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

J. Cliff 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

116 Citations (Scopus)

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

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Medical problems
Energy Metabolism
Insulin
Glycerolphosphate Dehydrogenase
Glucokinase
Glucose
Glucose-6-Phosphatase
Gene expression
Animals
Adenosine Triphosphate
Exocytosis
Membranes
Adenoviridae
Type 2 Diabetes Mellitus
Messenger RNA
Defects
Rodentia
Animal Models
Phenotype
Gene Expression

ASJC Scopus subject areas

  • Developmental Biology

Cite this

Yoon, J. C., Xu, G., Deeney, J. T., Yang, S. N., Rhee, J., Puigserver, P., ... 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

Suppression of β cell energy metabolism and insulin release by PGC-1α. / Yoon, J. Cliff; Xu, Gang; Deeney, Jude T.; Yang, Shao Nian; Rhee, James; Puigserver, Pere; Levens, Adah R.; Yang, Ruojing; Zhang, Chen Yu; Lowell, Bradford B.; Berggren, Per Olof; Newgard, Christopher B.; Bonner-Weir, Susan; Weir, Gordon; Spiegelman, Bruce M.

In: Developmental Cell, Vol. 5, No. 1, 01.07.2003, p. 73-83.

Research output: Contribution to journalArticle

Yoon, JC, Xu, G, Deeney, JT, Yang, SN, Rhee, J, Puigserver, P, Levens, AR, Yang, R, Zhang, CY, Lowell, BB, Berggren, PO, Newgard, CB, Bonner-Weir, S, Weir, G & Spiegelman, BM 2003, 'Suppression of β cell energy metabolism and insulin release by PGC-1α', Developmental Cell, vol. 5, no. 1, pp. 73-83. https://doi.org/10.1016/S1534-5807(03)00170-9
Yoon JC, Xu G, Deeney JT, Yang SN, Rhee J, Puigserver P et al. Suppression of β cell energy metabolism and insulin release by PGC-1α. Developmental Cell. 2003 Jul 1;5(1):73-83. https://doi.org/10.1016/S1534-5807(03)00170-9
Yoon, J. Cliff ; Xu, Gang ; Deeney, Jude T. ; Yang, Shao Nian ; Rhee, James ; Puigserver, Pere ; Levens, Adah R. ; Yang, Ruojing ; Zhang, Chen Yu ; Lowell, Bradford B. ; Berggren, Per Olof ; Newgard, Christopher B. ; Bonner-Weir, Susan ; Weir, Gordon ; Spiegelman, Bruce M. / Suppression of β cell energy metabolism and insulin release by PGC-1α. In: Developmental Cell. 2003 ; Vol. 5, No. 1. pp. 73-83.
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