التفاصيل البيبلوغرافية
| العنوان: |
Pioglitazone Therapy Restores the Coupling of Electron Transport to ATP Synthesis in Skeletal Muscle of Obese Zucker Rats. |
| المؤلفون: |
Moellering, Douglas R., Vestri, Helliner S., Andringa, Kelly K., Mantena, Sudheer K., Bailey, Shannon M., Garvey, W. T. |
| المصدر: |
Diabetes; Jun2007 Supplement 1, Vol. 56, pA85-A86, 2p |
| مصطلحات موضوعية: |
HYPOGLYCEMIC agents, ELECTRON transport, ADENOSINE triphosphate, CHEMICAL synthesis, OVERWEIGHT persons, MUSCLES, INSULIN |
| مستخلص: |
Insulin resistant patients exhibit dysregulated expression of mitochondria-related genes in skeletal muscle. Insulin-sensitizing thiazolidinedione (TZD) drugs function as PPAR-gamma agonists, which regulate mitochondrial genes involved in substrate metabolism. However, little is known regarding effects of TZDs on the function of the mitochondrial respiratory chain. To address this issue, we studied isolated mitochondria from soleus muscles of lean (Ln) and obese Zucker fa/fa rots (Ob), and Ob treated for 3 weeks with 10mg/kg/d pioglitazone (Pio). Mitochondrial oxidation rates were assessed by respirometry in response to carbohydrate substrates (9mM pyruvate/4mM malate) using a Clark-type electrode. Animal weights at 12 weeks were 353±7 g for Ln, 554±17 g for Ob, and 618±11 g for Pio. Ob had elevated serum glucose (123±4 vs 95±9 mg/dL), triglycerides (584±70 vs 95±11 mg/dL), FFAs (1.3±0.1 vs 0.8±0.1 mEq/L), and insulin (8.3±1.0 vs 0.4±0.l ng/ml) levels compared to Ln (all P<.05), and Pio decreased these serum values towards normal. In isolated mitochondria, Ob had significantly elevated rates of State 3 (St 3106.5±6.7 vs 83.4±3.6 nmol/ml), and enhanced-State 4 respiration using oligomycin (St 4- 6.58±10.91 vs 1.33:10.25 nmol/ml) compared to Ln (P<.05). Pin restored these elevated values in Ob to those observed in Ln (St 364.91±6.53; St 4- 1.42±0.63 nmol/ml). The coupling of electron transport to ATP generation as measured by respiratory control ratios (RCR; St 3/4) was impaired in Ob compared with Ln (16.6±1.5 vs 67.1±12.4; P<.01). Pio normalized the defect in coupling seen in Ob by restoring RCR (63.8±21.8) to the level seen in Ln (P=NS). In conclusion: in isolated soleus mitochondria, 1) St3 and St4 oxidation rates for carbohydrate substrates are elevated and coupling (RCR) is impaired in Ob Zucker rats. 2) Pioglitazone therapy in Ob normalizes oxidation rates and coupling of electron transport to ATP synthesis. Thus, Ob exerts effects on respiratory chain function assessed ex vivo in a manner that may not be predictable based on whole organism physiology, and Pin has been shown for the first time to modulate intrinsic respiratory chain function and ATP coupling. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
Complementary Index |
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