Is human Type 2 diabetes maternally inherited? Insights from an animal model
Is human Type 2 diabetes maternally inherited? Insights from an animal model
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DOI：
10.1111/j.1464-5491.2004.01225.x
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发表时间：
2004-07-01
影响因子：
3.5
通讯作者：
Alcolado, JC
中科院分区：
文献类型：
--
作者：
Gill-Randall, RJ;Adams, D;Alcolado, JC
目的2型糖尿病患者更经常报告的病史受影响的母亲比父亲。然而，在对父母和后代进行直接测试的少数研究中，这种明显的母体过剩尚未得到证实。啮齿类动物糖尿病模型的优点是，所有父母和后代都可以在成年后的特定年龄进行葡萄糖耐量试验。本研究的目的是获得洞察人类2型糖尿病的遗传通过使用大鼠模型。方法后藤Kakizaki（GK）大鼠（2型糖尿病模型）与非糖尿病Wistar大鼠交配。后代由20只GK雌性对Wistar雄性和20只Wistar雌性对GK雄性杂交产生。结果Wistar母鼠产活仔数为GK母鼠的2倍（14.1 vs.7.4，P <0.001），而GK母鼠产活仔数为Wistar母鼠的2倍（14.1 vs.7.4，P < 0.001）。尽管窝仔数较大，但两组中的后代在6周龄和6月龄时的体重相当。在3月龄时，Wistar母亲的雄性后代比GK母亲的后代重（415.7 g vs. 379.5 g，P = 0.016），但这种差异在6月龄时并不持续。空腹血糖在所有年龄段和平均血糖在葡萄糖耐量试验中是相似的，在这两个group.Conclusions，因此，我们的结论是，没有证据表明母亲在GK大鼠糖尿病的传播。母亲能够调整自己的牛奶供应，使后代达到类似的重量独立的窝。后代的体重保持独立的产仔数到成年生活。
Aims Patients with Type 2 diabetes mellitus more often report a history of an affected mother than father. However, in the few studies where both parents and offspring have been directly tested, this apparent maternal excess has not been confirmed. Rodent models of diabetes have the advantage that all parents and offspring can undergo glucose tolerance testing at a specific age in adult life. The aim of this study was to gain insights into the inheritance of human Type 2 diabetes by using a rat model.Methods Goto Kakizaki (GK) rats (a model of Type 2 diabetes) were mated with non-diabetic Wistar rats. Offspring were produced from 20 GK female vs. Wistar male and 20 Wistar female vs. GK male crosses. Fasting blood glucose was measured at 6 weeks and 3 months of age and an intravenous glucose tolerance test (0.8 g/kg) performed at 6 months of age.Results Wistar mothers produced litters with almost twice as many viable offspring as GK mothers (14.1 vs. 7.4, P < 0.001). Despite the larger litter size, offspring in the two groups were of comparable weight at 6 weeks and 6 months of age. At 3 months of age, male offspring of Wistar mothers were heavier than offspring of GK mothers (415.7 g vs. 379.5 g, P = 0.016) but this difference was not sustained at 6 months of age. Fasting blood glucose at all ages and average blood glucose during the glucose tolerance test were similar in both groups.Conclusions We therefore conclude that there is no evidence for maternal transmission of diabetes in the GK rat. Mothers were able to adjust their supply of milk so that offspring attained similar weights independent of litter size. The weight of the offspring remained independent of litter size into adult life.