Antenatal blockade of N-methyl-D-aspartate receptors by Memantine reduces the susceptibility to diabetes induced by a high-fat diet in rats with intrauterine growth restriction
点击次数：
影响因子：
3.322
DOI码：
10.1095/biolreprod.116.145011.
所属单位：
中南大学
发表刊物：
Biology of Reproduction
刊物所在地：
美国
关键字：
Memantine; NMDA receptor; beta cells; diabetes; intrauterine growth retardation; intrauterine hypoxia.
摘要：
Intrauterine growth retardation (IUGR) is closely related to the later development of type 2 diabetes in adulthood. Excessive activation of N-methly-D-aspartate receptors (NMDARs) causes excitatory neurotoxicity, resulting in neuronal injury or death. Inhibition of NMDARs enhances the glucose-stimulated insulin secretion and survival of islet cells in type 2 diabetic mouse and human islets. Here, we examined whether antenatal blockade of NMDARs by Memantine could decrease the risk of diabetes induced by a high-fat (HF) diet at adulthood in IUGR rats. Pregnant SD rats were assigned to four groups: control, IUGR, Memantine, and Memantine + IUGR. The pregnant rats were exposed to hypoxic conditions (FiO2 = 0.105) for 8 h/day (IUGR group) or given a daily Memantine injection (5 mg/kg, i.p.) before hypoxia exposure from embryonic day (E) 14.5 to E 20.5 (Memantine + IUGR). The offspring were fed an HF diet with 60% of the calories from age 4 to 12 weeks. We found that NMDAR mRNAs were expressed in the fetal rat pancreas. An HF diet resulted in a high rate of diabetes at adulthood in the IUGR group. Antenatal Memantine treatment decreased the risk of diabetes at adulthood of rats with IUGR, which was associated with rescued glucose tolerance, increased insulin release, improved the insulin sensitivity, and increased expression of genes related to beta-cell function in the pancreas. Together, our results suggest that antenatal blockade of NMDARs by Memantine in pregnant rats improves fetal development and reduces the susceptibility to diabetes at adulthood in offspring.
备注：
Q1区
合写作者：
Shaojie Yue, Chen Li, Jia Guo, Yanhong Huang, Jianzhong Han, Ziqiang Luo
第一作者：
Xiaoting Huang
论文类型：
期刊论文
通讯作者：
Dandan Feng
学科门类：
护理学
文献类型：
J
卷号：
96
期号：
5
页面范围：
960-970
是否译文：
否
收录刊物：
SCI
学位：医学博士学位
职称：教授
学科：护理学
所在单位：湘雅护理学院
