Skip to main content
SpringerLink
Log in

Effect of insulin on dexamethasone-induced ultrastructural changes in skeletal and cardiac muscle

  • Full Paper
  • Zoology
  • Published:
Biologia Aims and scope Submit manuscript

Abstract

Glucocorticoids help animals respond to stressors but excessive glucocorticoids cause muscle atrophy, while insulin can promote anabolism and growth. In order to compare the glucocorticoids-induced ultrastructural changes between skeletal muscle and cardiac muscle, and investigate the preventive effects of insulin on the changes, eighteen male chicks with similar initial weight were randomly divided into three groups. The two test groups were respectively treated with high-dose dexamethasone alone or together with low-dose insulin by intraperitoneal injection, and the control group was treated with an equal volume of saline solution. The experiment lasted for ten days, and then the body weight, muscle size and ultrastructure in skeletal and cardiac muscles of twelve chicks were qualitatively or quantitatively analyzed. The results showed that high-dose dexamethasone induced obvious skeletal and cardiac muscle atrophy. The differences of ultrastructural changes between skeletal muscle and cardiac muscle (such as for the former or the latter, the intermyofibrillar-and-interfilamentary spaces reducing or enlarging, the mitochondria swelling seriously or enlarging lightly, the myofibril filaments compacting or loosing) suggested that dexamethasone induced skeletal and cardiac muscle atrophy by different mechanisms. Low-dose insulin did not affect the dexamethasone-induced decreases of body weight and skeletal muscle size, but alleviated lightly the dexamethasone-induced ultrastructural changes in skeletal muscle. Different from skeletal muscle, low-dose insulin almost resisted the dexamethasone-induced ultrastructural changes in cardiac muscle.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  • Amthor H., Macharia R., Navarrete R., Schuelke M., Brown S.C., Otto A., Voit T., Muntoni F., Vrbóva G., Partridge T., Zammit P., Bunger L. & Patel K. 2007. Lack of myostatin results in excessive muscle growth but impaired force generation. PNAS 104(6): 1835–1840. DOI: 10.1073/pnas.0604893104

    Article  PubMed  CAS  Google Scholar 

  • Auclair D., Garrel D.R., Chaouki Zerouala A. & Ferland L.H. 1997. Activation of the ubiquitin pathway in rat skeletal muscle by catabolic doses of glucocorticoids. Am. J. Physiol. Cell Physiol. 272(3): C1007–C1016. PMID: 9124503

    CAS  Google Scholar 

  • Azad M.A.K., Kikusato M., Sudo S., Amo T. & Toyomizu M. 2010. Time course of ROS production in skeletal muscle mitochondria from chronic heat-exposed broiler chicken. Comp. Biochem. Phys. A: Mol. Integr. Physiol. 157(3): 266–271. DOI: 10.1016/j.cbpa.2010.07.011

    Article  CAS  Google Scholar 

  • Baehr L.M., David Furlow J. & Bodine S.C. 2010. The Role of MuRF1 in Glucocorticoid Induced Skeletal Muscle Atrophy. FASEB J. 24 (Meeting Abstract Supplement): 989.7. http://www.fasebj.org/cgi/content/meetingabstract/24/1 MeetingAbstracts/989.7

  • Barazzoni R., Zanetti M., Bosutti A., Stebel M., Cattin L., Biolo G. & Guarnieri G. 2004. Myostatin expression is not altered by insulin deficiency and replacement in streptozotocindiabetic rat skeletal muscles. Clinical Nutrition 23(6): 1413–1417. DOI: 10.1016/j.clnu.2004.06.007

    Article  PubMed  CAS  Google Scholar 

  • Chen Y.W., Cao L.Z., Ye J.W. & Zhu D.H. 2009. Upregulation of myostatin gene expression in streptozotocininduced type 1 diabetes mice is attenuated by insulin. Biochem. Biophys. Res. Commun. 388(1): 112–116. DOI: 10.1016/j.bbrc.2009.07.129

