-week-old SHR than the 24-week-old SHR. After pretreatments of phosphoinositide 3-kinase (PI3K) or NO synthase (NOS) inhibitors, the insulin- and IGF-1-mediated vasorelaxation became similar among four groups. The serum level of MDA was significantly increased, while the NO, catalase, and TAC were significantly reduced in the 48-week-old SHR compared with the 24-week-old SHR. This study demonstrated that the process of aging additively affected insulin- and IGF-1-mediated endothelial dysfunction in SHRs, which could be partly attributed to the reduced NO production and antioxidant deficiency.

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The effects of adenoidectomy of serum insulin-like growth factor-1 (IGF-1) and ghrelin in hypertrophied adenoids in children with otitis media with effusion

Otolaryngologia Polska ◽

10.5604/01.3001.0014.0223 ◽

2020 ◽

Vol 74 (4) ◽

pp. 13-17

Author(s):

Beata Żelazowska-Rutkowska ◽

Klaudia Jacewicz ◽

Edwina Kasprzycka ◽

Bożena Skotnicka ◽

Bogdan Cylwik

Keyword(s):

Growth Factor ◽

Otitis Media ◽

Otitis Media With Effusion ◽

Reference Group ◽

Serum Insulin ◽

Serum Levels ◽

Control Group ◽

Healthy Children ◽

Insulin Like Growth Factor ◽

Significant Difference

Aim: The aim of the current study was to assess the serum levels of insulin-like growth factor-1 (IGF-1) and ghrelin in hypertrophied adenoids in children suffering with or without otitis media with effusion before and after adenoidectomy. Material and methods: Serum IGF-1 and ghrelin concentrations were measured with specific enzyme-linked immunoassay (ELISA) methods. The study was carried out in 20 children with otitis media with effusion. The reference group comprised 24 children with hypertrophied adenoid, while control group included 19 children. Results: This mean values of IGF-1 in children with otitis media with effusion and children with hypertrophied adenoid before adenoidectomy were significantly lower than those found in healthy children. Serum levels of IGF-1 were higher after adenoidectomy. There was a significant difference of serum ghrelin levels between both examined groups and the control group. Conclusion: Our results suggest that adenoidectomy in children with hypertrophied adenoids and in children with otitis media with effusion significantly increases the level of IGF-1 in serum compared to before surgery through the effect of the GH-IGF-1 axis, which could contribute to children’s growth.

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Effects of Hibiscus sabdariffa Linn. on insulin-like growth factor binding protein 3 (IGFBP-3) to prevent overtraining syndrome

Medical Journal of Indonesia ◽

10.13181/mji.v23i4.991 ◽

2015 ◽

Vol 23 (4) ◽

pp. 187-91 ◽

Cited By ~ 2

Author(s):

Ermita I.I. Ilyas ◽

Neng T. Kartinah ◽

Trinovita Andraini ◽

Roman A. Goenarjo ◽

Donna N. Kahandjak

Keyword(s):

Growth Factor ◽

Binding Protein ◽

Male Rats ◽

Control Group ◽

Hibiscus Sabdariffa ◽

Insulin Like Growth Factor ◽

Factor Binding ◽

Overtraining Syndrome ◽

Significant Difference ◽

Igfbp 3

Background: Excessive physical exercises (overtraining) can increase the production of reactive oxygen species (ROS). One of the indicators of overtraining syndrome is a decrease in insulin-like growth factor binding protein 3 (IGFBP-3). Administration of Hibiscus sabdariffa Linn., a powerful antioxidant, is expected to boost endogenous antioxidants, and thus prevents overtraining. The aim of this study is to determine the effect of H. sabdariffa on IGFBP-3 levels in rats under ”overtraining physical excersice”.Methods: This experimental study was conducted on 30 male rats (Rattus norvegicus 200-250 grams), randomly allocated into 5 groups: 1) control group (C); 2) control with H. sabdariffa (C-Hib); 3) mild aerobic exercise (A-Ex); 4) overtraining exercise (OT); 5) overtraining exercise with H. Sabdariffa (OT-Hib). H. sabdariffa (400 mg/kg/d, 11 weeks) were administered orally via syringe cannula. IGFBP-3 was measured by using ELISA (Cusa bio kit) and data were analyzed with ANOVA test.Results: Plasma level of IGFBP-3 in the C and OT groups were 17.4 ± 10 mIU/L, the lowest in OT groups (10.7 ± 9.9 mIU/L) and the OT-Hib group had the highest level (31.5 ± 6.2 mIU/L). There was significant difference of the level IGFBP-3 in OT groups with A-Ex groups (10.7 ± 9.9 vs 23.5 ± 9.7 mIU/L; p < 0,05). The significant difference was also observed in the level of IGFBP 3 between C groups and the OT-Hib groups (17.4 ± 10 vs 31.5 ± 6.2; p < 0.05).Conclusion: Administration of H. sabdariffa can prevent the decrease of IGFBP-3 levels in overtraining rats, indicating its role in preventing overtraining syndrome.

