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Previous studies have suggested that, along with a decrease in GLUT-4 expression [67], [68], conditions of obesity and insulin resistance can be accompanied by increased expression of the constitutive glucose transporter GLUT-1 in adipose tissue (e.g., reference [69]).
We have also observed a decrease in Glut-4 mRNA in white fat of cachectic mice, which suggests altered glucose metabolism.
Interestingly, a decrease in GLUT-4 levels also occurred in CCR2 /– mice and may represent a potential explanation for lack of improvement in glucose-tolerance.
In cells treated with NSC-134754 (5 × GI50) for 6 or 24 h in hypoxia, an overall decrease in GLUT-1 staining compared with control cells was apparent.
Accordingly, after the initial increase, ROS production in normal chondrocytes exposed to high glucose concentrations for 18 hours returned to control levels, accompanying the decrease in GLUT-1 content – whereas ROS production remained elevated in OA chondrocytes, paralleling their inability to downregulate glucose uptake and the GLUT-1 content.
The plasma and myocardial adiponectin levels and the mRNA expression of myocardial adipoR2 are decreased, which may lead to the decrease in cardiac GLUT 4 and the increase in cardiac MCP-1 in diabetic rats.
Our results also indicate a marginal decrease in membrane GLUT-1 expression by prolonged hyperglycemia (slow onset).
Existing evidence indicates a decreased GLUT-1 activity and glucose clearance in chronic hyperglycemia, with a parallel decrease in expression of GLUT-1 at BBB [ 46], as confirmed by subsequent studies [ 47, 48].
The decrease of GLUT 4 expression in skeletal muscle was also reversed by the same repeated treatment rhodiola-water extract.
To determine the contribution of the major protein degradation pathways to the decrease in the total GLUT-1 protein content found in normal chondrocytes exposed to high glucose, specific inhibitors of the proteasome (MG-132) and lysosome (chloroquine) were used.
It would be interesting to know whether decrease in glucose uptake and GLUT protein levels in these cell types were related to the impairment of glucose metabolism in brain as indicated in METH abusers [21].
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