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      Resistance training increases fibroblast growth factor-21 and irisin levels in the skeletal muscle of Zucker diabetic fatty rats

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          Abstract

          [Purpose]

          Although the fibroblast growth factor-21 (FGF-21) and irisin roles are well demonstrated in metabolic disease, there have been no reports investigating the effect of resistance exercise on FGF-21 and irisin levels in diabetic skeletal muscles. Therefore, this study aimed to investigate the change of FGF-21 and irisin levels in various skeletal muscles, and their association with muscle strength, following 8 weeks of resistance training using Zucker diabetic fatty rats (type 2 diabetic animal models).

          [Methods]

          Twenty-four male lean (Zucker lean control, ZLC) and diabetic (Zucker diabetic fatty, ZDF) rats (age, 8 weeks old) were separated into 3 groups, lean control (ZLC-Con, n=8), diabetic control (ZDF-Con, n=8), and diabetic exercise-trained groups (ZDF-Ex, n=8). The rats in ZDF-Ex were trained to climb a 1-m vertical (85 degrees inclined) ladder with weights. Resistance training was performed with 10 repetitions/day for 12 weeks (3 days/week). The skeletal muscle levels of FGF-21 and irisin were measured using enzyme-linked immunosorbent assays.

          [Results]

          The levels of FGF-21 in the soleus (SOL) and extensor digitorum longus muscles of ZDF-Ex were higher (p<0.05) compared to levels in ZDF-Con. Additionally, we found a significantly higher irisin level in the SOL muscles of ZDF-Ex compared to that in ZDF-Con. Moreover, we found that the levels of FGF-21 (R=0.532, p=0.02) and irisin (R=0.498, p=0.03) had significant correlations with grip strength.

          [Conclusion]

          Based on these results, resistance training may be an efficient intervention for increasing FGF-21 and irisin levels in type 2 diabetic (T2DM) skeletal muscles.

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          Most cited references8

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          Muscles, exercise and obesity: skeletal muscle as a secretory organ.

          During the past decade, skeletal muscle has been identified as a secretory organ. Accordingly, we have suggested that cytokines and other peptides that are produced, expressed and released by muscle fibres and exert either autocrine, paracrine or endocrine effects should be classified as myokines. The finding that the muscle secretome consists of several hundred secreted peptides provides a conceptual basis and a whole new paradigm for understanding how muscles communicate with other organs, such as adipose tissue, liver, pancreas, bones and brain. However, some myokines exert their effects within the muscle itself. Thus, myostatin, LIF, IL-6 and IL-7 are involved in muscle hypertrophy and myogenesis, whereas BDNF and IL-6 are involved in AMPK-mediated fat oxidation. IL-6 also appears to have systemic effects on the liver, adipose tissue and the immune system, and mediates crosstalk between intestinal L cells and pancreatic islets. Other myokines include the osteogenic factors IGF-1 and FGF-2; FSTL-1, which improves the endothelial function of the vascular system; and the PGC-1α-dependent myokine irisin, which drives brown-fat-like development. Studies in the past few years suggest the existence of yet unidentified factors, secreted from muscle cells, which may influence cancer cell growth and pancreas function. Many proteins produced by skeletal muscle are dependent upon contraction; therefore, physical inactivity probably leads to an altered myokine response, which could provide a potential mechanism for the association between sedentary behaviour and many chronic diseases.
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            Lower circulating irisin is associated with type 2 diabetes mellitus.

