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Horm Metab Res 2008; 40(8): 528-532
DOI: 10.1055/s-2008-1073162
Original Basic

© Georg Thieme Verlag KG Stuttgart · New York

A High-fructose Diet Impairs Akt and PKCζ Phosphorylation and GLUT4 Translocation in Rat Skeletal Muscle

P. Li 1 , T. Koike 1 , 2 , B. Qin 1 , M. Kubota 1 , Y. Kawata 1 , Y. J. Jia 1 , Y. Oshida 1 , 2
  • 1Department of Sports Medicine, Graduate School of Medicine, Nagoya University, Nagoya, Japan
  • 2Research Center of Health, Physical Fitness and Sports, Nagoya University, Nagoya, Japan
Further Information

Publication History

received 16.05.2007

accepted 15.01.2008

Publication Date:
21 May 2008 (online)

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Abstract

The molecular mechanism of insulin resistance induced by high-fructose feeding is not fully understood. The present study investigated the role of downstream signaling molecules of phosphatidylinositol 3-kinase (PI3K) in the insulin-stimulated skeletal muscle of high-fructose-fed rats. Rats were divided into chow-fed and fructose-fed groups. The results of the euglycemic clamp study (insulin infusion rates: 6 mU/kg BW/min) showed a significant decrease in the glucose infusion rate (GIR) and the metabolic clearance rate of glucose (MCR) in fructose-fed rats compared with chow-fed rats. In skeletal muscle removed immediately after the clamp procedure, high-fructose feeding did not alter protein levels of protein kinase B (PKB/Akt), protein kinase C ζ (PKCζ), or glucose transporter 4 (GLUT4). However, insulin-stimulated phosphorylation of Akt and PKCζ and GLUT4 translocation to the plasma membrane were reduced. Our findings suggest that insulin resistance in fructose-fed rats is associated with impaired Akt and PKCζ activation and GLUT4 translocation in skeletal muscle.

Key words

insulin resistance - euglycemic clamp - protein kinase - glucose transporter - insulin signaling

