Intergenerational effects of prenatal ethanol on glucose tolerance and insulin response
Intergenerational effects of prenatal ethanol on glucose tolerance and insulin response
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DOI：
10.1152/physiolgenomics.00181.2013
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发表时间：
2014-03-01
影响因子：
4.6
通讯作者：
Redei, Eva E.
中科院分区：
文献类型：
--
作者：
Harper, Kathryn M.;Tunc-Ozcan, Elif;Redei, Eva E.
产前接触乙醇(E)的后果包括形态、生理和认知障碍，统称为胎儿酒精谱系障碍。成年产前暴露于E的子代出现胰岛素抵抗，鉴于宫内高血糖环境可导致后代代谢紊乱，我们研究了外祖母E对第二代功能血糖和胰岛素反应的影响。SD-Dawley(S)大鼠与雄性S交配，在妊娠第8~20天分别给予含E的流质饲料和两种不同的对照饲料。此外，由于同时给予甲状腺素(T4)可逆转孕期E所致的行为障碍，另一组母鼠在E饲料中给予0.3 mg/L T4。它们的第一代(F1)后代与对照棕色挪威(B)雄性或雌性交配，产生SB和BS F2后代。妊娠期摄入E的母鼠血糖升高，其F1后代在葡萄糖耐量试验(GTT)中表现出胰岛素抵抗。然而，F2对GTT的反应因产前暴露于E的父母的性别而异。雌鼠SB F2和雌鼠SB F2后代均表现出低血糖和高胰岛素的GTT反应模式。尽管给EDAM注射T4可以使F1代的甲状腺功能恢复正常，但并不能逆转E所致的胎儿期代谢功能障碍。相反，给饮酒的祖母注射T4逆转或减轻了F2后代的异常GTT反应。产前E诱导的葡萄糖代谢失调可能会影响下一代，可能是通过酒精对F1胎儿生殖系的影响。
Consequences of prenatal exposure to ethanol (E) include morphological, physiological, and cognitive deficits and are collectively classified as fetal alcohol spectrum disorders. Adult prenatal E exposed offspring show insulin resistance, and given that in utero hyperglycemic environment can cause metabolic disorders in subsequent generations; we investigated the effects of grandmaternal E on functional glucose and insulin responses of the second generation. Sprague-Dawley (S) rat dams, mated with S males, received E-containingliquid diet and two different control diets between gestational days 8 and 20. Additionally, because prenatal E-induced behavioral deficits can be reversed by simultaneous thyroxine (T4) treatment, another group of dams received 0.3 mg/l T4 in their E diet. Their first-generation (F1) offspring were mated with control Brown Norway (B) males or females to produce SB and BS F2 progeny. Dams consuming E during pregnancy were hyperglycemic, and their F1 offspring showed insulin resistance in the glucose tolerance test (GTT). However, F2 responses to GTT varied based on the sex of prenatal E-exposed parent. BS F2 females, and both male and female SB F2 progeny, displayed hypoglycemic and hyperinsulinemic GTT response patterns. Although administering T4 to E dams normalized thyroid function of the F1 generation, it did not reverse their prenatal E-induced metabolic dysfunction. In contrast, administration of T4 to the alcohol-consuming grandmother reversed or alleviated the aberrant GTT responses of the F2 progeny. Prenatal E-induced dysregulation of glucose metabolism can affect the next generation, possibly via ethanol effects on the germline of the F1 fetus.