Bradykinin B₂ Receptor Gene C-58T Polymorphism and Insulin Resistance. A Study on Obese Patients

 

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Abstract

The bradykinin B₂ receptor (B₂R) gene is a candidate in the pathogenesis of insulin resistance, which often clusters with other abnormalities in metabolic syndrome. We investigated the distribution of the C-58T B₂R gene polymorphism within a population of overweight/obese patients (BMI ≥ 25 kg/m²) potentially characterised by different levels of insulin resistance. Patients with type 2 diabetes, dyslipidemia and hypertension were excluded in order to distinguish the effect of obesity on insulin sensitivity from that of confounding factors. Ninety-two unrelated adults (41 men and 51 women, aged 33.7 ± 11.6 years) were recruited by random sampling from a general population evaluated for cardiovascular risk stratification. Measurements included BMI, waist circumference, body composition, blood pressure, serum leptin, and lipid profile. Insulin sensitivity was calculated according to the homeostasis model assessment (HOMA) method. C-58T genotypes - CC (n = 20), CT (n = 47) and TT (n = 25) - were determined by restriction fragment-length polymorphism PCR. Patients subdivided on the basis of C-58T polymorphism, showed no difference in any of the parameters examined, including HOMA index values, after adjustment for age, sex, BMI and waist circumference. The results indicate that the C-58T B₂R gene polymorphism is not associated with different levels of insulin resistance within a population of obese patients.

