Abstract

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 (SM) would have increased intramuscular triglyceride (IMTG) and diacylglycerol (DAG) concentration, and decreased fractional synthesis rate (FSR) compared to non-smokers (CON).

Methods: CON (n=18, 20±0.5 yrs, 22±0.4 kg/m², 20±2% fat, 0 cig/day) and SM (n=14, 21±0.7 yrs, 23±0.4 kg/m², 20±3% fat, 18±.7 cig/day) were studied fasted after a standardized diet. [U-¹³C]palmitate was infused for 4 hours of rest followed by a skeletal muscle biopsy and IVGTT.

Results: SM were less insulin sensitive compared to CON (Si: 5.28±0.5 CON vs 3.74±0.3 SM 10^-4/μU/ml, p=0.03). There were no differences in IMTG or DAG concentration (IMTG: 24.2±3.4 CON vs 27.2±5.9 SM μg/mg dry wt, DAG: 0.34±0.02 CON vs 0.35±0.02 SM μg/mg dry wt), or IMTG FSR between groups (0.66±0.1 CON vs 0.55±0.09 SM %/hr). Intramuscular lipid composition was different, with increased % saturation of IMTG (32.1±1.2 CON vs 35.2±1.0 SM %, p=0.05) and DAG (52.8±1.7 CON vs 58.8±2.2 SM %, p=0.04) in smokers. SM had significantly decreased PPAR-g (1.76±0.1 CON vs 1.42±0.11 SM %, p=0.03), and increased MCP-1 (3.11±0.41 CON vs 4.83±0.54 SM %, p=0.02) mRNA expression compared to CON. We also found increased IRS-1 ser⁶³⁶ phosphorylation in SM compared to CON (0.73±0.08 CON vs 1.14±0.09 SM 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 non-smokers, 2) increased saturation of IMTG and DAG in skeletal muscle may be related to insulin action, and 3) basal inhibition of IRS-1 may decrease insulin action in smokers.