Abstract
Quercetin (QC) is a dietary bioflavonoid that can be conjugated with nanoparticles to facilitate its brain bioavailability. We previously showed that quercetin-conjugated superparamagnetic iron oxide nanoparticles (QCSPIONs) reduced the level of blood glucose in diabetic rats. Glucose transporters (GLUTs), insulin-like growth factor-1 (IGF-1), and microRNA-29 (miR-29) play a critical role in brain glucose homeostasis. In the current study, we examined the effects of QCSPION on the expression of glucose metabolism-related genes, and the miR-29 family as a candidate regulator of glucose handling in the hippocampus of diabetic rats. Our in silico analyses introduce the miR-29 family as potential regulators of glucose transporters and IGF-1 genes. The expression level of the miR-29 family, IGF-1, GLUT1, GLUT2, GLUT3, and GLUT4 were measured by qPCR. Our results indicate that diabetes significantly results in upregulation of the miR-29 family and downregulation of the GLUT1, 2, 3, 4, and IGF-1 genes. Interestingly, QCSPIONs reduced miR-29 family expression and subsequently enhanced GLUT1, 2, 3, 4, and IGF-1expression. In conclusion, our findings suggest that QCSPION could regulate the expression of the miR-29 family, which in turn increases the expression of glucose transporters and IGF-1, thereby reducing diabetic complications.
Highlights
Quercetin (QC) is a dietary bioflavonoid that can be conjugated with nanoparticles to facilitate its brain bioavailability
We suggested that the concentration of QC in the brains of QCSPION-treated healthy rats was about 4.8 times for 50 mg k g−1 of QC and 8.6 times for 100 mg kg−1 of QC higher than rats treated with pure QC
The analysis was limited to the target 3′UTR region of GLUT2, 3, 4, and insulin-like growth factor-1 (IGF-1) genes of the rat because despite human GLUT1 data, no data is referring to rat GLUT1 gene in two databases
Summary
Quercetin (QC) is a dietary bioflavonoid that can be conjugated with nanoparticles to facilitate its brain bioavailability. A wide range of studies have shown that the expression, regulation, and activity of GLUTs can be disrupted during h yperglycemia[4,9,10] These changes negatively affect glucose metabolism in the brain which results in impairing of synaptic plasticity, neurogenesis, and cognitive function[11,12]. Several experimental studies have shown the role of GLUTs, IGF-1, and miR-29 family in the pathogenesis of diabetic complications, there is no enough knowledge about the effect of QC and QCSPIONs on the modulation of these genes. The purpose of the current study was to compare the effect of QC and QCSPIONs on the expression of GLUT1, GLUT2, GLUT3, GLUT4, and IGF-1 genes, as well as miR-29 family in the hippocampus of diabetic rats
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