Suppression of β Cell Energy Metabolism and Insulin Release by PGC-1α

Autor: Adah R. Levens, Susan Bonner-Weir, Ruojing Yang, J. Cliff Yoon, Christopher B. Newgard, Jude T. Deeney, Gang Xu, Bradford B. Lowell, Shao Nian Yang, Per Olof Berggren, James Rhee, Gordon C. Weir, Bruce M. Spiegelman, Pere Puigserver, Chen-Yu Zhang
Rok vydání: 2003
Předmět:
Male
medicine.medical_specialty
medicine.medical_treatment
Cell
Islets of Langerhans Transplantation
Action Potentials
030209 endocrinology & metabolism
Biology
Transfection
Rats
Mutant Strains
General Biochemistry
Genetics and Molecular Biology
Exocytosis
Diabetes Mellitus
Experimental
Islets of Langerhans
Mice
03 medical and health sciences
Adenosine Triphosphate
0302 clinical medicine
Diabetes mellitus
Internal medicine
Glucokinase
Insulin Secretion
medicine
Animals
Insulin
Molecular Biology
Cells
Cultured
030304 developmental biology
0303 health sciences
3T3 Cells
Cell Biology
medicine.disease
Rats
Rats
Zucker
Insulin oscillation
medicine.anatomical_structure
Endocrinology
Glucose-6-Phosphatase
biology.protein
GLUT2
Beta cell
Energy Metabolism
Transcription Factors
Developmental Biology
Zdroj: Developmental Cell. 5:73-83
ISSN: 1534-5807
DOI: 10.1016/s1534-5807(03)00170-9
Popis: 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.
Databáze: OpenAIRE
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