Inhibitors of RNA and protein synthesis cause Glut4 translocation and increase glucose uptake in adipocytes

• Published in: Scientific reports Vol. 12; no. 1; p. 15640
• Main Authors: Meriin, A. B., Zaarur, N., Bogan, J. S., Kandror, K. V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 19.09.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/45; 631/80; Adipocytes; Adipocytes - metabolism; AKT protein; Biosynthesis; Dactinomycin - metabolism; Diabetes; Emetine; Endocytosis; Exocytosis; Glucose; Glucose - metabolism; Glucose transporter; Humanities and Social Sciences; Insulin; Insulin - metabolism; Insulin - pharmacology; Kinases; Medical research; Membrane vesicles; Monoclonal antibodies; multidisciplinary; Plasma; Protein Biosynthesis; Protein synthesis; Protein transport; Protein turnover; Proteins; Proto-Oncogene Proteins c-akt - metabolism; Ribonucleic acid; RNA; RNA - metabolism; Science; Science (multidisciplinary); Transcription; Transferrins; Transferrins - metabolism; Translocation
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-19534-5

Insulin stimulates glucose uptake in adipocytes by triggering translocation of glucose transporter 4-containg vesicles to the plasma membrane. Under basal conditions, these vesicles (IRVs for insulin-responsive vesicles) are retained inside the cell via a “static” or “dynamic” mechanism. We have found that inhibitors of RNA and protein synthesis, actinomycin D and emetine, stimulate Glut4 translocation and glucose uptake in adipocytes without engaging conventional signaling proteins, such as Akt, TBC1D4, or TUG. Actinomycin D does not significantly affect endocytosis of Glut4 or recycling of transferrin, suggesting that it specifically increases exocytosis of the IRVs. Thus, the intracellular retention of the IRVs in adipocytes requires continuous RNA and protein biosynthesis de novo. These results point out to the existence of a short-lived inhibitor of IRV translocation thus supporting the “static” model.