Hormonal and Chemical Regulation of the Glut9 Transporter in Mice

Abstract

Glucose transporter (Glut) 9 plays an important role in maintaining the homeostasis of uric acid in the body. Although the physiologic functions of Glut9 have been well established, the regulation of Glut9 expression is less well understood. In this study, we showed that the mRNA and protein expression of Glut9 in mouse liver and kidney are female predominant. Ontogeny studies further revealed that the female-predominant Glut9 expression in mouse liver only occurs in adult mice, which is primarily attributable to the fact that Glut9 expression sustains in females but gradually decreases in males after it reaches the peak level at day 22. Hormone replacement studies in gonadectomized mice, lit/lit mice, and hypophysectomized mice demonstrated that female-predominant Glut9 expression in mouse liver and kidney are primarily due to the inhibitory effects of male-pattern growth hormone secretion, but not sex hormones. In silico analysis of DNA sequences revealed that conserved response elements of signal transducer and activator of transcription 5b, which is an established relay molecule in the growth hormone signaling pathway, are present in mouse and human Glut9/GLUT9 gene promoters, suggesting that Glut9/GLUT9 is a potential target gene of growth hormone. Analysis of mice treated with a panel of chemicals revealed that agonists of the aryl hydrocarbon receptor and the peroxisome proliferator-activated receptor a induced Glut9 mRNA expression in the liver, which is further supported by the presence of conserved xenobiotic response elements and direct repeat 1 DNA motifs in the mouse Glut9 gene promoter. In summary, Glut9 expression is downregulated by male-pattern growth hormone secretion but is upregulated by activation of aryl hydrocarbon receptor and peroxisome proliferator-activated receptor a signaling in mice.

Chicken serum uric acid level is regulated by glucose transporter 9

“…Similar to the findings of a previous study in mice [11], the results of the present study show that the cGLUT9 mRNA and protein is mainly expressed in the liver, followed by the jejunum, whereas the ileum and the kidney show less expression. The immunohistochemistry results indicate that the pattern of GLUT9 protein expression in the chicken liver is consistent with that in the humans and the mice; that is, it is mainly expressed in hepatocytes.…”

“…Furthermore, in mouse, GLUT9 expression is also related to the SUA level, and high GLUT9 expression may cause hyperuricemia by increasing UA reabsorption in mouse kidneys [6]. Research has shown that GLUT9 is mainly expressed in the liver, kidney and the intestine of mice and humans [10,11], and it plays a very important role in UA regulation in mice and humans. In mice, liver…”

Urate transport capacity of glucose transporter 9 and urate transporter 1 in cartilage chondrocytes

“…Similarly, the promoter region of URAT1 contains two GATA sites, which may be responsible for the binding of testosterone (37). In vivo studies with mice confirmed that GLUT9 expression was subject to the inhibitory effects of male-pattern growth hormone secretion (36), whereas URAT1 mRNA was 2.3 times higher in male mice than in female mice (38). In addition, IL-1β stimulation significantly increased the mRNA levels of GLUT9 in chondrocytes (39), whereas tumor suppressor p53 promoted GLUT9 mRNA levels by binding to the promoter region with increased UA transport in fibroblast cell lines and lung cancer cells (40).…”

“…Previous studies have reported that the two transporters are crucial for regulating UA homeostasis and are subject to various regulatory mechanisms. For example, at the transcriptional level, the GLUT9 promoter contains a conserved response element of STAT5b, which transduces the negative regulatory effects of growth hormone (36). Similarly, the promoter region of URAT1 contains two GATA sites, which may be responsible for the binding of testosterone (37).…”

Effects of recombinant human growth hormone on protein malnutrition and IGF-1 and IL-2 gene expression levels in chronic nephrotic syndrome

“…Additionally, the body's nutritional metabolism is in a state of disorder, and long-term malnutrition seriously affects the prognosis of patients ( 9 ). Previous findings have shown that hypoproteinemia is treated by the infusion of exogenous human albumin for symptomatic support treatment; however, albumin is expensive ( 10 ). Additionally, there are certain infusion complications, leading to loss of albumin while the total time of maintaining plasma protein after infusion is short ( 11 ).…”