Skip to main content
Key Specialties
Cardiology Diabetology Endocrinology Gastroenterology Geriatrics and Gerontology Gynecology and Obstetrics Hematology Infectious Disease Internal Medicine Nephrology Neurology Oncology Pediatrics Respiratory Medicine Rheumatology Surgery
Congress Coverage
2024 ACC Congress 2023 ESMO Congress 2023 EASD Congress 2023 ERS Congress 2023 ESC Congress
Clinical Collections
Advances in Alzheimer’s

At a glance: The ONWARDS insulin icodec trials

A round-up of the ONWARDS phase 3 clinical trials evaluating the novel weekly insulin icodec in people with diabetes.
ADVANCED SEARCH
Log in
Top
Endocrine
Published in: Endocrine 1/2014

01-05-2014 | Original Article

Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training

Authors: M. Molanouri Shamsi, Z. H. Hassan, R. Gharakhanlou, L. S. Quinn, K. Azadmanesh, L. Baghersad, A. Isanejad, M. Mahdavi

Published in: Endocrine | Issue 1/2014

Login to get access

Abstract

Skeletal muscle atrophy is associated with type-1 diabetes. Skeletal muscle is the source of pro- and anti-inflammatory cytokines that can mediate muscle hypertrophy and atrophy, while resistance exercise can modulate both muscle mass and muscle cytokine expression. This study determined the effects of a 5-week resistance exercise training regimen on the expression of muscle cytokines in healthy and streptozotocin-induced diabetic rats, with special emphasis on interleukin-15 (IL-15), a muscle-derived cytokine proposed to be involved in muscle hypertrophy or responses to stress. Induction of diabetes reduced muscle weight in both the fast flexor hallucis longus (FHL) and slow soleus muscles, while resistance training preserved FHL muscle weight in diabetic rats. IL-15 protein content was increased by training in both FHL and soleus muscles, as well as serum, in normal and diabetic rats. With regard to proinflammatory cytokines, muscle IL-6 levels were increased in diabetic rats, while training decreased muscle IL-6 levels in diabetic rats; training had no effect on FHL muscle IL-6 levels in healthy rats. Also, tumor necrosis factor-alpha (TNF-α) and IL-1β levels were increased by diabetes, but not changed by training. In conclusion, we found that in diabetic rats, resistance training increased muscle and serum IL-15 levels, decreased muscle IL-6 levels, and preserved FHL muscle mass.
Literature
1.
B.C. Frier, E.G. Noble, M. Locke, Diabetes-induced atrophy is associated with a muscle-specific alteration in NF-kappaB activation and expression. Cell Stress Chaperones 13(3), 287–296 (2008)PubMedCentralPubMedCrossRef
2.
H. Andersen, P.C. Gadeberg, B. Brock, J. Jakobsen, Muscular atrophy in diabetic neuropathy: a stereological magnetic resonance imaging study. Diabetologia 40(9), 1062–1069 (1997)PubMedCrossRef
3.
R.A. Frost, C.H. Lang, Regulation of muscle growth by pathogen-associated molecules. J. Anim. Sci. 86(14), 84–93 (2008)CrossRef
4.
G.Q. Chen, C.Y. Mou, Y.Q. Yang, S. Wang, Z.W. Zhao, Exercise training has beneficial anti-atrophy effects by inhibiting oxidative stress-induced MuRF1 upregulation in rats with diabetes. Life Sci. 89(1–2), 44–49 (2011)PubMedCrossRef
5.
R.B. Hunter, E. Stevenson, A. Koncarevic, H. Mitchell-Felton, D.A. Essig, S.C. Kandarian, Activation of an alternative NF-kappaB pathway in skeletal muscle during disuse atrophy. FASEB J 16(6), 529–538 (2002)PubMedCrossRef
