Glucose transporter gene expression in rat conceptus during high glucose culture

Takao, Yukio; Akazawa, Shoichi; Matsumoto, Kazunari; Takino, Hirofumi; Akazawa, M.; Trocino, R. A.; Maeda, Yasuo; Okuno, Shinichiro; Kawasaki, Eiji; Uotani, Shigeo; Yokota, Atsushi; Nagataki, Shigenobu

doi:10.1007/bf00401139

Cited by 28 publications

(23 citation statements)

References 59 publications

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“…Expression of Glut1, Glut2 and Glut3 is suppressed in preimplantation embryos of diabetic mice [46], and expression of Glut1 has been found to be both unchanged or suppressed by maternal diabetes or highglucose culture in postimplantation embryos [21,22]. However, in the present study, expression of Glut2 was unaffected by maternal diabetes.…”

Section: Discussioncontrasting

confidence: 60%

“…However, expression had not been examined during diabetic pregnancy. Whereas expression of Glut1 and Glut3 is not downregulated during maternal hyperglycaemia in the postimplantation embryo [21,22], expression of Glut1, Glut2 and Glut3 has been found to be downregulated by high glucose concentration in the preimplantation embryo [46]. Glut2 mRNA was assayed in embryos recovered on day 7.5, the day of embryonic development that is susceptible to subsequent development of NTD in response to maternal hyperglycaemia [34].…”

Section: Resultsmentioning

confidence: 99%

“…GLUT12 protein is not detected in early postimplantation embryos, but it is detected later, during fetal development [17,19]. Only expression of Glut1, Glut2 and Glut3 has been detected during the stage of postimplantation development that is susceptible to diabetic embryopathy (day 7.5) [12,13,[20][21][22][23]. Glut1 is expressed primarily in the ectoplacental cone, amnion, chorion and mesodermal layer of the yolk sac, and lower levels are expressed in the embryonic ectoderm.…”

Section: Introductionmentioning

confidence: 99%

“…Thus, during normal, non-diabetic gestation, glucose transporters with a low K m (high affinity) would transport glucose into the embryo cells more efficiently than the GLUT2 transporter. There have been some reports that GLUT1 and GLUT3, which are produced in the postimplantation embryo during early organogenesis, are not downregulated during exposure to a hyperglycaemic environment, and so could continue to transport glucose even during maternal hyperglycaemia [21,22]. However, the rate of glucose transport by GLUT1 and GLUT3 would saturate during hyperglycaemia.…”

Section: Introductionmentioning

confidence: 99%

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Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

Thorens

Loeken

2007

Diabetologia

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Aims/hypothesis Excess glucose transport to embryos during diabetic pregnancy causes congenital malformations. The early postimplantation embryo expresses the gene encoding the high-K m GLUT2 (also known as SLC2A2) glucose transporter. The hypothesis tested here is that high-K m glucose transport by GLUT2 causes malformations resulting from maternal hyperglycaemia during diabetic pregnancy. Materials and methods Glut2 mRNA was assayed by RT-PCR. The K m of embryo glucose transport was determined by measuring 0.5-20 mmol/l 2-deoxy[ 3 H]glucose transport. To test whether the GLUT2 transporter is required for neural tube defects resulting from maternal hyperglycaemia, Glut2 +/− mice were crossed and transient hyperglycaemia was induced by glucose injection on day 7.5 of pregnancy. Embryos were recovered on day 10.5, and the incidence of neural tube defects in wild-type, Glut2 +/− and Glut2 −/− embryos was scored. Results Early postimplantation embryos expressed Glut2, and expression was unaffected by maternal diabetes. Moreover, glucose transport by these embryos showed Michaelis-Menten kinetics of 16.19 mmol/l, consistent with transport mediated by GLUT2. In pregnancies made hyperglycaemic on day 7.5, neural tube defects were significantly increased in wild-type embryos, but Glut2 +/− embryos were partially protected from neural tube defects, and Glut2 −/− embryos were completely protected from these defects. The frequency of occurrence of wild-type, Glut2 +/− and Glut2 −/− embryos suggests that the presence of Glut2 alleles confers a survival advantage in embryos before day 10.5. Conclusions/interpretations High-K m glucose transport by the GLUT2 glucose transporter during organogenesis is responsible for the embryopathic effects of maternal diabetes.