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Effect of long-term low dose glucocorticoid on children with bronchial asthma

10.1101/2021.09.28.21264243 ◽

2021 ◽

Author(s):

Xueping Du ◽

Yanjun Guo ◽

Junzheng Yang

Keyword(s):

Growth Factor ◽

Treatment Group ◽

Bronchial Asthma ◽

Low Dose ◽

Control Group ◽

Insulin Like Growth Factor ◽

Act Scores ◽

Group A ◽

Group B

Objectives: To investigate the clinical efficacy of long-term of low-dose inhaled glucocorticoid (ICS) in the treatment on children with bronchial asthma, and to evaluate its effects on the height, weight and expression of serum insulin-like growth factor of children with bronchial asthma. Methods: 91 children with bronchial asthma treated in our hospital from January 2017 to December 2017 were chosen, and 31 healthy children without asthma history in our hospital were selected as the control group (Group C); For the different treatment methods comparison, 91 children with bronchial asthma were divided into treatment group A (48 children) and treatment group B (43 children) randomly. In treatment group A, children were treated with low-dose ICS for more than 1 year; in treatment group B, children were treated with low-dose ICS for less than 1 year or received low-dose ICS for less than 2 months/year. For treatment evaluation, the asthma control test (C-ACT) were scored at 0 months, 12 months and 24 months in three groups, and the height and weight of children, the levels of insulin-like growth factor-1 (IGF-1) and insulin-like growth factor binding protein-3 (IGFBP-3) in serum in each group were also measured. Results: In the control group, the C-ACT scores were increased with time (P<0.01); the C-ACT scores of treatment group A at 12 months and at 24 months was significantly higher than that of treatment group B (P<0.05); there was no significant difference in height and weight between the treatment group and the control group at 0 months, 12 months and 24 months after treatment (P>0.05); there was no significant difference in the expression levels of IGF-1 and IGFBP-3 in serum between treatment group and control group (P>0.05). Compared with the C-ACT scores in treatment group A and treatment group B at 0 month, the C-ACT scores were significantly higher at 12 months and at 24 months , and there was a statistical difference among 0 month, 12 months and at 24 months in treatment group A and treatment group B (P<0.01); The C-ACT score of treatment group A at the 12 month was significantly higher than that in treatment group B at the 12 months(P<0.05), and the C-ACT score in treatment group A at the 24 months was significantly higher than that of treatment group B (P<0.001). Conclusions: Treatment for children with bronchial asthma by long-term use of low-dose ICS is safe and effective, it does not affect health and development of children with bronchial asthma; children with bronchial asthma were treated with low-dose ICS for more than 1 year had a better effective than children were treated with low-dose ICS for less than 1 year or received low-dose ICS for less than 2 months/year.

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Effect of trenbolone acetate plus estradiol on transcriptional regulation of metabolism pathways in bovine liver

Hormone Molecular Biology and Clinical Investigation ◽

10.1515/hmbci.2010.029 ◽

2010 ◽

Vol 2 (2) ◽

Cited By ~ 5

Author(s):

Christiane Becker ◽

Irmgard Riedmaier ◽

Martina Reiter ◽

Ales Tichopad ◽

Michael W. Pfaffl ◽

...

Keyword(s):

Growth Factor ◽

Insulin Receptor ◽

Target Genes ◽

Anabolic Steroids ◽

Quantitative Polymerase Chain Reaction ◽

Regulatory Protein ◽

Bovine Liver ◽

Control Group ◽

Insulin Like Growth Factor ◽

Trenbolone Acetate

AbstractThe use of anabolic steroids is forbidden for food producing animals in the EU. Owing to the advantages of anabolics for production profitability, illegal application is appealing. Anabolics are known to influence gene expression of several tissues. We focused on the liver because of its important role in nutrient and hormone metabolism. The aim of the present study was to find differentially regulated metabolic pathways, which might be used as treatment biomarkers.A total of 18 Nguni heifers were allocated equally to a control group and a treatment group and were implanted with Revalor H. Expression of 34 target genes was measured using reverse transcriptase quantitative polymerase chain reaction (RT-qPCR).Upregulation of androgen receptor and insulin-like growth factor 1 (IGF-1) and downregulation of IGF-2, insulin-like growth factor binding protein 2, steroid hormone binding globulin, insulin receptor α, insulin receptor β, tyrosine aminotransferase, 17β-hydroxy steroid dehydrogenase 2,3-hydroxy-methylglutaryl-coenzym-A-synthase, cathepsin B, hepatocyte growth factor, steroidogenic acute regulatory protein, apolipoprotein 2 and tumor necrosis factor α was demonstrated.Several biochemical pathways showed different regulations on mRNA level under the influence of trenbolone acetate plus estradiol. The inhibition of nutrient metabolism and protein breakdown seems to support growth processes. IGF-1 plays an important role in growth and development and thus the upregulation of IGF-1 could be responsible for the stimulation of growth in treated animals. The upregulation of IGF-1 could also be revealed as a possible risk factor for the generation of artherosclerotic plaques, which are known as long-term side effects following the use of anabolic steroids. Principal components analysis of RT-qPCR results showed that both groups arrange together and can be clearly separated. Therefore, these might be used as possible biomarkers in bovine liver.

