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Publication : Maternal hyperglycemia alters glucose transport and utilization in mouse preimplantation embryos.

First Author  Moley KH Year  1998
Journal  Am J Physiol Volume  275
Issue  1 Pt 1 Pages  E38-47
PubMed ID  9688872 Mgi Jnum  J:48796
Mgi Id  MGI:1275829 Doi  10.1152/ajpendo.1998.275.1.E38
Citation  Moley KH, et al. (1998) Maternal hyperglycemia alters glucose transport and utilization in mouse preimplantation embryos. Am J Physiol 275(1 Pt 1):E38-47
abstractText  Glucose utilization was studied in preimplantation embryos from normal and diabetic mice. With use of ultramicrofluorometric enzyme assays, intraembryonic free glucose in single embryos recovered from control and streptozotocin-induced hyperglycemic mice was measured at 24, 48, 72, and 96 h after mating. Free glucose concentrations dropped significantly in diabetics at 48 and 96 h, corresponding to the two-cell and blastocyst stages (48 h: diabetic 0.23 +/- 0.09 vs. control 2.30 +/- 0.43 mmol/kg wet wt; P < 0.001; 96 h: diabetic 0.31 +/- 0.29 vs. control 5.12 +/- 0.17 mmol/kg wet wt; P < 0.001). Hexokinase activity was not significantly different in the same groups. Transport was then compared using nonradioactive 2-deoxyglucose uptake and microfluorometric enzyme assays. The 2-deoxyglucose uptake was significantly lower at both 48 and 96 h in embryos from diabetic vs. control mice (48 h diabetic, 0.037 +/- 0. 003; control, 0.091 +/- 0.021 mmol . kg wet wt-1 . 10 min-1, P < 0. 05; 96 h diabetic, 0.249 +/- 0.008; control, 0.389 +/- 0.007 mmol . kg wet wt-1 . 10 min-1, P < 0.02). When competitive quantitative reverse transcription-polymerase chain reaction was used, there was 44 and 68% reduction in the GLUT-1 mRNA at 48 h (P < 0.001) and 96 h (P < 0.05), respectively, in diabetic vs. control mice. GLUT-2 and GLUT-3 mRNA values were decreased 63 and 77%, respectively (P < 0.01, P < 0.01) at 96 h. Quantitative immunofluorescence microscopy demonstrated 49 +/- 6 and 66 +/- 4% less GLUT-1 protein at 48 and 96 h and 90 +/- 5 and 84 +/- 6% less GLUT-2 and -3 protein, respectively, at 96 h in diabetic embryos. These findings suggest that, in response to a maternal diabetic state, preimplantation mouse embryos experience a decrease in glucose utilization directly related to a decrease in glucose transport at both the mRNA and protein levels.
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