            Irisin is a novel myokine secreted in response to PPAR-γ co-activator-1α (PGC-1α) activation. Earlier studies suggested that PGC-1α expression and activity were lower in myocytes in type 2 diabetes mellitus (T2DM). Therefore, we hypothesize that circulating irisin levels are lower in T2DM patients. In this observational study, we recruited 96 T2DM subjects and 60 non-diabetic control subjects. Among T2DM subjects, 38% were on insulin treatment, 78% were taking statins and 72% were taking renin-angiotensin system antagonists. Circulating irisin was quantified by ELISA and its association with markers of metabolic phenotype was analyzed by Pearson bivariate correlation and multiple linear regression. Circulating irisin was significantly lower in individuals with T2DM compared with non-diabetic controls (T2DM 204 ± 72 ng/ml vs. non-diabetic control 257 ± 24 ng/ml, p < 0.0001). In non-diabetic subjects, circulating irisin was correlated with age (r = 0.398, p < 0.01), BMI (r = 0.387, p < 0.01), total cholesterol (r = 0.341, p < 0.01), total triglycerides (r = 0.299, p < 0.05), fasting blood glucose (r = 0.430, p < 0.01) and diastolic blood pressure (r = 0.306, p < 0.05). Multiple linear regression model revealed that BMI (β = 0.407, p = 0.012) and FBG (β = 0.315, p = 0.034) were associated with irisin in non-diabetic subjects after adjusting for multiple co-variates. However, similar analysis in T2DM subjects didn't reveal significant association between circulating irisin and major markers of metabolic phenotype. Circulating irisin is lower in T2DM compared with non-diabetic controls. Plasma irisin levels appear to be associated with important metabolic factors in non-diabetic subjects but not in individuals with type 2 diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.
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              Serum irisin levels in new-onset type 2 diabetes.

              Irisin has been identified as a novel myokine that drives brown-fat-like conversion of white adipose tissue. In this cross-sectional study, we investigated whether serum irisin levels are decreased in patients with type 2 diabetes (T2D) compared with control subjects with normal glucose tolerance (NGT), and assessed the association between serum irisin levels and various metabolic parameters. The study population was selected from a population-based study and included 104 subjects with NGT and 104 subjects with new-onset T2D. Serum irisin and adiponectin levels and metabolic parameters were measured. Multivariate logistic regression analysis was performed to assess the association between irisin levels and newly diagnosed T2D. Serum irisin levels were significantly decreased in the new-onset T2D group compared with the NGT control group (p=0.003). In a multivariable model adjusted for various metabolic parameters, increased irisin levels were associated with reduced odds (OR 0.64, 95% CI 0.47-0.88, p=0.006) of prevalent newly diagnosed T2D. Furthermore, multiple regression analysis showed that 2 h plasma glucose was an independent variable influencing serum irisin levels (p=0.004). In the present study, we found that serum irisin levels were decreased in T2D patients and inversely associated with newly diagnosed T2D, suggesting that irisin may play a crucial role in glucose intolerance and T2D. Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.
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                Author and article information

                Journal
                J Exerc Nutrition Biochem
                J Exerc Nutrition Biochem
                JENB
                Journal of Exercise Nutrition & Biochemistry
                한국운동영양학회
                2233-6834
                2233-6842
                30 September 2017
                30 September 2017
                : 21
                : 3
                : 50-54
                Affiliations
                [1. ]Physical activity and performance institute, Konkuk University, Seoul Republic of Korea,
                [2. ]Health and Exercise Science, Institute of sport science, Seoul National University, Seoul Republic of Korea,
                [3. ]Institute on Aging, Seoul National University, Seoul Republic of Korea,
                Author notes
                *Wook Song Health and Exercise Science Laboratory, Institute of Sports Science, Seoul National University, 599 Gwanang-no, Gwanak-gu, Seoul 151-742, Korea. Tel : +82-2-880-7791 Email : songw3@ 123456snu.ac.kr
                Article
                JENB_2017_v21n3_50
                10.20463/jenb.2017.0008
                5643202
                29036766
                456eb650-a477-433a-854e-c6ac8461159e
                ©2017 The Korean Society for Exercise Nutrition

                ©2017 Nana Chung et al.; Licensee Journal of Exercise Nutrition and Biochemistry. This is an open accessarticle distributed under the terms of the creative commons attribution license ( http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the orginal work is properly cited.

                History
                : 13 March 2017
                : 17 July 2017
                : 16 August 2017
                Funding
                Funded by: Ministry of Education
                Award ID: NRF-2016S1A5B5A02021643
                Funded by: National Research Foundation of Korea
                Award ID: NRF-2014R1A1A2058645
                Categories
                Research Note

                fgf-21,irisin,resistance training,diabetes,zucker diabetic fatty rat

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