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Circulating Insulin-like Growth Factor-1 Levels in Patients with Rheumatoid Arthritis: A Meta-analysis

Current Pharmaceutical Design ◽

10.2174/1381612825666190319124009 ◽

2019 ◽

Vol 25 (10) ◽

pp. 1091-1098 ◽

Cited By ~ 1

Author(s):

Yu-Lan Zhao ◽

Jun Wu ◽

Tian-Ping Zhang ◽

Qian-Yao Cheng ◽

Xue-Ping Wang ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Growth Factor ◽

Fixed Effects ◽

Meta Analysis ◽

Pathological Process ◽

Cochrane Library ◽

Control Group ◽

Insulin Like Growth Factor ◽

Standard Mean Difference ◽

Significant Difference

Conclusion: Patients with RA have lower circulating IGF-1 level than healthy controls, particularly for patients from Asia and Europe. Further studies are necessary to elucidate the role of IGF-1 in the pathological process of RA. Results: A total of eleven articles with 334 cases and 261 controls were finally included. Compared with the healthy group, the RA group had lower circulating IGF-1 levels (pooled SMD= -0.936, 95% CI= -1.382 to -0.489, p<0.001). The subgroup analysis showed that RA patients from Asia (SMD= -0.645, 95% CI= -1.063 to -0.228, p= 0.002) and Europe (SMD= -1.131, 95% CI= -1.767 to -0.495, p<0.001) had lower circulating IGF-1 levels, no significant difference in plasma/serum IGF-1 levels was observed in RA patients from America. Sensitivity analysis indicated the stability and credibility of the overall effect sizes. Methods: PubMed, Embase and the Cochrane Library databases were searched up to December 2018 in English, and the studies comparing serum/plasma IGF-1 levels between RA group and healthy control group were what we are interested in. The Newcastle-Ottawa Scale (NOS) was used to assess the methodological quality of the included studies. The heterogeneity test was performed by the Cochrane Q statistic and I2 –statistic. The publication bias was evaluated by the funnel plot and Egger’s test. The standard mean difference (SMD) with 95% confidence interval (CI) was calculated by the fixed-effects or random-effects model. Background and Objectives: Insulin-like growth factor-1 (IGF-1) levels have been investigated in rheumatoid arthritis (RA), however, produced inconsistent results. The purpose of this meta-analysis was to derive a more precise conclusion about serum/plasma IGF-1 levels in RA patients.

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The Effect of Insulin-Like Growth Factor 1 Incorporated into a Hyaluronic Acid-Based Nasal Pack on Nasal Mucosal Healing in a Healthy Sheep Model and a Sheep Model of Chronic Sinusitis

American Journal of Rhinology ◽

10.1177/194589240501900307 ◽

2005 ◽

Vol 19 (3) ◽

pp. 251-256 ◽

Cited By ~ 16

Author(s):

Suresh Rajapaksa ◽

David McIntosh ◽

Allison Cowin ◽

Damian Adams ◽

Peter-John Wormald

Keyword(s):

Hyaluronic Acid ◽

Growth Factor ◽

Chronic Rhinosinusitis ◽

Chronic Sinusitis ◽

Sinus Surgery ◽

Control Group ◽

Insulin Like Growth Factor ◽

Sheep Model ◽

Significant Difference ◽

Healthy Sheep

Background Endoscopic sinus surgery (ESS) is the accepted surgical treatment for chronic refractory rhinosinusitis. Prolonged healing and adhesion formation remain common problems. This study investigates the use of a hyaluronic acid-based pack impregnated with insulin-like growth factor (IGF) 1 to facilitate more rapid and effective healing after ESS in a healthy sheep model and a sheep model of chronic sinusitis. Methods This study used 12 healthy sheep and 9 sheep with chronic sinusitis. In each sheep one side (computer randomized) was used as a control. Under endoscopic guidance, mucosal injuries and adhesions were created on both sides and were either packed with a hyaluronic acid pack impregnated with IGF-1 or left unpacked as a control. Serial biopsies were performed for 4 months. Results In the healthy sheep there was a statistically significant (p < 0.05) improvement in reepithelialization in IGF-1 packed wounds at day 28 (89% for IGF-1 versus 44% for controls). In both healthy sheep and sheep with sinusitis there was no significant difference in mucosal reepithelialization at any of the other measured time points. In the sinusitis group, there was a significant decrease in ciliary regeneration at day 56 in the Merogel/IGF-1 group compared with the control group: 59.20% versus 77.68% (p < 0.01) and at day 112, 69.70% versus 87.26% (p < 0.01). Conclusion Hyaluronic acid impregnated with IGF-1 improved reepithelialization in the healthy sheep but not in the sheep with chronic rhinosinusitis. These packs had a detrimental effect on mucosal ciliary regeneration in the sheep with chronic rhinosinusitis.

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