Effect of the Gly972Arg, SNP43 and Prol2Ala polymorphisms of the genes IRS1
, CAPN10 and PPARG2 on secondary failure to sulphonylurea and metformin in patients with type 2 diabetes in Yucatan, Mexico.
As a sex-specific interaction between the IRS1 variant rs2943641 and dietary factors on risk of type 2 diabetes was observed in a prior report (26), statistical analysis was performed in men and women separately in both BPRHS and MESA.
In both BPRHS and MESA, no significant difference for anthropometric traits was observed among different IRS1 genotypes (see Supplemental Tables 1 and 2, which accompany the online version of this article at http://www.
We examined 1 tag SNP of IRS1 rs2943641 in each of 3 populations separately (Figs.
Metaanalysis indicated that the circulating 25(OH)D (continuous) showed a significant interaction with IRS1 variant rs2943641 on fasting insulin (pooled [beta] = -0.
In muscle increased levels of DAG and ceramide activate the serine kinase PKC [theta], which phosphorylates IRS1
at the Ser307 site and inhibits tyrosine phosphorylation resulting in attenuated downstream insulin signalling via IRS1
In linear regression analyses, IRS1 Gly972Arg was associated with none of the markers of glycaemia, insulin resistance or insulin sensitivity, both overall and in participants with and without diabetes taken separately, with no evidence of significant statistical interaction by diabetes status (all interaction p [greater than or equal to] 0.
Our study investigated the frequency of the IRS1 Gly972Arg variant in the mixed-ancestry population of SA.
Epidemiological studies on the association between the IRS1 Gly972Arg (rs1801278) SNP and various cardiometabolic traits have reported conflicting results.
It causes a 40-per-cent reduction in the IRS1
gene, and even more important, a 40-per-cent reduction in its activity.
In EAT, there were increases in the insulin receptor ( IR) and IR substrate 2 ( IRS2) mRNA, but CE-induced increases in mRNA expression of IRS1
, phosphoinositide-3-kinase, AKT1, glucose transporters 1 and 4, and glycogen synthase 1 expression and decreased trends in mRNA expression of glycogen synthase kinase 3beta were not statistically significant.
Among the intracellular components in the insulin-signaling pathway, IGF2 expression was the most abundant, followed by AKT1, IGF2R, INSR, IRS1
and IGF1R, but the mRNA levels of INS1, INS2, PIK3CB, and SHC1 were very low in the adipocytes.