Decreased Expression of the GLUT4 Glucose Transporter Protein in Adipose Tissue During Pregnancy

Okuno, Shiro; Akazawa, Satoru; Yasuhi, Ichiro; Kawasaki, Emi; Matsumoto, Keitaro; Yamasaki, Hironori; Matsuo, Hiroshi; Yamaguchi, Yoshihiro; Nagataki, S

doi:10.1055/s-2007-979946

Cited by 48 publications

(26 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Expression of IRS-1 is reduced in experimental animals during pregnancy [19], a finding that has been confirmed in the skeletal muscle of normotolerant and GDM women in the last weeks of pregnancy: tyrosine phosphorylation of IRS-1 is reduced, compared to the prepregnancy state, by 28% in normal pregnancy and by 41% in a pregnancy with GDM [20]. Finally, in the late stage of pregnancy, and to a greater extent in GDM, a GLUT4 reduction has been reported [21][22][23]. The alterations of the insulinsignaling cascade is likely to be modulated by humoral factors.…”

Section: Insulin Resistancementioning

confidence: 61%

Intermediate metabolism in normal pregnancy and in gestational diabetes

Cianni

Miccoli

Volpe

et al. 2003

Diabetes Metabolism Res

341

279

View full text Add to dashboard Cite

Complex though integrated hormonal and metabolic changes characterize pregnancy. In the face of progressive decline in insulin action, glucose homeostasis is maintained through a compensatory increase in insulin secretion. This switches energy production from carbohydrates to lipids, making glucose readily available to the fetus. This precise and entangled hormonal and metabolic condition can, however, be disrupted and diabetic hyperglycemia can develop (gestational diabetes). The increase in plasma glucose level is believed to confer significant risk of complications to both the mother and the fetus and the newborn. Moreover, exposition of fetal tissues to the diabetic maternal environment can translate into an increased risk for development of diabetes and/or the metabolic syndrome in the adult life. In women with previous gestational diabetes, the risk of developing type 2 diabetes is greatly enhanced, to the point that GDM represents an early stage in the natural history of type 2 diabetes. In these women, accurate follow-up and prevention strategies are needed to reduce the subsequent development of overt diabetes. This paper will review current knowledge on the modifications occurring in normal pregnancy, while outlining the mechanisms. In this paper, we will review the changes of intermediary metabolism occurring during pregnancy. In particular, we will outline the mechanisms responsible for gestational diabetes; the link between these alterations and associated maternal and neonatal morbidity will be examined.

show abstract

Section: Insulin Resistancementioning

confidence: 61%

Intermediate metabolism in normal pregnancy and in gestational diabetes

Cianni

Miccoli

Volpe

et al. 2003

Diabetes Metabolism Res

341

279

View full text Add to dashboard Cite

show abstract

“…In both diseases, defects in glucose transporter expression have been observed (6,7). Taken together, these changes clearly demonstrate that estrogen plays an important role in glucose homeostasis.…”

Section: Muscle Glut4 Regulation By Estrogen Receptors Er␤ and Er␣mentioning

confidence: 76%

Muscle GLUT4 regulation by estrogen receptors ERβ and ERα

Barros

Machado

Warner

et al. 2006

Proc. Natl. Acad. Sci. U.S.A.

235

184

View full text Add to dashboard Cite

Estrogen is known to influence glucose homeostasis with dominant effects in the liver, but the role of estrogen receptors in muscle glucose metabolism is unknown. In the present study, we investigated the expression of the two estrogen receptors, ERα and ERβ, and their influence on regulation of the glucose transporter, GLUT4, and its associated structural protein, caveolin-1, in mouse gastrocnemius muscle. Immunohistochemical analysis revealed that ERα and ERβ are coexpressed in the nuclei of most muscle cells, and that their levels were not affected by absence of estradiol [in aromatase-knockout (ArKO) mice]. GLUT4 expression on the muscle cell membrane was not affected by loss of ERβ but was extremely reduced in ERα -/- mice and elevated in ArKO mice. RT-PCR confirmed a parallel reduction in GLUT4 mRNA levels in ERα -/- mice. Upon treatment of ArKO mice with the ERβ agonist 2,3-bis(4-hydroxyphenyl)propionitrile, GLUT4 expression was reduced. By immunofluorescence and Western blotting, caveolin-1 expression was higher in ArKO mice and lower in ERβ -/- and ERα -/- mice than in WT littermates. GLUT4 and caveolin-1 were colocalized in WT and ArKO mice but not in ERβ -/- and ERα -/- mice. These results reveal that ERα is a positive regulator of GLUT4 expression, whereas ERβ has a suppressive role. Both ERβ and ERα are necessary for optimal caveolin-1 expression. Taken together, these results indicate that colocalization of caveolin-1 and GLUT4 is not an absolute requirement for muscle glucose metabolism but that reduction in GLUT4 could be contributing to the insulin resistance observed in ERα -/- mice.

show abstract

“…This process is mediated mainly by P 4 and, to a certain degree, E 2 . Because recent studies have shown that these steroid hormones play a role in glucose utilization by altering expression of several facilitative GLUTs in human breast cancer cell lines and murine muscle and adipose tissue (17,18,31,32), we used a primary culture of murine ESCs to examine the possible effects of P 4 and E 2 on glucose utilization in these cells.…”

Section: Discussionmentioning

confidence: 99%

Facilitative Glucose Transporter Type 1 Is Differentially Regulated by Progesterone and Estrogen in Murine and Human Endometrial Stromal Cells

et al. 2008

View full text Add to dashboard Cite

Embryo implantation is a highly synchronized event between an activated blastocyst and a receptive endometrium. The success of this process relies on the dynamic interplay of estrogen (E(2)) and progesterone (P(4)), however, the details of this interaction are not entirely clear. Recent data implicate E(2) and P(4) in the regulation of glucose utilization by affecting facilitative glucose transporter (GLUT) expression. In this study we examine GLUT1 expression in murine and human endometrial stromal cells (ESCs) using a primary culture system. We show that expression of GLUT1 is increased during ESC decidualization in vitro. P(4) up-regulates, whereas E(2) down-regulates, GLUT1 expression. In addition, P(4) increases and E(2) decreases glucose uptake in ESCs, suggesting that GLUT1 may be a major player in glucose utilization in these cells. Moreover, GLUT1 expression is increased in human ESCs when decidualized in vitro with P(4) and dibutyryl cAMP, suggesting a similar role for P(4) in human endometrium. In conclusion, an imbalance between P(4) and E(2) seen in patients with polycystic ovary syndrome, luteal phase defect, and recurrent pregnancy loss may have a critical impact on glucose utilization in the endometrial stroma, and, thus, may be responsible for endometrial dysfunction and failure of embryo implantation in these patient populations.

show abstract

Decreased Expression of the GLUT4 Glucose Transporter Protein in Adipose Tissue During Pregnancy

Cited by 48 publications

References 5 publications

Intermediate metabolism in normal pregnancy and in gestational diabetes

Intermediate metabolism in normal pregnancy and in gestational diabetes

Muscle GLUT4 regulation by estrogen receptors ERβ and ERα

Facilitative Glucose Transporter Type 1 Is Differentially Regulated by Progesterone and Estrogen in Murine and Human Endometrial Stromal Cells

Contact Info

Product

Resources

About