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Suppression of beta cell energy metabolism and insulin release by PGC-1alpha.

Publication ,  Journal Article
Yoon, JC; Xu, G; Deeney, JT; Yang, S-N; Rhee, J; Puigserver, P; Levens, AR; Yang, R; Zhang, C-Y; Lowell, BB; Berggren, P-O; Newgard, CB ...
Published in: Dev Cell
July 2003

beta cell dysfunction is an important component of type 2 diabetes, but the molecular basis for this defect is poorly understood. The transcriptional coactivator PGC-1alpha mRNA and protein levels are significantly elevated in islets from multiple animal models of diabetes; adenovirus-mediated expression of PGC-1alpha to levels similar to those present in diabetic rodents produces a marked inhibition of glucose-stimulated insulin secretion from islets in culture and in live mice. This inhibition coincides with changes in metabolic gene expression associated with impaired beta cell function, including the induction of glucose-6-phosphatase and suppression of GLUT2, glucokinase, and glycerol-3-phosphate dehydrogenase. These changes result in blunting of the glucose-induced rise in cellular ATP levels and membrane electrical activity responsible for Ca(2+) influx and insulin exocytosis. These results strongly suggest that PGC-1alpha plays a key functional role in the beta cell and is involved in the pathogenesis of the diabetic phenotype.

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Published In

Dev Cell

DOI

ISSN

1534-5807

Publication Date

July 2003

Volume

5

Issue

1

Start / End Page

73 / 83

Location

United States

Related Subject Headings

  • Transfection
  • Transcription Factors
  • Rats, Zucker
  • Rats, Mutant Strains
  • Rats
  • Mice
  • Male
  • Islets of Langerhans Transplantation
  • Islets of Langerhans
  • Insulin Secretion
 

Citation

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Yoon, J. C., Xu, G., Deeney, J. T., Yang, S.-N., Rhee, J., Puigserver, P., … Spiegelman, B. M. (2003). Suppression of beta cell energy metabolism and insulin release by PGC-1alpha. Dev Cell, 5(1), 73–83. https://doi.org/10.1016/s1534-5807(03)00170-9
Yoon, J Cliff, Gang Xu, Jude T. Deeney, Shao-Nian Yang, James Rhee, Pere Puigserver, Adah R. Levens, et al. “Suppression of beta cell energy metabolism and insulin release by PGC-1alpha.Dev Cell 5, no. 1 (July 2003): 73–83. https://doi.org/10.1016/s1534-5807(03)00170-9.
Yoon JC, Xu G, Deeney JT, Yang S-N, Rhee J, Puigserver P, et al. Suppression of beta cell energy metabolism and insulin release by PGC-1alpha. Dev Cell. 2003 Jul;5(1):73–83.
Yoon, J. Cliff, et al. “Suppression of beta cell energy metabolism and insulin release by PGC-1alpha.Dev Cell, vol. 5, no. 1, July 2003, pp. 73–83. Pubmed, doi:10.1016/s1534-5807(03)00170-9.
Yoon JC, Xu G, Deeney JT, Yang S-N, Rhee J, Puigserver P, Levens AR, Yang R, Zhang C-Y, Lowell BB, Berggren P-O, Newgard CB, Bonner-Weir S, Weir G, Spiegelman BM. Suppression of beta cell energy metabolism and insulin release by PGC-1alpha. Dev Cell. 2003 Jul;5(1):73–83.
Journal cover image

Published In

Dev Cell

DOI

ISSN

1534-5807

Publication Date

July 2003

Volume

5

Issue

1

Start / End Page

73 / 83

Location

United States

Related Subject Headings

  • Transfection
  • Transcription Factors
  • Rats, Zucker
  • Rats, Mutant Strains
  • Rats
  • Mice
  • Male
  • Islets of Langerhans Transplantation
  • Islets of Langerhans
  • Insulin Secretion