Metabolic syndrome diminishes insulin-induced Akt activation and causes a redistribution of Akt-interacting proteins in cardiomyocytes

PLoS One. 2020 Jan 29;15(1):e0228115. doi: 10.1371/journal.pone.0228115. eCollection 2020.

Abstract

Metabolic syndrome (MetS) is a cluster of cardiometabolic risk factors, with insulin resistance as a critical component for its development. Insulin signaling in the heart leads to Akt (also known as PKB) activation, a serine/threonine protein kinase, which regulates cardiac glucose metabolism and growth. Cardiac metabolic inflexibility, characterized by impaired insulin-induced glucose uptake and oxidation, has been reported as an early and consistent change in the heart of different models of MetS and diabetes; however, the evaluation of Akt activation has yielded variable results. Here we report in cardiomyocytes of MetS rats, diminished insulin-induced glucose uptake and Akt activation, evaluated by its impaired mobilization towards the plasma membrane and phosphorylation, and reflected in a re-distribution of its interacting proteins, assessed by label-free mass spectrometry (data are available via ProteomeXchange with identifier PXD013260). We report 45 proteins with diminished abundance in Akt complex of MetS cardiomyocytes, mainly represented by energy metabolism-related proteins, and also, 31 Akt-interacting proteins with increased abundance, which were mainly related to contraction, endoplasmic reticulum stress, and Akt negative regulation. These results emphasize the relevance of Akt in the regulation of energy metabolism in the heart and highlight Akt-interacting proteins that could be involved in the detrimental effects of MetS in the heart.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Caveolin 3 / metabolism
  • Deoxyglucose / metabolism
  • Enzyme Activation / drug effects
  • Glucose Tolerance Test
  • Insulin / pharmacology*
  • Male
  • Metabolic Syndrome / enzymology*
  • Myocytes, Cardiac / drug effects
  • Myocytes, Cardiac / metabolism*
  • Phosphorylation / drug effects
  • Protein Binding / drug effects
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Rats, Wistar
  • Reproducibility of Results

Substances

  • Caveolin 3
  • Insulin
  • Deoxyglucose
  • Proto-Oncogene Proteins c-akt

Grants and funding

This work was supported by Cinvestav-IPN and partially by CONACYT/SEP Research Grant 167673 (to J.A.O-R.); CONACYT/SEP Research Grant A1-S-9082 (to A.R.); PRODEP-SEP grant to the Academic Group Cinvestav-CA-10, ID 28915/2018 (to A.R. and J.A.O-R.); SEP-CINVESTAV 2018 grant #2 (to A.R.); Estimulo a la Investigacion Medica “Miguel Aleman Valdes” 2018 (to J.A.O-R.) and by a CONACYT scholarship grant, No. 278067 (to H.V.L-G.) and No. 295776 (to T.R-G.).