Effects of insulin and myo-inositol on embryo growth and development during early organogenesis in streptozocin-induced diabetic rats.
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 less than 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 less than 0.01; somite no. 27.5 +/- 0.2 vs. 29.1 +/- 0.2, P less than 0.01) and a significantly increased incidence of the neural lesions (17.6 vs. 1.9%, P less than 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 less than 0.05; somite no. 28.2 +/- 0.13 vs. 27.5 +/- 0.2, P less than 0.05) and a significantly lowered incidence of neural lesions (2.5 vs. 17.6%, P less than 0.01) compared with those of the untreated diabetic rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Akashi
M
M
First Department of Internal Medicine, Nagasaki University School of Medicine, Japan.
Akazawa
S
S
Akazawa
M
M
Trocino
R
R
Hashimoto
M
M
Maeda
Y
Y
Yamamoto
H
H
Kawasaki
E
E
Takino
H
H
Yokota
A
A
D000818:Animals; D001835:Body Weight / Q000187:drug effects; D003921:Diabetes Mellitus, Experimental / Q000188:drug therapy / Q000503:physiopathology*; D004032:Diet; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D007294:Inositol / Q000494:pharmacology*; D007328:Insulin / Q000627:therapeutic use*; D008431:Maternal-Fetal Exchange; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000188:drug therapy / Q000503:physiopathology*; D051381:Rats; D011919:Rats, Inbred Strains; D012016:Reference Values
D007328:Insulin; D007294:Inositol