Skip Navigation

This Article
Right arrow Full Text Freely available
Right arrow FREE Full Text (PDF) Freely available
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Add to My Personal Archive
Right arrow Download to citation manager
Right arrow Search for citing articles in:
ISI Web of Science (37)
Right arrowRequest Permissions
Google Scholar
Right arrow Articles by Mammarella, S.
Right arrow Articles by Cama, A.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Mammarella, S.
Right arrow Articles by Cama, A.
Social Bookmarking
Add to CiteULike   Add to Connotea   Add to Del.icio.us  
What's this?

Human Molecular Genetics, 2000, Vol. 9, No. 17 2517-2521
© 2000 Oxford University Press

Interaction between the G1057D variant of IRS-2 and overweight in the pathogenesis of type 2 diabetes

Sandra Mammarella1, Ferdinando Romano2, Annalisa Di Valerio1, Beatrice Creati1, Diana L. Esposito1, Raffaele Palmirotta1, Fabio Capani3, Paola Vitullo4, Giustino Volpe4, Pasquale Battista1, Fulvio Della Loggia5, Renato Mariani-Costantini1 and Alessandro Cama1,+

1Department of Oncology and Neurosciences, Section of Molecular Pathology, 2Department of Biomedical Sciences, Section of Epidemiology and Public Health and 3Department of Medicine and Aging Sciences, University ‘Gabriele D’Annunzio’, 66013 Chieti, Italy, 4Pierangeli Clinic, 65125 Pescara, Italy and 5Center for the Study of Diabetes, 66100 Chieti, Italy

The insulin receptor substrate-2 (IRS-2) is a major insulin signalling molecule. IRS-2 inactivation in mice induces a form of diabetes characterized by peripheral insulin resistance and reduced beta cell mass. We tested the hypothesis that a common non-conservative amino acid substitution of IRS-2 (G1057D) might interact with overweight in the pathogenesis of type 2 diabetes. The variant was genotyped in 193 Italian patients with type 2 diabetes and 206 control subjects. In the absence of overweight, the risk of type 2 diabetes decreased according to the dosage of the D1057 allele (odds ratio for GD genotype 0.46 [95% CI 0.25–0.86]; DD genotype 0.18 [0.04–0.68]; P for trend = 0.0012). Conversely, the interaction between overweight and genotype increased the risk of type 2 diabetes according to the dosage of the D1057 allele (odds ratio for GD genotype 2.50 [1.11–5.65]; DD genotype 5.74 [1.11–29.78]; P for trend = 0.0047). Among controls, fasting C-peptide levels, after adjustment for plasma glucose, were inversely related to the dosage of the D1057 allele (P = 0.020). This finding suggested that carriers of the D1057 allele may have higher insulin sensitivity and supported the protective effect of this allele. Conversely, among overweight patients there was a parallel increase in fasting plasma glucose (P for trend = 0.037) and fasting C-peptide according to the dosage of the D1057 allele, suggesting that higher insulin resistance and relative beta cell failure contributed to the increased risk of type 2 diabetes in overweight carriers of this allele. These data provide evidence for a strong association between type 2 diabetes and the G1057D common genetic variant of IRS-2, which appears to be protective against type 2 diabetes in a codominant fashion. Overweight appears to modify the effect of this polymorphism toward a higher risk of type 2 diabetes. Carriers of this polymorphism may represent an elective target for prevention of type 2 diabetes through preventing or treating excessive weight.

+ To whom correspondence should be addressed. Tel: +39 0871 355 4108 or 4102; Fax: +39 0871 3554110; Email: cama@unich.it


Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us    What's this?


This article has been cited by other articles:


Home page
 J Gerontol A Biol Sci Med SciHome page
M. Barbieri, M. R. Rizzo, M. Papa, V. Boccardi, A. Esposito, M. F. White, and G. Paolisso
The IRS2 Gly1057Asp Variant Is Associated With Human Longevity
J Gerontol A Biol Sci Med Sci, November 3, 2009; (2009) glp154v1.
[Abstract] [Full Text] [PDF]

Home page
 Am. J. Clin. Nutr.Home page
J. Shea, C. R French, J. Bishop, G. Martin, B. Roebothan, D. Pace, D. Fitzpatrick, and G. Sun
Changes in the transcriptome of abdominal subcutaneous adipose tissue in response to short-term overfeeding in lean and obese men
Am. J. Clinical Nutrition, January 1, 2009; 89(1): 407 - 415.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
G. Cai, S. A. Cole, N. F. Butte, V. S. Voruganti, and A. G. Comuzzie
A Quantitative Trait Locus on Chromosome 13q Affects Fasting Glucose Levels in Hispanic Children
J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4893 - 4896.
[Abstract] [Full Text] [PDF]

Home page
 GENES CELLSHome page
Y. Matsubara, I. Kawasaki, S. Urushiyama, T. Yasuda, M. Shirakata, Y. Iino, H. Shibuya, and Y. Yamanashi
The adaptor-like protein ROG-1 is required for activation of the Ras-MAP kinase pathway and meiotic cell cycle progression in Caenorhabditis elegans
Genes Cells, March 1, 2007; 12(3): 407 - 420.
[Abstract] [Full Text] [PDF]

