Suppression of β cell energy metabolism and insulin release by PGC-1α

John Yoon, Gang Xu, Jude T. Deeney, Shao Nian Yang, James Rhee, Pere Puigserver, Adah R. Levens, Ruojing Yang, Chen Yu Zhang, Bradford B. Lowell, Per Olof Berggren, Christopher B. Newgard, Susan Bonner-Weir, Gordon Weir, Bruce M. Spiegelman

Research output: Contribution to journalArticle

120 Scopus citations

Abstract

β cell dysfunction is an important component of type 2 diabetes, but the molecular basis for this defect is poorly understood. The transcriptional coactivator PGC-1α mRNA and protein levels are significantly elevated in islets from multiple animal models of diabetes; adenovirus-mediated expression of PGC-1α 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 β 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 Ca2+ influx and insulin exocytosis. These results strongly suggest that PGC-1α plays a key functional role in the β cell and is involved in the pathogenesis of the diabetic phenotype.

Original languageEnglish (US)
Pages (from-to)73-83
Number of pages11
JournalDevelopmental Cell
Volume5
Issue number1
DOIs
StatePublished - Jul 1 2003
Externally publishedYes

ASJC Scopus subject areas

  • Developmental Biology

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    Yoon, J., Xu, G., Deeney, J. T., Yang, S. N., Rhee, J., Puigserver, P., Levens, A. R., Yang, R., Zhang, C. Y., Lowell, B. B., Berggren, P. O., Newgard, C. B., Bonner-Weir, S., Weir, G., & Spiegelman, B. M. (2003). Suppression of β cell energy metabolism and insulin release by PGC-1α. Developmental Cell, 5(1), 73-83. https://doi.org/10.1016/S1534-5807(03)00170-9