    Article  PubMed  CAS  Google Scholar 

  • Cohn R.D., Liang H.Y., Shetty R., Abraham T. & Wagner K.R. 2007. Myostatin does not regulate cardiac hypertrophy or fibrosis. Neuromuscular Disorders 17(4): 290–296. DOI: 10.1016/j.nmd.2007.01.011

    Article  PubMed  Google Scholar 

  • Combaret L., Adegoke O.A.J., Bedard N., Baracos V., Attaix D. & Wing S.S. 2005. USP19 is a ubiquitin-specific protease regulated in rat skeletal muscle during catabolic states. Am. J. Physiol. Endocrinol. Metab.288: E693–E700. DOI: 10.1152/ajpendo.00281.2004

    Article  CAS  Google Scholar 

  • Dong H., Lin H., Jiao H.C., Song Z.G., Zhao J.P. & Jiang K.J. 2007. Altered development and protein metabolism in skeletal muscles of broiler chickens (Gallus gallus domesticus) by corticosterone. Comp. Biochem. Phys. A: Mol. Integr. Physiol. 147(1): 189–195. DOI: 10.1016/j.cbpa.2006.12.034

    Article  CAS  Google Scholar 

  • Du R., An X.R., Chen Y.F. & Qin J. 2007. Some motifs were important for myostatin transcriptional regulation in sheep. J. Biochem. Mol. Biol. 40(4): 547–553. PMID: 17669271

    Article  PubMed  CAS  Google Scholar 

  • Fujita S., Rasmussen B.B., Cadenas J.G., Grady J.J. & Volpi E. 2006. Effect of insulin on human skeletal muscle protein synthesis is modulated by insulin-induced changes in muscle blood flow and amino acid availability. Am. J. Physiol. Endocrinol. Metab. 291(4): E745–E754. DOI: 10.1152/ajpendo.00271.2005

    Article  PubMed  CAS  Google Scholar 

  • Gilson H., Schakman O., Combaret L., Lause P., Grobet L., Attaix D., Ketelslegers J. M. & Thissen, J. P. 2007. Myostatin gene deletion prevents glucocorticoid-induced muscle atrophy. Endocrinology 148(1): 452–460. DOI: 10.1210/en.2006-0539

    Article  PubMed  CAS  Google Scholar 

  • Hasselgren P.O. 1999. Glucocorticoids and muscle catabolism. Curr. Opin. Clin. Nutr. Metab. Care 2(3): 201–205. PMID: 10456248

    Article  PubMed  CAS  Google Scholar 

  • Hull K.L., Cockrem J.F., Bridges J.P., Candy E.J. & Davidson C.M. 2007. Effects of corticosterone treatment on growth, development, and the corticosterone response to handling in young Japanese quail (Coturnix coturnix japonica). Comp. Biochem. Phys. A: Mol. Integr. Physiol. 148(3): 531–543. DOI: 10.1016/j.cbpa.2007.06.423

    Article  CAS  Google Scholar 

  • Kimball S.R., Horetsky R.L. & Jefferson L.S. 1998. Signal transduction pathways involved in the regulation of protein synthesis by insulin in L6 myoblasts. Am. J. Physiol. Cell Physiol. 274(1): C221–C228. PMID: 9458731

    CAS  Google Scholar 

  • Kimball S.R., Jurasinski C.V., Lawrence Jr J.C. & Jefferson L.S. 1997. Insulin stimulates protein synthesis in skeletal muscle by enhancing the association of eIF-4E and eIF-4G. Am. J. Physiol. Cell Physiol.272(2): C754–C759. PMID: 9124320

    CAS  Google Scholar 

  • Komamura K., Shirotani-Ikejima H., Tatsumi R., Tsujita-Kuroda Y., Kitakaze M., Miyatake K., Sunagawa K. & Miyata T. 2003. Differential gene expression in the rat skeletal and heart muscle in glucocorticoid-induced myopathy: analysis by microarray. Cardiovasc. Drugs. Ther. 17(4): 303–310. DOI: 10.1023/A:1027352703783

