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Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β Cell Metabolism in the Absence of Overnutrition.

Publication ,  Journal Article
Peterson, BS; Campbell, JE; Ilkayeva, O; Grimsrud, PA; Hirschey, MD; Newgard, CB
Published in: Cell Rep
July 3, 2018

SIRT3 is a nicotinamide adenine dinucleotide (NAD+)-dependent mitochondrial protein deacetylase purported to influence metabolism through post-translational modification of metabolic enzymes. Fuel-stimulated insulin secretion, which involves mitochondrial metabolism, could be susceptible to SIRT3-mediated effects. We used CRISPR/Cas9 technology to manipulate SIRT3 expression in β cells, resulting in widespread SIRT3-dependent changes in acetylation of key metabolic enzymes but no appreciable changes in glucose- or pyruvate-stimulated insulin secretion or metabolomic profile during glucose stimulation. Moreover, these broad changes in the SIRT3-targeted acetylproteome did not affect responses to nutritional or ER stress. We also studied mice with global SIRT3 knockout fed either standard chow (STD) or high-fat and high-sucrose (HFHS) diets. Only when chronically fed HFHS diet do SIRT3 KO animals exhibit a modest reduction in insulin secretion. We conclude that broad changes in mitochondrial protein acetylation in response to manipulation of SIRT3 are not sufficient to cause changes in islet function or metabolism.

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Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

July 3, 2018

Volume

24

Issue

1

Start / End Page

209 / 223.e6

Location

United States

Related Subject Headings

  • Transgenes
  • Sucrose
  • Sirtuin 3
  • Secretagogues
  • Rats
  • Proteome
  • Overnutrition
  • Mutation
  • Mitochondrial Proteins
  • Mice, Knockout
 

Citation

APA
Chicago
ICMJE
MLA
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Peterson, B. S., Campbell, J. E., Ilkayeva, O., Grimsrud, P. A., Hirschey, M. D., & Newgard, C. B. (2018). Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β Cell Metabolism in the Absence of Overnutrition. Cell Rep, 24(1), 209-223.e6. https://doi.org/10.1016/j.celrep.2018.05.088
Peterson, Brett S., Jonathan E. Campbell, Olga Ilkayeva, Paul A. Grimsrud, Matthew D. Hirschey, and Christopher B. Newgard. “Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β Cell Metabolism in the Absence of Overnutrition.Cell Rep 24, no. 1 (July 3, 2018): 209-223.e6. https://doi.org/10.1016/j.celrep.2018.05.088.
Peterson BS, Campbell JE, Ilkayeva O, Grimsrud PA, Hirschey MD, Newgard CB. Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β Cell Metabolism in the Absence of Overnutrition. Cell Rep. 2018 Jul 3;24(1):209-223.e6.
Peterson, Brett S., et al. “Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β Cell Metabolism in the Absence of Overnutrition.Cell Rep, vol. 24, no. 1, July 2018, pp. 209-223.e6. Pubmed, doi:10.1016/j.celrep.2018.05.088.
Peterson BS, Campbell JE, Ilkayeva O, Grimsrud PA, Hirschey MD, Newgard CB. Remodeling of the Acetylproteome by SIRT3 Manipulation Fails to Affect Insulin Secretion or β Cell Metabolism in the Absence of Overnutrition. Cell Rep. 2018 Jul 3;24(1):209-223.e6.
Journal cover image

Published In

Cell Rep

DOI

EISSN

2211-1247

Publication Date

July 3, 2018

Volume

24

Issue

1

Start / End Page

209 / 223.e6

Location

United States

Related Subject Headings

  • Transgenes
  • Sucrose
  • Sirtuin 3
  • Secretagogues
  • Rats
  • Proteome
  • Overnutrition
  • Mutation
  • Mitochondrial Proteins
  • Mice, Knockout