2. Academic Validation
  3. p300 or CBP is required for insulin-stimulated glucose uptake in skeletal muscle and adipocytes

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

  • JCI Insight. 2022 Jan 11;7(1):e141344. doi: 10.1172/jci.insight.141344.
Vitor F Martins 1 2,  Samuel A LaBarge 1,  Alexandra Stanley 1,  Kristoffer Svensson 1,  Chao-Wei Hung 3,  Omer Keinan 3,  Theodore P Ciaraldi 3 4,  Dion Banoian 1,  Ji E Park 1,  Christina Ha 1,  Byron Hetrick 5,  Gretchen A Meyer 6,  Andrew Philp 7 8,  Larry L David 9,  Robert R Henry 3 4,  Joseph E Aslan 9 10 11,  Alan R Saltiel 3,  Carrie E McCurdy 5,  Simon Schenk 1 2
Affiliations

Affiliations

  • 1 Department of Orthopedic Surgery and.
  • 2 Biomedical Sciences Graduate Program, University of California, San Diego, La Jolla, California, USA.
  • 3 Department of Medicine, University of California San Diego School of Medicine, La Jolla, California, USA.
  • 4 VA San Diego Healthcare System, San Diego, California, USA.
  • 5 Department of Human Physiology, University of Oregon, Eugene, Oregon, USA.
  • 6 Program in Physical Therapy, Washington University in St. Louis, St. Louis, Missouri, USA.
  • 7 Garvan Institute of Medical Research, Darlinghurst, New South Wales, Australia.
  • 8 St Vincent's Clinical School, UNSW Medicine, UNSW Sydney, Sydney, New South Wales, Australia.
  • 9 Department of Biochemistry and Molecular Biology.
  • 10 Knight Cardiovascular Institute, and.
  • 11 Department of Biomedical Engineering, School of Medicine, Oregon Health & Science University, Portland, Oregon, USA.
PMID: 34813504 DOI: 10.1172/jci.insight.141344
Abstract

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.

Keywords

Endocrinology; Glucose metabolism; Insulin signaling; Muscle Biology; Skeletal muscle.

Figures
Products