Intramuscular Lipid Metabolism in the Insulin Resistance of Smoking
| Autor: | Devon M. Hunerdosse, Ali M. Samek, Leigh Perreault, Robert H. Eckel, Mary C. Koehler, Bryan C. Bergman |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
medicine.medical_specialty
Endocrinology Diabetes and Metabolism Arbitrary unit medicine.medical_treatment 030209 endocrinology & metabolism Type 2 diabetes Body Mass Index Diglycerides Young Adult 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Insulin resistance Reference Values Internal medicine Diabetes mellitus Internal Medicine medicine Humans Retinoid X Receptor gamma PPAR alpha RNA Messenger Muscle Skeletal Exercise Triglycerides 030304 developmental biology 2. Zero hunger 0303 health sciences biology Triglyceride Reverse Transcriptase Polymerase Chain Reaction business.industry Insulin Smoking medicine.disease Lipids Diet Insulin receptor Metabolism Endocrinology chemistry biology.protein Original Article Insulin Resistance Energy Intake business Body mass index Stearoyl-CoA Desaturase |
| Zdroj: | Diabetes |
| ISSN: | 1939-327X 0012-1797 |
| DOI: | 10.2337/db09-0481 |
| Popis: | OBJECTIVE Smoking decreases insulin action and increases the risk of type 2 diabetes in humans. Mechanisms responsible for smoking-induced insulin resistance are unclear. We hypothesized smokers would have increased intramuscular triglyceride (IMTG) and diacylglycerol (DAG) concentration and decreased fractional synthesis rate (FSR) compared with nonsmokers. RESEARCH DESIGN AND METHODS Nonsmokers (n = 18, aged 20 ± 0.5 years, BMI 22 ± 0.4 kg/m2, body fat 20 ± 2%, 0 cigarettes per day) and smokers (n = 14, aged 21 ± 0.7 years, BMI 23 ± 0.4 kg/m2, body fat 20 ± 3%, 18 ± 0.7 cigarettes per day) were studied in a fasted condition after a standardized diet. [U-13C]palmitate was infused during 4 h of rest followed by a skeletal muscle biopsy and intravenous glucose tolerance test. RESULTS Smokers were less insulin sensitive (Si) compared with nonsmokers (Si 5.28 ± 0.5 nonsmokers vs. 3.74 ± 0.3 smokers 10−4 · μU−1 · ml−1, P = 0.03). There were no differences in IMTG or DAG concentration (IMTG 24.2 ± 3.4 nonsmokers vs. 27.2 ± 5.9 smokers μg/mg dry wt, DAG 0.34 ± 0.02 nonsmokers vs. 0.35 ± 0.02 smokers μg/mg dry wt) or IMTG FSR between groups (0.66 ± 0.1 nonsmokers vs. 0.55 ± 0.09 smokers %/hr). Intramuscular lipid composition was different, with increased percent saturation of IMTG (32.1 ± 1.2 nonsmokers vs. 35.2 ± 1.0 smokers %, P = 0.05) and DAG (52.8 ± 1.7 nonsmokers vs. 58.8 ± 2.2 smokers %, P = 0.04) in smokers. Smokers had significantly decreased peroxisome proliferator–activated receptor-γ (1.76 ± 0.1 nonsmokers vs. 1.42 ± 0.11 smokers arbitrary units [AU], P = 0.03) and increased monocyte chemotactic protein-1 (3.11 ± 0.41 nonsmokers vs. 4.83 ± 0.54 smokers AU, P = 0.02) mRNA expression compared with nonsmokers. We also found increased insulin receptor substrate-1 Ser636 phosphorylation in smokers compared with nonsmokers (0.73 ± 0.08 nonsmokers vs. 1.14 ± 0.09 smokers AU, P = 0.002). CONCLUSIONS These data suggest: 1) IMTG concentration and turnover are not related to alterations in insulin action in smokers compared to nonsmokers, 2) increased saturation of IMTG and DAG in skeletal muscle may be related to insulin action, and 3) basal inhibition of insulin receptor substrate-1 may decrease insulin action in smokers. |
| Databáze: | OpenAIRE |
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