    Article  PubMed  CAS  Google Scholar 

  • Lang C.H., Silvis C., Nystrom G. & Frost R.A. 2001. Regulation of myostatin by glucocorticoids after thermal injury. FASEB J. 15: 1807–1809. PMID: 11481237

    PubMed  CAS  Google Scholar 

  • Lin H., Sui S.J., Jiao H.C., Buyse J. & Decuypere E. 2006. Impaired development of broiler chickens by stress mimicked by corticosterone exposure. Comp. Biochem. Phys. A: Mol. Integr. Physiol. 143(3): 400–405. DOI: 10.1016/j.cbpa.2005.12.030

    Article  CAS  Google Scholar 

  • Liu Z.Q., Li G.L., Kimball S.R., Jahn L.A. & Barrett E.J. 2004. Glucocorticoids modulate amino acid-induced translation initiation in human skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 287(2): E275–E281. DOI: 10.1152/ajpendo.00457. 2003

    Article  PubMed  CAS  Google Scholar 

  • Ma K., Mallidis C., Artaza J., Taylor W., Gonzalez-Cadavid N. & Bhasin S. 2001. Characterization of 5′-regulatory region of human myostatin gene: regulation by dexamethasone in vitro. Am. J. Physiol. Endocrinol. Metab. 281(6): E1128–E1136. PMID: 11701425

    PubMed  CAS  Google Scholar 

  • Ma K., Mallidis C., Bhasin S., Mahabadi V., Artaza J., Gonzalez-Cadavid N., Arias J. & Salehian B. 2003. Glucocorticoidinduced skeletal muscle atrophy is associated with upregulation of myostatin gene expression. Am. J. Physiol. Endocrinol. Metab. 285(2): E363–E371. DOI: 10.1152/ajpendo.00487.2002

    PubMed  CAS  Google Scholar 

  • Marinovic A.C., Zheng B., Mitch W.E. & Price S.R. 2002. Ubiquitin (UbC) expression in muscle cells is increased by glucocorticoids through a mechanism involving Sp1 and MEK1. J. Biol. Chem. 277(19): 16673–16681. DOI: 10.1074/jbc.M200501200

    Article  PubMed  CAS  Google Scholar 

  • Morissette M.R., Cook S.A., Foo S.Y., McKoy G., Ashida N., Novikov M., Scherrer-Crosbie M., Li L., Matsui T., Brooks G. & Rosenzweig A. 2006. Myostatin regulates cardiomyocyte growth through modulation of akt signaling. Circulation Res. 99(1): 15–24. DOI: 10.1161/01.RES.0000231290.45676.d4

    Article  PubMed  CAS  Google Scholar 

  • O’Connor P.M.J., Kimball S.R., Suryawan A., Bush J.A., Nguyen H.V., Jefferson L.S. & Davis T.A. 2003. Regulation of translation initiation by insulin and amino acids in skeletal muscle of neonatal pigs. Am. J. Physiol. Endocrinol. Metab. 285(1): E40–E53. DOI: 10.1152/ajpendo.00563.2002

    PubMed  Google Scholar 

  • Orellana R.A., Gazzaneo M.C., Wilson F.A., Nguyen H.V., Suryawan A., Almonaci R. & Davis T.A. 2009. Insulin accelerates global and mitochondrial protein synthesis rates in neonatal muscle during sepsis. FASEB J. 23 (Meeting Abstract Supplement): 33.2. http://www.fasebj.org/cgi/content/meeting abstract/23/1 MeetingAbstracts/33.2

  • Paul M.K. & Mukhopadhyay A.K. 2007. Cancer — the mitochondrial connection. Biologia 62(4): 371–380. DOI: 10.2478/s11756-007-0094-4

    Article  CAS  Google Scholar 

  • Penner G., Gang G., Sun X., Wray C. & Hasselgren, P.O. 2002. C/EBP DNA-binding activity is upregulated by a glucocorticoid-dependent mechanism in septic muscle. Am. J. Physiol. Regul. Integr. Comp. Physiol. 282(2): R439–R444. DOI: 10.1152/ajpregu.00512.2001

