Download PDF
Horm Metab Res 2009; 41(3): 213-220
DOI: 10.1055/s-0028-1105919
Animals, Clinical

© Georg Thieme Verlag KG Stuttgart · New York

Effect of Miglitol, an α-Glucosidase Inhibitor, on Atherogenic Outcomes in Balloon-injured Diabetic Rats

A. Hirata 1 , M. Igarashi 1 , H. Iwai 1 , M. Tominaga 1
  • 1Department of Laboratory Medicine, Yamagata University School of Medicine, Yamagata, Japan
Further Information

Publication History

received 10.04.2008

accepted 02.10.2008

Publication Date:
15 December 2008 (online)

Also available at
    Permissions and Reprints

Abstract

This study investigates the effects of miglitol, an α-glucosidase inhibitor, on the development of balloon-injured neointimal thickening in left common carotid artery, and the changes of glucose metabolism and inflammatory responses in Wistar fatty rats, an obese-hyperglycemic animal model, and their littermates, Wistar lean rats. Miglitol was orally administered at 40 mg/100 g of high-fat diet containing 45% kcal as fat to 12-week-old rats for 29 days, and age-matched rats without the agent were used as the respective controls. Balloon catheterization in the left common carotid artery was performed on day 15, and the artery was removed on day 29. Compared with the area ratio of the neointima/media in fatty rats without treatment, those in fatty rats with miglitol and lean rats without treatment were significantly decreased to 80%. The administration of miglitol significantly decreased the levels of plasma glucose, glycoalbumin and high-sensitivity C-reactive protein, and elevated the high-density lipoprotein-cholesterol level in fatty rats. These findings suggest that miglitol could be effective for the suppression of atherogenic outcomes in diabetic Wistar fatty rat, suggesting that the agent may have clinical benefits and contribute to prevent diabetic macroangiopathy.

Key words

miglitol - α-glucosidase inhibitor - diabetes mellitus - Wistar fatty rat - balloon catheterization - neointimal thickening

