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Exp Clin Endocrinol Diabetes 2008; 116(10): 606-613
DOI: 10.1055/s-2008-1073126
Article

© Georg Thieme Verlag KG Stuttgart · New York

Metabolic Profile and Nitric Oxide Synthase Expression of Skeletal Muscle Fibers are Altered in Patients with Type 1 Diabetes

K. Fritzsche 1 , M. Blüher 2 , S. Schering 1 , I. B. Buchwalow 3 , M. Kern 2 , A. Linke 4 , A. Oberbach 2 , V. Adams 4 , K. Punkt 1
  • 1Institute of Anatomy, University of Leipzig, Germany
  • 2Department of Medicine, University of Leipzig, Leipzig, Germany
  • 3Gerhard Domagk Institute of Pathology, University of Münster, Germany
  • 4Heart Center, Department of Cardiology, University of Leipzig, Leipzig, Germany
Further Information

Publication History

received 04.02.2008 first decision 11.03.2008

accepted 19.03.2008

Publication Date:
09 May 2008 (online)

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Abstract

We investigate muscle fiber composition, fiber-specific glycolytic and oxidative enzyme capacity and nitric oxide synthase (NOS) expression in skeletal muscle of patients with type 1 diabetes (T1D) compared to individuals with normal glucose tolerance (NGT). Vastus lateralis muscle was obtained by percutaneous biopsy from 7 T1D patients and 10 healthy controls with similar characteristics. Using cytophotometry, muscle fiber composition and fiber type–specific glycolytic and oxidative enzyme activities were measured in slow oxidative (SO), fast oxidative glycolytic (FOG) and fast glycolytic (FG) fibers. In addition, NOS 1-3 protein expression was mea­sured. The glycolytic fiber fraction was 1.4 fold higher, whereas FOG and SO fiber fractions were significantly reduced by 13.5% and 6.2% in skeletal muscle from T1D patients. Glycolytic enzyme activities and fiber-specific ratio of glycolytic relative to oxidative enzyme activity were significantly higher in all fiber types of T1D patients and correlated with HbA1c. Expression of NOS1-3 isoforms was reduced in skeletal muscle of T1D subjects. Increased glycolytic enzyme activity in muscle of T1D patients is most likely due to both a higher number of fast glycolytic fibers and a shift towards increased glycolytic metabolism in all fiber types. Alterations in muscle fiber distribution and enzyme activities seem to be due to impaired long-term glycemic control.

