Sustained hyperglycemia in vitro down-regulates the GLUT1 glucose transport system of cultured human term placental trophoblast: a mechanism to protect fetal development?

被引:80
作者
Hahn, T
Barth, S
Weiss, U
Mosgoeller, W
Desoye, G
机构
[1] Graz Univ, Sch Med, Dept Obstet & Gynecol, A-8036 Graz, Austria
[2] Univ Vienna, Inst Histol & Embryol, A-1090 Vienna, Austria
关键词
placenta; glucose; transport;
D O I
10.1096/fasebj.12.12.1221
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The trophoblast of human placenta is directly exposed to the maternal circulation. It forms the main barrier to maternal-fetal glucose transport. The present study investigated the effect of sustained hyperglycemia in vitro on the glucose transport system of these cells. Trophoblasts isolated from term placentas and immunopurified were cultured for 24, 48, and 96 h in DMEM containing either 5.5 (normoglycemia) or 25 mmol/l D-glucose (hyperglycemia), respectively. Initial uptake of glucose was measured using 3-O-[C-14]methyl-D-glucose. Kinetic parameters were calculated as K-M = 73 mmol/l and V-max = 29 fmol s(-1) per trophoblast cell. Uptake rates of cells cultured under hyperglycemic conditions did not differ at exogenous D-glucose concentrations in the physiological range (1, 5.5, 10, and 15 mmol/l), but were significantly decreased by 25% (P<0.05) at diabetes-like concentrations (20 and 25 mmol/l) as compared to normoglycemic conditions. This effect was due to a decrease in V-max (-50%), whereas K-M remained virtually unaffected. GLUT1 mRNA levels were lower by 50% (P<0.05; Northern blotting) and GLUT1 protein was reduced by 16% (P<0.05; Western blotting) in trophoblast cells cultured under hyperglycemic vs, normoglycemic conditions. We conclude that prolonged hyperglycemia in vitro reduces trophoblast glucose uptake at substrate concentrations corresponding to blood levels of poorly controlled diabetic gravidas. This effect is due to diminished GLUT1 mRNA and protein expression in the trophoblast.-Hahn, T., Earth, S., Weiss, U., Mosgoeller, W., Desoye, G. Sustained hyperglycemia in vitro down-regulates the GLUT1 glucose transport system of cultured human term placental trophoblast: a mechanism to protect fetal development?.
引用
收藏
页码:1221 / 1231
页数:11
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