author_facet Santini, Eleonora
Fallahi, Poupak
Ferrari, Silvia Martina
Masoni, Antonio
Antonelli, Alessandro
Ferrannini, Ele
Santini, Eleonora
Fallahi, Poupak
Ferrari, Silvia Martina
Masoni, Antonio
Antonelli, Alessandro
Ferrannini, Ele
author Santini, Eleonora
Fallahi, Poupak
Ferrari, Silvia Martina
Masoni, Antonio
Antonelli, Alessandro
Ferrannini, Ele
spellingShingle Santini, Eleonora
Fallahi, Poupak
Ferrari, Silvia Martina
Masoni, Antonio
Antonelli, Alessandro
Ferrannini, Ele
Diabetes
Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
Endocrinology, Diabetes and Metabolism
Internal Medicine
author_sort santini, eleonora
spelling Santini, Eleonora Fallahi, Poupak Ferrari, Silvia Martina Masoni, Antonio Antonelli, Alessandro Ferrannini, Ele 0012-1797 1939-327X American Diabetes Association Endocrinology, Diabetes and Metabolism Internal Medicine http://dx.doi.org/10.2337/diabetes.53.suppl_3.s79 <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 &amp;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 &amp;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 &amp;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 &amp;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> Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells Diabetes
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title Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_unstemmed Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_full Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_fullStr Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_full_unstemmed Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_short Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_sort effect of ppar-γ activation and inhibition on glucose-stimulated insulin release in ins-1e cells
topic Endocrinology, Diabetes and Metabolism
Internal Medicine
url http://dx.doi.org/10.2337/diabetes.53.suppl_3.s79
publishDate 2004
physical S79-S83
description <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 &amp;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 &amp;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 &amp;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 &amp;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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author Santini, Eleonora, Fallahi, Poupak, Ferrari, Silvia Martina, Masoni, Antonio, Antonelli, Alessandro, Ferrannini, Ele
author_facet Santini, Eleonora, Fallahi, Poupak, Ferrari, Silvia Martina, Masoni, Antonio, Antonelli, Alessandro, Ferrannini, Ele, Santini, Eleonora, Fallahi, Poupak, Ferrari, Silvia Martina, Masoni, Antonio, Antonelli, Alessandro, Ferrannini, Ele
author_sort santini, eleonora
container_issue suppl_3
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container_title Diabetes
container_volume 53
description <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 &amp;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 &amp;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 &amp;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 &amp;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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spelling Santini, Eleonora Fallahi, Poupak Ferrari, Silvia Martina Masoni, Antonio Antonelli, Alessandro Ferrannini, Ele 0012-1797 1939-327X American Diabetes Association Endocrinology, Diabetes and Metabolism Internal Medicine http://dx.doi.org/10.2337/diabetes.53.suppl_3.s79 <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 &amp;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 &amp;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 &amp;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 &amp;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> Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells Diabetes
spellingShingle Santini, Eleonora, Fallahi, Poupak, Ferrari, Silvia Martina, Masoni, Antonio, Antonelli, Alessandro, Ferrannini, Ele, Diabetes, Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells, Endocrinology, Diabetes and Metabolism, Internal Medicine
title Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_full Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_fullStr Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_full_unstemmed Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_short Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
title_sort effect of ppar-γ activation and inhibition on glucose-stimulated insulin release in ins-1e cells
title_unstemmed Effect of PPAR-γ Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells
topic Endocrinology, Diabetes and Metabolism, Internal Medicine
url http://dx.doi.org/10.2337/diabetes.53.suppl_3.s79