# The role of p300/CBP and acetylation towards skeletal muscle insulin action

> **NIH NIH F30** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $50,520

## Abstract

PROJECT SUMMARY
Insulin resistance is a common metabolic complication in aged and obese skeletal muscle that is central to the
pathophysiology of type 2 diabetes (T2D). In order to develop strategies to treat insulin resistance it is
necessary to define the signaling transduction steps that lead to insulin-stimulated glucose uptake, particularly
in skeletal muscle and adipocytes; remarkably, these steps have yet to be fully elucidated. Thus, the long-term
objective of this research is to expand the knowledge of the molecular regulation of insulin-stimulated glucose
transport. Currently, phosphorylation-based signaling from the insulin receptor through phosphoinositide 3-
kinase (PI3K)-Akt, to Akt substrate of 160 kDa (AS160) and actin remodeling-related proteins, is considered
the major mechanism regulating insulin-stimulated GLUT4 translocation to the plasma membrane and glucose
uptake. In contrast to this `classical' model, herein this project proposes a new model in which lysine
acetylation (in combination with phosphorylation-based signaling) of key insulin signaling and GLUT4
trafficking proteins is necessary for insulin-stimulated glucose uptake. Accordingly, the primary objective of this
proposal is to elucidate the importance of the acetyltransferases (KATs), p300 (E1A binding protein p300) and
CBP (cAMP response element-binding protein [CREB] binding protein), to insulin-stimulated glucose transport.
The central hypothesis of this proposal is that acetylation, by p300 and/or CBP, of actin remodeling-related
proteins are required for insulin-stimulated GLUT4 translocation and, therefore, the insulin-mediated increase
in glucose uptake. To address this hypothesis, insulin-induced skeletal muscle glucose uptake, actin
remodeling and GLUT4 translocation will be measured in murine and cell models in which p300 and CBP
activity are manipulated. This proposal predicts that loss of both p300 and CBP activity will abolish insulin-
stimulated actin reorganization, GLUT4 translocation and glucose transport. Specifically, in Aim #1 the
necessity and redundancy of p300 and CBP for insulin-stimulated glucose uptake in skeletal muscle will be
elucidated, whilst in Aim #2, the importance of p300/CBP to actin remodeling and polymerization, and GLUT4
translocation will be assessed. Overall, these studies will broaden the understanding of the contribution of
p300, CBP and acetylation to skeletal muscle glucose uptake in response to insulin. Ultimately, knowledge
gathered from this work is expected to manifest novel targets for the development of therapies to improve
insulin sensitivity and treat type 2 diabetes, with enhancement of human health and quality of life being
anticipated outcomes.

## Key facts

- **NIH application ID:** 9975145
- **Project number:** 5F30DK115035-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Vitor Fernandes Martins
- **Activity code:** F30 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $50,520
- **Award type:** 5
- **Project period:** 2018-07-01 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9975145

## Citation

> US National Institutes of Health, RePORTER application 9975145, The role of p300/CBP and acetylation towards skeletal muscle insulin action (5F30DK115035-03). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9975145. Licensed CC0.

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