Key words

skeletal muscle fiber type - type 1 diabetes

References

  • 1 Bruce CR, Anderson MJ, Carey AL, Newman DG, Bonen A, Kriketos AD, Cooney GJ, Hawley JA. Muscle oxidative capacity is a better predictor of insulin sensitivity than lipid status.  J Clin Endocrinol Metab. 2003;  88 5444-5451
    CrossrefPubMedGoogle Scholar
  • 2 Buchwalow IB. Increasing the power of immunohistochemistry.  Proc Royal Micr Soc. 2001;  36 57-59
    PubMedGoogle Scholar
  • 3 Crowther GJ, Milstein JM, Jubrias SA, Kushmerick MJ, Gronka RK, Conley KE. Altered energetic properties in skeletal muscle of men with well-controlled insulin-dependent (type 1) diabetes.  Am J Phys Endocrinol Metab. 2003;  284 E655-E662
    PubMedGoogle Scholar
  • 4 Expert Committee on the Diagnosis Classification of Diabetes Mellitus: . Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.  Diabetes Care. 2000;  23 S4-S19
    PubMedGoogle Scholar
  • 5 Gaster M, Staehr P, Beck-Nielsen H, Schroder HD, Handberg A. GLUT4 is reduced in slow muscle fibers of type 2 diabetic patients.  Diabetes. 2001;  50 1324-1329
    CrossrefPubMedGoogle Scholar
  • 6 Gath I, Closs EI, Gödtel-Armbrust U, Schmitt S, Nakane M, Wessler I, Förstermann U. Inducible NO synthase II and neuronal NO synthase I are constitutively expressed in different structures of guinea pig skeletal muscle: implications for contractile function.  FASEB J. 1996;  10 1614-1620
    CrossrefPubMedGoogle Scholar
  • 7 Guth L, Samaha FJ. Procedure for the histochemical demonstration of actomyosin ATPase.  Exp Neurol. 1970;  28 365-367
    CrossrefPubMedGoogle Scholar
  • 8 He J, Watkins S, Kelley DE. Skeletal muscle lipid content and oxidative enzyme activity in relation to muscle fiber type in type 2 diabetes and obesity.  Diabetes. 2001;  50 817-823
    CrossrefPubMedGoogle Scholar
  • 9 Hickey MS, Carey JO, Azevedo JL, Houmard JA, Pories WJ, Israel RG, Dohm GL. Skeletal muscle fiber composition is related to adiposity and in vitro glucose transport rate in humans.  Am J Physiol. 1995;  268 E453-E457
    PubMedGoogle Scholar
  • 10 Johansson BL, Wahren J, Pernow J. C-peptide increases forearm blood flow in patients with type 1 diabetes via a nitric oxide-dependent mechanism.  Am J Phys Endocrinol Metab. 2003;  285 E864-E870
    PubMedGoogle Scholar
  • 11 Kelley DE, He J, Menshikova EV, Ritov VB. Dysfunction of mitochondria in human skeletal muscle in type 2 diabetes.  Diabetes. 2002;  51 2944-2950
    CrossrefPubMedGoogle Scholar
  • 12 Kelley D, Mandarino L. Fuel selection in human skeletal muscle in insulin resistance: a re-examination.  Diabetes. 2000;  49 677-683
    CrossrefPubMedGoogle Scholar
  • 13 Kobzik L, Stringer B, Balligand JL, Reid MB, Stamler JS. Endothelial type nitric oxide synthase in skeletal muscle fibers: mitochondrial relationships.  Bioch Biophys Res Comm. 1995;  211 375-381
    CrossrefPubMedGoogle Scholar
  • 14 Lillioja S, Young AA, Culter CL, Ivy JL, Abbott WG, Zawadzki JK, Yki-Jarvinen H, Christin L, Secomb TW, Bogardus C. Skeletal muscle capillary density and fiber type are possible determinants of in vivo insulin resistance in man.  J Clinical Invest. 1987;  80 415-424
    CrossrefPubMedGoogle Scholar
  • 15 Lithell H, Lindgarde F, Hellsing K, Lundqvist G, Nygaard E, Vessby B, Saltin B. Body weight, skeletal muscle morphology, and enzyme activities in relation to fasting serum insulin concentration and glucose tolerance in 48-year-old men.  Diabetes. 1981;  30 19-25
    CrossrefPubMedGoogle Scholar
  • 16 Lojda Z, Gutmann E. Histochemistry of some acid hydrolases in striated muscles of the rat.  Histochemistry. 1976;  49 337-342
    CrossrefPubMedGoogle Scholar
  • 17 Oberbach A, Bossenz Y, Lehmann S, Niebauer J, Adams V, Paschke R, Schon MR, Blüher M, Punkt K. Altered fiber distribution and fiber-specific glycolytic and oxidative enzyme activity in skeletal muscle of patients with type 2 diabetes.  Diabetes Care. 2006;  27 895-900
    PubMedGoogle Scholar
  • 18 Petersen KF, Dufour S, Befroy D, Garcia R, Shulman GI. Impaired mitochondrial activity in the insulin-resistant offspring of patients with type 2 diabetes.  N Engl J Med. 2004;  350 664-671
    CrossrefPubMedGoogle Scholar
  • 19 Punkt K. Fibre types in skeletal muscles.  Adv Anat Embryol Cell Biol. 2002;  162 1-112
    PubMedGoogle Scholar
  • 20 Punkt K, Naupert A, Wellner M, Asmussen G, Schmidt C, Buchwalow IB. Nitric oxide synthase II in rat skeletal muscles.  Histochem Cell Biol. 2002;  118 371-379
    CrossrefPubMedGoogle Scholar
  • 21 Punkt K, Schering S, Fritzsche M, Asmussen G, Minin EA, Samoilova VE, Muller FU, Schmitz W, Hasselblatt M, Paulus W, Muller-Werdan U, Slezak J, Koehler G, Boecker W, Buchwalow IB. Fibre-related nitric oxide synthase (NOS) in Duchenne muscular dystrophy.  Acta Histochem. 2007;  109 228-236
    CrossrefPubMedGoogle Scholar
  • 22 Simoneau JA, Bouchard C. Human variation in skeletal muscle fiber-type proportion and enzyme activities.  Am J Physiol. 1989;  257 E567-E572
    PubMedGoogle Scholar
  • 23 Simoneau JA, Colberg SR, Thaete FL, Kelley DE. Skeletal muscle glycolytic and oxidative enzyme capacities are determinants of insulin sensitivity and muscle composition in obese women.  FASEB J. 1995;  9 273-278
    CrossrefPubMedGoogle Scholar
  • 24 Simoneau JA, Kelley DE. Altered glycolytic and oxidative capacities of skeletal muscle contribute to insulin resistance in type 2 diabetes.  J Appl Phys. 1997;  83 166-171
    PubMedGoogle Scholar
  • 25 Simoneau JA, Veerkamp JH, Turcotte LP, Kelley DE. Markers of capacity to utilize fatty acids in human skeletal muscle: relation to insulin resistance and obesity and effects of weight loss.  FASEB J. 1999;  13 2051-2060
    CrossrefPubMedGoogle Scholar
  • 26 Toft I, Lindal S, Bønaa KH, Jenssen T. Quantitative measurement of muscle fiber composition in a normal population.  Muscle Nerve. 2003;  28 101-108
    CrossrefPubMedGoogle Scholar
  • 27 Laarse WJ Van der, Diegenbach PC, Hemminga MA. Calcium-stimulated myofibrillar ATPase activity correlates with shortening velocity of muscle fibres in Xenopis laevis.  J Histochem Cytochem. 1986;  18 487-496
    PubMedGoogle Scholar

Correspondence

M. BlüherMD 

University of Leipzig

Department of Medicine

Ph.-Rosenthal-Str. 27

04103 Leipzig

Germany

Phone: +49/341/971 59 84

Fax: +49/341/972 24 39

Email: bluma@medizin.uni-leipzig.de

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