Skip to main content

Induction of the ChREBPβ Isoform Is Essential for Glucose-Stimulated β-Cell Proliferation.

Publication ,  Journal Article
Zhang, P; Kumar, A; Katz, LS; Li, L; Paulynice, M; Herman, MA; Scott, DK
Published in: Diabetes
December 2015

Carbohydrate-responsive element-binding protein (ChREBP) is a glucose-sensing transcription factor required for glucose-stimulated proliferation of pancreatic β-cells in rodents and humans. The full-length isoform (ChREBPα) has a low glucose inhibitory domain (LID) that restrains the transactivation domain when glucose catabolism is minimal. A novel isoform of ChREBP (ChREBPβ) was recently described that lacks the LID domain and is therefore constitutively and more potently active. ChREBPβ has not been described in β-cells nor has its role in glucose-stimulated proliferation been determined. We found that ChREBPβ is highly expressed in response to glucose, particularly with prolonged culture in hyperglycemic conditions. In addition, small interfering RNAs that knocked down ChREBPβ transcripts without affecting ChREBPα expression or activity decreased glucose-stimulated expression of carbohydrate response element-containing genes and glucose-stimulated proliferation in INS-1 cells and in isolated rat islets. Quantitative chromatin immunoprecipitation, electrophoretic mobility shift assays, and luciferase reporter assays were used to demonstrate that ChREBP binds to a newly identified powerful carbohydrate response element in β-cells and hepatocytes, distinct from that in differentiated 3T3-L1 adipocytes. We conclude that ChREBPβ contributes to glucose-stimulated gene expression and proliferation in β-cells, with recruitment of ChREBPα to tissue-specific elements of the ChREBPβ isoform promoter.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

December 2015

Volume

64

Issue

12

Start / End Page

4158 / 4170

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription Factors
  • Recombinant Proteins
  • Rats, Wistar
  • Rats
  • RNA Interference
  • Protein Isoforms
  • Nuclear Proteins
  • Mice
  • Insulin-Secreting Cells
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Zhang, P., Kumar, A., Katz, L. S., Li, L., Paulynice, M., Herman, M. A., & Scott, D. K. (2015). Induction of the ChREBPβ Isoform Is Essential for Glucose-Stimulated β-Cell Proliferation. Diabetes, 64(12), 4158–4170. https://doi.org/10.2337/db15-0239
Zhang, Pili, Anil Kumar, Liora S. Katz, Lucy Li, Martine Paulynice, Mark A. Herman, and Donald K. Scott. “Induction of the ChREBPβ Isoform Is Essential for Glucose-Stimulated β-Cell Proliferation.Diabetes 64, no. 12 (December 2015): 4158–70. https://doi.org/10.2337/db15-0239.
Zhang P, Kumar A, Katz LS, Li L, Paulynice M, Herman MA, et al. Induction of the ChREBPβ Isoform Is Essential for Glucose-Stimulated β-Cell Proliferation. Diabetes. 2015 Dec;64(12):4158–70.
Zhang, Pili, et al. “Induction of the ChREBPβ Isoform Is Essential for Glucose-Stimulated β-Cell Proliferation.Diabetes, vol. 64, no. 12, Dec. 2015, pp. 4158–70. Pubmed, doi:10.2337/db15-0239.
Zhang P, Kumar A, Katz LS, Li L, Paulynice M, Herman MA, Scott DK. Induction of the ChREBPβ Isoform Is Essential for Glucose-Stimulated β-Cell Proliferation. Diabetes. 2015 Dec;64(12):4158–4170.

Published In

Diabetes

DOI

EISSN

1939-327X

Publication Date

December 2015

Volume

64

Issue

12

Start / End Page

4158 / 4170

Location

United States

Related Subject Headings

  • Up-Regulation
  • Transcription Factors
  • Recombinant Proteins
  • Rats, Wistar
  • Rats
  • RNA Interference
  • Protein Isoforms
  • Nuclear Proteins
  • Mice
  • Insulin-Secreting Cells