Diabetic pregnancy in rats leads to impaired glucose metabolism in offspring involving tissue-specific dysregulation of 11beta-hydroxysteroid dehydrogenase type 1 expression.
Population-based studies have shown that the offspring of diabetic mothers have an increased risk of developing obesity, insulin resistance, type 2 diabetes and hypertension in later life. To investigate mechanism for the high incidence of metabolic diseases in the offspring of diabetic mothers, we focused on the tissue-specific glucocorticoid regulation by 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) and studied offspring born to streptozotocin-induced diabetic rats. The body weights of newborn rats from diabetic mothers were heavier than those from control mothers. Offspring born to diabetic mothers demonstrated insulin resistance and mild glucose intolerance after glucose loading at 10 weeks and showed significantly increased 11beta-HSD1 mRNA and enzyme activity in adipose tissue at 12 weeks of age without obvious obesity. Hepatic 11beta-HSD1 mRNA was also elevated. We propose that the 11beta-HSD1 in adipose tissue and liver may play a key role in the development of metabolic syndrome in the offspring of diabetic mothers. Tissue-specific glucocorticoid dysregulation provides a candidate mechanism for the high incidence of metabolic diseases in the offspring of diabetic mothers. Therefore early analyses before apparent obesity are needed to elucidate the molecular mechanisms that may be programmed during the fetal period.
Fujisawa
Yasuko
Y
Department of Pediatrics, Hamamatsu University School of Medicine, Handa-yama 1-20-1, Hamamatsu-city 431-3192, Japan. yasu627@fc4.so-net.ne.jp
Nakagawa
Yuichi
Y
Li
Ren-Shan
RS
Liu
Yan-Jun
YJ
Ohzeki
Takehiko
T
D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1 / Q000096:biosynthesis*; D000273:Adipose Tissue / Q000201:enzymology*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D003345:Corticosterone / Q000378:metabolism; D003921:Diabetes Mellitus, Experimental / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D005260:Female; D005947:Glucose / Q000378:metabolism*; D007333:Insulin Resistance; D008099:Liver / Q000201:enzymology*; D008297:Male; D009928:Organ Specificity; D011247:Pregnancy; D011254:Pregnancy in Diabetics / Q000097:blood / Q000201:enzymology / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001786:Blood Glucose; D043205:11-beta-Hydroxysteroid Dehydrogenase Type 1; D005947:Glucose; D003345:Corticosterone