Shepherd and Kahn (1999) discussed in detail the role of glucose transporters in insulin action and the implications for
insulin resistance and diabetes mellitus. Glucose transporter is an integral membrane glycoprotein that is involved in transporting glucose into most cells. Insulin
increases glucose uptake in responsive cells by inducing the rapid translocation of glucose transporters from an intracellular
storage pool to the plasma membrane. Complementary DNAs encoding the human protein have been isolated, and the
predicted amino acid sequence indicates that this protein lacks a signal sequence and possesses 12 potential
membrane-spanning domains.
NCBI Summary:
This gene encodes a major glucose transporter in the mammalian blood-brain barrier. The encoded protein is found primarily in the cell membrane and on the cell surface, where it can also function as a receptor for human T-cell leukemia virus (HTLV) I and II. Mutations in this gene have been found in a family with paroxysmal exertion-induced dyskinesia. [provided by RefSeq, Apr 2013]
General function
Channel/transport protein
Comment
Agus et al. (1997) provided evidence that GLUT1 also transports dehydroascorbic acid (the
oxidized form of vitamin C) into the brain.
Acute fasting decreases the expression of GLUT1 and glucose utilisation involved in mouse oocyte maturation and cumulus cell expansion. Han Y et al. Acute fasting impairs meiotic resumption and glucose consumption in mouse cumulus cell and oocyte complexes (COCs). This study examines the effects of acute fasting on the regulation of glucose transporter 1 (GLUT1) expression and glucose consumption in oocyte maturation. Our results indicate that the restriction of glucose utilisation by 2-deoxyglucose (2-DG) mimicked the inhibitory effects of acute fasting on oocyte meiotic resumption and cumulus cell expansion, effects that were rescued by high glucose concentrations in the culture medium. GLUT1 protein levels were higher in cumulus cells compared with oocytes, and GLUT1 expression in COCs increased with FSH treatment in vitro. However, under acute fasting conditions, GLUT1 expression in COCs decreased and the response to FSH disappeared. Exposure to high glucose conditions (27.5mM and 55mM), significantly increased both glucose consumption and GLUT1 levels in COCs. Inhibition of GLUT1 function using an anti-GLUT1 antibody significantly inhibited FSH-induced oocyte meiotic resumption. Taken together, these results suggest that acute fasting decreases GLUT1 expression and glucose utilisation, inhibiting the processes of oocyte maturation and cumulus cell expansion.
Kol et al characterizes the rat ovary as a site of hormonally dependent glucose transporter (Glut) expression, and explores
the potential role of interleukin (IL)-1, a putative intermediary in the ovulatory process, in this regard. Molecular probing
throughout a simulated estrous cycle revealed a significant surge in ovarian Glut3 (but not Glut1) expression at the time of
ovulation. Treatment of cultured whole ovarian dispersates from immature rats with IL-1beta resulted in upregulation of the
relative abundance of the Glut1 (4.5-fold) and Glut3 (3.5-fold) proteins as determined by Western blot analysis. Other
members of the Glut family (i.e., Gluts 2, 4, and 5) remained undetectable. The ability of IL-1 to upregulate Glut1 and Glut3
transcripts proved time-, dose-, nitric oxide-, and protein biosynthesis-dependent but glucose independent. Other ovarian
agonists (i.e., TNF alpha, IGF-I, interferon-gamma, and insulin) were without effect. Taken together,
the mammalian ovary is a site of cyclically determined Glut1 and Glut3 expression.
Expression regulated by
FSH, LH, Steroids, Growth Factors/ cytokines, NO
Comment
cGMP/PKG-I pathway-mediated GLUT1/4 regulation by NO (nitric oxide) in female rat granulosa cells. Tian Y et al. (2018) Nitric oxide (NO) is a multifunctional gaseous molecule that plays important roles in mammalian reproductive functions including follicular growth and development. Although our previous study showed that NO mediated 3,5,3'-triiodothyronine (T3) and follicle-stimulating hormone (FSH)-induced granulosa cell development via upregulation of GLUT1 (glucose transporter protein ) and GLUT4 in granulosa cells, little is known about the precise mechanisms regulating ovarian development via glucose. The objective of the present study was to determine the cellular and molecular mechanism by which NO regulates GLUT expression and glucose uptake in granulosa cells. Our results indicated that NO increased GLUT1/GLUT4 expression and translocation in cells, as well as glucose uptake. These changes were accompanied by upregulation of cGMP level and PKG-I protein content. The results of siRNA analysis showed that knockdown of PKG-I significantly attenuated gene expression, translocation and glucose uptake. Moreover, the PKG-I inhibitor also blocked the above processes. Furthermore, NO induced CREB phosphorylation, and CREB siRNA attenuated NO-induced GLUT expression, translocation, and glucose uptake in granulosa cells. These findings suggest that NO increases cellular glucose uptake via GLUT upregulation and translocation, which are mediated through the activation of the cGMP/PKG pathway. Meanwhile, the activated CREB is also involved in the regulation. These findings indicate that NO has an important influence on the glucose uptake of granulosa cells.//////////////////
Kodaman PH et al reported that Northern and Western analysis
of GLUT1 in granulosa cells following 24 h coincubation with FSH and IGF-I revealed up-regulation of GLUT1 at both the
messenger RNA and protein levels (1.6- and 1.3-fold of control, respectively), suggesting that the stimulatory effects of FSH
and IGF-I on dehydroascorbic acid (DHAA) transport are mediated by the induction of GLUT1. GLUT4 protein was not detectable by Western
analysis.
