Prior Thiazolidinedione Treatment Preserves Insulin Sensitivity in Normal Rats during Acute Fatty Acid Elevation: Role of the Liver
| Autor: | Nicholas Dzamko, Ji-Ming Ye, Georgia Frangioudakis, Stuart M. Furler, Edward W. Kraegen, Gregory J. Cooney, Bronwyn A. Ellis, Miguel A. Iglesias |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Blood Glucose
Male Fat Emulsions Intravenous medicine.medical_specialty medicine.drug_class medicine.medical_treatment Fatty Acids Nonesterified Protein Serine-Threonine Kinases Endocrinology Insulin resistance Hyperinsulinism Proto-Oncogene Proteins Internal medicine Diabetes mellitus medicine Animals Hypoglycemic Agents Insulin Phosphorylation Rats Wistar Thiazolidinedione Muscle Skeletal Protein kinase B chemistry.chemical_classification Pioglitazone Adiponectin Heparin business.industry Proteins Fatty acid medicine.disease Rats Thiazoles Glucose Liver chemistry Glucose Clamp Technique Intercellular Signaling Peptides and Proteins Thiazolidinediones lipids (amino acids peptides and proteins) Acyl Coenzyme A Insulin Resistance business Proto-Oncogene Proteins c-akt medicine.drug |
| Zdroj: | Endocrinology. 143:4527-4535 |
| ISSN: | 1945-7170 0013-7227 |
| DOI: | 10.1210/en.2002-220387 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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