    PubMed  CAS  Google Scholar 

  • Qi D. & Rodrigues B. 2007. Glucocorticoids produce whole body insulin resistance with changes in cardiac metabolism. Am. J. Physiol. Endocrinol. Metab. 292(3): E654–E667. DOI: 10.1152/ajpendo.00453.2006

    Article  PubMed  CAS  Google Scholar 

  • Sandri M., Sandri C., Gilbert A., Skurk C., Calabria E., Picard A., Walsh K., Schiaffino S., Lecker S.H. & Goldberg A.L. 2004. Foxo transcription factors induce the atrophy-related ubiquitin ligase atrogin-1 and cause skeletal muscle atrophy. Cell 117(3): 399–412. DOI: 10.1016/S0092-8674(04)00400-3

    Article  PubMed  CAS  Google Scholar 

  • Schakman O., Gilson H. & Thissen J.P. 2008a. Mechanisms of glucocorticoid-induced myopathy. J. Endocrinol. 197(1): 1–10. DOI: 10.1677/JOE-07-0606

    Article  PubMed  CAS  Google Scholar 

  • Schakman O., Kalista S., Bertrand L., Lause P., Verniers J., Ketelslegers J.M. & Thissen J.P. 2008b. Role f Akt/GSK-3β/β-Catenin transduction pathway in the muscle anti-atrophy action of insulin-like growth factor-I in glucocorticoid-treated rats. Endocrinology 149(8): 3900–3908. DOI: 10.1210/en.2008-0439

    Article  PubMed  CAS  Google Scholar 

  • Shah O.J., Kimball S.R. & Jefferson L.S. 2000a. Acute attenuation of translation initiation and protein synthesis by glucocorticoids in skeletal muscle. Am. J. Physiol. Endocrinol. Metab. 278(1): E76–E82.

    PubMed  CAS  Google Scholar 

  • Shah O.J., Kimball S.R. & Jefferson L.S. 2000b. Among translational effectors, p70S6k is uniquely sensitive to inhibition by glucocorticoids. Biochem. J. 347(Pt2): 389–397. PMID: 10749668

    Article  PubMed  CAS  Google Scholar 

  • Stump C.S., Short K.R.., Bigelow M.L., Schimke J.M. & Sreekumaran N.K. 2003. Effect of insulin on human skeletal muscle mitochondrial ATP production, protein synthesis, and mRNA transcripts. PNAS 100(13): 7996–8001. DOI: 10.1073/pnas.1332551100

    Article  PubMed  CAS  Google Scholar 

  • Yuan L., Lin H., Jiang K.J., Jiao H.C. & Song Z.G.. 2008. Corticosterone administration and high-energy feed results in enhanced fat accumulation and insulin resistance in broiler chickens. Brit. Poultry Sci. 49(4): 487–495. DOI: 10.1080/00071660802251731

    Article  CAS  Google Scholar 

  • Zheng B., Ohkawa S., Li H., Roberts-Wilson T.K. & Russ Price S. 2010. FOXO3a mediates signaling crosstalk that coordinates ubiquitin and atrogin-1/MAFbx expression during glucocorticoid-induced skeletal muscle atrophy. FASEB J. 24(8): 2660–2669. DOI: 10.1096/fj.09-151480

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. College of Animal Science and Veterinary Medicine, Shanxi Agricultural University, Taigu, Shanxi, 030801, P.R. China

    Jian Qin, Rong Du, Yaqun Yang, Hongqiang Zhang & Ying Zhou

  2. Center for Electron Microscope, College of Information Science and Engineering, Shanxi Agricultural University, Taigu, Shanxi, 030801, P.R. China

    Jian Qin

Authors
  1. Jian Qin
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rong Du
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yaqun Yang
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Hongqiang Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Ying Zhou
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Rong Du.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Qin, J., Du, R., Yang, Y. et al. Effect of insulin on dexamethasone-induced ultrastructural changes in skeletal and cardiac muscle. Biologia 67, 602–609 (2012). https://doi.org/10.2478/s11756-012-0031-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.2478/s11756-012-0031-z

Key words

Search

Navigation