Animal studies revealed that VK supplementation dose-dependently upregulated plasma cGas6; stimulated the protein expression of cGas6, PI3K, pAKT, and GLUT4 in skeletal muscle; and reduced hyperglycemia in HFD-fed T2D mice.
Solute carrier family 2 member 4- (SLC2A4-) retinol binding protein-4- (RBP4-) phosphoenolpyruvate carboxykinase 1 (PCK1)/phosphoinositide 3-kinase (PI3K) is an adipocyte derived "signalling pathway" that may contribute to the pathogenesis of type 2 diabetes mellitus (T2DM).
Expression of the glucose transporter GLUT4, encoded by Slc2a4 gene, is reduced in both type 1 and type 2 diabetes (T1D and T2D), contributing to glycemic impairment.
In the late 1980s, when GLUT4, the major insulin-regulated glucose transporter, was identified, my lab observed that it was downregulated in adipocytes but not in skeletal muscle in insulin-resistant states, such as obesity and type 2 diabetes, in humans and rodents.
The present study demonstrates that liquorice flavonoid oil (LFO) improves type 2 diabetes mellitus through GLUT4 translocation to the plasma membrane by activating both the adenosine monophosphate-activated protein kinase (AMPK) pathway and Akt pathway in muscle of KK-A<sup>y</sup> mice.
The aim of the present study was to determine the effect of pomegranate seed oil (PSO) on the GLUT-4 gene expression and glycemic control in obese people with T2DM.
However, it is currently unknown how insulin signaling targeting WNK1 regulates GLUT4 trafficking in skeletal muscle, and whether this regulation is perturbed in T2D.
The expressions of phosphatidylinositol-3-kinase (PI-3K), protein kinase B (Akt), glucose transporters-4 (GLUT4) Mrna, and p-PI-3K, p-Akt, GLUT4 protein involved in the PI-3K/Akt signaling pathway of T2DM were markedly up-regulated.
These findings unraveled a novel mechanism for IR that involves repression of GLUT4 by miR-17 and suggested miR-17 as a potential molecular target for the development of new therapeutic approaches for the treatment of T2DM.
This study produced new evidence that intermittent exposure to mild hypoxia (0.15 FiO2) for four weeks resulted in normalisation of FBG, improvement in whole body insulin sensitivity, and a significant increase of GLUT4 translocation in the skeletal muscle, that were similar to the effects of exercise intervention during the same time period, in mice with diet-induced type 2 diabetes.
Exercise was protective against paternal HF-diet-induced insulin resistance by increasing the expression of insulin signaling (GLUT4, IRS1 and PI3K) markers in skeletal muscle resulting in normal T2D risk.
The results of the present study show that DOPE retains cell surface GLUT4 by suppressing PKCα-driven endocytic internalization of GLUT4, to enhance glucose uptake into cells and restrict an increase in the blood glucose levels after glucose loading in type 2 DM.
The blood glucose level of DM_V rats was significantly reduced, while the glucose transporter 4 (GLUT4) expression and blood microcirculation of DM_V rats were significantly enhanced in comparison to those of DM rats.
The downregulation of phosphorylation-AKT (p-AKT) and glucose transporter-4 (GLUT4) in skeletal muscle of T2DM rats was restored and abnormal pathological changes in pancreas tissues were also improved.
Defects in translocation of the glucose transporter GLUT4 are associated with peripheral insulin resistance, preclinical diabetes, and progression to type 2 diabetes.
Molecular mechanism studies demonstrated impairment of signaling cascade, IRS1/PI3K/Akt/AMPK/p 38/GLUT4, in glucose metabolism in the skeletal muscle of T2D rats.
In patients with type 2 diabetes, the expression levels of glucose transporter 4 (GLUT‑4) in skeletal muscles are significantly decreased, indicating decreased glucose‑processing ability.
Thus, our results suggest that downregulation of GLUT4 in skeletal muscle may be associated with insulin resistance in chronic kidney disease and could lead to type 2 diabetes in predisposed animals.