References

  • 1 O’Doherty R, Stein D, Foley J. Insulin resistance.  Diabetologia. 1997;  40 ((Suppl 3)) B10-B15
    CrossrefPubMedSearch in Google Scholar
  • 2 Sleder J, Chen YD, Cully MD, Reaven GM. Hyperinsulinemia in fructose-induced hypertriglyceridemia in the rat.  Metabolism. 1980;  29 303-305
    CrossrefPubMedSearch in Google Scholar
  • 3 Thorburn AW, Storlien LH, Jenkins AB, Khouri S, Kraegen EW. Fructose-induced in vivo insulin resistance and elevated plasma triglyceride levels in rats.  Am J Clin Nutr. 1989;  49 1155-1163
    CrossrefPubMedSearch in Google Scholar
  • 4 Hwang IS, Ho H, Hoffman BB, Reaven GM. Fructose-induced insulin resistance and hypertension in rats.  Hypertension. 1987;  10 512-516
    CrossrefPubMedSearch in Google Scholar
  • 5 Kamari Y, Grossman E, Oron-Herman M, Peleg E, Shabtay Z, Shamiss A, Sharabi Y. Metabolic stress with a high carbohydrate diet increases adiponectin levels.  Horm Metab Res. 2007;  39 384-388
    Thieme ConnectPubMedSearch in Google Scholar
  • 6 Ohmura E, Hosaka D, Yazawa M, Tsuchida A, Tokunaga M, Ishida H, Minagawa S, Matsuda A, Imai Y, Kawazu S, Sato T. Association of free fatty acids (FFA) and tumor necrosis factor-alpha(TNF-alpha) and insulin-resistant metabolic disorder.  Horm Metab Res. 2007;  39 212-217
    Thieme ConnectPubMedSearch in Google Scholar
  • 7 Shibasaki M, Bujo H, Takahashi K, Murakami K, Unoki H, Saito Y. Catalytically inactive lipoprotein lipase overexpression increases insulin sensitivity in mice.  Horm Metab Res. 2006;  38 491-496
    Thieme ConnectPubMedSearch in Google Scholar
  • 8 Rösen P, Osmers A. Oxidative stress in young zucker rats with impaired glucose tolerance is diminished by acarbose.  Horm Metab Res. 2006;  38 575-580
    Thieme ConnectPubMedSearch in Google Scholar
  • 9 Qin B, Nagasaki M, Ren M, Bajotto G, Oshida Y, Sato Y. Cinnamon extract prevents the insulin resistance induced by a high-fructose diet.  Horm Metab Res. 2004;  36 119-125
    Thieme ConnectPubMedSearch in Google Scholar
  • 10 Bezerra RM, Ueno M, Silva MS, Tavares DQ, Carvalho CR, Saad MJ. A high fructose diet affects the early steps of insulin action in muscle and liver of rats.  J Nutr. 2000;  130 1531-1535
    CrossrefPubMedSearch in Google Scholar
  • 11 Ueno M, Bezerra RM, Silva MS, Tavares DQ, Carvalho CR, Saad MJ. A high-fructose diet induces changes in pp185 phosphorylation in muscle and liver of rats.  Braz J Med Biol Res. 2000;  33 1421-1427
    CrossrefPubMedSearch in Google Scholar
  • 12 Hyakukoku M, Higashiura K, Ura N, Murakami H, Yamaguchi K, Wang L, Furuhashi M, Togashi N, Shimamoto K. Tissue-specific impairment of insulin signaling in vasculature and skeletal muscle of fructose-fed rats.  Hypertens Res. 2003;  26 169-176
    CrossrefPubMedSearch in Google Scholar
  • 13 Tremblay F, Lavigne C, Jacques H, Marette A. Defective insulin-induced GLUT4 translocation in skeletal muscle of high fat-fed rats is associated with alterations in both Akt/protein kinase B and atypical protein kinase C (zeta/lambda) activities.  Diabetes. 2001;  50 1901-1910
    CrossrefPubMedSearch in Google Scholar
  • 14 Dombrowski L, Roy D, Marette A. Selective impairment in GLUT4 translocation to transverse tubules in skeletal muscle of streptozotocin-induced diabetic rats.  Diabetes. 1998;  47 5-12
    CrossrefPubMedSearch in Google Scholar
  • 15 King PA, Horton ED, Hirshman MF, Horton ES. Insulin resistance in obese Zucker rat (fa/fa) skeletal muscle is associated with a failure of glucose transporter translocation.  J Clin Invest. 1992;  90 1568-1575
    CrossrefPubMedSearch in Google Scholar