References

• 1 Isami S, Kishikawa H, Araki E, Uehara M, Kaneko K, Shirotani T, Todaka T, Ura S, Motoyoshi S, Matsumoto K, Miyamura N, Shichiri M. Bradykinin enhances GLUT4 translocation through the increase of insulin receptor tyrosine kinase in primary adipocytes: evidence that bradykinin stimulates the insulin signalling pathway.  Diabetologia. 1996;  39 412-420
  PubMedGoogle Scholar
• 2 Figueroa C D, Dietze G, Muller-Esterl W. Immunolocalization of bradykinin B2 receptors on skeletal muscle cells.  Diabetes. 1996;  45 (suppl 1) S24-S28
  PubMedGoogle Scholar
• 3 Motoshima H, Araki E, Nishiyama T, Taguchi T, Kaneko T, Hirashima Y, Yoshizato K, Shirakami A, Sakai K, Kawashima J, Shirotani T, Kishikawa H, Shichiri M. Bradykinin enhances insulin receptor tyrosine kinase in 32D cells reconstituted with bradykinin and insulin signalling pathways.  Diabetes Res Clin Pract. 2000;  48 55-170
  PubMedGoogle Scholar
• 4 Duka I, Shenouda S, Johns C, Kintsurashvili E, Gavras I, Gavras H. Role of the B(2) receptor of bradykinin in insulin sensitivity.  Hypertension. 2001;  38 1355-1360
  CrossrefPubMedGoogle Scholar
• 5 Tomiyama H, Kushiro T, Abeta H, Ishii T, Takahashi A, Furukawa L, Asagami T, Hino T, Saito F, Otsuka Y, Korumatani H, Kobayashi F, Kanmatsuse K, Kajiwara N. Kinins contribute to the improvement of insulin sensitivity during treatment with angiotensin converting enzyme inhibitor.  Hypertension. 1994;  23 450-455
  PubMedGoogle Scholar
• 6 Morel Y, Gadient A, Keller U, Vadas L, Galay A. Insulin sensitivity in obese hypertensive dyslipidemic patients treated with enalapril or atenolol.  J Cardiovasc Pharmacol. 1995;  26 306-311
  PubMedGoogle Scholar
• 7 Braun A, Kammerer S, Maier E, Bohme E, Roscher A A. Polymorphisms in the gene for the human B2-bradykinin receptor: new tools assessing a genetic risk for bradykinin-associated diseases.  Immunopharmacology. 1996;  33 32-35
  CrossrefPubMedGoogle Scholar
• 8 Reaven G M. Banting Lecture 1988: role of insulin resistance in human disease.  Diabetes. 1988;  37 1595-1607
  CrossrefPubMedGoogle Scholar
• 9 DeFronzo R A, Ferrannini E. Insulin resistance: a multifaceted syndrome responsible for NIDDM, obesity, hypertension, dyslipidemia, and atherosclerotic cardiovascular disease.  Diabetes Care. 1991;  114 173-194
  PubMedGoogle Scholar
• 10 National Institutes of Health. National Heart, Lung and Blood Institute. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: the evidence report.  Obes Res. 1998;  6 (Suppl. 2) S51-S210
  PubMedGoogle Scholar
• 11 Heitmann B L. Prediction of body water and fat adult Danes from measurement of electrical impedance. A validation study.  Int J Obes. 1990;  14 789-902
  PubMedGoogle Scholar
• 12  . Report of the Expert Committee on the Diagnosis and Classification of Diabetes Mellitus.  Diabetes Care. 1998;  21 (suppl 1) S5-S19
  PubMedGoogle Scholar
• 13  . 1999 World Health Organization-International Society of Hypertension Guidelines for the management of hypertension.  J Hypertens. 1999;  17 151-183
  PubMedGoogle Scholar
• 14 Vettor R, De Pergola G, Pagano C, Englaro P, Laudadio E, Giorgino F, Blum W, Giorgino R, Federspil G. Gender differences in serum leptin in obese people: relationship with testosterone, body fat distribution, and insulin sensitivity.  Eur J Clin Invest. 1997;  27 1016-1024
  CrossrefPubMedGoogle Scholar
• 15 Matthews D R, Hosker J P, Rudenski A S, Naylor B A, Treacher D F, Turner R C. Homeostasis model assessment: insulin resistance and β cell function from fasting plasma glucose and insulin concentration in man.  Diabetologia. 1985;  28 412-419
  Google Scholar
• 16 Bonora E, Targher G, Alberiche M, Bonadonna R C, Saggiani F, Zenere M B, Monauni T, Muggeo M. Homeostasis model assessment closely mirrors the glucose clamp technique in the assessment of insulin sensitivity.  Diabetes Care. 2000;  23 57-63
  CrossrefPubMedGoogle Scholar
• 17 Sartori M T, Vettor R, De Pergola G, De Mitrio V, Maggiorato G, Della Mea P, Patrassi G M, Lombardi A M, Fabris R, Girolami A. Role of the 4G/5G polymorphism of PAI-1 gene promoter on PAI-1 levels in obese patients.  Thromb Haemost. 2001;  86 1161-1169
  PubMedGoogle Scholar
• 18 Mulatero P, Williams T A, Milan A, Paglieri C, Rabbia F, Fallo F, Veglio F. Blood pressure in patients with primary aldosteronism is influenced by bradykinin B₂ receptor and α-adducin gene polymorphism.  J Clin Endocrinol Metab. 2002;  87 3337-3343
  CrossrefPubMedGoogle Scholar
• 19 Gainer J V, Brown N J, Bachvarova M, Bastien L, Maltais I, Marceau F, Bachvarov D R. Altered frequency of a promoter polymorphism in the kinin B₂-receptor gene in hypertensive African-Americans.  Am J Hypertens. 2000;  13 1268-1273
  CrossrefPubMedGoogle Scholar
• 20 Tai E S, Emmanuel S C, Chew S K, Tan B Y, Tan C E. Isolated low HDL cholesterol: an insulin resistant state only in the presence of fasting hypertriglyceridemia.  Diabetes. 1999;  48 1088-1092
  PubMedGoogle Scholar
• 21 Szanto I, Kahan R. Selective interaction between leptin and insulin signalling pathways in hepatic cell line.  Proc Natl Acad Sci USA. 2000;  97 2355-2360
  CrossrefPubMedGoogle Scholar
• 22 Regoli D, Barabe J. Pharmacology of bradykinin and related kinins.  Pharmacol Rev. 1980;  32 1-46
  PubMedGoogle Scholar
• 23 Tsukahara Y, Itakura A, Ohno Y, Ando H, Mizutani S. Umbilical plasma kininase I activity in fetal hypoxya.  Horm Metab Res. 2003;  13 1268-1273
  PubMedGoogle Scholar
• 24 Ferrannini E, Buzzigoli G, Bonadonna R, Giorico M A, Oleggini M, Graziadei L, Pedrinelli R, Brandi L, Bevilacqua S. Insulin resistance and hypertension.  N Engl J Med. 1987;  317 350-356
  CrossrefPubMedGoogle Scholar

F. Fallo, M. D.

Department of Medical and Surgical Sciences · Clinica Medica 3 · University of Padua ·

Via Ospedale 105 · 35128 Padova · Italy

Phone: +39(49)8213018

Fax: +39(49)657391 ·

Email: francesco.fallo@unipd.it