Potentiation of Insulin Signaling in Tissues of Zucker Obese Rats After Acute and Long-Term Treatment With PPARγ Agonists
| Autor: | David E. Moller, Qing Dallas-Yang, Thomas W. Doebber, Gaochao Zhou, Xiaolan Shen, Deborah Szalkowski, Franklin Liu, Zhihua Li, Margaret Wu, Guoqiang Jiang, Bei B. Zhang, Joel Berger |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism medicine.medical_treatment Receptors Cytoplasmic and Nuclear Adipose tissue AKT2 Fatty Acids Nonesterified Protein Serine-Threonine Kinases Biology Rosiglitazone Phosphoserine Proto-Oncogene Proteins Internal medicine Insulin receptor substrate Internal Medicine medicine Animals Insulin Obesity Phosphorylation Muscle Skeletal Phosphotyrosine Protein kinase B 3T3-L1 Phosphoproteins Receptor Insulin Rats Rats Zucker Kinetics Thiazoles Insulin receptor Endocrinology Adipose Tissue Liver Insulin Receptor Substrate Proteins biology.protein Female Thiazolidinediones Proto-Oncogene Proteins c-akt Signal Transduction Transcription Factors |
| Zdroj: | Diabetes. 51:2412-2419 |
| ISSN: | 1939-327X 0012-1797 |
| Popis: | Thiazolidinediones (TZDs), agonists of peroxisome proliferator-activated receptor-gamma (PPARgamma), improve insulin sensitivity in vivo, and the mechanism remains largely unknown. In this study, we showed that, in Zucker obese (fa/fa) rats, acute (1-day) treatment with both rosiglitazone (a TZD) and a non-TZD PPARgamma agonist (nTZD) reduced plasma free fatty acid and insulin levels and, concomitantly, potentiated insulin-stimulated Akt phosphorylation at threonine 308 (Akt-pT308) in adipose and muscle tissues. A similar effect on Akt was observed in liver after a 7-day treatment. The increase in Akt-pT308 was correlated with an increase in Akt phosphorylation at serine 473 (Akt-pS473), tyrosine phosphorylation of insulin receptor beta subunit and insulin receptor substrate-1, and serine phosphorylation of glycogen synthase kinase-3alpha/beta. The agonists appeared to potentiate Akt1 phosphorylation in muscle and liver and both Akt1 and Akt2 in adipose. Finally, potentiation of insulin signaling was also observed in isolated adipose tissue ex vivo and differentiated 3T3 L1 adipocytes in vitro, but not in rat primary hepatocytes in vitro. These results suggest that 1) PPARgamma agonists acutely potentiate insulin signaling in adipose and muscle tissues and such regulation may be physiologically relevant to insulin sensitization in vivo; 2) the agonists directly target adipose tissues; and 3) the metabolic and signaling effects of the agonists are mediated by structurally distinct PPARgamma agonists. |
| Databáze: | OpenAIRE |
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