Zhou J, et al 2000 reported reduced GLUT1 expression in Igf1-I- null oocytes and follicles.
They used in situ hybridization and immunohistochemistry to examine
glucose transporter (GLUTs 1, 3 & 4) expression in follicles from pre-pubertal
Igf1-/- and littermate wildtype (wt) mice. GLUT1 mRNA and immunoreactivity were most abundant in oocytes and in granulosa cells
immediately surrounding the oocyte. Expression of this transporter was
significantly reduced in Igf1 null oocytes and granulosa cells and was
restored by exogenous IGF1 treatment to wt levels. These effects on GLUT
expression were significant at both the mRNA and immunoreactive protein
levels. Oestrogen treatment significantly increased GLUT1 levels in oocytes
and granulosa from both wt and Igf1-/-, although the latter were still
significantly lower than wt. Oocyte glycogen stores, determined by PAS
staining, did not appear different in Igf1-/- and wt mice.
Ovarian localization
Oocyte, Cumulus, Granulosa, Theca, Luteal cells
Comment
Comparative expression profiles of genes related to oocyte development in goats after long-term feeding with biodiesel castor industry residues. Silva LM 2014 et al.
The aim of this study was to determine whether the consumption of detoxified castor meal (DCM) by goats over a long period of time affects mRNA levels in oocytes, and in mural granulosa and cumulus cells. A total of 41 adult does were supplemented (DCM group, n=21) or not (control group, n=20) with detoxified castor meal (DCM) for a period of 500 days. Then, 13 and 12 does were randomly selected for slaughter from the DCM and control treatments groups, respectively, for the determination of the number of visible ovarian follicles, retrieved cumulus-oocyte complexes (COCs), and viable and non-viable oocytes. The relative expression levels for distinct genes were determined by quantitative PCR in viable immature oocytes prior to in vitro maturation (IVM), in oocytes attaining or not the metaphase stage after IVM, as well as in granulosa cells obtained upon oocyte collection, and in cumulus cells obtained after IVM. The number of follicles =4mm did not differ between treatments (overall mean 23.32.0) and no significant differences were observed in the recovery of viable, non-viable, or total mean numbers of oocytes (control group: 44.74.6, DCM group: 54.95.9, respectively) between control and DCM fed goats. The maturation rate was significantly higher for control than DCM oocytes (58.0% vs. 45.3%; P<0.05). The mRNA levels in immature COC for controls were significantly higher for GLUT1 and lower for HSP70 (P<0.05) than for DCM. Following maturation, MII oocytes from both treatments had mRNA levels that were significantly higher for GDF9 and lower for BMP15 than for NC oocytes (P<0.05). In cumulus cells, the mRNA levels were significantly higher for LHR, FSHR, LeptinR, and IGF1, and lower for MnSOD in the control group compared with the DCM group (P<0.05). In conclusion, the inclusion of DCM in goat feed for long periods of time changed gene expression in immature oocytes and in cumulus cells. This was reflected by a decrease in the in vitro oocyte maturation rate.
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Brevini-Gandolfi TA et al reported that the length of the poly(A) tail of
glucose transporter type 1was determined in the bovine oocyte at the germinal vesicle (GV)
and metaphase II (MII) stage. The results indicated that the poly(A) tail of this gene is shorter
after in vitro maturation (IVM).
