Laboratory of Endocrine Physiology, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Laboratory of Ultrastructure and Tissue Biology, Institute of Biology, State University of Rio de Janeiro, Rio de Janeiro, Brazil.
Endocrine. 2021 Apr;72(1):104-115. doi: 10.1007/s12020-020-02579-9. Epub 2021 Jan 9.
Maternal nicotine exposure negatively impacts offspring's health and metabolism, leading to obesity and insulin resistance. Here we investigated the pancreatic islet function, glycemic homeostasis, and insulin signaling in adult rat offspring that were nicotine-exposed during breastfeeding.
For this, lactating Wistar rat dams were divided into two groups: Nicotine (implanted with osmotic minipumps containing 6 mg/Kg, NIC) and Control (saline, CON). Solutions were released from postnatal (PN) day 2-16. At PN110 and PN170, 10 offspring per litter/sex/group were submitted to the oral glucose tolerance test (OGTT). PN180 offspring were killed and glycemia, insulinemia, adiponectinemia, pancreas morphology as well as pancreatic islet protein expression (related to insulin secretion) and skeletal muscle (related to insulin action) were evaluated. Males and females were compared to their respective controls.
Adult NIC offspring of both sexes showed glucose intolerance in the OGTT. Despite normoglycemia, NIC males showed hyperinsulinemia while females, although normoinsulinemic, had hyperglycemia. Both sexes showed increased IRI, reduced adiponectin/visceral fat mass ratio and higher ectopic deposition of lipids in the pancreatic tissue adipocytes. In pancreatic islets, NIC males showed lower PDX-1 expression while females had higher PDX-1 and GLUT2 expressions plus lower α2 adrenergic receptor. In the muscle, NIC offspring of both sexes showed reduction of GLUT4 expression; NIC males also had lower insulin receptor and pAKT expressions.
Thus, glycemic homeostasis and peripheral insulin signaling in adult offspring of both sexes are affected by nicotine exposure through the milk, increasing the risk for type 2 diabetes development.
母体尼古丁暴露会对后代的健康和代谢产生负面影响，导致肥胖和胰岛素抵抗。本研究旨在探讨哺乳期暴露于尼古丁的成年大鼠后代的胰岛功能、血糖稳态和胰岛素信号。
为此，将哺乳期 Wistar 大鼠分为两组：尼古丁组（植入含有 6mg/kg 尼古丁的渗透微型泵，NIC）和对照组（生理盐水，CON）。溶液从产后（PN）第 2-16 天释放。在 PN110 和 PN170 时，每窝每性别每组 10 只后代进行口服葡萄糖耐量试验（OGTT）。PN180 后代处死，评估血糖、胰岛素血症、脂联素血症、胰腺形态以及胰腺胰岛蛋白表达（与胰岛素分泌相关）和骨骼肌（与胰岛素作用相关）。雄性和雌性与各自的对照组进行比较。
成年 NIC 后代无论性别均在 OGTT 中表现出葡萄糖耐量受损。尽管血糖正常，但 NIC 雄性表现出高胰岛素血症，而雌性虽然胰岛素正常，但血糖升高。两性均表现出胰岛素原升高、脂联素/内脏脂肪质量比降低以及胰腺组织脂肪细胞中异位脂质沉积增加。在胰岛中，NIC 雄性的 PDX-1 表达降低，而雌性的 PDX-1 和 GLUT2 表达升高，α2 肾上腺素能受体表达降低。在肌肉中，雌雄 NIC 后代的 GLUT4 表达均降低；NIC 雄性还表现出胰岛素受体和 pAKT 表达降低。
因此，通过乳汁暴露于尼古丁会影响成年后代的血糖稳态和外周胰岛素信号，增加 2 型糖尿病发生的风险。