References

  • 1 Kannel WB, MacGee DL. Diabetes and cardiovascular disease: The Framingham study.  JAMA. 1979;  241 2035-2038
    CrossrefPubMedGoogle Scholar
  • 2 Purnell JQ, Hokanson JE, Marcovina SM, Steffes MW, Cleary PA, Brunzell JD. Effect of excessive weight gain with intensive therapy of Type-1 diabetes on lipid levels and blood pressure.  JAMA. 1998;  280 140-146
    CrossrefPubMedGoogle Scholar
  • 3 Haffner SM, Lehto S, Rönnemaa T, Pyörälä K, Laakso M. Mortality from coronary heart diseases and in non-diabetic subjects with and without prior myocardial infarction.  N Eng J Med. 1998;  339 229-234
    CrossrefPubMedGoogle Scholar
  • 4 Reaven GM. Role of insulin resistance in human disease.  Diabetes. 1998;  37 1595-1606
    CrossrefPubMedGoogle Scholar
  • 5 Stratton IM, Adler AI, Neil HA, Matthews DR, Manley SE, Cull CA, Hadden D, Turner RC, Holman RR. Association of glycaemia with macrovascular and microvascular complications of type 2 diabetes (UKPDS 35): Prospective observational study.  BMJ. 2000;  321 405-412
    CrossrefPubMedGoogle Scholar
  • 6 Tominaga M, Eguchi H, Manaka H, Igarashi K, Kato T, Sekikawa A. Impaired glucose tolerance is a risk factor for cardiovascular disease, but not impaired fasting glucose: The Funagata Diabetes Study.  Diabetes Care. 1999;  22 920-924
    CrossrefPubMedGoogle Scholar
  • 7 DECODE study group . Glucose tolerance and cardiovascular mortality: Comparison of fasting and 2-h diagnostic criteria.  Ann Intern Med. 2001;  161 397-405
    CrossrefPubMedGoogle Scholar
  • 8 Kaline K, Bornstein SR, Bergmann A, Hauner H, Schwartz PE. The importance and effect of dietary fiber in diabetes prevention with particular consideration of whole grain products.  Horm Metab Res. 2007;  39 687-693
    Article in Thieme ConnectPubMedGoogle Scholar
  • 9 Jessen N, Selmer Buhl E, Pold R, Schmitz O, Lund S. A novel insulin sensitizer (S15511) enhances insulin-stimulated glucose uptake in rat skeletal muscles.  Horm Metab Res. 2008;  40 269-275
    Article in Thieme ConnectPubMedGoogle Scholar
  • 10 Hulin B. New hypoglycemic agents.  Prog Med Chem. 1994;  31 1-58
    PubMedGoogle Scholar
  • 11 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. STOP-NIDDM Trial Research Group . Acarbose for prevention of type 2 diabetes mellitus: The STOP-NIDDM randomized trial.  Lancet. 2002;  359 2072-2077
    CrossrefPubMedGoogle Scholar
  • 12 Chiasson JL, Josse RG, Gomis R, Hanefeld M, Karasik A, Laakso M. STOP-NIDDM Trial Research Group . Acarbose treatment and the risk of cardiovascular disease and hypertension in patients with impaired glucose tolerance: The STOP-NIDDM Trial.  JAMA. 2003;  290 486-494
    CrossrefPubMedGoogle Scholar
  • 13 Hanefeld M, Chiasson JL, Koehler C, Henkel E, Schaper F, Temelkova-Kurktschiev T. Acarbose slows progression of intima-dedia thickeness of the carotid arteries in subjects with impaired glucose tolerance.  Stroke. 2004;  35 1073-1078
    CrossrefPubMedGoogle Scholar
  • 14 Hanefeld M, Cagatay M, Petrowitsch T, Neuser D, Petzinna D, Rupp M. Acarbose reduces the risk for myocardial infarction in type 2 diabetic patients: Meta-analysis of seven long-term studies.  Eur Heart J. 2005;  25 10-16
    PubMedGoogle Scholar
  • 15 Yamasaki Y, Katakami N, Hayashi-Okano R, Matsuhisa M, Kajimoto Y, Kosugi, Hatano M, Hori M. glucosidase inhibitor reduces the progression of carotid intima-media thickeness.  Diabetes Res Clin Pract. 2005;  67 204-210
    CrossrefPubMedGoogle Scholar