The effect of monosaccharide sugars and pyruvate on the differentiation and metabolism of sheep granulosa cells in vitro. Campbell BK et al. The objective of this study was to investigate the effect of three monosaccharides or pyruvate on the ability of gonadotrophins to induce cellular proliferation and differentiation of cultured sheep granulosa cells. Lactate production and levels of mRNA expression for the glucose transporters SLC2A1,4,5,8 were also determined. No energy source in the culture media reduced cell number (50%) and oestradiol production. Dose and type of monosaccharide had a highly significant (P<0.001) effect on FSH-induced differentiation of the granulosa cells and there was a highly significant interaction (P<0.001). Glucose supported higher levels of oestradiol production than fructose which was in turn higher than galactose (P<0.001). In contrast, pyruvate at low doses supported similar levels of oestradiol production as glucose but higher doses were markedly inhibitory to oestradiol production (P<0.001). Cells responded positively to insulin (P<0.001) in the presence of all three monosaccharides. Glucose and the high doses of fructose resulted in the accumulation of lactate (P<0.001) but pyruvate, galactose and the low dose of fructose resulted in low lactate production. SLC2A5 expression was not detected and SLC2A8 expression was not affected but SLC2A1 and 4 expression was depressed (P<0.05) by culture in the presence of fructose and glucose. These data show that glucose, metabolized under anoxic conditions to lactate, is the preferred energy substrate to support the gonadotrophin-induced differentiation of ovine granulosa cells in vitro and that fructose and pyruvate, but not galactose, are alternative energy substrates despite marked differences in the way these substrates are metabolised.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
Williams SA, et al reported the effect of nutritional supplementation on quantities of glucose
transporters 1 and 4 in sheep granulosa and theca cells.
The stimulatory effect of nutritional supplementation on ovarian activity in sheep
has been linked to an increase in glucose availability that, with insulin, directly
decreases follicular steroidogenesis. Glucose uptake occurs by glucose
transporters, but it is not known which glucose transporters are present in the
sheep ovary or whether they are affected by nutritional stimulation. The aim of
this study was to determine whether widely distributed glucose transporter 1
(GLUT1) or insulin-responsive GLUT4 are present in the granulosa or theca cells
of sheep ovarian follicles, and whether their concentrations are affected by
nutritional stimulation. Merino ewes (n = 49-51 per group) were stimulated
nutritionally for 5 days before luteolysis with lupin grain or with one of two
regimens of a glucogenic mixture, administered orally, which increases blood
glucose concentrations towards the upper end of the normal range. Water was
used as a control. Ovaries (n = 3 per group) were dissected and the granulosa
cells and thecal shell from individual follicles were examined for glucose
transporters using western blotting. GLUT1 concentration was 7-18 times higher
in the granulosa than in the theca cells. GLUT4 was detected at a similar
concentration in both types of cell. Nutritional treatment had no effect on the
concentration of GLUT1 or GLUT4 in either tissue, and did not increase
ovulation rate, despite increased concentrations of glucose and insulin.
Concentrations of glucose transporters were not correlated with follicular
concentrations of oestradiol or androstenedione. The presence of GLUT1 and
GLUT4 in the granulosa and theca of sheep follicles indicates that the transporters
have a role within the ovary in the modulation of follicular function.
Gene expression of glucose transporter (GLUT) 1, 3 and 4 in bovine follicle and corpus luteum Nishimoto H, et al .
Glucose is the main energy substrate in the bovine ovary, and a sufficient supply of it is necessary to sustain the ovarian activity. Glucose cannot permeate the plasma membrane, and its uptake is mediated by a number of glucose transporters (GLUT). In the present study, we investigated the gene expression of GLUT1, 3 and 4 in the bovine follicle and corpus luteum (CL). Ovaries were obtained from Holstein x Japanese Black F1 heifers. Granulosa cells and theca interna layers were harvested from follicles classified into five categories by their physiologic status: follicular size (>/= 8.5 mm: dominant; < 8.5 mm: subordinate), ratio of estradiol (E(2)) to progesterone in follicular fluid (>/= 1: E(2) active;<1: E(2) inactive), and stage of estrous cycle (luteal phase, follicular phase). CL were also classified by the stage of estrous cycle. Expression levels of GLUT1, 3 and 4 mRNA were quantified by a real-time PCR. The mRNA for GLUT1 and 3 were detected in the bovine follicle and CL at comparable levels to those in classic GLUT-expressing organs such as brain and heart. Much lower but appreciable levels of GLUT4 were also detected in these tissues. The gene expression of these GLUT showed tissue- and stage-specific patterns. Despite considerable differences in physiologic conditions, similar levels of GLUT1, 3 and 4 mRNA were expressed in subordinate follicles as well as dominant E(2)-active follicles in both luteal and follicular phases, whereas a notable increase in the gene expression of these GLUT was observed in dominant E(2)-inactive follicles undergoing the atretic process. In these follicles, highly significant negative correlations were observed between the concentrations of glucose in follicular fluid and the levels of GLUT1 and 3 mRNA in granulosa cells, implying that the local glucose environment affects glucose uptake of follicles. These results indicate that GLUT1 and 3 act as major transporters of glucose while GLUT4 may play a supporting role in the bovine follicle and CL.