6.
L.G. Karagounis, B.B. Yaspelkis 3rd, D.W. Reeder, G.I. Lancaster, J.A. Hawley, V.G. Coffey, Contraction-induced changes in TNF alpha and Akt mediated signalling are associated with increased myofibrillar protein in rat skeletal muscle. Eur. J. Appl. Physiol. 109(5), 48–839 (2010)CrossRef
7.
L.S. Quinn, B.G. Anderson, R.H. Drivdahl, B. Alvarez, J.M. Argilés, Overexpression of interleukin15 induces skeletal muscle hypertrophy in vitro: implications for treatment of muscle wasting disorders. Exp. Cell Res. 280(1), 55–63 (2002)PubMedCrossRef
8.
F.S. Lira, C.H. Koyama, A.S. Yamashita, J.C. Rosa, N.E. Zanchi, M.L. Batista Jr et al., Chronic exercise decreases cytokines production in healthy rat skeletal muscle. Cell Biochem. Funct. 27, 458–461 (2009)PubMedCrossRef
9.
N.E. Zanchi, F.S. Lira, M.A. de Siqueira Filho, J.C. Rosa, C.R. de Oliveira Carvalho, M. Seelaender et al., Chronic low frequency/low volume resistance training reduces pro-inflammatory cytokine protein levels and TLR4 mRNA in rat skeletal muscle. Eur. J. Appl. Physiol. 109(6), 1095–1102 (2010)PubMedCrossRef
10.
S.C. Forbes, J.P. Little, D.G. Candow, Exercise and nutritional interventions for improving aging muscle health. Endocrine 42(1), 29–38 (2012)PubMedCrossRef
11.
B.K. Pedersen, M.A. Febbraio, Muscle as an endocrine organ: focus on muscle-derived interleukin-6. Physiol. Rev. 88(4), 1379–1406 (2008)PubMedCrossRef
12.
F. Haddad, G.R. Adams, Selected contribution: acute cellular and molecular responses to resistance exercise. J. Appl. Physiol. 93, 394–403 (2002)PubMed
13.
T.O. Takala, P. Nuutila, J. Knuuti, M. Luotolahti, H. Yki-Järvinen, Insulin action on heart and skeletal muscle glucose uptake in weight lifters and endurance athletes. Am. J. Physiol. 276(4 Pt 1), E706–E711 (1999)PubMed
14.
J.O. Holloszy, Exercise-induced increase in muscle insulin sensitivity. J. Appl. Physiol. 99(1), 338–343 (2005)PubMedCrossRef
15.
A.L. Carey, G.R. Steinberg, S.L. Macaulay, W.G. Thomas, A.G. Holmes, G. Ramm et al., Interleukin-6 increases insulin-stimulated glucose disposal in humans and glucose uptake and fatty acidoxidation in vitro via AMP-activated protein kinase. Diabetes 55(10), 2688–2697 (2006)PubMedCrossRef
16.
K.H. Grabstein, J. Eisenman, K. Shanebeck, C. Rauch, S. Srinivasan, V. Fung et al., Cloning of a T cell growth factor that interacts with the beta chain of the interleukin-2 receptor. Science 264(5161), 965–968 (1994)PubMedCrossRef
17.
H.C. Kim, H.Y. Cho, Y.S. Hah, Role of IL-15 in sepsis-induced skeletal muscle atrophy and proteolysis. Tuberc. Respir. Dis. (Seoul) 73(6), 312–319 (2012)PubMedCentralCrossRef
18.
M. Figueras, S. Busquets, N. Carbó, E. Barreiro, V. Almendro, J.M. Argilés et al., Interleukin 15 is able to suppress the increased DNA fragmentation associated with musclewasting in tumour-bearing rats. FEBS Lett 569(1–3), 201–206 (2004)PubMedCrossRef
19.
J. Xia, W. Liu, B. Hu, Z. Tian, Y. Yang, IL-15promotes regulatory T cell function and protects against diabetes development in NK-depleted NOD mice. Clin Immunol 134(2), 130–139 (2010)PubMedCrossRef
20.
S. Kuczyński, H. Winiarska, M. Abramczyk, K. Szczawińska, B. Wierusz-Wysocka, M. Dworacka, IL-15 is elevated in serum patients with type 1 diabetes mellitus. Diabetes Res. Clin. Pract. 69(3), 231–236 (2005)PubMedCrossRef
21.