  • 16 Bollen M, Stalmans W. The antiglycogenolytic action of 1-deoxynojirimycin results from a specific inhibition of the α-1,6-glucosidase activity of the debranching enzyme.  Eur J Biochem. 1989;  181 775-780
    CrossrefPubMedGoogle Scholar
  • 17 Bischoff H. Pharmacology of α-glucosidase inhibition.  Eur J Clin Invest. 1994;  24 ((Suppl 3)) 3-10
    CrossrefPubMedGoogle Scholar
  • 18 Bollen M, Vanderbroeck A, Stalmans W. 1-Deoxynojirimycin and related compounds inhibit glycogenolysis in the liver without affecting the concentration of phosphorylase a.  Biochem Phamacol. 1988;  37 593-600
    PubMedGoogle Scholar
  • 19 Axen KV, Li X, Sclafani A. Miglitol (Bay m 1099) treatment of diabetic hypothalamic-dietary obese rats improves islet response to glucose.  Obes Res. 1999;  7 83-89
    PubMedGoogle Scholar
  • 20 Russsel JC, Graham SE, Dolphin PJ. Glucose tolerance and insulin resistance in the JCR: LA-corpulent rat: Effect of miglitol (Bay m 1099).  Metabolism. 1999;  48 701-706
    CrossrefPubMedGoogle Scholar
  • 21 Wang N, Minatoguchi S, Chen X, Uno Y, Arai M, Lu CJ, Takemura G, Fujiwara T, Fujiwara H. Antidiabetic drug miglitol inhibits myocardial apoptosis involving decreased hydroxy radical production and Bax expression in an ischaemia/reperfusion rabbit heart.  Br J Phamacol. 2004;  142 983-990
    PubMedGoogle Scholar
  • 22 Ikeda H, Shino A, Matsuo T, Iwatsuka HZ, Suzuoki Z. A new geneti-cally obese-hyperglycemic rat (Wistar fatty).  Diabetes. 1981;  30 1045-1050
    CrossrefPubMedGoogle Scholar
  • 23 Heek M Van, Compton DS, France CF, Tedesco RP, Frawzi AB, Graziano MP, Sybertz EJ, Strader CD, Davis Jr HR. Diet-induced obese mice develop peripheral, but not central, resistance to leptin.  J Clin Invest. 1997;  99 385-390
    CrossrefPubMedGoogle Scholar
  • 24 Hirata A, Igarashi M, Yamaguchi H, Suwabe A, Daimon M, Kato T, Tominaga M. Nifedipine suppresses neointimal thickening by its inhibitory effect on vascular smooth muscle cell growth via a MEK-ERK pathway coupling with Pyk2.  Br J Pharmacol. 2000;  131 1521-1530
    CrossrefPubMedGoogle Scholar
  • 25 Igarashi M, Hirata A, Yamaguchi H, Tsuchiya H, Ohnuma H, Tominaga M, Daimon M, Kato T. Candesartan inhibits carotid intimal thickening and ameliorates insulin resistance in balloon-injured diabetic rats.  Hypertension. 2001;  38 1255-1259
    PubMedGoogle Scholar
  • 26 Igarashi M, Takeda Y, Ishibashi N, Takahashi K, Mori S, Tominaga M, Saito Y. Pioglitazone reduces smooth muscle cell density of rat carotid arterial intima induced by balloon catheterization.  Horm Metab Res. 1997;  29 444-449
    Article in Thieme ConnectPubMedGoogle Scholar
  • 27 Yamaguchi H, Igarashi M, Hirata A, Sugae N, Tsuchiya H, Jimbu Y, Tominaga M, Kato T. Altered PDGF-BB-induced p38 MAP kinase activation in diabetic vascular smooth muscle cells: Role of protein kinase C-δ.  Arterioscler Thromb Vasc Biol. 2004;  24 2095-2101
    CrossrefPubMedGoogle Scholar
  • 28 Aiello LP, Wong JS. Role of vascular endothelial growth factor in diabetic vascular complications.  Kidney Int. 2000;  77 ((Suppl)) S113-S119
    PubMedGoogle Scholar
  • 29 Greene D, Lattimer SA, Sima AAF. Sorbitol, phosphoinositides and sodium-potassium ATPase in the pathogenesis of diabetic complications.  N Engl J Med. 1987;  316 599-606
    PubMedGoogle Scholar
  • 30 Brownlee M, Cerami A, Vlassara H. Advanced glycosylation end products in tissue and biochemical basis of diabetic complications.  N Engl J Med. 1998;  318 1315-1321
    PubMedGoogle Scholar
  • 31 Williamson JR, Chang K, Frangos M, Hasan KS, Ido Y, Kawamura T, Nyengaard JR, Enden M van den, Kilo C, Tilton RG. Hypergly-cemic pseudhypoxia and diabetic complications.  Diabetes. 1993;  42 801-813
