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Diabetes 53:S79-S83, 2004
© 2004 by the American Diabetes Association, Inc.

Section II: Beta-Cell Therapeutic Targets Other Than ATP-Sensitive K+ Channels

Effect of PPAR-{gamma} Activation and Inhibition on Glucose-Stimulated Insulin Release in INS-1e Cells

Eleonora Santini, Poupak Fallahi, Silvia Martina Ferrari, Antonio Masoni, Alessandro Antonelli, and Ele Ferrannini

From the Department of Internal Medicine and C.N.R. Institute of Clinical Physiology, University of Pisa School of Medicine, Pisa, Italy

Peroxisome proliferator-activated receptor (PPAR)-{gamma} is expressed in human ß-cells and in the rat ß-cell line INS-1. Previous studies have suggested that PPAR-{gamma} 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-{gamma} agonist (Ro4389679-000-001 at 0.2 and 0.4 µmol/l) and a PPAR-{gamma} 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 < 0.0001 by ANOVA). Preincubation for 48 h with the PPAR-{gamma} agonist potentiated GSIS (to 154 ± 14 and 156 ± 12 ng/ml at 20 mmol/l glucose, P < 0.01). Cell insulin content was not altered by either acute glucose challenge or PPAR-{gamma} 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 < 0.0001); adding Ro4389679-000-001 or SR202 to these preincubations reduced GSIS to the respective levels seen in the absence of oleate (P < 0.0001 for both effects). In conclusion, INS-1e cells display a PPAR-{gamma} tone that is symmetrically modulated and competitively stimulated by oleate.

Address correspondence and reprint requests to Ele Ferrannini, MD, Department of Internal Medicine, Via Roma, 67, 56100, Pisa, Italy. E-mail: ferranni{at}ifc.cnr.it


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Copyright © 2004 by the American Diabetes Association.