S.R. Gray, T. Kamolrat, The effect of exercise induced cytokines on insulin stimulated glucose transport in C2C12 cells. Cytokine 55(2), 221–228 (2011)PubMedCrossRef
22.
S.E. Riechman, G. Balasekaran, S.M. Roth, R.E. Ferrell, Association of interleukin-15 protein and interleukin-15 receptor genetic variation with resistance exercise training responses. J. Appl. Physiol. 97, 2214–2219 (2004)PubMedCrossRef
23.
A.R. Nielsen, R. Mounier, P. Plomgaard, O.H. Mortensen, M. Penkowa, T. Speerschneider et al., Expression of interleukin-15 in human skeletal muscle effect of exercise and muscle fibre type composition. J. Physiol. 584(Pt 1), 305–312 (2007)PubMedCentralPubMedCrossRef
24.
L.S. Quinn, B.G. Anderson, L. Strait-Bodey, T. Wolden-Hanson, Serum and muscle interleukin-15 levels decrease in aging mice: correlation with declines in soluble interleukin-15 receptor alpha expression. Exp. Gerontol. 45(2), 106–112 (2010)PubMedCentralPubMedCrossRef
25.
E. Marzetti, C.S. Carter, S.E. Wohlgemuth, H.A. Lees, S. Giovannini, B. Anderson et al., Changes in IL-15 expression and death-receptor apoptotic signaling in rat gastrocnemius muscle with aging and life-long calorie restriction. Mech. Ageing Dev. 130(4), 272–280 (2009)PubMedCentralPubMedCrossRef
26.
E.E. Pistilli, P.M. Siu, S.E. Alway, Interleukin-15 responses to aging and unloading-induced skeletal muscle atrophy. Am. J. Physiol. Cell Physiol. 292(4), C1298–C1304 (2007)PubMedCrossRef
27.
Y. Tamura, K. Watanabe, T. Kantani, J. Hyashi, N. Ishida, M. Kaneki, Upregulation of circulating IL-15 by treadmill running in healthy individuals: is IL-15 an endocrine mediator of the beneficial effects of endurance exercise? Endocr. J. 58, 211–215 (2011)PubMedCrossRef
28.
S. Lee, E.R. Barton, H.L. Sweeney, R.P. Farrar, Viral expression of insulin-like growth factor-I enhances muscle hypertrophy in resistance-trained rats. J. Appl. Physiol. 96(3), 1097–1104 (2004)PubMedCrossRef
29.
P.A. Farrell, M.J. Fedele, J. Hernandez, J.D. Fluckey, J.L. Miller 3rd, C.H. Lang et al., Hypertrophy of skeletal muscle in diabetic rats in response to chronic resistance exercise. J. Appl. Physiol. 87(3), 1075–1082 (1999)PubMed
30.
E. Talebi-Garakani, A. Safarzade, Resistance training decreases serum inflammatory markers in diabetic rats. Endocrine 43(3), 564–570 (2013)PubMedCrossRef
31.
K.J. Livak, T.D. Schmittgen, Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4), 402–408 (2001)PubMedCrossRef
32.
M.M. Bradford, A rapid and sensitive method for quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248–254 (1976)PubMedCrossRef
33.
T.A. Hornberger Jr, R.P. Farrar, Physiological hypertrophy of the FHL muscle following 8 weeks of progressive resistance exercise in the rat. Can. J. Appl. Physiol. 29(1), 16–31 (2004)PubMedCrossRef
34.
H. Yang, J. Chang, W. Chen, L. Zhao, B. Qu, C. Tang et al., Treadmill exercise promotes interleukin 15 expression in skeletal muscle and interleukin 15 receptor alphaexpression in adipose tissue of high-fat diet rats. Endocrine 43(3), 579–585 (2013)PubMedCrossRef
35.
T.A. Fehniger, M.A. Caligiuri, Interleukin 15: biology and relevance to human disease. Blood 97, 14–32 (2001)PubMedCrossRef
36.
V. Budagian, E. Bulanova, R. Paus, S. Bulfone-Paus, IL-15/IL-15 receptor biology: a guided tour through an expanding universe. Cytokine Growth Factor Rev. 17(4), 259–280 (2006)PubMedCrossRef
37.
