Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA.
Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA.
Mol Cell Endocrinol. 2025 Jan 1;595:112405. doi: 10.1016/j.mce.2024.112405. Epub 2024 Oct 29.
Insulin is an important regulator of whole-body glucose homeostasis. In insulin sensitive tissues such as muscle and adipose, insulin induces the translocation of glucose transporter 4 (GLUT4) to the cell membrane, thereby increasing glucose uptake. However, insulin also signals in tissues that are not generally associated with glucose homeostasis. In the human reproductive endocrine axis, hyperinsulinemia suppresses the secretion of gonadotropins from gonadotrope cells of the anterior pituitary, thereby linking insulin dysregulation to suboptimal reproductive health. In the mouse, gonadotropes express the insulin receptor which has the canonical signaling response of IRS, AKT, and mTOR activation. However, the functional outcomes of insulin action on gonadotropes are unclear. Here, we demonstrate through use of an optimized cell fractionation protocol that insulin stimulation of the LβT2 gonadotropic cell line results in the unexpected translocation of GLUT1 to the plasma membrane. Using our high purity fractionation protocol, we further demonstrate that though Akt signaling in response to insulin is intact, insulin-induced translocation of GLUT1 occurs independently of Akt activation in LβT2 cells.
胰岛素是全身葡萄糖稳态的重要调节剂。在胰岛素敏感组织如肌肉和脂肪组织中，胰岛素诱导葡萄糖转运蛋白 4（GLUT4）向细胞膜易位，从而增加葡萄糖摄取。然而，胰岛素也在通常与葡萄糖稳态无关的组织中发出信号。在人类生殖内分泌轴中，高胰岛素血症抑制垂体前叶促性腺激素细胞分泌促性腺激素，从而将胰岛素失调与生殖健康不佳联系起来。在小鼠中，促性腺激素细胞表达胰岛素受体，该受体具有 IRS、AKT 和 mTOR 激活的经典信号反应。然而，胰岛素对促性腺激素的作用的功能结果尚不清楚。在这里，我们通过使用优化的细胞分级分离方案证明，胰岛素刺激 LβT2 促性腺细胞瘤系导致 GLUT1 意外向质膜易位。使用我们的高纯度分级分离方案，我们进一步证明，尽管胰岛素刺激后 Akt 信号传导完整，但 LβT2 细胞中 GLUT1 的胰岛素诱导易位发生在 Akt 激活之外。