  • 16 Zierath JR, He L, Guma A, Odegoard Wahlstrom E, Klip A, Wallberg-Henriksson H. Insulin action on glucose transport and plasma membrane GLUT4 content in skeletal muscle from patients with NIDDM.  Diabetologia. 1996;  39 1180-1189
    CrossrefPubMedSearch in Google Scholar
  • 17 Oshida Y, Tachi Y, Morishita Y, Kitakoshi K, Fuku N, Han YQ, Ohsawa I, Sato Y. Nitric oxide decreases insulin resistance induced by high-fructose feeding.  Horm Metab Res. 2000;  32 339-342
    Thieme ConnectPubMedSearch in Google Scholar
  • 18 Oshida Y, Kako M, Nakai N, Shimomura Y, Li L, Sato J, Ohsawa I, Sato Y. Troglitazone improves insulin-stimulated glucose utilization associated with an increased muscle glycogen content in obese Zucker rats.  Endocr J. 1999;  46 723-730
    CrossrefPubMedSearch in Google Scholar
  • 19 Li L, Oshida Y, Kusunoki M, Yamanouchi K, Johansson BL, Wahren J, Sato Y. Rat C peptide I and II stimulate glucose utilization in STZ-induced diabetic rats.  Diabetologia. 1999;  42 958-964
    CrossrefPubMedSearch in Google Scholar
  • 20 Dombrowski L, Roy D, Marcotte B, Marette A. A new procedure for the isolation of plasma membranes, T tubules, and internal membranes from skeletal muscle.  Am J Physiol. 1996;  270 E667-E676
    PubMedSearch in Google Scholar
  • 21 Gavete ML, Martin MA, Alvarez C, Escriva F. Maternal food restriction enhances insulin-induced GLUT-4 translocation and insulin signaling pathway in skeletal muscle from suckling rats.  Endocrinology. 2005;  146 3368-3378
    CrossrefPubMedSearch in Google Scholar
  • 22 Koshinaka K, Oshida Y, Han YQ, Kubota M, Viana AY, Nagasaki M, Sato Y. Insulin-nonspecific reduction in skeletal muscle glucose transport in high-fat-fed rats.  Metabolism. 2004;  53 912-917
    CrossrefPubMedSearch in Google Scholar
  • 23 DeFronzo RA, Bonadonna RC, Ferrannini E. Pathogenesis of NIDDM. A balanced overview.  Diabetes Care. 1992;  15 318-368
    CrossrefPubMedSearch in Google Scholar
  • 24 DeFronzo RA, Jacot E, Jequier E, Maeder E, Wahren J, Felber JP. The effect of insulin on the disposal of intravenous glucose. Results from indirect calorimetry and hepatic and femoral venous catheterization.  Diabetes. 1981;  30 1000-1007
    CrossrefPubMedSearch in Google Scholar
  • 25 Accili D, Drago J, Lee EJ, Johnson MD, Cool MH, Salvatore P, Asico LD, Jose PA, Taylor SI, Westphal H. Early neonatal death in mice homozygous for a null allele of the insulin receptor gene.  Nat Genet. 1996;  12 106-109
    CrossrefPubMedSearch in Google Scholar
  • 26 Araki E, Lipes MA, Patti ME, Bruning JC, Haag  B III, Johnson RS, Kahn CR. Alternative pathway of insulin signaling in mice with targeted disruption of the IRS-1 gene.  Nature. 1994;  372 186-190
    CrossrefPubMedSearch in Google Scholar
  • 27 Tamemoto H, Kadowaki T, Tobe K, Yagi T, Sakura H, Hayakawa T, Terauchi Y, Ueki K, Kaburagi Y, Satoh S, Sekihara H, Yoshioka S, Horikoshi H, Furuta Y, Ikawa Y, Kasuga M, Yazaki Y, Aizama S. Insulin resistance and growth retardation in mice lacking insulin receptor substrate-1.  Nature. 1994;  372 182-186
    CrossrefPubMedSearch in Google Scholar
  • 28 Withers DJ, Gutierrez JS, Towery H, Burks DJ, Ren JM, Previs S, Zhang Y, Bernal D, Pons S, Shulman GI, Bonner-Weir S, White MF. Disruption of IRS-2 causes type 2 diabetes in mice.  Nature. 1998;  391 900-904
    CrossrefPubMedSearch in Google Scholar
  • 29 Cheatham B, Vlahos CJ, Cheatham L, Wang L, Blenis J, Kahn CR. Phosphatidylinositol 3-kinase activation is required for insulin stimulation of pp70 S6 kinase, DNA synthesis, and glucose transporter translocation.  Mol Cell Biol. 1994;  14 4902-4911
    CrossrefPubMedSearch in Google Scholar