K. Baar, K. Esser, Phosphorylation of p70(S6k) correlates with increased skeletal muscle mass following resistance exercise. Am. J. Physiol. 276(1 Pt 1), C120–C127 (1999)PubMed
38.
M. Cesari, B.W. Penninx, M. Pahor, F. Lauretani, A.M. Corsi, W.G. Rhys et al., Inflammatory markers and physical performance in older persons: the In CHIANTI study. J. Gerontol. A Biol. Sci. Med. Sci. 59, 242–248 (2004)PubMedCrossRef
39.
L.H. Colbert, M. Visser, E.M. Simonsick, R.P. Tracy, A.B. Newman, S.B. Kritchevsky et al., Physical activity, exercise, inflammatory markers in older adults: findings from the health, aging and body composition study. J. Am. Geriatr. Soc. 52, 1098–1104 (2004)PubMedCrossRef
40.
N.H. Yeo, J. Woo, K.O. Shin, J.Y. Park, S. Kang, The effects of different exercise intensity on myokine and angiogenesis factors. J. Sport. Med. Phys. Fit. 52(4), 448–454 (2012)
41.
42.
N.B. Abdulrazaq, M.M. Cho, N.N. Win, R. Zaman, M.T. Rahman, Beneficial effects of ginger (Zingiber officinale) on carbohydrate metabolism in streptozotocin-induced diabetic rats. Br. J. Nutr. 12, 1–8 (2011)
43.
O. Bozkurt, M. Severcan, F. Severcan, Diabetes induces compositional, structural and functional alterations on rat skeletal soleus muscle revealed by FTIR spectroscopy: a comparative study with EDL muscle. Analyst 135(12), 3110–3119 (2010)PubMedCrossRef
44.
J.F. Liu, W.Y. Chang, K.H. Chan, W.Y. Tsai, C.L. Lin, M.C. Hsu, Blood lipid peroxides and muscle damage increased following intensive resistance training of female weightlifters. Ann. N. Y. Acad. Sci. 1042, 255–261 (2005)PubMedCrossRef
45.
C. Scheele, S. Nielsen, B.K. Pedersen, ROS and myokines promote muscle adaptation to exercise. Trends Endocrinol. Metab. 20(3), 95–99 (2009)PubMedCrossRef
46.
S. Copray, R. Liem, N. Brouwer, P. Greenhaff, F. Habens, P. Fernyhough, Contraction-induced muscle fiber damage is increased in soleus muscle of streptozotocin-diabetic rats and is associateed with elevated expression of brain derived neurotrophic factor mRNA in muscle fibers and activated satellite cells. Exp. Neurol. 161(2), 597–608 (2000)PubMedCrossRef
47.
A. Rabinovitch, W.L. Suarez-Pinzon, Cytokines and their roles in pancreatic islet h-cell destruction and insulin-dependent diabetes mellitus. Biochem. Pharmacol. 55, 1139–1149 (1998)PubMedCrossRef
48.
S.K. Jain, K. Kannan, G. Lim, R. McVie, J.A. Bocchini, Hyperketonemia increases TNF-α secretion in cultured U937 monocytes and type-1 diabetic patients. Diabetes 51, 2287–2293 (2002)PubMedCrossRef
49.
M.G. Cavallo, P. Pozzilli, C. Bird, M. Wadhwa, A. Meager, N. Visalli et al., Cytokines in sera from insulin dependent diabetic patients at diagnosis. Clin. Exp. Immunol. 86, 256–259 (1991)PubMedCentralPubMedCrossRef
50.
R.A. Frost, G.J. Nystrom, C.H. Lang, Lipopolysaccharide and proinflammatory cytokines stimulate interleukin-6 expression in C2C12 myoblasts: role of the Jun NH2-terminal kinase. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285, R1153–R1164 (2003)PubMed
51.
H. Klitgaard, A model for quantitative strength training of hindlimb muscles of the rat. J. Appl. Physiol. 64(4), 1740–1745 (1988)PubMed
52.
G. Whyte, The Physiology of Training (Advances in Sport and Exercise Science) (Amazon, 2006), pp. 135–161
53.
R.S. Staron, R.S. Hikida, T.F. Murray, M.M. Nelson, P. Johnson, F.C. Hagerman, Assessment of skeletal muscle damage in successive biopsies from strength-trained and untrained men and women. Eur. J. Appl. Physiol. 65, 258–264 (1992)CrossRef
