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Prior thiazolidinedione treatment preserves insulin sensitivity in normal rats during acute fatty acid elevation: role of the liver
Citation
Ye, JM and Frangioudakis, G and Iglesias, MA and Furler, SM and Ellis, B and Dzamko, N and Cooney, GJ and Kraegen, EW, Prior thiazolidinedione treatment preserves insulin sensitivity in normal rats during acute fatty acid elevation: role of the liver, Endocrinology, 143, (12) pp. 4527-35. ISSN 0013-7227 (2002) [Refereed Article]
Copyright Statement
Copyright 2002 by The Endocrine Society
DOI: doi:10.1210/en.2002-220387
Abstract
Thiazolidinediones lower lipids, but it is unclear whether this is essential for their insulin-sensitizing action. We investigated relationships between lipid-lowering and insulin-sensitizing actions of a thiazolidinedione. Normal rats were pretreated with or without Pioglitazone (Pio, 3 mg/kg.d) for 2 wk. Insulin sensitivity was assessed by hyperinsulinemic-euglycemic clamp with elevation of free fatty acids (FFA) by Intralipid/heparin infusion over 6 h. In untreated rats insulin sensitivity decreased by 46% over 3-6 h of elevated FFA, whereas it remained normal but with a 50% increase in FFA clearance in Pio-treated rats. After matching plasma FFA, insulin sensitivity was still partially (30%) protected in Pio-treated rats, substantially by maintaining insulin suppressibility of hepatic glucose output. This was associated with lower hepatic long-chain acyl-coenzyme A. Plasma adiponectin was increased 2-fold in Pio-treated rats and was negatively correlated with hepatic glucose output (r2 = 0.70, P < 0.001) and liver long-chain acyl-coenzyme A (r2 = 0.39, P < 0.005). Pio-induced muscle insulin sensitization was largely diminished after matching plasma FFA elevation, but insulin-stimulated protein kinase B phosphorylation was protected. We conclude that thiazolidinediones can protect against lipid-induced insulin resistance with a significant component (mainly liver) of the protective effect not requiring lipid lowering. This may be related to chronic elevation of adiponectin by thiazolidinediones.
Item Details
Item Type: | Refereed Article |
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Research Division: | Biomedical and Clinical Sciences |
Research Group: | Medical biochemistry and metabolomics |
Research Field: | Metabolic medicine |
Objective Division: | Health |
Objective Group: | Clinical health |
Objective Field: | Clinical health not elsewhere classified |
UTAS Author: | Iglesias, MA (Dr Miguel Iglesias) |
ID Code: | 80268 |
Year Published: | 2002 |
Web of Science® Times Cited: | 32 |
Deposited By: | Health Sciences A |
Deposited On: | 2012-10-25 |
Last Modified: | 2012-11-28 |
Downloads: | 0 |
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