Details

Autor(en) / Beteiligte

• Fritsche, Andreas
• Madaus, Alexander
• Renn, Walter
• Tschritter, Otto
• Teigeler, Anna
• Weisser, Melanie
• Maerker, Elke
• Machicao, Fausto
• Häring, Hans
• Stumvoll, Michael

Titel

The Prevalent Gly1057Asp Polymorphism in the Insulin Receptor Substrate-2 Gene Is Not Associated with Impaired Insulin Secretion

Ist Teil von

• The journal of clinical endocrinology and metabolism, 2001-10, Vol.86 (10), p.4822-4825

Ort / Verlag

Endocrine Society

Erscheinungsjahr

2001

Link zum Volltext

Quelle

Oxford Journals 2020 Medicine

Beschreibungen/Notizen

• Disruption of the insulin receptor substrate-2 was shown to cause type 2 diabetes in mice. This could be largely attributed to abnormalβ -cell development. In humans, a prevalent polymorphism in insulin receptor substrate-2 (Gly1057Asp) was not found be associated with type 2 diabetes in linkage and association studies. We tested the hypothesis that an extreme challenge of the β cell might reveal subtle abnormalities in carriers of this polymorphism undetected by conventional insulin secretion tests. Therefore, in addition to assessing β-cell function by oral glucose tolerance testing (n = 318, normal glucose tolerance), we measured the secretory response to maximal stimulation by hyperglycemia (10 mm), glucagon-like peptide-1, and arginine administered in an additive fashion (n = 77, nondiabetic). The allelic frequency of the Asp allele was ∼37%. Neither the β-cell function indices from the oral glucose tolerance test nor the secretory response during the hyperglycemic clamp differed measurably between carriers and controls. Moreover, maximal plasma C-peptide concentrations in response to the combined glucose, glucagon-like peptide-1, and arginine stimulus was not different between Gly/Gly (10,745 ± 1,186 pmol/liter) and X/Asp (10,800 ± 490 pmol/liter, P = 0.99). In conclusion, our findings strongly suggest that the Gly1057Asp polymorphism in insulin receptor substrate-2 is not associated withβ -cell dysfunction. The normal maximal insulin secretory response makes it unlikely that this common polymorphism results in abnormalβ -cell development.