TY - JOUR
T1 - Maternal hyperglycemia alters glucose transport and utilization in mouse preimplantation embryos
AU - Moley, Kelle H.
AU - Chi, Maggie M.Y.
AU - Mueckler, Mike M.
PY - 1998/7
Y1 - 1998/7
N2 - 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.
AB - 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.
KW - Cleavage-stage embryos
KW - Glucose toxicity
KW - Glucose transport downregulation
KW - Maternal diabetes
UR - http://www.scopus.com/inward/record.url?scp=0031859217&partnerID=8YFLogxK
U2 - 10.1152/ajpendo.1998.275.1.e38
DO - 10.1152/ajpendo.1998.275.1.e38
M3 - Article
C2 - 9688872
AN - SCOPUS:0031859217
VL - 275
SP - E38-E47
JO - American Journal of Physiology - Endocrinology and Metabolism
JF - American Journal of Physiology - Endocrinology and Metabolism
SN - 0193-1849
IS - 1 38-1
ER -