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Section: Discussioncontrasting

confidence: 60%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

Thorens

Loeken

2007

Diabetologia

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“…At post-implantation stages, Glut-1 mRNA is present in extraembryonic membranes and ectoplacental cone at gestational day (gd) 7.5, widespread within the embryo at gd 8.5, and significantly decreased by gd 12.5 in the mouse (Smith and Gridley 1992). A similar pattern of Glut-1 expression is present in the post-implantation rat embryo Takao et al 1993;Trocino et al 1994). No previous studies have focused on Glut-1 expression in the embryonic heart during organogenesis and its response to hypoglycemia.…”

Section: Introductionsupporting

confidence: 48%

Glut-1 expression and its response to hypoglycemia in the embryonic mouse heart

Smoak¹,

Branch

2000

Anatomy and Embryology

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The embryonic heart depends on glucose during early organogenesis. Glut-1 functions in constitutive glucose uptake in adult tissues and is the predominant glucose transporter in embryonic and fetal tissues. This study focuses on Glut-1 expression in the heart during normal organogenesis using immunohistochemistry for Glut-1 distribution, Western analysis for Glut-1 protein levels, and reverse transcriptase polymerase chain reaction for Glut-1 mRNA levels. The role of Glut in glucose uptake response to hypoglycemia in the embryonic heart is evaluated using the Glut inhibitor cytochalasin B. Cardiac Glut-1 expression is also evaluated after in vitro hypoglycemic exposure. Glut-1 levels are highest on gestational days 9-10, intermediate on gestational day 10.5, and lowest on gestational days 11.5-13.5 in the normal embryonic heart. Cardiac Glut-1 mRNA levels similarly decline between gestational days 9.5 and gd 13.5. Cytochalasin B produces a dose-dependent decrease in glucose uptake in hearts exposed to hypoglycemia for 30 min or 6 h, implicating Glut in this response. Glut-1 protein expression is unchanged after 2 or 6 h but increased after 12 and 24 h of hypoglycemia in the gestational day 9.5 heart. Thus, Glut-1 expression is prominent in the embryonic heart and is correlated with changes in cardiac glucose requirements during normal organogenesis. Glut activity increases in response to acute hypoglycemia and the expression of Glut-1 increases in response to prolonged hypoglycemia. These results support the importance of Glut-1 during normal cardiogenesis and in response to hypoglycemia in the embryonic heart.

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Mouse embryonic cardiac metabolism under euglycemic and hypoglycemic conditions

Peet¹,

Sadler

1996

Teratology

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Children of mothers with insulin‐dependent diabetic mothers (IDDM) have a 2–4 times higher incidence of congenital birth defects as compared to the general population, including cardiac abnormalities, of unknown etiology. Using rodent embryos to explore potential teratogenic factors of the altered IDDM metabolism, it has been shown that exposure to hypoglycemia in vitro results in a variety of defects, including cardiac malformations. Since pregnant diabetics experience frequent episodes of low blood glucose, it was hypothesized that hypoglycemia may play a role in the generation of heart abnormalities seen in children born to IDDM mothers. Several studies have indicated that during embryogenesis the heart is dependent on glucose for energy production such that, under hypoglycemic conditions, insufficient amounts of ATP may be produced resulting in abnormalities. To test this hypothesis, cardiac ATP content was monitored in D10–D12 (plug day = D1) hearts. In addition, the contribution of glycolysis and the Krebs cycle to ATP production was monitored. D10 hearts exposed to euglycemic control conditions were found to be primarily dependent on glycolysis for ATP production from glucose before switching to the Krebs cycle and oxidative phosphorylation for energy production from this substrate on D11. Exposure to hypoglycemia did not alter the timing of this maturation process or deplete cardiac ATP content. However, cardiac lactate levels increased approximately twofold in the presence of hypoglycemia on D10. Since increased concentrations of lactate are harmful to many tissues and have been shown to be detrimental to the adult rat heart, lactic acidosis may explain the origin of cardiac defects produced by hypoglycemia, and not a deficiency of ATP. © 1996 Wiley‐Liss, Inc.

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Glucose transporter gene expression in rat conceptus during high glucose culture

Cited by 28 publications

References 59 publications

Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

Expression of the gene encoding the high-K m glucose transporter 2 by the early postimplantation mouse embryo is essential for neural tube defects associated with diabetic embryopathy

Glut-1 expression and its response to hypoglycemia in the embryonic mouse heart

Mouse embryonic cardiac metabolism under euglycemic and hypoglycemic conditions

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