Since the insulin receptor substrate-1 (IRS-1) is the major substrate of the insulin receptor tyrosine kinase and has been shown to activate phosphatidylinositol (PI) 3-kinase and promote GLUT4 translocation, the IRS-1 gene is a potential candidate for development of non-insulin-dependent diabetes mellitus (NIDDM).
Genetic contribution of polymorphism of the GLUT1 and GLUT4 genes to the susceptibility to type 2 (non-insulin-dependent) diabetes mellitus in different populations.
The nucleotide sequence of Glut4, a candidate gene for Nidd1nsy (a susceptibility gene for Type II diabetes) on Chromosome 11, encoding insulin-sensitive glucose transporter, was determined in NSY and C3H mice.
We examined the effect of troglitazone on the expression of glucose transporter 4 (GLUT4) in muscle and adipose tissue from Otsuka Long-Evans Tokushima Fatty (OLETF) rat, an animal model of obese type 2 diabetes mellitus.
The human insulin-responsive glucose transporter 4 gene (GLUT4) has been related to non-insulin-dependent diabetes mellitus (NIDDM) in several studies.
Compared with control patients, GLUT4 protein levels were 30% lower in human cardiac muscle biopsies from patients with HL and/or type 2 diabetes mellitus, whereas GLUT4 mRNA levels were unchanged.
In conclusion, the uncoupling of insulin action on Akt/AS160 signaling and glucose transport implicates defective GLUT4 trafficking as an early event in the pathogenesis of type 2 diabetes.
Type 2 diabetes mellitus and obesity are associated with impaired regulation of GLUT4 gene expression and elevated levels of free fatty acids and proinflammatory factors.
Gene expressions of insulin receptor (INSR), vitamin D receptor, insulin degrading enzyme, Akt, insulin receptor substrate-1 (IRS-1), IRS-2, glucose transporter 4 (GLUT4), and enzymes of the glycolytic pathway were decreased at least 50% in T2DM than in controls.
Adaptation to states of enhanced metabolic demand is associated with increased glucose metabolism and GLUT4 gene expression, whereas states of insulin resistance such as type 2 diabetes mellitus (DM2), obesity, and aging are associated with impaired regulation of GLUT4 gene expression and function.
The goal of the present study is to develop a cell-based assay for identifying negative regulators of GLUT4 translocation as potential targets for the treatment of Type 2 diabetes.
Haplotype analysis revealed that two common haplotypes H1 (111, P = 0.001, OR 1.23[1.08-1.40]) and H2 (222, P = 0.002 OR 0.73[0.59-0.89]) in STRA6, H6 (2121, P = 0.006, OR 1.69[1.51-2.48]) in RBP4 and H4 (2121, P = 0.01 OR 1.41[1.07-1.85]) in GLUT4 were associated with type 2 diabetes.
The GLUT4 gene was sequenced in 25 normal glucose tolerance (NGT) and 25 T2DM subjects, and the variants found were then genotyped by polymerase chain reaction-restriction fragment length polymorphism in a pilot study population of 552 NGT and 643 T2DM subjects, randomly selected from the Chennai Urban Rural Epidemiology Study.
GLUT4 protein levels may therefore play a role in the pathology behind type 2 diabetes mellitus among subgroups of patients, and this may explain the heterogeneous response to insulin treatment.
In conclusion, a single bout of exercise increased skeletal muscle GLUT4 mRNA expression in patients with T2D to a similar extent as in control subjects.
The changes in AMPK-α protein content significantly related (p < 0.001) to the changes in GLUT-4 translocation (r = 0.78) and Hb1Ac levels (r = -0.68), suggesting that AMPK signaling may be implicated in the effects of supplementation on glucose uptake in type 2 diabetes.
All our results have thus highlighted the potential of Rut as both a valuable lead compound for anti-T2DM drug discovery and a promising chemical probe for GLUT4 associated pathways exploration.
All our results have thus highlighted the potential of Rut as both a valuable lead compound for anti-T2DM drug discovery and a promising chemical probe for GLUT4 associated pathways exploration.