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p300 or CBP is required for insulin-stimulated glucose uptake in skeletal muscle and adipocytes


While current thinking posits that insulin signaling to glucose transporter 4 (GLUT4) exocytic translocation and glucose uptake in skeletal muscle and adipocytes is controlled by phosphorylation-based signaling, many proteins in this pathway are acetylated on lysine residues. However, the importance of acetylation and lysine acetyltransferases to insulin-stimulated glucose uptake is incompletely defined. Here, we demonstrate that combined loss of the acetyltransferases E1A binding protein p300 (p300) and cAMP response element binding protein binding protein (CBP) in mouse skeletal muscle caused a complete loss of insulin-stimulated glucose uptake. Similarly, brief (i.e., 1 hour) pharmacological inhibition of p300/CBP acetyltransferase activity recapitulated this phenotype in human and rodent myotubes, 3T3-L1 adipocytes, and mouse muscle. Mechanistically, these effects were due to p300/CBP-mediated regulation of GLUT4 exocytic translocation and occurred downstream of Akt signaling. Taken together, we highlight a fundamental role for acetylation and p300/CBP in the direct regulation of insulin-stimulated glucose transport in skeletal muscle and adipocytes.

Type Journal
ISBN 2379-3708 (Electronic) 2379-3708 (Linking)
Authors Martins, V. F.; LaBarge, S. A.; Stanley, A.; Svensson, K.; Hung, C. W.; Keinan, O.; Ciaraldi, T. P.; Banoian, D.; Park, J. E.; Ha, C.; Hetrick, B.; Meyer, G. A.; Philp, A.; David, L. L.; Henry, R. R.; Aslan, J. E.; Saltiel, A. R.; McCurdy, C. E.; Schenk, S.
Publisher Name Journal of Clinical Investigation Insight
Published Date 2022-01-11
Published Volume 7
Published Issue 1
Status Published in-print
DOI 10.1172/jci.insight.141344
URL link to publisher's version