An optimized fractionation method reveals insulin-induced membrane surface localization of GLUT1 to increase glycolysis in LβT2 cells.

Autor: Molinar-Inglis O; Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Wiggins K; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA., Varma A; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA., Del Mundo Z; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA., Adame JM; Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Cozzo A; Department of Obstetrics, Gynecology and Reproductive Sciences, and Center for Reproductive Science and Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Muñoz O; Department of Obstetrics, Gynecology and Reproductive Sciences, and Center for Reproductive Science and Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Le UV; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA., Trinh D; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA., Garcia AC; Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Cisneros-Aguirre M; Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Gonzalez Ramirez ML; Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Keyes J; Department of Biology, Pennsylvania State University Erie, The Behrend College, Erie, PA, USA., Zhang J; Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Lawson MA; Department of Obstetrics, Gynecology and Reproductive Sciences, and Center for Reproductive Science and Medicine, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Trejo J; Department of Pharmacology, School of Medicine, University of California, San Diego, La Jolla, CA, 92093, USA., Nicholas DA; Department of Molecular Biology and Biochemistry, University of California, Irvine, CA, 92697, USA. Electronic address: dequinaa@uci.edu.
Jazyk: angličtina
Zdroj: Molecular and cellular endocrinology [Mol Cell Endocrinol] 2024 Oct 29; Vol. 595, pp. 112405. Date of Electronic Publication: 2024 Oct 29.
DOI: 10.1016/j.mce.2024.112405
Abstrakt: 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.
Competing Interests: Declaration of competing interest None.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
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