Although the mechanisms underlying the regulation of IRS-1 in the nutrient-rich conditions associated with diabetes and insulin resistance have been well studied, those under nutrient-poor conditions remain unknown.
Erratum to: Metformin treatment ameliorates diabetes-associated decline in hippocampal neurogenesis and memory via phosphorylation of insulin receptor substrate 1.
The decreased hepatic expression of IRS1 and β-catenin in NAFLD is linked to histological progression such as ballooning, and might lead to diabetes as a result of impaired glucose metabolism.
Although chronic therapy with metformin fails to achieve recovery from hyperglycemia, a key feature of diabetes in middle-aged diabetic mice, it improves hippocampal-dependent spatial memory functions accompanied by increased phosphorylation of adenosine monophosphate-activated protein kinase (AMPK), atypical protein kinase C ζ (aPKC ζ), and insulin receptor substrate 1 (IRS1) at selective serine residues in the hippocampus.
Our study suggests that HD prevents the development of diabetes and improves renal function in the <i>db/db</i> mice and HD regulation of the IRS1-PI3K-GLUT signaling pathway significantly improves diabetic nephropathy.
Moreover, ER stress CHOP, GRP78 and ATF4 biomarkers level were significantly attenuated in PCr treated animals comparing to STZ diabetes associated liver-damage model with significant improving in insulin-resistance Akt and IRS-1.
Because IRS-1 is down-regulated in states of insulin resistance that occur in response to metabolic stresses such as obesity and cytokine stimulation, the findings provide a mechanism for understanding how patients with metabolic stress and/or diabetes are predisposed to developing vascular complications.
Proliferator-activated receptor gamma Pro12Ala interacts with the insulin receptor substrate 1Gly972Arg and increase the risk of insulin resistance and diabetes in the mixed ancestry population from South Africa.
The diabetes risk variant rs7578326 located near the IRS1 locus was associated with both macroscopic (OR = 0.73, p = 0.011) and microscopic (OR = 0.71, p = 0.009) infarct pathology.
We also observed a weak interaction of the IGF1R IVS2+46329T>C and IGF2R Ex45+11C>T (L2222L) genotypes with diabetes (P(interaction)=.05) and interaction of IGF2R and IRS1 genotypes with alcohol consumption (P(interaction)=.03 and .019, respectively) on increased pancreatic cancer risk.
These studies demonstrate that TF induces cellular insulin resistance in primary murine and human adipocytes through a reduction of IRS-1 expression and protein stability, raising concern about the potential for this fungicide to disrupt metabolism and thereby contribute to the pathogenesis of diabetes.
We provide such a demonstration here by showing that the hippocampal formation (HF) and, to a lesser degree, the cerebellar cortex in AD cases without diabetes exhibit markedly reduced responses to insulin signaling in the IR→IRS-1→PI3K signaling pathway with greatly reduced responses to IGF-1 in the IGF-1R→IRS-2→PI3K signaling pathway.
Notably, the body-fat-decreasing allele near IRS1 is associated with decreased IRS1 expression and with an impaired metabolic profile, including an increased visceral to subcutaneous fat ratio, insulin resistance, dyslipidemia, risk of diabetes and coronary artery disease and decreased adiponectin levels.
The ENPP1 121Gln and IRS-1 972Arg polymorphisms were detected in 28.7% and 18.1% of patients and associated with increased body weight/dyslipidaemia and diabetes risk, respectively.
Subjects with at least 1 copy of the Gly972Arg polymorphism of the IRS1 gene showed a greater risk for diabetes, with a crude odds ratio of 3.26 (95% confidence interval, 2.00-5.33); after adjusting for BMI, age, family history of T2D, and sex, the odds ratio was 2.91 (95% confidence interval, 1.73-4.90).
The X-Arg genotype of IRS-1 was significantly associated with a positive family history of diabetes in NGT (P = .006) and neared significance in GDM (P = .057).
The aim of this study was to evaluate the role of the IRS-1 gene G972R variant in 61 subjects with "uncomplicated" obesity [i.e. without diabetes, hypertension, dyslipidemia, coronary artery disease (CAD)], studied by hyperinsulinemic-euglycemic clamp.
Also, the diagnostic test to exclude diabetes amongst control subjects interacted with the association between the IRS-1Gly972Arg variant and Type 2 diabetes (p=0.03).
Investigating the causes of the reduced tyrosine phosphorylation of IRS-1, we found a more than twofold increase in the basal phosphorylation of IRS-1 on serine 636 in myotubes from patients with diabetes.
We conclude the following: 1) physiological hyperinsulinemia induces sustained activation of insulin-signaling molecules in human skeletal muscle; 2) the more distal insulin-signaling components (Akt, GSK-3) are activated much more rapidly than the proximal signaling molecules (IRTK as well as insulin receptor substrate 1 and phosphatidylinositol 3-kinase [Wojtaszewski et al., Diabetes 46:1775-1781, 1997]); and 3) prior exercise increases insulin stimulation of both glucose uptake and glycogen synthase activity in the absence of an upregulation of signaling events in human skeletal muscle.