Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance.
Maternal bisphenol A exposure alters rat offspring hepatic and skeletal muscle insulin signaling protein abundance.
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DOI：
10.1016/j.ajog.2016.08.041
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发表时间：
2017-03
影响因子：
9.8
通讯作者：
Jellyman JK
中科院分区：
文献类型：
--
作者：
Galyon KD;Farshidi F;Han G;Ross MG;Desai M;Jellyman JK
The obesogenic and diabetogenic effects of the environmental toxin BPA during critical windows of development are well-recognized. Liver and skeletal muscle play a central role in the control of glucose production, utilization and storage. We hypothesized that maternal BPA exposure disrupts insulin signaling in rat offspring liver and skeletal muscle. We determined the protein expression of hepatic and skeletal muscle insulin signaling molecules including insulin receptor beta (IR-β), its downstream target insulin receptor substrate 1 (IRS-1) and glucose transporters (GLUT2; GLUT4) and hepatic glucose regulating enzymes phosphoenolpyruvate carboxykinase (PEPCK) and glucokinase (GCK). Rat dams had ad libitum access to filtered drinking water (Control) or drinking water with BPA from 2 weeks prior to mating and through pregnancy and lactation. Offspring litters were standardized to 4 males and 4 females and nursed by the same dam. At weaning, BPA exposure was removed from all offspring. Glucose tolerance was tested at 6 weeks and 6 months. Liver and skeletal muscle was collected from 3 week-old and 10 month-old offspring for protein expression (Western Blot) of IR-β, IRS-1, GLUT2, GLUT4, PEPCK and GCK. Male, but not female BPA offspring had impaired glucose tolerance at 6 weeks and 6 months. Both male and female adult offspring had higher glucose-stimulated insulin secretion as well as ratio of stimulated insulin to glucose. Male BPA offspring had higher liver protein abundance of the 200 kD IR-β precursor (2-fold), and IRS-1 (1.5-fold), while GLUT2 was 0.5-fold of the control at 3 weeks of age. In adult male BPA offspring the abundance of IR-β was higher (2-fold) and GLUT4 was 0.8-fold of the control in skeletal muscle. In adult female BPA offspring the skeletal muscle protein abundance of GLUT4 was 0.4–fold of the control. Maternal BPA had sex- and tissue-specific effects on insulin signaling components, which may contribute to increased risk of glucose intolerance in offspring. Glucose transporters were consistently altered at both ages as well as in both sexes and may contribute to glucose intolerance. These data suggest that maternal BPA exposure should be limited during pregnancy and lactation.
