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.
NCBI Summary:
This gene is a member of the solute carrier family 2 (facilitated glucose transporter) family and encodes a protein that functions as an insulin-regulated facilitative glucose transporter. In the absence of insulin, this integral membrane protein is sequestered within the cells of muscle and adipose tissue. Within minutes of insulin stimulation, the protein moves to the cell surface and begins to transport glucose across the cell membrane. Mutations in this gene have been associated with noninsulin-dependent diabetes mellitus (NIDDM). [provided by RefSeq, Jul 2008]
General function
Channel/transport protein
Comment
Cellular localization
Plasma membrane
Comment
candidate123
Ovarian function
Comment
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.
Expression regulated by
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.//////////////////
Ovarian localization
Granulosa, Theca
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.
Follicle stages
Antral, Preovulatory, Corpus luteum
Comment
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.
Phenotypes
PCO (polycystic ovarian syndrome)
Mutations
2 mutations
Species: mouse
Mutation name: None
type: null mutation fertility: unknown Comment:Katz et al. (1995) disrupted the Glut4 gene in 'knockout' mice and found that, surprisingly, the Glut4-null mice had
nearly normal glycemia but that Glut4 was absolutely essential for sustained growth, normal cellular glucose and
fat metabolism, and expected longevity. They observed increased expression of other glucose transporters in the
liver (Glut2) and heart (Glut1) but not in skeletal muscle. Insulin tolerance tests indicated that these mice were
less sensitive to insulin action.
Species: human
Mutation name: type: naturally occurring fertility: subfertile Comment: Changes in the expression of insulin signaling pathway molecules in endometria from polycystic ovary syndrome women with or without hyperinsulinemia. Fornes R et al. (2010) Polycystic ovary syndrome (PCOS) is an endocrine-metabolic disorder associated with insulin resistance and compensatory hyperinsulinemia. Scarce information is available on the expression of molecules involved in the insulin pathway in endometria from women with PCOS. Therefore, we examined the protein levels of insulin-signaling molecules, like insulin receptor, insulin-receptor substrate (IRS)-1, pIRS-1Y612, Akt, AS160, pAS160T642 and GLUT4 in endometria from PCOS women with or without hyperinsulinemia. Protein levels were assessed by Western blot and immunohistochemistry in 21 proliferative-phase endometria from control women (CE = 7), normoinssulinemic PCOS women (PCOSE-NI = 7) and hyperinsulinemic PCOS women (PCOSE-HI = 7). The data show no differences in the expression of insulin receptor between all groups as assessed by Western blot; however, IRS-1 and pIRS-1Y612 were lower in PCOSE-HI than controls and PCOSE-NI (P < 0.05). AS160 was detected in all analyzed tissues with similar expression levels between groups. Importantly, PCOSE-HI exhibited lower levels of pAS160T642 (P < 0.05) and of GLUT4 (P < 0.05) compared with CE. The immunohistochemistry for insulin receptor, IRS-1, Akt, AS160 and GLUT4 showed epithelial and stromal localization; IRS-1 staining was lower in PCOSE-HI (P < 0.05). In conclusion, human endometrium has the machinery for glucose uptake mediated by insulin. The diminished expression of GLUT4, as well as the lower level of pIRS-1Y612 and pAS160T642 exhibited by PCOSE-HI, suggests a disruption in the translocation of vesicles with GLUT4 to the cell surface in these patients.//////////////////