  • 30 Liu LZ, Zhao HL, Zuo J, Ho SK, Chan JC, Meng Y, Fang FD, Tong PC. Protein kinase Czeta mediates insulin-induced glucose transport through actin remodeling in L6 muscle cells.  Mol Biol Cell. 2006;  17 2322-2330
    CrossrefPubMedSearch in Google Scholar
  • 31 Liu LZ, He AB, Liu XJ, Li Y, Chang YS, Fang FD. Protein kinase Czeta and glucose uptake.  Biochemistry. 2006;  71 701-706
    CrossrefPubMedSearch in Google Scholar
  • 32 Ueki K, Yamamoto-Honda R, Kaburagi Y, Yamauchi T, Tobe K, Burgering BM, Coffer PJ, Komuro I, Akanuma Y, Yazaki Y, Kadowaki T. Potential role of protein kinase B in insulin-induced glucose transport, glycogen synthesis, and protein synthesis.  J Biol Chem. 1998;  273 5315-5322
    CrossrefPubMedSearch in Google Scholar
  • 33 Tanti JF, Grillo S, Gremeaux T, Coffer PJ, Van Obberghen E, Le Marchand-Brustel Y. Potential role of protein kinase B in glucose transporter 4 translocation in adipocytes.  Endocrinology. 1997;  138 2005-2010
    CrossrefPubMedSearch in Google Scholar
  • 34 Wang Q, Somwar R, Bilan PJ, Liu Z, Jin J, Woodgett JR, Klip A. Protein kinase B/Akt participates in GLUT4 translocation by insulin in L6 myoblasts.  Mol Cell Biol. 1999;  19 4008-4018
    CrossrefPubMedSearch in Google Scholar
  • 35 Kim YB, Nikoulina SE, Ciaraldi TP, Henry RR, Kahn BB. Normal insulin-dependent activation of Akt/protein kinase B, with diminished activation of phosphoinositide 3-kinase, in muscle in type 2 diabetes.  J Clin Invest. 1999;  104 733-741
    CrossrefPubMedSearch in Google Scholar
  • 36 Kim YB, Zhu JS, Zierath JR, Shen HQ, Baron AD, Kahn BB. Glucosamine infusion in rats rapidly impairs insulin stimulation of phosphoinositide 3-kinase but does not alter activation of Akt/protein kinase B in skeletal muscle.  Diabetes. 1999;  48 310-320
    CrossrefPubMedSearch in Google Scholar
  • 37 Krook A, Roth RA, Jiang XJ, Zierath JR, Wallberg-Henriksson H. Insulin-stimulated Akt kinase activity is reduced in skeletal muscle from NIDDM subjects.  Diabetes. 1998;  47 1281-1286
    CrossrefPubMedSearch in Google Scholar
  • 38 Krook A, Kawano Y, Song XM, Efendic S, Roth RA, Wallberg-Henriksson H, Zierath JR. Improved glucose tolerance restores insulin-stimulated Akt kinase activity and glucose transport in skeletal muscle from diabetic Goto-Kakizaki rats.  Diabetes. 1997;  46 2110-2114
    CrossrefPubMedSearch in Google Scholar
  • 39 Kanoh Y, Sajan MP, Bandyopadhyay G, Miura A, Standaert ML, Farese RV. Defective activation of atypical protein kinase C zeta and lambda by insulin and phosphatidylinositol-3,4,5-(PO4)(3) in skeletal muscle of rats following high-fat feeding and streptozotocin-induced diabetes.  Endocrinology. 2003;  144 947-954
    CrossrefPubMedSearch in Google Scholar
  • 40 Bhanot S, Salh BS, Verma S, MacNeill JH, Pelech SL. In vivo regulation of protein-serine kinases by insulin in skeletal muscle of fructose-hypertensive rats.  Am J Physiol. 1999;  277 E299-E307
    PubMedSearch in Google Scholar
  • 41 Cushman SW, Wardzala LJ. Potential mechanism of insulin action on glucose transport in the isolated rat adipose cell. Apparent translocation of intracellular transport systems to the plasma membrane.  J Biol Chem. 1980;  255 4758-4762
    PubMedSearch in Google Scholar
  • 42 Barnard RJ, Youngren JF. Regulation of glucose transport in skeletal muscle.  Faseb J. 1992;  6 3238-3244
    CrossrefPubMedSearch in Google Scholar

Correspondence

Y. OshidaMD, PhD 

Department of Sports Medicine

Graduate School of Medicine

Nagoya University

464-8601 Nagoya

Japan

Phone: +81/52/789 39 61

Fax: +81/52/789 39 57

Email: oshida@htc.nagoya-u.ac.jp