IRS1G972R polymorphism and type 2 diabetes: a paradigm for the difficult ascertainment of the contribution to disease susceptibility of 'low-frequency-low-risk' variants.
A breakdown analysis by gender revealed that IRS‑1 promoter methylation was not associated with an increased risk of T2D for either gender (P>0.1), although there were significantly lower methy-lation levels of CpG1 (P=0.002) and CpG2 (P=0.043) within the IRS‑1 gene promoter in males than in females.
A low IRS-1 expression in fat cells is a marker of insulin resistance and risk for type 2 diabetes and is associated with evidence of early vascular complications.
A reduction in tyrosine phosphorylation of both the insulin receptor (IR) and the insulin receptor substrate-1 (IRS-1) has been noted in both animal and human type 2 diabetes.
Additional studies of IRS1 variation will be required to obtain a robust estimate of the overall contribution of IRS1 variation to type 2 diabetes susceptibility, but the current study suggests that previous studies have overestimated the magnitude of this effect.
Although IR and T2D may be mechanistically linked to CAD via subclinical atherosclerosis, an alternate mechanism for the IR-T2D-CAD associations at 2q36.3-IRS1 must be postulated.
Amino acid polymorphism Gly 972 Arg in IRS-1 is not associated to lower clamp-derived insulin sensitivity in young healthy first degree relatives of patients with type 2 diabetes.
Analysis of the phenotypes showed that patients with NIDDM who had IRS-1 variants did not differ in their degree of insulin resistance compared with patients without known IRS-1 polymorphisms.
Analysis of the phenotypes showed that patients with NIDDM who had IRS-1 variants did not differ in their degree of insulin resistance compared with patients without known IRS-1 polymorphisms.
As a consequence, mTORC1 downstream effects were also affected in T2D: feedback signaling by insulin to signal-mediator insulin receptor substrate-1 (IRS1) was attenuated, mitochondria were impaired and autophagy was strongly upregulated.
Associations between two single-nucleotide polymorphisms (rs1801278 and rs2943641) of insulin receptor substrate 1 gene and type 2 diabetes susceptibility: a meta-analysis.
Background Previous genome-wide association studies (GWAS) identified IGF1, IRS1, GCKR, PPARG, GCK1 and KCTD1 as candidate genes for insulin resistance and type 2 diabetes (T2D).
Because of the role of insulin receptor substrate-1 in insulin action, the insulin receptor substrate-1 gene is a candidate gene for noninsulin-dependent diabetes mellitus (NIDDM).
Beta-3-adrenergic receptor (beta-3-AR) and insulin receptor substrate 1 (IRS-1) have been implicated in the pathogenesis of obesity and in obesity related increase in insulin resistance which is associated with, among other diseases, dyslipidemia and type 2 diabetes mellitus.
Bone insulin signaling is known to support bone metabolism; therefore, we also tested the hypothesis that OVX DMII rats (DOVX) would exhibit greater reductions in the expression of proteins important in insulin signaling, including IRS-1, IRS-2, and IGF-1.
By using a Cox proportional hazard model, common variants in the PPARG (P12A), CAPN10 (SNP43 and 44), KCNJ11 (E23K), UCP2 (-866G>A), and IRS1 (G972R) genes were studied for their ability to predict T2D in 2,293 individuals participating in the Botnia study in Finland.
Carriers of the PPARγ variant allele had statistically significantly lower rates of type 2 diabetes (P = 0.04), lower BMI (P = 0.01), and HOMA scores [P = 0.004; non-Hispanic White (NHWs) only]; carriers of the TNF-α variant A allele had higher serum glucose (P = 0.004, NHW only); and the IRS-1 variant was associated with higher leptin levels (P = 0.003, Hispanics only).