    CrossrefPubMedGoogle Scholar
  • 32 Sakakibara F, Hotta N, Koh N, Sakamoto N. Effects of high glucose concentrations and epalrestat on sorbitol and myo-inositol metabolism in cultured rabbit aortic smooth muscle cells.  Diabetes. 1993;  42 1594-1600
    CrossrefPubMedGoogle Scholar
  • 33 King GL, Kunisaki M, Nishi N, Inoguchi T, Shiba T, Xia P. Biochemical and molecular mechanisms in the development of diabetic vascular complications.  Diabetes. 1996;  45 ((Suppl. 3)) S105-S108
    CrossrefPubMedGoogle Scholar
  • 34 Meyers CC, Kashyad ML. Pharmacologic elevation of high-density lipoproteins: Recent insights on mechanism of action and atherosclerosis protection.  Curr Opin Cardiol. 2004;  19 366-373
    CrossrefPubMedGoogle Scholar
  • 35 Schofield I, Malik R, Izzard A, Austin C, Heagerty A. Vascular structural and functional changes in type 2 diabetes mellitus: Evidence for the roles of abnormal myogenic responsiveness and dyslipidemia.  Circulation. 2002;  106 3037-3043
    CrossrefPubMedGoogle Scholar
  • 36 Pandolfi A, Grilli A, Cilli C, Patruno A, Giaccari A, Silvestre S Di, Lutiis MA De, Pellegrini G, Capani F, Consoli A, Felaco M. Phenotype modulation in cultures of vascular smooth muscle cells from diabetic rats: Association with increased nitric oxide synthase expression and superoxide anion generation.  J Cell Physiol. 2003;  196 378-385
    CrossrefPubMedGoogle Scholar
  • 37 Igarashi M, Hirata A, Nozaki H, Kadomoto-Antsuki Y, Tominaga M. Role of angiotensin II type-1 and type-2 receptors on vasular smooth muscle cell growth and glucose metabolism in diabetic rats.  Diabetes Res Clin Pract. 2007;  75 267-277
    CrossrefPubMedGoogle Scholar
  • 38 Hanley AJ, Festa A, D’Agostino Jr RB, Wagenknecht LE, Savage PJ, Tracy RP, Saad MF, Haffner SM. Metabolic and inflammation variable clusters and prediction of type 2 diabetes: Factor analysis using directly measured insulin sensitivity.  Diabetes. 2004;  53 1773-1781
    CrossrefPubMedGoogle Scholar
  • 39 Schaumberg DA, Glynn RJ, Jenkins AJ, Lyons TJ, Rifai N, Manson JE, Ridker PM, Nathan DM. Effect of intensive glycemic control on levels of markers of inflammation in type 1 diabetes mellitus in the diabetes control and complications trial.  Circulation. 2005;  111 2446-2453
    CrossrefPubMedGoogle Scholar
  • 40 Alexandraki K, Piperi C, Kalofoutis C, Singh J, Alaveras A, Kalofoutis A. Inflammatory process in type 2 diabetes: The role of cytokines.  Ann N Y Acad Sci. 2006;  1084 89-117
    CrossrefPubMedGoogle Scholar
  • 41 Ridker PM, Rifal N, Rose L, Buring JE, Cook NR. Comparison of C-reactive protein and low-density lipoprotein cholesterol levels in the prediction of first cardiovascular events.  N Engl J Med. 2002;  347 1557-1565
    CrossrefPubMedGoogle Scholar
  • 42 Zhang H, Chen S, Deng X, Yamg X, Huang X. Danggui-Buxue-Tang deoction has an anti-inflammatory effects in diabetic atherosclerosis rat model.  Diabetes Res Clin Pract. 2006;  74 194-196
    CrossrefPubMedGoogle Scholar
  • 43 Yokoyama H, Kannno S, Ishimura I, Node K. Miglitol increases the adiponectin level and decreases urinary albumin excretion in patients with type 2 diabetes mellitus.  Metabolism. 2007;  56 1458-1463
    CrossrefPubMedGoogle Scholar

Correspondence

M. IgarashiMD 

Department of Laboratory Medicine

Yamagata University School of Medicine

2-2-2 Iida-nishi

Yamagata 990-9585

Japan

Phone: +81/23/628 54 06

Fax: +81/23/628 54 09

Email: migarasi@med.id.yamagata-u.ac.jp

      >