Home page
 Hum ReprodHome page
G. Villuendas, J. I. Botella-Carretero, B. Roldan, J. Sancho, H. F. Escobar-Morreale, and J. L. S. Millan
Polymorphisms in the insulin receptor substrate-1 (IRS-1) gene and the insulin receptor substrate-2 (IRS-2) gene influence glucose homeostasis and body mass index in women with polycystic ovary syndrome and non-hyperandrogenic controls
Hum. Reprod., November 1, 2005; 20(11): 3184 - 3191.
[Abstract] [Full Text] [PDF]

Home page
 Cancer Epidemiol. Biomarkers Prev.Home page
C. Sweeney, M. A. Murtaugh, K. B. Baumgartner, T. Byers, A. R. Giuliano, J. S. Herrick, R. Wolff, B. J. Caan, and M. L. Slattery
Insulin-Like Growth Factor Pathway Polymorphisms Associated with Body Size in Hispanic and Non-Hispanic White Women
Cancer Epidemiol. Biomarkers Prev., July 1, 2005; 14(7): 1802 - 1809.
[Abstract] [Full Text] [PDF]

Home page
 Endocr. Rev.Home page
H. F. Escobar-Morreale, M. Luque-Ramirez, and J. L. San Millan
The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome
Endocr. Rev., April 1, 2005; 26(2): 251 - 282.
[Abstract] [Full Text] [PDF]

Home page
 CarcinogenesisHome page
K. Wagner, K. Hemminki, E. Grzybowska, R. Klaes, D. Butkiewicz, J. Pamula, W. Pekala, H. Zientek, D. Mielzynska, E. Siwinska, et al.
The insulin-like growth factor-1 pathway mediator genes: SHC1 Met300Val shows a protective effect in breast cancer
Carcinogenesis, December 1, 2004; 25(12): 2473 - 2478.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
W.-D. Li, C. Dong, D. Li, H. Zhao, and R. A. Price
An Obesity-Related Locus in Chromosome Region 12q23-24
Diabetes, March 1, 2004; 53(3): 812 - 820.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
N. Stefan, P. Kovacs, M. Stumvoll, R. L. Hanson, A. Lehn-Stefan, P. A. Permana, L. J. Baier, P. A. Tataranni, K. Silver, and C. Bogardus
Metabolic Effects of the Gly1057Asp Polymorphism in IRS-2 and Interactions With Obesity
Diabetes, June 1, 2003; 52(6): 1544 - 1550.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
R. D'Alfonso, M. A. Marini, L. Frittitta, R. Sorge, S. Frontoni, O. Porzio, L. M. Mariani, D. Lauro, S. Gambardella, V. Trischitta, et al.
Polymorphisms of the Insulin Receptor Subtrate-2 in Patients with Type 2 Diabetes
J. Clin. Endocrinol. Metab., January 1, 2003; 88(1): 317 - 322.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
D. A. Ehrmann, X. Tang, I. Yoshiuchi, N. J. Cox, and G. I. Bell
Relationship of Insulin Receptor Substrate-1 and -2 Genotypes to Phenotypic Features of Polycystic Ovary Syndrome
J. Clin. Endocrinol. Metab., September 1, 2002; 87(9): 4297 - 4300.
[Abstract] [Full Text] [PDF]

Home page
 HypertensionHome page
M. Abe, J. Nakura, M. Yamamoto, J. J. Jin, Z. Wu, Y. Tabara, Y. Yamamoto, M. Igase, K. Kohara, and T. Miki
Association of GNAS1 Gene Variant With Hypertension Depending on Smoking Status
Hypertension, September 1, 2002; 40(3): 261 - 265.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
L. M. 't Hart, G. Nijpels, J. M. Dekker, J. A. Maassen, R. J. Heine, and T. W. van Haeften
Variations in Insulin Secretion in Carriers of Gene Variants in IRS-1 and -2
Diabetes, March 1, 2002; 51(3): 884 - 887.
[Abstract] [Full Text] [PDF]

Home page
 J. Clin. Endocrinol. Metab.Home page
A. Fritsche, A. Madaus, W. Renn, O. Tschritter, A. Teigeler, M. Weisser, E. Maerker, F. Machicao, H. Haring, and M. Stumvoll
The Prevalent Gly1057Asp Polymorphism in the Insulin Receptor Substrate-2 Gene Is Not Associated with Impaired Insulin Secretion
J. Clin. Endocrinol. Metab., October 1, 2001; 86(10): 4822 - 4825.
[Abstract] [Full Text] [PDF]

Home page
 FASEB J.Home page
G. SESTI, M. FEDERICI, M. L. HRIBAL, D. LAURO, P. SBRACCIA, and R. LAURO
Defects of the insulin receptor substrate (IRS) system in human metabolic disorders
FASEB J, October 1, 2001; 15(12): 2099 - 2111.
[Abstract] [Full Text] [PDF]

Home page
 DiabetesHome page
H. Wang, J. Rissanen, R. Miettinen, P. Karkkainen, P. Kekalainen, J. Kuusisto, L. Mykkanen, P. Karhapaa, and M. Laakso
New Amino Acid Substitutions in the IRS-2 Gene in Finnish and Chinese Subjects With Late-Onset Type 2 Diabetes
Diabetes, August 1, 2001; 50(8): 1949 - 1951.
[Abstract] [Full Text] [PDF]


Disclaimer: Please note that abstracts for content published before 1996 were created through digital scanning and may therefore not exactly replicate the text of the original print issues. All efforts have been made to ensure accuracy, but the Publisher will not be held responsible for any remaining inaccuracies. If you require any further clarification, please contact our Customer Services Department.