We have previously shown that myo-inositol depletion in the embryonic tissue at a critical stage of organogenesis has a crucial role in hyperglycemia-induced embryopathy. This study tested whether myo-inositol depletion in early organogenesis contributes to the pathogenesis of streptozocin-induced diabetic embryopathy. Rats were made diabetic by streptozocin administration before conception, and the diabetic rats were treated with diet supplemented by 2% myo-inositol or insulin from 6 to 11 gestational days during the period of maximum teratological susceptibility. In each group on the 11th gestational day, growth retardation and incidence of malformations were recorded, and myo-inositol and sorbitol content in the embryonic and extraembryonic tissues were examined. In diabetic rats, the myo-inositol content of the embryos was decreased by 36% (P < 0.01) compared with control rats, and there was growth retardation (crown-rump length 3.37 ± 0.04 vs. 3.87 ± 0.03 mm, P < 0.01; somite no. 27.5 ± 0.2 vs. 29.1 ± 0.2, P < 0.01) and a significantly increased incidence of the neural lesions (17.6 vs. 1.9%, P < 0.01). Insulin treatment resulted in near normalization of maternal serum glucose and complete restoration of myo-inositol content in the embryos with significant improvement of the growth retardation (crown-rump length 3.55 ± 0.06 vs. 3.37 ± 0.04 mm, P < 0.05; somite no. 28.2 ± 0.13 vs. 27.5 ± 0.2, P < 0.05) and a significantly lowered incidence of neural lesions (2.5 vs. 17.6%, P < 0.01) compared with those of the untreated diabetic rats. Despite complete restoration of myo-inositol content in the embryos by oral supplementation with myo-inositol of the diabetic rats, the embryos showed no improvement of growth retardation and had partially lowered incidence of neural lesions (9.6 vs. 17.6%, P < 0.05) but still had higher incidence of neural lesions than controls (9.6 vs. 1.9%, P < 0.05). We demonstrated that metabolic improvement of maternal diabetes by insulin treatment could prevent early growth retardation and dysmorphogenesis, whereas correction of only myo-inositol depletion did not. These data suggest that diabetes-induced growth retardation and dysmorphogenesis during early organogenesis may be caused by multifactorial factors and cannot be explained solely by the myo-inositol depletion hypothesis.
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December 01 1991
Effects of Insulin and myo-Inositol on Embryo Growth and Development During Early Organogenesis in Streptozocin-Induced Diabetic Rats
Masaharu Akashi;
Masaharu Akashi
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Shoichi Akazawa;
Shoichi Akazawa
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Mihoko Akazawa;
Mihoko Akazawa
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Romulo Trocino;
Romulo Trocino
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Masumi Hashimoto;
Masumi Hashimoto
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Yasuo Maeda;
Yasuo Maeda
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Hidefumi Yamamoto;
Hidefumi Yamamoto
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Eiji Kawasaki;
Eiji Kawasaki
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Hirofumi Takino;
Hirofumi Takino
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Atsushi Yokota;
Atsushi Yokota
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Shigenobu Nagataki
Shigenobu Nagataki
First Department of Internal Medicine, Nagasaki University School of Medicine
Nagasaki, Japan
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Address correspondence and reprint requests to Dr. Shigenobu Nagataki, The First Department of Internal Medicine, Nagasaki University School of Medicine, Nagasaki 852, Japan.
Diabetes 1991;40(12):1574–1579
Article history
Received:
January 22 1991
Revision Received:
July 26 1991
Accepted:
July 26 1991
Citation
Masaharu Akashi, Shoichi Akazawa, Mihoko Akazawa, Romulo Trocino, Masumi Hashimoto, Yasuo Maeda, Hidefumi Yamamoto, Eiji Kawasaki, Hirofumi Takino, Atsushi Yokota, Shigenobu Nagataki; Effects of Insulin and myo-Inositol on Embryo Growth and Development During Early Organogenesis in Streptozocin-Induced Diabetic Rats. Diabetes 1 December 1991; 40 (12): 1574–1579. https://doi.org/10.2337/diab.40.12.1574
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