Maternal hyperglycemia alters glucose transport and utilization in mouse preimplantation embryos

• Published in: American journal of physiology: endocrinology and metabolism Vol. 275; no. 1; pp. E38 - E47
• Main Authors: Moley, K.H, Chi, M.M.Y, Mueckler, M.M
• Format: Journal Article
• Language: English
• Published: United States 01.07.1998
• Subjects: Animals; Biological Transport; Blastocyst - drug effects; Blastocyst - physiology; Chorionic Gonadotropin - pharmacology; Deoxyglucose - metabolism; DIABETE; DIABETES; Diabetes Mellitus, Experimental; Embryonic and Fetal Development; EXPERIMENTACION; EXPERIMENTATION; Female; GLUCOSA; GLUCOSE; Glucose - metabolism; Glucose Transporter Type 1; Glucose Transporter Type 2; Glucose Transporter Type 3; Hexokinase - metabolism; Hyperglycemia; MATERNAL DIABETES; MICE; Mice, Inbred Strains; Monosaccharide Transport Proteins - biosynthesis; Nerve Tissue Proteins; Polymerase Chain Reaction; Pregnancy; Pregnancy in Diabetics; RATON; Reference Values; SOURIS
• ISSN: 0002-9513; 0193-1849; 2163-5773; 1522-1555
• DOI: 10.1152/ajpendo.1998.275.1.e38

Departments of 1  Obstetrics and Gynecology and of 2  Cell Biology and Physiology, Washington University School of Medicine, St. Louis, Missouri 63110 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. glucose toxicity; cleavage-stage embryos; glucose transport downregulation; maternal diabetes