Morphological and functional adaptations of pancreatic alpha-cells during late pregnancy in the mouse.

小鼠妊娠后期胰腺 α 细胞的形态和功能适应。

  • 影响因子:5.69
  • DOI:10.1016/j.metabol.2019.153963
  • 作者列表:"Quesada-Candela C","Tudurí E","Marroquí L","Alonso-Magdalena P","Quesada I","Nadal Á
  • 发表时间:2020-01-01

BACKGROUND:Pregnancy represents a major metabolic challenge for the mother, and involves a compensatory response of the pancreatic beta-cell to maintain normoglycemia. However, although pancreatic alpha-cells play a key role in glucose homeostasis and seem to be involved in gestational diabetes, there is no information about their potential adaptations or changes during pregnancy. MATERIAL AND METHODS:Non-pregnant (controls) and pregnant C57BL/6 mice at gestational day 18.5 (G18.5) and their isolated pancreatic islets were used for in vivo and ex vivo studies, respectively. The effect of pregnancy hormones was tested in glucagon-secreting α-TC1.9 cells. Immunohistochemical analysis was performed in pancreatic slices. Glucagon gene expression was monitored by RT-qPCR. Glucagon secretion and plasma hormones were measured by ELISA. RESULTS:Pregnant mice on G18.5 exhibited alpha-cell hypertrophy as well as augmented alpha-cell area and mass. This alpha-cell mass expansion was mainly due to increased proliferation. No changes in alpha-cell apoptosis, ductal neogenesis, or alpha-to-beta transdifferentiation were found compared with controls. Pregnant mice on G18.5 exhibited hypoglucagonemia. Additionally, in vitro glucagon secretion at low glucose levels was decreased in isolated islets from pregnant animals. Glucagon content was also reduced. Experiments in α-TC1.9 cells indicated that, unlike estradiol and progesterone, placental lactogens and prolactin stimulated alpha-cell proliferation. Placental lactogens, prolactin and estradiol also inhibited glucagon release from α-TC1.9 cells at low glucose levels. CONCLUSIONS:The pancreatic alpha-cell in mice undergoes several morphofunctional changes during late pregnancy, which may contribute to proper glucose homeostasis. Gestational hormones are likely involved in these processes.


背景: 妊娠对母亲来说是一个主要的代谢挑战,涉及胰腺 β 细胞维持正常血糖的代偿性反应。然而,尽管胰腺 α 细胞在葡萄糖稳态中起着关键作用,似乎参与了妊娠期糖尿病,但没有关于其潜在适应性或妊娠期变化的信息。 材料和方法: 妊娠 18.5 天 (G18.5) 的非妊娠 (对照) 和妊娠 C57BL/6 小鼠及其分离的胰岛分别用于体内和离体研究。在分泌胰高血糖素的 α-tc1.9 细胞中检测妊娠激素的作用。在胰腺切片中进行免疫组织化学分析。通过 RT-qPCR 监测胰高血糖素基因表达。用 ELISA 法测定胰高血糖素分泌量和血浆激素。 结果: G18.5 孕鼠表现出 α 细胞肥大,α 细胞面积和质量增加。这种 α-细胞团扩张主要是由于增殖增加。与对照组相比,未发现 α 细胞凋亡、导管新生或 α 至 β 转分化的变化。G18.5 的妊娠小鼠表现出低胰高血糖素血症。此外,体外低葡萄糖水平下的胰高血糖素分泌在妊娠动物的离体胰岛中减少。胰高血糖素含量也降低。在 α-tc1.9 细胞中的实验表明,与雌二醇和孕酮不同,胎盘催乳素和催乳素刺激 α 细胞增殖。胎盘催乳素、催乳素和雌二醇也抑制低血糖水平下 α-tc1.9 细胞的胰高血糖素释放。 结论: 小鼠胰腺 α 细胞在妊娠晚期经历了几种形态功能变化,这可能有助于正常的葡萄糖稳态。妊娠激素可能参与这些过程。



作者列表:["Schander J","Aisemberg J","Correa FG","Wolfson ML","Juriol L","Cymeryng C","Jensen F","Franchi AM"]

