Troglitazone prevents and reverses dexamethasone induced insulin resistance on glycogen synthesis in 3T3 adipocytes

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...

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Bibliographic Details
Published in:British journal of pharmacology 2000-05, Vol.130 (2), p.351-358
Main Authors: Anil Kumar, K L, Marita, A R
Format: Article
Language:English
Subjects:
3T3 adipocytes
3T3 Cells
Abortifacient Agents, Steroidal - pharmacology
Adipocytes - drug effects
Adipocytes - metabolism
Animals
Binding Sites
Chromans - pharmacology
dexamethasone
Dexamethasone - antagonists & inhibitors
Dexamethasone - pharmacology
Dose-Response Relationship, Drug
Drug Interactions
Glucocorticoids - pharmacology
Glycogen - biosynthesis
Glycogen synthesis
Hypoglycemic Agents - pharmacology
in vitro model
Insulin - pharmacology
Insulin Resistance
Iodine Radioisotopes
metformin
Mice
Mifepristone - pharmacology
Thiazoles - pharmacology
Thiazolidinediones
troglitazone
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Summary: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 μM) 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 14C‐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 μM) 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
ISSN:0007-1188
1476-5381
DOI:10.1038/sj.bjp.0703313