Troglitazone prevents and reverses dexamethasone induced insulin resistance on glycogen synthesis in 3T3 adipocytes
Autor: | A R Marita, K L Anil Kumar |
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Rok vydání: | 2000 |
Předmět: |
Pharmacology
medicine.medical_specialty biology Glycogen business.industry Insulin medicine.medical_treatment Glucose uptake Troglitazone medicine.disease Metformin chemistry.chemical_compound Endocrinology Insulin resistance chemistry Internal medicine medicine biology.protein business Glycogen synthase Dexamethasone medicine.drug |
Zdroj: | British Journal of Pharmacology. 130:351-358 |
ISSN: | 0007-1188 |
DOI: | 10.1038/sj.bjp.0703313 |
Popis: | Troglitazone lowers blood glucose levels in Type II diabetic patients. To evaluate the insulin sensitizing action of troglitazone on glycogen synthesis we have used dexamethasone-treated 3T3 adipocytes as an in vitro model. Differentiated 3T3 adipocytes were incubated with 100 nM dexamethasone for 6 days. Troglitazone (1.0 microM) or metformin (1.0 mM) with or without 200 nM insulin was added during the last 4 days. At the end, insulin (100 nM) stimulated glycogen synthesis was determined using (14)C-glucose. Dexamethasone caused a 50% reduction in glycogen synthesis. Troglitazone caused an approximately 3 fold increase in glycogen synthesis from 43.9+/-3.4 to 120+/-16.2 nmols h(-1). Under identical conditions metformin had no significant effect. When cells were incubated with troglitazone and dexamethasone simultaneously for 6 days, troglitazone but not metformin completely prevented dexamethasone-induced insulin resistance. RU 486 (1.0 microM) also completely prevented the insulin resistance. Chronic incubation with dexamethasone and insulin resulted in a 73% reduction in glycogen synthesis. In these adipocytes, troglitazone was partially active with glycogen synthesis rising from 23.1+/-3.0 to 44.4+/-4.5 nmol h(-1), P |
Databáze: | OpenAIRE |
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