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β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.

Publication ,  Journal Article
Huynh, FK; Peterson, BS; Anderson, KA; Lin, Z; Coakley, AJ; Llaguno, FMS; Nguyen, T-TN; Campbell, JE; Stephens, SB; Newgard, CB; Hirschey, MD
Published in: Am J Physiol Endocrinol Metab
October 1, 2020

Sirtuins are a family of proteins that regulate biological processes such as cellular stress and aging by removing posttranslational modifications (PTMs). We recently identified several novel PTMs that can be removed by sirtuin 4 (SIRT4), which is found in mitochondria. We showed that mice with a global loss of SIRT4 [SIRT4-knockout (KO) mice] developed an increase in glucose- and leucine-stimulated insulin secretion, and this was followed by accelerated age-induced glucose intolerance and insulin resistance. Because whole body SIRT4-KO mice had alterations to nutrient-stimulated insulin secretion, we hypothesized that SIRT4 plays a direct role in regulating pancreatic β-cell function. Thus, we tested whether β-cell-specific ablation of SIRT4 would recapitulate the elevated insulin secretion seen in mice with a global loss of SIRT4. Tamoxifen-inducible β-cell-specific SIRT4-KO mice were generated, and their glucose tolerance and glucose- and leucine-stimulated insulin secretion were measured over time. These mice exhibited normal glucose- and leucine-stimulated insulin secretion and maintained normal glucose tolerance even as they aged. Furthermore, 832/13 β-cells with a CRISPR/Cas9n-mediated loss of SIRT4 did not show any alterations in nutrient-stimulated insulin secretion. Despite the fact that whole body SIRT4-KO mice demonstrated an age-induced increase in glucose- and leucine-stimulated insulin secretion, our current data indicate that the loss of SIRT4 specifically in pancreatic β-cells, both in vivo and in vitro, does not have a significant impact on nutrient-stimulated insulin secretion. These data suggest that SIRT4 controls nutrient-stimulated insulin secretion during aging by acting on tissues external to the β-cell, which warrants further study.

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Published In

Am J Physiol Endocrinol Metab

DOI

EISSN

1522-1555

Publication Date

October 1, 2020

Volume

319

Issue

4

Start / End Page

E805 / E813

Location

United States

Related Subject Headings

  • Sirtuins
  • Protein Processing, Post-Translational
  • Nutrients
  • Mitochondrial Proteins
  • Mitochondria
  • Mice, Knockout
  • Mice
  • Leucine
  • Islets of Langerhans
  • Insulin-Secreting Cells
 

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Huynh, F. K., Peterson, B. S., Anderson, K. A., Lin, Z., Coakley, A. J., Llaguno, F. M. S., … Hirschey, M. D. (2020). β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice. Am J Physiol Endocrinol Metab, 319(4), E805–E813. https://doi.org/10.1152/ajpendo.00170.2020
Huynh, Frank K., Brett S. Peterson, Kristin A. Anderson, Zhihong Lin, Aeowynn J. Coakley, Fiara M. S. Llaguno, Thi-Tina N. Nguyen, et al. “β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.Am J Physiol Endocrinol Metab 319, no. 4 (October 1, 2020): E805–13. https://doi.org/10.1152/ajpendo.00170.2020.
Huynh FK, Peterson BS, Anderson KA, Lin Z, Coakley AJ, Llaguno FMS, et al. β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice. Am J Physiol Endocrinol Metab. 2020 Oct 1;319(4):E805–13.
Huynh, Frank K., et al. “β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice.Am J Physiol Endocrinol Metab, vol. 319, no. 4, Oct. 2020, pp. E805–13. Pubmed, doi:10.1152/ajpendo.00170.2020.
Huynh FK, Peterson BS, Anderson KA, Lin Z, Coakley AJ, Llaguno FMS, Nguyen T-TN, Campbell JE, Stephens SB, Newgard CB, Hirschey MD. β-Cell-specific ablation of sirtuin 4 does not affect nutrient-stimulated insulin secretion in mice. Am J Physiol Endocrinol Metab. 2020 Oct 1;319(4):E805–E813.

Published In

Am J Physiol Endocrinol Metab

DOI

EISSN

1522-1555

Publication Date

October 1, 2020

Volume

319

Issue

4

Start / End Page

E805 / E813

Location

United States

Related Subject Headings

  • Sirtuins
  • Protein Processing, Post-Translational
  • Nutrients
  • Mitochondrial Proteins
  • Mitochondria
  • Mice, Knockout
  • Mice
  • Leucine
  • Islets of Langerhans
  • Insulin-Secreting Cells