Artikel
The PPARgamma-Activating Angiotensin Type 1 Receptor Blocker Telmisartan Improves Insulin Sensitivity and Prevents Weight Gain in Diet Induced Obese Mice
Der PPARgamma-aktivierende Angiotensin Typ 1 Rezeptor Blocker Telmisartan verbessert die Insulinsensitivität und verhindert Gewichtszunahme in Diät-induzierten adipösen Mäusen
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Autoren
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M.H. Clemenz
- Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
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A. Foryst-Ludwig
- Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
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M. Harge
- Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
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C. Sprang
- Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
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T. Unger
- Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
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U. Kintscher
- Charité - Universitätsmedizin Berlin, Center for Cardiovascular Research (Berlin, D)
| Veröffentlicht: | 8. August 2006 |
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Gliederung
Text
Telmisartan has been recently identified as an activator of the insulin-sensitizing nuclear hormone receptor Peroxisome Proliferator-Activated Receptor (PPAR)gamma, acting like a selective PPAR gamma modulator in vitro.
The use of currently available PPAR gamma agonists is limited due to side effects including weight gain, edema and fluid retention. Selective PPAR gamma modulation is a new pharmacological approach which maintains potent insulin sensitization in the absence of PPAR gamma-mediated adverse effects. Here we investigate the selective PPAR gamma modulating ARB telmisartan in diet-induced obese mice regarding its metabolic efficiency.
Obese male C57BL/6J mice were treated with either telmisartan (3mg/kg/d, n=8), pioglitazone (10mg/kg/d, n=8) or vehicle by oral gavage for 10 weeks. Body weight, food intake, body composition, serum insulin, serum glucose and blood pressure were determined. An oral glucose tolerance test (oGTT) and an insulin tolerance test (ITT) were performed. After treatment body weight was significantly reduced in the telmisartan group (44.3±1.86g; p<0.05) compared to the other treatment groups (pioglitazone 53.1±1.92g; vehicle 49.9±0.98g), which was mainly mediated by a significant decrease in total body fat as assessed by MRI measurement (telmisartan -2.69±1.41g, p<0.05; pioglitazone 3.82±1.69g; vehicle 1.6±0.47g). In parallel, telmisartan and pioglitazone improved oral glucose tolerance and insulin tolerance measured by oGTT and ITT (oGTT 30min: telmisartan 324±31mg/dl, p<0.05; pioglitazone 284±15mg/dl, p<0.05; vehicle 421±26mg/dl). Both substances attenuated the obesity-mediated insulin-resistance, however only telmisartan was able to lower body weight in these animals.
The present study demonstrates that selective PPAR gamma modulation by telmisartan may reduce the weight promoting effects of PPAR gamma activation, and in parallel retains PPAR gamma-mediated metabolic efficacy providing a new therapeutic option for patients suffering from diabetes or the metabolic syndrome.
