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Insulin signaling and mitochondrial phenotype of skeletal muscle are programmed in utero by maternal diabetes
Molecular and Cellular Endocrinology ( IF 4.1 ) Pub Date : 2024-03-27 , DOI: 10.1016/j.mce.2024.112199
Eduardo Klöppel , Larissa L. Cruz , Laura F.L. Prado-Souza , Adam Eckhardt , José E. Corrente , Daniela C. dos Santos , Luís A. Justulin , Tiago Rodrigues , Gustavo T. Volpato , Débora C. Damasceno

Maternal diabetes may influence glucose metabolism in adult offspring, an area with limited research on underlying mechanisms. Our study explored the impact of maternal hyperglycemia during pregnancy on insulin resistance development. Adult female Sprague-Dawley rats from control and diabetic mothers were mated, and their female offspring were monitored for 150 days. The rats were euthanized for blood and muscle samples. Maternal diabetes led to heightened insulin levels, increased HOMA-IR, elevated triglycerides, and a raised TyG index in adult offspring. Muscle samples showed a decreased protein expression of AMPK, PI3K, MAPK, DRP1, and MFF. These changes induced intergenerational metabolic programming in female pups, resulting in insulin resistance, dyslipidemia, and glucose intolerance by day 150. Findings highlight the offspring’s adaptation to maternal hyperglycemia, involving insulin resistance, metabolic alterations, the downregulation of insulin signaling sensors, and disturbed mitochondrial morphology. Maintaining maternal glycemic control emerges as crucial in mitigating diabetes-associated disorders in adult offspring.

中文翻译:

胰岛素信号传导和骨骼肌线粒体表型在子宫内由母亲糖尿病编程

母亲糖尿病可能会影响成年后代的葡萄糖代谢,这一领域对潜在机制的研究有限。我们的研究探讨了妊娠期间母亲高血糖对胰岛素抵抗发展的影响。将对照组和糖尿病母亲的成年雌性 Sprague-Dawley 大鼠交配,并对它们的雌性后代进行为期 150 天的监测。对大鼠进行安乐死以获取血液和肌肉样本。母亲糖尿病导致成年后代胰岛素水平升高、HOMA-IR 升高、甘油三酯升高和 TyG 指数升高。肌肉样本显示 AMPK、PI3K、MAPK、DRP1 和 MFF 的蛋白表达降低。这些变化诱导了雌性幼崽的代际代谢编程,导致第 150 天出现胰岛素抵抗、血脂异常和葡萄糖不耐受。研究结果强调了后代对母体高血糖的适应,包括胰岛素抵抗、代谢改变、胰岛素信号传感器下调和线粒体紊乱。形态学。维持母体血糖控制对于减轻成年后代糖尿病相关疾病至关重要。
更新日期:2024-03-27
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