Kisspeptin-10通过激活环AMP/蛋白激酶A通路抑制胎盘滋养细胞胰岛素抵抗改善妊娠糖尿病大鼠症状

IF 3.3 4区 医学 Q2 BIOCHEMISTRY & MOLECULAR BIOLOGY
Jianhua Li, Jinhuan Chen, Lin Lu, Bei Gan
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引用次数: 0

摘要

妊娠期糖尿病(GDM)是一种常见的妊娠并发症,可导致胰岛素抵抗(IR)并对母体和胎儿健康产生不利影响。Kisspeptin-10 (Kp-10)是一种通过G蛋白偶联受体54 (Gpr54)起作用的肽,已显示出调节胰岛素分泌的潜力,但其在GDM中的作用尚不清楚。本研究探讨了Kp-10通过靶向胎盘组织IR对GDM的治疗作用。我们使用GDM大鼠模型(高脂肪饮食和链脲佐菌素诱导)和高糖处理的HTR8/SVneo滋养细胞来研究Kp-10对葡萄糖代谢、胰岛素信号和cAMP/PKA通路的影响。我们的研究结果表明Gpr54在GDM大鼠胎盘组织中表达显著下调,这与葡萄糖摄取和IR受损有关。Kp-10治疗改善了空腹血糖(FBG)水平、胰岛素敏感性和胎儿结局,包括胎儿体重增加和胎儿血糖降低。此外,Kp-10通过上调胎盘组织和HTR8/SVneo细胞中Glut-4、Insr和Irs1的表达,恢复环磷酸腺苷(cAMP)/蛋白激酶A (PKA)信号通路,增强葡萄糖摄取。cAMP抑制剂SQ22536可逆转Kp-10的作用,证实cAMP/PKA通路参与其抗ir作用。我们的研究结果表明,Kp-10具有作为缓解GDM中IR和改善母胎结局的治疗药物的潜力。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Kisspeptin-10 Improves Gestational Diabetes Mellitus Symptoms in Rats by Suppressing Insulin Resistance in Placental Trophoblast Cells by Activating the Cyclic AMP/Protein Kinase A Pathway

Kisspeptin-10 Improves Gestational Diabetes Mellitus Symptoms in Rats by Suppressing Insulin Resistance in Placental Trophoblast Cells by Activating the Cyclic AMP/Protein Kinase A Pathway

Gestational diabetes mellitus (GDM) is a common pregnancy complication that leads to insulin resistance (IR) and adversely affects both maternal and fetal health. Kisspeptin-10 (Kp-10), a peptide acting via G Protein-Coupled Receptor 54 (Gpr54), has shown potential in modulating insulin secretion, but its role in GDM remains unclear. This study explores Kp-10's therapeutic effects on GDM by targeting IR in placental tissues. We used GDM rat models (induced by a high-fat diet and streptozotocin) and high-glucose-treated HTR8/SVneo trophoblast cells to investigate Kp-10's effects on glucose metabolism, insulin signaling, and the cAMP/PKA pathway. Our results show that Gpr54 expression was significantly downregulated in the placental tissues of GDM rats, which was associated with impaired glucose uptake and IR. Kp-10 treatment improved fasting blood glucose (FBG) levels, insulin sensitivity, and fetal outcomes, including increased fetal weight and decreased fetal blood glucose. Moreover, Kp-10 restored the cyclic adenosine monophosphate (cAMP)/protein kinase A (PKA) signaling pathway and enhanced glucose uptake by upregulating Glut-4, Insr, and Irs1 expression in both placental tissues and HTR8/SVneo cells. The effects of Kp-10 were reversed by the cAMP inhibitor SQ22536, confirming the involvement of the cAMP/PKA pathway in its anti-IR effects. Our findings suggest that Kp-10 has the potential as a therapeutic agent for alleviating IR in GDM and improving maternal–fetal outcomes.

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来源期刊
Chemical Biology & Drug Design
Chemical Biology & Drug Design 医学-生化与分子生物学
CiteScore
5.10
自引率
3.30%
发文量
164
审稿时长
4.4 months
期刊介绍: Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.
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