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Diabetologia 50, 7 (2007) 1384-7
Direct rosiglitazone-induced modifications in insulin secretion, action and clearance: a single-dose hyperglycaemic clamp study.
A. Farret, H. Chevassus, B. Roux, P. Petit 1, 2, 3, 4, 5, 6, F. Galtier 7

AIMS/HYPOTHESIS: In addition to the improvement in insulin sensitivity, it has been shown that thiazolidinediones modulate beta cell function and insulin clearance in type 2 diabetic subjects. However, interactions between all these actions, and confounding factors due to co-morbidities and co-treatments in diabetic individuals, complicate the identification of specific effects. The aim of this pilot study was to investigate the potential acute effects of rosiglitazone on beta cell function and insulin sensitivity by the hyperglycaemic clamp technique in healthy volunteers. SUBJECTS AND METHODS: Twelve healthy men were included in a randomised, double-blind crossover study. Rosiglitazone (8 mg) or placebo was given orally 45 min before the hyperglycaemic clamp (10 mmol/l for 2 h). RESULTS: The second phase of the insulin response was significantly decreased by rosiglitazone: 13,066 +/- 1,531 vs 16,316 +/- 2,813 pmol l(-1) 110 min in controls (p < 0.05), without change in the first phase. Serum C-peptide was not modified. Rosiglitazone treatment significantly increased insulin clearance (molar ratio of the C-peptide to insulin AUCs: 12.80 +/- 1.34 vs 11.38 +/- .33, p < 0.05) and the insulin sensitivity index (12.0 +/- 1.5 vs 8.5 +/- 1.1 micromol m(-2) min(-1) pmol(-1)l, p < 0.01). CONCLUSIONS/INTERPRETATION: The present results show that a single dose of rosiglitazone rapidly increases insulin clearance and insulin sensitivity index in healthy volunteers, with no direct effect on insulin secretion. The precise mechanisms mediating these actions remain to be determined.
1 :  Institut Charles Sadron (ICS)
2 :  Laboratoire Astrophysique de Toulouse-Tarbes (LATT)
CNRS : UMR5572 – INSU – Observatoire Midi-Pyrénées – Université Paul Sabatier (UPS) - Toulouse III
3 :  Institut des matériaux Jean Rouxel (IMN)
CNRS : UMR6502 – Université de Nantes
4 :  European Synchrotron Radiation Facility (ESRF)
5 :  Centre d'Economie de l'Université de Paris Nord (ancienne affiliation) (CEPN)
Université Paris 13 – CNRS : UMR7115
6 :  Centre de pharmacologie et innovation dans le diabète (CPID)
CNRS : UMR5232 – CHRU Montpellier – Université Montpellier I
7 :  Endocrinologie moléculaire et cellulaire des cancers
INSERM : U540 – Université Montpellier I
Sciences du Vivant/Médecine humaine et pathologie/Endocrinologie et métabolisme