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Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
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| Zeitschriftentitel: | Diabetes |
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| Personen und Körperschaften: | , , , , , |
| In: | Diabetes, 53, 2004, suppl_3, S. S79-S83 |
| Format: | E-Article |
| Sprache: | Englisch |
| veröffentlicht: |
American Diabetes Association
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| Schlagwörter: |
| Zusammenfassung: | <jats:p>Peroxisome proliferator-activated receptor (PPAR)-γ is expressed in human β-cells and in the rat β-cell line INS-1. Previous studies have suggested that PPAR-γ agonism (e.g., thiazolidinediones) enhances glucose-stimulated insulin secretion (GSIS) from islets or INS-1 cells. We tested the direct effect on insulin release by INS-1e of a PPAR-γ agonist (Ro4389679-000-001 at 0.2 and 0.4 μmol/l) and a PPAR-γ antagonist (SR202 at 0.2 and 0.4 mmol/l). Cells were incubated in 11 mmol/l glucose for 96 h and then challenged with 3.3, 7.5, 11.0, and 20.0 mmol/l glucose for 1 h. Under these control conditions, insulin concentrations in the medium rose from 19 ± 4 ng/ml (mean ± SE) to 82 ± 5, 107 ± 11, and 103 ± 10 ng/ml (P &lt; 0.0001 by ANOVA). Preincubation for 48 h with the PPAR-γ agonist potentiated GSIS (to 154 ± 14 and 156 ± 12 ng/ml at 20 mmol/l glucose, P &lt; 0.01). Cell insulin content was not altered by either acute glucose challenge or PPAR-γ agonist coincubation. Preincubation for 48 h with SR202 at the higher dose caused a 30% inhibition of GSIS, with no change in cell insulin contents. When cells were preincubated with 11 mmol/l glucose plus 1 mmol/l oleate, GSIS was significantly potentiated (by 30%, P &lt; 0.0001); adding Ro4389679-000-001 or SR202 to these preincubations reduced GSIS to the respective levels seen in the absence of oleate (P &lt; 0.0001 for both effects). In conclusion, INS-1e cells display a PPAR-γ tone that is symmetrically modulated and competitively stimulated by oleate.</jats:p> |
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| Umfang: | S79-S83 |
| ISSN: |
0012-1797
1939-327X |
| DOI: | 10.2337/diabetes.53.suppl_3.s79 |