Impact Factor:3.322
DOI number:10.1095/biolreprod.116.145011.
Affiliation of Author(s):中南大学
Journal:Biology of Reproduction
Place of Publication:美国
Key Words:Memantine; NMDA receptor; beta cells; diabetes; intrauterine growth retardation; intrauterine hypoxia.
Abstract: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.
Note:Q1区
Co-author:Shaojie Yue, Chen Li, Jia Guo, Yanhong Huang, Jianzhong Han, Ziqiang Luo
First Author:Xiaoting Huang
Indexed by:Journal paper
Correspondence Author:Dandan Feng
Discipline:护理学
Document Type:J
Volume:96
Issue:5
Page Number:960-970
Translation or Not:no
Included Journals:SCI