1989 Fiscal Year Final Research Report Summary
Diabetes Mellitus and Teratogenicity - Embryotoxic Effects of Insulin-induced Hypoglycemic Serum during Early Organogenesis in Rat Embryo Culture
| Project/Area Number |
61570556
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| Research Category |
Grant-in-Aid for General Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Research Field |
内分泌・代謝学
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| Research Institution | Nagasaki University |
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Principal Investigator |
AKAZAWA Shoichi Instructor, Nagasaki University School of Medicine, 医学部, 助手 (10145261)
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| Project Period (FY) |
1987 – 1988
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| Keywords | Hypoglycemia / Malformation / Diabetes mellitus / rat Embryo Culture |
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| Research Abstract |
We have shown that exposure to insulin induced-hypoglycemic serum during early phase of organogenesis can adversely affect the embryonic development in rat embryo culture and these effects are mediated through interruption of glycolytic flux that constitutes principal pathway at this stage of embryo (Diabetologia 30: 791, 1987). Further experiments were performed to determine whether or not even brief exposure to hypoglycemic serum during the critical periods has adverse effects on embryogenesis. Rat embryos of 9.5 days of gestation at early head-fold stage were grown in vitro for 48-hr until neural tube closure. Basal culture media consisted of control media containing 1.2mg/ml glucose (75% normal rat serum) and hyperglycemic media supplemented isosmotically with 6.0mg/ml glucose to control media, in which dysmorphogenic lesions were not elicited. Hypoglycemic media (0.4mg/ml glucose) were sera that were obtained from rats given insulin intraperitoneally. Postimplantation embryos were
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briefly (for 1-hr) exposed to the insulin-induced hypoglycemic serum at day 10.3 of gestation in early neural tube formation during the basal culture. On brief exposure to hypoglycemic media for 1-hr during culture with control media, embryos showed minor growth retardation [crown-rump (C-R) 3.24 <plus-minus> 0.05 VS 3.46 <plus-minus> 0.05mm, P<0.01; somite number 27.3 <plus-minus> 0.4 VS 28.2 <plus-minus> 0.1, P<0.05] and small but significant dysmorphogenic lesions (7% open neural pore, 13% microencephaly, 11% skeltal abnormality). Exposure to hypoglycemic serum for 1h during the culture with hyperglycemic media supplemented with subteratogenic dosis of glucose (6.0mg/ml) resulted in greater growth retardation (C-R 3.12 <plus-minus> 0.03 VS 3.35 <plus-minus> 0.06, P<0.01; somite number 26.9 <plus-minus> 0.02 VS 28.27 <plus-minus> 0.18, P<0.01) and marked dysmorphogenic lesions (24% open neural pore, 25% microencepaly, 14% skeltal abnormality, 10% eye abnormality, 5% heart abnormality). These results indicate that even brief hypoglycemia can adversely affect the embryogenesis at critical developing periods and these effects are enhanced when embryogs were cultured in hype Less
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