54.
S.M. Roth, G.F. Martel, F.M. Ivey, J.T. Lemmer, E.J. Metter, B.F. Hurley, M.A. Rogers, High-volume, heavy-resistance strength training and muscle damage in young and older women. J. Appl. Physiol. 88(3), 1112–1118 (2000)PubMed
55.
N.E. Zanchi, F.S. Lira, M. Seelaender, A.H. Lancha-Jr, Experimental chronic low-frequency resistance training produces skeletal muscle hypertrophy in the absence of muscle damage and metabolic stress markers. Cell Biochem. Funct. 28(3), 232–238 (2010)PubMedCrossRef
56.
D. Hansen, B.O. Eijnde, M. Roelants, T. Broekmans, J.L. Rummens, K. Hensen et al., Clinical benefits of the addition of lower extremity low-intensity resistance muscle training to early aerobic endurance training intervention in patients with coronary artery disease: a randomized controlled trial. J. Rehabil. Med. 43(9), 800–807 (2011)PubMedCrossRef
57.
S.L. Lee, K.W. Chen, S.T. Chen, P.J. Chu, C.S. Chen, M.C. Hsu et al., Effect of passive repetitive isokinetic training on cytokines and hormonal changes. Chin. J. Physiol. 54(1), 55–66 (2011)PubMedCrossRef
58.
A.L. Mackey, M. Kjaer, S. Dandanell, K.H. Mikkelsen, L. Holm, S. Dossing et al., The influence of anti-inflammatory medication on exercise-induced myogenic precursor cell responses in humans. J. Appl. Physiol. 103, 425–431 (2007)PubMedCrossRef
59.
Q.A. Soltow, J.L. Betters, J.E. Sellman, V.A. Lira, J.H. Long, D.S. Criswell, Ibuprofen inhibits skeletal muscle hypertrophy in rats. Med. Sci. Sport. Exerc. 38, 840–846 (2006)CrossRef
Metadata
Title
Expression of interleukin-15 and inflammatory cytokines in skeletal muscles of STZ-induced diabetic rats: effect of resistance exercise training
Authors
M. Molanouri Shamsi
Z. H. Hassan
R. Gharakhanlou
L. S. Quinn
K. Azadmanesh
L. Baghersad
A. Isanejad
M. Mahdavi
Publication date
01-05-2014
Publisher
Springer US
Published in
Endocrine / Issue 1/2014
Print ISSN: 1355-008X
Electronic ISSN: 1559-0100
DOI
https://doi.org/10.1007/s12020-013-0038-4

Other articles of this Issue 1/2014

Endocrine 1/2014 Go to the issue

Meta-Analysis

Clinical characteristics as predictors of malignancy in patients with indeterminate thyroid cytology: a meta-analysis

Editorial

99mTc-MIBI imaging in thyroid nodules: Is it useful?

Letter to the Editor

Panhypopituitarism in a pregnant women caused by a cystic sellar lesion

Original Article

A large deletion of the AVPR2 gene causing severe nephrogenic diabetes insipidus in a Turkish family

Original Article

Urinary Smad1 is a new biomarker for diagnosis and evaluating the severity of diabetic nephropathy

Original Article

The clinical and pathological significance of nitric oxide synthase in human pituitary adenomas: a comparison with MIB-1

ACC 2024 Congress Coverage

Heart Failure Video

Year in Review: Heart failure and cardiomyopathies

Watch now

Watch this official video from ACC.24. Dr. Biykem Bozkurt discuss last year's major advances in heart failure and cardiomyopathies.

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

16-04-2024 Type 2 Diabetes News

Incentivised to exercise

11-04-2024 Lifestyle Modifications News

New intervention for STEMI-related cardiogenic shock

10-04-2024 Myocardial Infarction News

» View more highlights on the ACC 2024 congress hub page

Image Credits