METHODS::Maternal lifestyle affects both mother health and pregnancy outcome in humans. Several studies have demonstrated that interventions oriented towards reducing stress and anxiety have positive effects on pregnancy complications such as preeclampsia, excessive gestational weight, gestational diabetes and preterm birth. In this work, we showed that the environmental enrichment (EE), defined as a noninvasive and biological significant stimulus of the sensory pathway combined with voluntary physical activity, prevented preterm birth (PTB) rate in a 41% in an inflammatory mouse model induced by the systemic administration of bacterial lipopolysaccharide (LPS). Furthermore, we found that EE modulates maternal metabolism and produces an anti-inflammatory environment that contributes to pregnancy maintenance. In pregnant mice uterus, EE reduces the expression of TLR4 and CD14 (the LPS receptor and its coactivator protein), preventing the LPS-induced increase in PGE2 and PGF2α release and nitric oxide synthase (NOS) activity. In cervical tissue, EE inhibits cervical ripening events, such as PGE2 release, matrix metalloproteinase (MMP)-9 increased activity and neutrophil recruitment, therefore conserving cervical function. It seems that EE exposure could mimic the stress and anxiety-reducing techniques mentioned above, explaining, at least partially, the beneficial effects of having a healthy lifestyle before and during gestation. Furthermore, we propose that designing an EE protocol for humans could be a noninvasive and preventive therapy for pregnancy complications, averting pre-term birth occurrence and dreaded sequelae that are present in the offspring born to soon.

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作者列表:["Bilibio JP","Belém Gama T","Nascimento I","José Conceição Meireles A","Aguiar A","do Nascimento FC","Lorenzzoni PL"]

METHODS:PROBLEM:We aimed to investigate the main causes of recurrent miscarriage (RM) in patients with losses after spontaneous gestation (SG) and after in vitro fertilization (IVF). METHOD OF STUDY:A prospective case-control study was conducted. The eligible patients were women who had experienced two or more consecutive abortions after less than 12 weeks gestation, two consecutive losses after SG or two consecutive losses after IVF. All patients were subjected to the following evaluations: karyotyping of the aborted material, alloimmune and autoimmune marker testing, and acquired and hereditary thrombophilia marker testing. RESULTS:In total, 58 patients were eligible: 32 patients with RM after SG and 26 patients with RM after IVF. The factors associated with RM were genetic (29%), immune (14%), thrombophilic (21%), and thrombophilic and immune (24%), and only 12% of the cases were idiopathic. Comparing the two study groups (SG and IVF), all studied factors were similar, except for a higher ANA positivity observed in the SG group (SG 30.4% versus IVF 5.3%, OR 8.6 (CI 1.1 - 21.1, P 0.048). CONCLUSIONS:Our study identified the possibly factors associated with recurrent miscarriage in 86% of the cases, and these factors appear to be similar in patients with recurrent miscarriage after spontaneous gestation and IVF. This study demonstrates that IVF with PGT-A with euploid embryo transfer could reduce abortions by up to 29%, but other factors needs to be investigated even in patients undergoing in vitro fertilization.

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作者列表:["Belloeil V","Tessier Cazeneuve C","Leclercq A","Mercier MB","Legendre G","Corroenne R"]

METHODS:OBJECTIVES:To evaluate the impact of pre-operative Music Therapy (MT) on pain in first-trimester abortion under local anaesthesia (ALA). DESIGN:Randomised controlled trial comparing patients undergoing a first-trimester ALA with or without a pre-operative MT session. SETTING:University hospital of Angers from November 2016 to August 2017. POPULATION:Patients who underwent first-trimester abortion under ALA. METHODS:Patients allocated to MT group underwent a pre-operative 20 minutes session of MT. MAIN OUTCOME MEASURES:Pain was assessed using a visual analogue scale (VAS) just before the procedure, during the procedure, at the end of the procedure and upon returning to the ward. RESULTS:159 patients were randomised (80 in MT group, and 79 in the control group). 2 patients were excluded from the control group and 6 from the MT group. Therefore, 77 patients were analysed in the control group and 74 in the MT group. The intensity of pain were similar in both the MT group and the Control group just before the procedure (VAS: 4.0±2.9 vs. 3.6±2.5, p=0.78), during the procedure (VAS: 5.3±2.5 vs. 4.9±2.9, p=0.78), at the end of the procedure (VAS: 2.7±2.4 vs. 2.6±2.4, p=0.43) and upon returning to the ward (VAS:1.8±2.0 vs. 1.5±2.0, p=0.84). The difference in pain between entering the department and returning to the room after the procedure was similar between the MT and Control groups (0.3±2.5 vs. 0.3±2.4 VAS levels difference; p=0.92). CONCLUSION:Music therapy session before an ALA procedure resulted in no improvement in patient perception of pain during a first-trimester abortion.

关键词: 流产 焦虑 音乐 疼痛
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