Effects of hyperglycaemia on sorbitol and myo-inositol contents of cultured embryos: treatment with aldose reductase inhibitor and myo-inositol supplementation.
To demonstrate the myo-inositol depletion hypothesis in hyperglycaemia-induced embryopathy, rat conceptuses of 9.5 days of gestation in the early head-fold stage were grown in vitro during neural tube formation for 48 h with increasing amounts of glucose. The effects of an aldose reductase inhibitor and the myo-inositol supplementation were also investigated. Sorbitol and myo-inositol contents were measured in separated embryos and extra-embryonic membranes including yolk sac and amnion at the end of culture. After addition of 33.3 mmol/l and 66.7 mmol/l glucose to the culture media, the myo-inositol content of the embryos was significantly decreased by 43.1% (p less than 0.05) and 64.6% (p less than 0.01) of the control group, while a marked accumulation of sorbitol was observed (25 and 41 times that of the control). Although the addition of an aldose reductase inhibitor (0.7 mmol/l) to the hyperglycaemic culture media containing an additional 66.7 mmol/l glucose significantly reduced the sorbitol content of embryos to approximately one-eighth, the myo-inositol content of embryos remained decreased and the frequency of neural lesions was unchanged (23.1% vs 23.9%, NS). Supplementation of the myo-inositol (0.28 mmol/l) completely restored the myo-inositol content of the embryos and resulted in a significant decrease in the frequency of neural lesions (7.1% vs 23.9%, p less than 0.01) and a significant increase in crown-rump length and somite numbers. Much less significantly, sorbitol accumulation was also observed in the extra-embryonic membrane in response to hyperglycaemia, neither hyperglycaemia nor the myo-inositol supplementation modified the myo-inositol contents of the extra-embryonic membrane.(ABSTRACT TRUNCATED AT 250 WORDS)
Hashimoto
M
M
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Akazawa
S
S
Akazawa
M
M
Akashi
M
M
Yamamoto
H
H
Maeda
Y
Y
Yamaguchi
Y
Y
Yamasaki
H
H
Tahara
D
D
Nakanishi
T
T
D000449:Aldehyde Reductase / Q000037:antagonists & inhibitors*; D000818:Animals; D004622:Embryo, Mammalian / Q000737:chemistry / Q000378:metabolism; D005314:Embryonic and Fetal Development / Q000187:drug effects; D005260:Female; D005315:Fetal Diseases / Q000378:metabolism*; D005947:Glucose / Q000494:pharmacology; D006943:Hyperglycemia / Q000378:metabolism*; D007294:Inositol / Q000737:chemistry* / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D013012:Sorbitol / Q000737:chemistry*
D007294:Inositol; D013012:Sorbitol; D000449:Aldehyde Reductase; D005947:Glucose