We investigated the significance of Gly1057Asp and Leu647Val insulin receptor substrate (IRS)-2 polymorphisms in two Italian cohorts comprising 186 glucose-tolerant subjects and 240 subjects with type 2 diabetes from the Lazio region (i.e. representative of central Italy), and 123 glucose-tolerant subjects from the Sicily region (i.e. representative of south Italy). The allelic frequency of Gly1057Asp variant did not differ between diabetics (32.9%) and nondiabetic subjects, whatever their ethnicity was (35.8% and 33.7% from Lazio and Sicily, respectively). As compared with Gly/Gly subjects within each group, Asp/Asp individuals showed no differences in quantitative traits, including fasting insulin and C-peptide, and several indices of insulin sensitivity and secretion. Only one of the diabetic patients was heterozygous for the Leu647Val variant, and none of the control subjects carried this variant. This patient had three children who were also heterozygous for this variant. They were glucose tolerant, and their insulin sensitivity and insulin secretion indices were within the range of age-matched controls. We also analyzed IRS-2 function in fibroblasts from carriers of Gly1057Asp or Leu647Val variant. No defects in IRS-2 expression, insulin-stimulated phosphorylation, or binding to the p85 subunit of phosphatidylinositol 3-kinase were observed. These results strongly argue against a major role of IRS-2 polymorphisms in the pathogenesis of type 2 diabetes.

D'Alfonso, R., Marini, M., Frittitta, L., Sorge, R., Frontoni, S., Porzio, O., et al. (2003). Polymorphisms of the insulin receptor subtrate-2 in patients with type 2 diabetes. THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, 88(1), 317-322 [10.1210/jc.2002-020807].

Polymorphisms of the insulin receptor subtrate-2 in patients with type 2 diabetes

D'ALFONSO, ROSSELLA;MARINI, MARIA ADELAIDE;SORGE, ROBERTO PIETRO;FRONTONI, SIMONA;PORZIO, OTTAVIA;LAURO, DAVIDE;GAMBARDELLA, SERGIO;FEDERICI, MASSIMO;LAURO, RENATO;SESTI, GIORGIO
2003-01

Abstract

We investigated the significance of Gly1057Asp and Leu647Val insulin receptor substrate (IRS)-2 polymorphisms in two Italian cohorts comprising 186 glucose-tolerant subjects and 240 subjects with type 2 diabetes from the Lazio region (i.e. representative of central Italy), and 123 glucose-tolerant subjects from the Sicily region (i.e. representative of south Italy). The allelic frequency of Gly1057Asp variant did not differ between diabetics (32.9%) and nondiabetic subjects, whatever their ethnicity was (35.8% and 33.7% from Lazio and Sicily, respectively). As compared with Gly/Gly subjects within each group, Asp/Asp individuals showed no differences in quantitative traits, including fasting insulin and C-peptide, and several indices of insulin sensitivity and secretion. Only one of the diabetic patients was heterozygous for the Leu647Val variant, and none of the control subjects carried this variant. This patient had three children who were also heterozygous for this variant. They were glucose tolerant, and their insulin sensitivity and insulin secretion indices were within the range of age-matched controls. We also analyzed IRS-2 function in fibroblasts from carriers of Gly1057Asp or Leu647Val variant. No defects in IRS-2 expression, insulin-stimulated phosphorylation, or binding to the p85 subunit of phosphatidylinositol 3-kinase were observed. These results strongly argue against a major role of IRS-2 polymorphisms in the pathogenesis of type 2 diabetes.
Pubblicato
Rilevanza internazionale
Articolo
Sì, ma tipo non specificato
Settore MED/13 - Endocrinologia
Settore MED/09 - Medicina Interna
Settore MED/50 - Scienze Tecniche Mediche Applicate
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
English
Con Impact Factor ISI
HOMEOSTASIS MODEL ASSESSMENT; GLUCOSE-TOLERANCE; SUBSTRATE-2 GENE; IRS-2; SENSITIVITY; RESISTANCE; SECRETION; SYSTEM
D'Alfonso, R., Marini, M., Frittitta, L., Sorge, R., Frontoni, S., Porzio, O., et al. (2003). Polymorphisms of the insulin receptor subtrate-2 in patients with type 2 diabetes. THE JOURNAL OF CLINICAL ENDOCRINOLOGY AND METABOLISM, 88(1), 317-322 [10.1210/jc.2002-020807].
D'Alfonso, R; Marini, Ma; Frittitta, L; Sorge, Rp; Frontoni, S; Porzio, O; Mariani, L; Lauro, D; Gambardella, S; Trischitta, V; Federici, M; Lauro, R; Sesti, G
Articolo su rivista
File in questo prodotto:
Non ci sono file associati a questo prodotto.

I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.

Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2108/50473
Citazioni
  • ???jsp.display-item.citation.pmc??? ND
  • Scopus 25
  • ???jsp.display-item.citation.isi??? 23
social impact